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LABORATORY AND EXPERIMENTAL MEDICINE (99 journals)

Showing 1 - 99 of 99 Journals sorted alphabetically
AAPS PharmSciTech     Hybrid Journal   (Followers: 9)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 7)
Adipocyte     Open Access   (Followers: 1)
African Journal of Laboratory Medicine     Open Access   (Followers: 2)
American Journal of Experimental and Clinical Research     Open Access   (Followers: 4)
American Journal of Medical and Biological Research     Open Access   (Followers: 10)
Animal Models and Experimental Medicine     Open Access  
Annals of Clinical Chemistry and Laboratory Medicine     Open Access   (Followers: 5)
Applied In Vitro Toxicology     Hybrid Journal   (Followers: 2)
Archives of Clinical and Experimental Medicine     Open Access  
Archives of Medical Research     Hybrid Journal   (Followers: 3)
Archives of Pathology & Laboratory Medicine     Full-text available via subscription   (Followers: 31)
Archives of Preventive Medicine     Open Access   (Followers: 3)
Biomedical Engineering     Hybrid Journal   (Followers: 3)
Bulletin of Experimental Biology and Medicine     Hybrid Journal  
Clinica Chimica Acta     Hybrid Journal   (Followers: 30)
Clinical & Experimental Metastasis     Hybrid Journal  
Clinical and Experimental Medical Journal     Full-text available via subscription   (Followers: 1)
Clinical and Experimental Medicine     Hybrid Journal   (Followers: 4)
Clinical Trials     Hybrid Journal   (Followers: 21)
Clinical Trials in Degenerative Diseases     Open Access  
Clinical Trials in Orthopedic Disorders     Open Access   (Followers: 1)
Current Medicine Research and Practice     Full-text available via subscription  
Current Research in Drug Discovery     Open Access   (Followers: 1)
Drug Design, Development and Therapy     Open Access   (Followers: 4)
Ecography     Hybrid Journal   (Followers: 28)
European Journal of Hospital Pharmacy : Science and Practice (EJHP)     Hybrid Journal   (Followers: 8)
European Journal of Medical Research     Open Access   (Followers: 1)
European Journal of Nanomedicine     Hybrid Journal   (Followers: 1)
Experimental & Molecular Medicine     Open Access   (Followers: 1)
Experimental Aging Research: An International Journal Devoted to the Scientific Study of the Aging Process     Hybrid Journal   (Followers: 3)
Experimental and Therapeutic Medicine     Full-text available via subscription   (Followers: 1)
Experimental Biology and Medicine     Hybrid Journal   (Followers: 3)
Expert Opinion on Drug Delivery     Hybrid Journal   (Followers: 20)
Frontiers in Laboratory Medicine     Open Access  
Frontiers in Medical Technology     Open Access   (Followers: 1)
IN VIVO     Full-text available via subscription   (Followers: 5)
International Archives of Biomedical and Clinical Research     Open Access  
International Journal of Experimental Pathology     Hybrid Journal   (Followers: 1)
International Journal of Health Research and Innovation     Open Access   (Followers: 1)
International Journal of Research in Medical Sciences     Open Access   (Followers: 5)
International Journal of Statistics in Medical Research     Hybrid Journal   (Followers: 5)
Journal of Cell Science & Therapy     Open Access   (Followers: 1)
Journal of Applied Biomaterials & Functional Materials     Hybrid Journal   (Followers: 1)
Journal of Biomedical and Clinical Research     Open Access  
Journal of Clinical Laboratory Analysis     Open Access   (Followers: 14)
Journal of Clinical Medicine and Research     Open Access  
Journal of Clinical Medicine Research     Open Access   (Followers: 4)
Journal of Clinical Trials     Open Access   (Followers: 6)
Journal of Current and Advance Medical Research     Open Access   (Followers: 1)
Journal of Current Medical Research and Practice     Open Access  
Journal of Current Research in Scientific Medicine     Open Access  
Journal of Current Researches on Health Sector     Open Access  
Journal of Drug Delivery and Therapeutics JDDT     Open Access   (Followers: 1)
Journal of Enzyme Inhibition and Medicinal Chemistry     Open Access   (Followers: 4)
Journal of Experimental & Clinical Medicine     Full-text available via subscription   (Followers: 1)
Journal of Experimental & Clinical Cancer Research     Open Access   (Followers: 2)
Journal of Experimental and Clinical Medicine     Open Access  
Journal of Experimental Medicine     Full-text available via subscription   (Followers: 45)
Journal of Experimental Pharmacology     Open Access   (Followers: 2)
Journal of Histotechnology     Hybrid Journal   (Followers: 2)
Journal of International Medical Research     Open Access   (Followers: 3)
Journal of Investigative Medicine High Impact Case Reports     Open Access  
Journal of Medicine and Biomedical Research     Open Access   (Followers: 1)
Journal of Muhammadiyah Medical Laboratory Technologist     Open Access  
Journal of Operating Department Practitioners     Full-text available via subscription   (Followers: 2)
Journal of the American Society of Cytopathology     Hybrid Journal   (Followers: 6)
Journal of Trace Elements in Medicine and Biology     Hybrid Journal   (Followers: 1)
Lab on a Chip     Full-text available via subscription   (Followers: 42)
Laboratory Investigation     Hybrid Journal   (Followers: 3)
Medical Devices & Sensors     Hybrid Journal  
Medical Image Analysis     Hybrid Journal   (Followers: 15)
Medical Instrumentation     Open Access  
Medical Laboratory Observer     Full-text available via subscription  
Medical Laboratory Technology Journal     Open Access  
Medicinal Chemistry Research     Hybrid Journal   (Followers: 12)
Medtech Insight     Full-text available via subscription   (Followers: 4)
Nanomedicine: Nanotechnology, Biology and Medicine     Hybrid Journal   (Followers: 7)
New Zealand Journal of Medical Laboratory Science     Full-text available via subscription   (Followers: 1)
Oriental Pharmacy and Experimental Medicine     Partially Free   (Followers: 3)
Pathology and Laboratory Medicine International     Open Access   (Followers: 7)
Physical Biology     Hybrid Journal   (Followers: 4)
Practical Laboratory Medicine     Open Access   (Followers: 2)
Proceedings of the Institution of Mechanical Engineers Part H: Journal of Engineering in Medicine     Hybrid Journal   (Followers: 3)
Prosthetics and Orthotics International     Hybrid Journal   (Followers: 9)
Pulse     Full-text available via subscription  
Qualitative Research in Medicine & Healthcare     Open Access  
Recent Advances in Biology and Medicine     Open Access  
Regulatory Toxicology and Pharmacology     Hybrid Journal   (Followers: 43)
Reproduction     Full-text available via subscription   (Followers: 7)
Revista Peruana de Medicina Experimental y Salud Pública     Open Access  
Revista Romana de Medicina de Laborator     Open Access  
RSC Medicinal Chemistry     Full-text available via subscription   (Followers: 6)
SA Pharmacist's Assistant     Open Access  
Savannah Journal of Medical Research and Practice     Full-text available via subscription  
SLAS Technology     Hybrid Journal   (Followers: 2)
Statistics in Medicine     Hybrid Journal   (Followers: 190)
Trends in Molecular Medicine     Full-text available via subscription   (Followers: 14)
Turkish Journal of Clinics and Laboratory     Open Access   (Followers: 1)
Similar Journals
Journal Cover
Experimental Biology and Medicine
Journal Prestige (SJR): 0.928
Citation Impact (citeScore): 3
Number of Followers: 3  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1535-3702 - ISSN (Online) 1535-3699
Published by Sage Publications Homepage  [1093 journals]
  • Direct conversion of adult human retinal pigmented epithelium cells to
           neurons with photoreceptor properties
    • Authors: Bo Li, Houbo Jiang, Hong Li, Boyang Zhang, Malcolm Slaughter, Zhen Yan, Jian Feng
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Degeneration of photoreceptors is a major cause of blindness. Identifying new methods for the generation of photoreceptors offers valuable options for a cell replacement therapy of blindness. Here, we show that primary adult human retinal pigmented epithelium (hRPE) cells were directly converted to postmitotic neurons with various properties of photoreceptors by the neurogenic transcription factor ASCL1 and microRNA124. At Day 8 after the induction of ASCL1 and miRNA124 expression in hRPE cells, 91% of all cells were Tuj1+, and 83% of all cells were MAP2+ neurons. The cone photoreceptor marker L/M-opsin, the rod photoreceptor marker rhodopsin, and the generic photoreceptor marker recoverin were expressed in 76%, 86%, and 92% of all cells, respectively. Real-time quantitative PCR measurements showed significant and continuous increases in the expression of photoreceptor markers phosducin and recoverin, rod cell markers phosphodiesterases 6 b and arrestin S-antigen, and cone cell markers L/M-opsin and S-opsin in three independent lines of primary hRPE cells at different days of transdifferentiation. Transmission electron microscopy of converted neurons showed disc-like structures similar to those found in photoreceptors. While the converted neurons had voltage-dependent Na+, K+, and Ca2+ currents, light-induced change in membrane potential was not detected. The study demonstrates the feasibility of rapid and efficient transdifferentiation of adult hPRE cells to neurons with many properties of photoreceptors. It opens up a new possibility in cell replacement therapy of blindness caused by photoreceptor degeneration.Impact statementThe degeneration of photoreceptors is a leading cause of blindness. Retinal pigment epithelium (RPE) cells are mitotic cells that support the function of photoreceptors. We found that lentivirus-mediated overexpression of ASCL1 and microRNA124 directly converted primary adult human RPE cells to postmitotic neurons with many properties of photoreceptors. This study identifies a new method toward the generation of human photoreceptors and provides a new avenue in cell-based therapies for blindness caused by photoreceptor degeneration.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-10-19T04:13:56Z
      DOI: 10.1177/1535370220963755
       
  • Epigallocatechin gallate decreases plasma triglyceride, blood pressure,
           and serum kisspeptin in obese human subjects
    • Authors: Saimai Chatree, Chantacha Sitticharoon, Pailin Maikaew, Kitchaya Pongwattanapakin, Issarawan Keadkraichaiwat, Malika Churintaraphan, Chanakarn Sripong, Rungnapa Sririwichitchai, Sompol Tapechum
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Obesity is one of major risk factors increasing chronic diseases including type II diabetes, cardiovascular diseases, and hypertension. The effects of epigallocatechin gallate (EGCG), the major active compound in green tea, on reduced obesity and improved metabolic profiles are still controversial. Furthermore, the effects of EGCG on human adipocyte lipolysis and browning of white adipocytes have not been elucidated. This study aimed to investigate the effects of EGCG on obesity, lipolysis, and browning of human white adipocytes. The results showed that, when compared to the baseline values, EGCG significantly decreased fasting plasma triglyceride levels (P
      Citation: Experimental Biology and Medicine
      PubDate: 2020-10-13T04:23:57Z
      DOI: 10.1177/1535370220962708
       
  • Silencing p53 inhibits interleukin 10-induced activated hepatic stellate
           cell senescence and fibrotic degradation in vivo
    • Authors: Qilan Guo, Minghua Chen, Qingduo Chen, Guitao Xiao, Zhixin Chen, Xiaozhong Wang, Yuehong Huang
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Activated hepatic stellate cells are reported to play a significant role in liver fibrogenesis. Beside the phenotype reversion and apoptosis of activated hepatic stellate cells, the senescence of activated hepatic stellate cells limits liver fibrosis. Our previous researches have demonstrated that interleukin-10 could promote hepatic stellate cells senescence via p53 signaling pathway in vitro. However, the relationship between expression of p53 and senescence of activated hepatic stellate cells induced by interleukin-10 in fibrotic liver is unclear. The purpose of present study was to explore whether p53 plays a crucial role in the senescence of activated hepatic stellate cells and degradation of collagen mediated by interleukin-10. Hepatic fibrosis animal model was induced by carbon tetrachloride through intraperitoneal injection and transfection of interleukin-10 gene to liver was performed by hydrodynamic-based transfer system. Depletions of p53 in vivo and in vitro were carried out by adenovirus-based short hairpin RNA against p53. Regression of fibrosis was assessed by liver biopsy and collagen staining. Cellular senescence in the liver was observed by senescence-associated beta-galactosidase (SA-β-Gal) staining. Immunohistochemistry, immunofluorescence double staining, and Western blot analysis were used to evaluate the senescent cell and senescence-related protein expression. Our data showed that interleukin-10 gene treatment could lighten hepatic fibrosis induced by carbon tetrachloride and induce the aging of activated hepatic stellate cells accompanied by up-regulating the expression of aging-related proteins. We further demonstrated that depletion of p53 could abrogate up-regulation of interleukin-10 on the expression of senescence-related protein in vivo and vitro. Moreover, p53 knockout in fibrotic mice could block not only the senescence of activated hepatic stellate cells, but also the degradation of fibrosis induced by interleukin-10 gene intervention. Taken together, our results suggested that interleukin-10 gene treatment could attenuate carbon tetrachloride-induced hepatic fibrosis by inducing senescence of activated hepatic stellate cells in vivo, and this induction was closely related to p53 signaling pathway.Impact statementThis work further expanded the knowledge of the molecular mechanisms underlying IL-10 anti-fibrogenic effect by exploring the function of p53 in IL-10-induced activated HSCs senescence and fibrotic degradation in vivo. Our data showed that IL-10 gene intervention could lighten hepatic fibrosis induced by CCL4 and induce the senescence of activated HSCs accompanied by up-regulating the expression of senescence-related proteins. In addition, depletion of p53 could abrogate up-regulation of IL-10 on the expression of aging-related proteins in vivo and vitro. Moreover, p53 knockout in fibrotic mice could block the senescence of activated HSCs and the degradation of fibrosis induced by IL-10 gene treatment. In summary, our results suggested that IL-10 gene intervention could attenuate CCL4-induced hepatic fibrosis by inducing senescence of activated HSCs in vivo, and this induction was closely related to p53 signaling pathway. Our study sheds important light into the anti-fibrogenic therapy of IL-10.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-10-08T05:55:36Z
      DOI: 10.1177/1535370220960391
       
  • Identification of a three-long non-coding RNA signature for predicting
           survival of temozolomide-treated isocitrate dehydrogenase mutant low-grade
           gliomas
    • Authors: Ruichun Li, Wei Chen, Ping Mao, Jia Wang, Jiangpeng Jing, Qinli Sun, Maode Wang, Xiao Yu
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Temozolomide (TMZ) is the major chemotherapy agent in glioma, and isocitrate dehydrogenase (IDH) is a well-known prognostic marker in glioma. O6-methylguanine-DNA methyltransferase promoter methylation (MGMTmethyl) is a predictive biomarker in overall gliomas rather than in IDH mutant gliomas. To discover effective biomarkers that could predict TMZ efficacy in IDH mutant low-grade gliomas (LGGs), we retrieved data of IDH mutant LGGs from TMZ arm of the EORTC22033-26033 trial as the training-set (n = 83), analyzed correlations between long non-coding RNAs (lncRNAs) and progression-free survival (PFS) using Lasso-Cox regression, and created a risk score (RS) to stratify patients. We identified a three-lncRNA signature in TMZ-treated IDH mutant LGGs. All of the three lncRNAs, as well as the RS derived, were significantly correlated with PFS. Patients were classified into high-risk and low-risk groups according to RS. PFS of the high-risk group was significantly worse than that of the low-risk group (P 
      Citation: Experimental Biology and Medicine
      PubDate: 2020-10-08T05:55:36Z
      DOI: 10.1177/1535370220962715
       
  • Long non-coding RNA CCAT1 promotes non-small cell lung cancer progression
           by regulating the miR-216a-5p/RAP2B axis
    • Authors: Lingling Pang, Qianqian Zhang, Yanmin Wu, Qingru Yang, Jinghao Zhang, Yuanyuan Liu, Ruoran Li
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      The long non-coding RNA colon cancer-associated transcript 1 (CCAT1) has been investigated to involve in the progression of non-small cell lung cancer (NSCLC). Thus, this study aims to explore the detailed molecular mechanisms of CCAT1 in NSCLC. The expression of CCAT1, miR-216a-5p, RAP2B, Bax, Bcl-2, and cleaved caspase 3 was detected by qRT-PCR or Western blot. Cell proliferation, apoptosis, migration, and invasion were analyzed using cell counting kit-8, flow cytometry or Transwell assays, respectively. The interaction between miR-216a-5p and CCAT1 or RAP2B was analyzed by luciferase reporter, RNA immunoprecipitation, and pull-down assays. The expression of CCAT1 was elevated in NSCLC, and CCAT1 deletion could inhibit NSCLC cell proliferation, migration, and invasion but induce apoptosis in vitro as well as imped tumor growth in vivo. MiR-216a-5p was confirmed to be a target of CCAT1, and silencing miR-216a-5p could reverse CCAT1 depletion-mediated inhibitory effects on cell tumorigenesis in NSCLC. Besides that, miR-216a-5p was decreased in NSCLC, and miR-216a-5p restoration inhibited cell tumorigenesis by regulating RAP2B, which was verified to be a target of miR-216a-5p. Additionally, co-expression analysis suggested that CCAT1 indirectly regulated RAP2B level by targeting miR-216a-5p in NSCLC cells. Taken together, CCAT1 deletion could inhibit cell progression in NSCLC through miR-216a-5p/RAP2B axis, indicating a novel pathway underlying NSCLC cell progression and providing new potential targets for NSCLC treatment.Impact statementWe investigated that CCAT1 expression was elevated in NSCLC and CCAT1 deletion was identified to inhibit cell carcinogenic phenotypes in NSCLC cells via miR-216a-5p/RAP2B axis, which reveals a novel pathway underlying progression in NSCLC cells and providing potential targets for NSCLC treatment.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-10-07T06:32:58Z
      DOI: 10.1177/1535370220961013
       
  • Lnc-ATG9B-4 aggravates progress of hepatocellular carcinoma through cell
           proliferation and migration by upregulating CDK5
    • Authors: Ming Li, Le Wei, Pin-Yue Liu, Xue-Mei Zhang, Fang Liu, Fen Yang, Xiang-Shang Hu, Zhong-Cheng Mo
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Long noncoding RNAs play an important role in the occurrence, invasion, as well as metastasis of various human cancers, including hepatocellular carcinoma. Long noncoding RNAs can affect the biological functions of hepatocellular carcinoma cells by regulating various genes; however, only a small fraction of molecular mechanisms of long noncoding RNAs have been elucidated. In the present study, lnc AC010973.1 (lnc-ATG9B-4) was first identified by microarray analysis from 8 patients with hepatocellular carcinoma and confirmed by quantitative PCR in 176 patients with hepatocellular carcinoma. We demonstrated that lnc-ATG9B-4 was tightly relative to the tumorous size, TNM stages, portal vein tumor thrombus (PVTT), the tumor capsule, metastasis, degree of differentiation, and poor prognosis of hepatocellular carcinoma according to long-term follow-up data. In hepatocellular carcinoma cells, overexpression of lnc-ATG9B-4 promoted proliferation, invasion, as well as migration, while inhibiting lnc-ATG9B-4 by siRNA significantly attenuated the proliferation, invasion, as well as migration. Interestingly, lnc-ATG9B-4 increased the expression of cyclin-dependent kinase 5 (CDK5), which was closely related to the development and chemotherapy sensitivity of hepatocellular carcinoma. In summary, our results revealed that lnc-ATG9B-4 suggests an unfavorable prognosis of hepatocellular carcinoma and facilitates the proliferation, invasion, as well as migration of hepatocellular carcinoma cells by upregulating CDK5. This research suggests that lnc-ATG9B-4 may be a new biomarker for predicting the prognosis of hepatocellular carcinoma; meanwhile, targeting lnc-ATG9B-4 might serve as a potential strategy for the treatment hepatocellular carcinoma.Impact statementIn this study, we explored the expression profile of lncRNA in HCC tumor tissues and paracancerous tissues using microarray assays. Furthermore, a new lncRNA (lnc-ATG9B-4) was identified, which was about 3.5 times more expressed in tumor tissues than in paracancerous tissues. Through clinicopathological analysis, lnc-ATG9B-4 was determined to be related to the tumorous size, TNM stages, portal vein tumor thrombus (PVTT), the tumor capsule, metastasis, and the degree of differentiation. Lnc-ATG9B-4 promoted the proliferation, invasion, as well as migration of the HCC cells by upregulating the expression of CDK5. Here, we further exploited the molecular mechanisms of lnc-ATG9B-4 to screen new drug intervention targets for recurrence and metastasis of HCC.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-10-07T06:32:58Z
      DOI: 10.1177/1535370220963197
       
  • Attenuation of acute and chronic inflammation using compounds derived from
           plants
    • Authors: Stephen C Bondy, Meixia Wu, Kedar N Prasad
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      The appearance of excessive inflammatory activity is associated with onset of many disease states. Such non-productive responses are often the basis of the mortality consequent to incurring numerous disorders. The current outbreak of coronavirus disease 2019 caused by the virus “severe acute respiratory syndrome coronavirus 2” is a striking reflection of the inadequacy of current medical science to adequately address this issue. The usefulness of a range of materials of botanical origin in the attenuation of both chronic and acute inflammatory responses to various disease stressors is described. The properties of preparations of plant-based origin often parallel those of synthesized pharmacologics, but differ from them in some key respects. These differences can lead to more traditional preparations having distinct therapeutic advantages but also a number of specific shortcomings. The strengths and weaknesses of these materials are objectively contrasted with that of a more orthodox pharmacological approach. Each of these emphases in style has specific advantages and they should not be considered as competitors, but rather as accomplices in combating adverse states involving derangement of immune function.Impact statementA large component of many disease states is the improper regulation of immune function. This commonly leads to the appearance of redundant inflammation which does not effectively address any underlying issue but actually impedes a successful response to disease-induced metabolic derangement. There is currently no means of successfully addressing this problem which is especially relevant in the ongoing viral pandemic of SARS-CoV-2. In view of this failure, new courses of action need to be contemplated. This review proposes reconsideration of the potential utility of natural compounds originating from plants in order to address this deficit. Such a new direction, in concert with more conventional strategies could help to alleviate this wide-ranging crisis.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-10-07T06:32:57Z
      DOI: 10.1177/1535370220960690
       
  • Serum-derived exosomes from neurofibromatosis type 1 congenital tibial
           pseudarthrosis impaired bone by promoting osteoclastogenesis and
           inhibiting osteogenesis
    • Authors: Ge Yang, Hui Yu, Yaoxi Liu, Weihua Ye, Guanghui Zhu, An Yan, Qian Tan, Haibo Mei
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Treatment of congenital pseudarthrosis of the tibia (CPT) still is full of challenges in pediatric orthopedist. Serum-derived exosomes (SDEs) have been proven to be participated in bone remodeling. However, the molecular changes in SDEs of CPT children and their pathologies have not been elucidated. In this study, SDEs were isolated and purified from CPT patients (CPT-SDEs) associated with neurofibromatosis type 1 (NF1) and normal children (Norm-SDEs). Then we obtained the proteomics profile of SDEs by combining liquid chromatography-tandem mass spectrometry (LC-MS/MS) and tandem mass tag label-based quantitation. In vitro, the efficacy of SDEs on osteoblastic differentiation of MC3T3-E1 cells and osteoclastogenesis ability of RAW264.7 cells were evaluated by quantitative real-time PCR (qRT-PCR) and cytochemical staining. In vivo, we used micro-CT to assess cortical bone mass and trabecular microstructures to reflect the influence of SDEs on bone remodeling after injection into the tail vein of rats. Based on proteomics analysis, 410 differentially expressed proteins, including 289 downregulated proteins and 121 upregulated proteins, were identified in the CPT-SDEs. These proteins have multiple biological functions associated with cellular metabolic processes, catalytic activity, and protein binding, which are important for cell differentiation and proliferation. In vitro, CPT-SDEs decreased the osteogenic differentiation of MC3T3-E1 cells and promoted the osteoclastogenesis of RAW264.7 cells. Injection of CPT-SDEs into the tail vein for two months resulted in bone loss in rats, as indicated by the decrease in trabecular and cortical bone mass. Our findings demonstrated the differences in proteins in SDEs between normal and CPT children with NF1. These differentially expressed proteins in CPT-SDEs contributed to deteriorating trabecular bone microstructures by inhibiting bone formation and stimulating bone resorption.Impact statementCongenital pseudarthrosis of the tibia (CPT) is an uncommon and puzzling disease associated with a high rate of disability. To date, the biological mechanisms related to this disease have largely not been elucidated. In this study, we determined the biological functions of serum-derived exosomes (SDEs) from children with neurofibromatosis type 1 (NF1) associated with CPT (CPT-SDEs) and compared their proteomic profiles with those of SDEs from normal children. Based on proteomics analysis, 410 differentially expressed proteins, including 289 downregulated proteins and 121 upregulated proteins, were identified in the CPT-SDEs. In addition, CPT-SDEs decreased the osteogenic differentiation of MC3T3-E1 cells and promoted the osteoclastogenesis ability of RAW264.7 cells. Moreover, injecting CPT-SDEs into the tail veins led to bone loss in rats, as detected by the reduction in trabecular and cortical bone mass. These findings indicate that CPT-SDEs impair bone quality, which may provide a reasonable explanation for the low bone quality and tibial nonunion in children with NF1 associated with congenital tibial pseudarthrosis.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-10-07T06:32:57Z
      DOI: 10.1177/1535370220962737
       
  • Prevalence of class I–III BRAF mutations among 114,662 cancer patients
           in a large genomic database
    • Authors: Jeff Owsley, Matt Stein, Jason Porter, Gino K In, Mohamed Salem, Steven O’Day, Andrew Elliott, Kelsey Poorman, Geoffrey Gibney, Ari VanderWalde
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      BRAF mutations are relatively common in many cancers, particularly melanoma, colorectal cancer, and thyroid cancer and to a lesser extent in lung cancer. These mutations can be targeted by BRAF and MEK inhibitors, which exhibit good clinical activity. There are conflicting reports of the various relative rates of BRAF Class I mutations (V600 locus), defined as those that exhibit extremely strong kinase activity by stimulating monomeric activation of BRAF, Class II, define as non-V600 mutations that activate BRAF to signal as a RAS-independent dimer, and Class III mutations, defined as “kinase-dead” with low kinase activity as compared to wild type BRAF. Prospective studies have largely focused on patients with tumors harboring Class I BRAF mutations (limited to the V600 locus) where response rates up to 70% with BRAF plus MEK inhibition have been demonstrated. We report on the relative prevalence of various types of BRAF mutations across human cancers in a cohort of 114,662 patients that received comprehensive genomic profiling using next-generation sequencing. Of these patients, 4517 (3.9%) a pathogenic or presumed pathogenic BRAF mutation (3.9%). Of these, 1271 were seen in melanoma, representing 39.7% of all melanomas sequenced, representing the highest rate in all tumors. Class I (V600) mutations were seen overall in 2841 patients (62.1% of BRAF mutations, 2.4% of total cancers). Class II mutations were seen in 746 tumors (16.5% of BRAF mutant, 0.7% of total), and Class III mutations were seen in 801 tumors (17.7% of BRAF, 0.7% of total). Knowledge of the relative prevalence of these types of mutations can aid in the development of agents that might better address non-V600 mutations in cancer.Impact statementThese data represent the largest aggregation of BRAF mutations within a single clinical database to our knowledge. The relative proportions of both BRAF V600 mutations and non-V600 mutations are informative in all cancers and by malignancy, and can serve as a definitive gold-standard for BRAF mutation cancer incidence by malignancy. The rate of BRAF mutation in human cancer in a real-world large database is lower than previously reported likely representing testing more broadly across tumor types. The relative percentages of Class II and Class III BRAF mutations are higher than previously reported, representing almost 35% of BRAF mutations in cancer. These findings provide support for the development of effective treatments for non-V600 BRAF mutations in cancer.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-10-06T05:10:52Z
      DOI: 10.1177/1535370220959657
       
  • Localization and function of a Plasmodium falciparum protein
           (PF3D7_1459400) during erythrocyte invasion
    • Authors: Emmanuel Amlabu, Prince B Nyarko, Grace Opoku, Damata Ibrahim-Dey, Philip Ilani, Henrietta Mensah-Brown, Grace A Akporh, Ojo-Ajogu Akuh, Evelyn A Ayugane, David Amoh-Boateng, Kwadwo A Kusi, Gordon A Awandare
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Nearly 60% of Plasmodium falciparum proteins are still uncharacterized and their functions are unknown. In this report, we carried out the functional characterization of a 45 kDa protein (PF3D7_1459400) and showed its potential as a target for blood stage malaria vaccine development. Analysis of protein subcellular localization, native protein expression profile, and erythrocyte invasion inhibition of both clinical and laboratory parasite strains by peptide antibodies suggest a functional role of PF3D7_1459400 protein during erythrocyte invasion. Also, immunoreactivity screens using synthetic peptides of the protein showed that adults resident in malaria endemic regions in Ghana have naturally acquired plasma antibodies against PF3D7_1459400 protein. Altogether, this study presents PF3D7_1459400 protein as a potential target for the development of peptide-based vaccine for blood-stage malaria.Impact statementPlasmodium falciparum malaria is a global health problem. Erythrocyte invasion by P. falciparum merozoites appears to be a promising target to curb malaria. We have identified and characterized a novel protein that is involved in erythrocyte invasion. Our data on protein subcellular localization, stage-specific protein expression pattern, and merozoite invasion inhibition by α-peptide antibodies suggest a role for PF3D7_1459400 protein during P. falciparum erythrocyte invasion. Even more, the human immunoepidemiology data present PF3D7_1459400 protein as an immunogenic antigen which could be further exploited for the development of new anti-infective therapy against malaria.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-10-06T05:10:51Z
      DOI: 10.1177/1535370220961764
       
  • H2S attenuates oxidative stress via Nrf2/NF-κB signaling to regulate
           restenosis after percutaneous transluminal angioplasty
    • Authors: Ken Ling, Wei Zhou, Yi Guo, Guofu Hu, Jie Chu, Fen Xie, Yiqing Li, Weici Wang
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Restenosis after angioplasty of peripheral arteries is a clinical problem involving oxidative stress. Hydrogen sulfide (H2S) participates in oxidative stress regulation and activates nuclear factor erythroid 2-related factor 2 (Nrf2). This study investigated the effect of H2S and Nrf2 on restenosis-induced arterial injury. Using an in vivo rat model of restenosis, we investigated whether H2S inhibits restenosis after percutaneous transluminal angioplasty (PTA) and the oxidative stress-related mechanisms implicated therein. The involvement of Nrf2 was explored using Nrf2-shRNA. Neointimal formation and the deposition of elastic fibers were assessed histologically. Inflammatory cytokine secretion and the expression of proteins associated with oxidative stress and inflammation were evaluated. The artery of rats subjected to restenosis showed increased arterial intimal thickness, with prominent elastic fiber deposition. Sodium hydrosulfide (NaHS), an H2S donor, counteracted these changes in vivo. Restenosis caused a decrease in anti-oxidative stress signaling. This phenomenon was inhibited by NaHS, but Nrf2-shRNA counteracted the effects of NaHS. In terms of inflammation, inflammatory cytokines were upregulated, whereas NaHS suppressed the induced inflammatory reaction. Similarly, Nrf2 downregulation blocked the effect of NaHS. In vitro studies using aortic endothelial and vascular smooth muscle cells isolated from experimental animals showed consistent results as those of in vivo studies, and the participation of the nuclear factor-kappa B signaling pathway was demonstrated. Collectively, H2S played a role in regulating post-PTA restenosis by alleviating oxidative stress, modulating anti-oxidant defense, and targeting Nrf2-related pathways via nuclear factor-kappa B signaling.Impact statementThis work advances the field of vascular pharmacology as it addresses the issue of neointimal hyperplasia, which is a severe problem that results in restenosis after percutaneous transluminal angioplastic surgery. The effectiveness of vascular surgery is impacted negatively because of this phenomenon, and a solution is urgently needed. Here, we report in a rat model of angioplasty-induced vessel injury that hydrogen sulfide (H2S) counteracts post-percutaneous transluminal angioplasty neointimal formation and inflammation. Importantly, we demonstrated that the action of H2S requires Nrf2 signaling and is associated with the regulation of oxidative stress and inflammation via the nuclear factor-kappa B signaling pathway. Notably, our findings offer a potential strategy to address post-vascular surgery restenosis, which remains a clinical problem.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-30T10:28:36Z
      DOI: 10.1177/1535370220961038
       
  • Overexpression of p53 accelerates puberty in high-fat diet–fed mice
           through Lin28/let-7 system
    • Authors: Ting Chen, Cailong Chen, Haiying Wu, Xiuli Chen, Rongrong Xie, Fengyun Wang, Hui Sun, Linqi Chen
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      High fat intake is one of the most important reasons of the surging prevalence of childhood obesity all over the world. Obesity and high fat intake have been revealed to cause premature activation of hypothalamo-pituitary-gonadal axis and central precocious puberty. The onset of puberty is controlled by neuroendocrine mechanisms containing overlapping and interacting gene networks. The latter contains five major transcriptional level hubs, among which the transcriptional factor p53, a well-established tumor suppressor protein, also plays a crucial role in obesity and metabolic disorders. In the current study, we repeated prior observations that high-fat diet advances vaginal opening in rodents and extended these findings by demonstrating that high-fat diet mice had higher expression of p53 in hypothalami than mice fed with normal chow. More importantly, in high-fat diet mice, hypothalamus-specific overexpression of p53 can make vaginal opening much earlier, while inhibition of p53 expression relatively delayed vaginal opening. The c-Myc and Lin28b levels increased, while let-7a mRNA levels decreased in the high-fat diet mice. Overexpression of p53 reduced c-Myc and Lin28b mRNA and protein levels, whereas elevated let-7a mRNA levels in high-fat diet mice. Inhibition of p53 expression by pifithrin-α elevated c-Myc and Lin28b but reduced let-7a levels in high-fat diet mice. In conclusion, high fat intake can accelerate the onset of puberty by up-regulation of p53 expression in hypothalamus. Overexpressed p53 may accelerate hypothalamo-pituitary-gonadal axis activation partially through the c-Myc/Lin28/let-7 system.Impact statement High-fat intake and subsequent obesity are associated with premature onset of puberty, but the exact neuroendocrine mechanisms are still unclear. The transcriptional factor p53 has been predicted to be a central hub of the gene networks controlling the pubertal onset. Besides, p53 also plays crucial roles in metabolism. Here, we explored p53 in the hypothalami of mice fed a high-fat diet (HFD), which showed an up-regulated expression. Besides, we also revealed that overexpressed p53 may accelerate hypothalamo-pituitary-gonadal (HPG) axis activation partially through the c-Myc/Lin28/let-7 system. These results can deepen our understanding of the interaction between metabolic regulation and puberty onset control, and may shed light on the neuroendocrine mechanisms of obesity-related central precocious puberty.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-30T10:28:35Z
      DOI: 10.1177/1535370220961320
       
  • Whole exome sequencing identifies rare coding variants in novel
           human-mouse ortholog genes in African individuals diagnosed with
           non-syndromic hearing impairment
    • Authors: Oluwafemi G Oluwole, Kevin K Esoh, Edmond Wonkam-Tingang, Noluthando Manyisa, Jean Jacques Noubiap, Emile R Chimusa, Ambroise Wonkam
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Physiologically, the human and murine hearing systems are very similar, justifying the extensive use of mice in experimental models for hearing impairment (HI). About 340 murine HI genes have been reported; however, whether variants in all human-mouse ortholog genes contribute to HI has been rarely investigated. In humans, nearly 120 HI genes have been identified to date, with GJB2 and GJB6 variants accounting for half of congenital HI cases, of genetic origin, in populations of European and Asian ancestries, but not in most African populations. The contribution of variants in other known genes of HI among the populations of African ancestry is poorly studied and displays the lowest pick-up rate. We used whole exome sequencing (WES) to investigate pathogenic and likely pathogenic (PLP) variants in 34 novel human-mouse orthologs HI genes, in 40 individuals from Cameroon and South Africa diagnosed with non-syndromic hearing impairment (NSHI), and compared the data to WES data of 129 ethnically matched controls. In addition, protein modeling for selected PLP gene variants, gene enrichment, and network analyses were performed. A total of 4/38 murine genes, d6wsu163e, zfp719, grp152 and minar2, had no human orthologs. WES identified three rare PLP variants in 3/34 human-mouse orthologs genes in three unrelated Cameroonian patients, namely: OCM2, c.227G>C p.(Arg76Thr) and LRGI1, c.1657G>A p.(Gly533Arg) in a heterozygous state, and a PLP variant MCPH1, c.2311C>G p.(Pro771Ala) in a homozygous state. In silico functional analyses suggest that these human-mouse ortholog genes functionally co-expressed interactions with well-established HI genes: GJB2 and GJB6. The study found one homozygous variant in MCPH1, likely to explain HI in one patient, and suggests that human-mouse ortholog variants could contribute to the understanding of the physiology of hearing in humans.Impact statementDespite, human and murine hearing system being very similar, the contribution of variants in relevant mouse-ortholog genes to hearing impairment (HI) has not been fully investigated. The contribution of variants in the known non-syndromic hearing impairment (NSHI) genes among Africans is poorly studied, suggesting that the novel gene(s) and mutations are yet to be discovered in NSHI in the African populations. Using whole exome sequencing (WES), this study identified rare candidate pathogenic and likely pathogenic (PLP) variants in 3/34 novel human-mouse ortholog genes in 3/40 individuals, with one homozygous variant, MCPH1, c.2311C>G p.(Pro771Ala), likely to explain HI in one patient. In silico functional analyses suggest that these human-mouse ortholog genes could contribute to the understanding of the physiology of hearing in humans and thus the variants identified in those genes deserve additional investigations.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-30T09:58:00Z
      DOI: 10.1177/1535370220960388
       
  • Modeling the pathophysiology of Parkinson’s disease in
           patient-specific neurons
    • Authors: Jian Feng
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      The 30 trillion cells that self-assemble into a human being originate from the pluripotent stem cells in the inner cell mass of a human blastocyst. The discovery of induced pluripotent stem cells (iPSCs) makes it possible to approximate various aspects of this natural developmental process artificially by generating materials that can be used in invasive mechanistic studies of virtually all human conditions. In Parkinson’s disease, instructions computed by the basal ganglia to control voluntary motor functions break down, leading to widespread rhythmic bursting activities in the basal ganglia and beyond. It is thought that these oscillatory neuronal activities, which disrupt aperiodic neurotransmission in a normal brain, may reduce information content in the instructions for motor control. Using midbrain neuronal cultures differentiated from iPSCs of Parkinson’s disease patients with parkin mutations, we find that parkin mutations cause oscillatory neuronal activities when dopamine D1-class receptors are activated. This system makes it possible to study the molecular basis of rhythmic bursting activities in Parkinson’s disease. Further development of stem cell models of Parkinson’s disease will enable better approximation of the situation in the brain of Parkinson’s disease patients. In this review, I will discuss what has been found in the past about the pathophysiology of motor dysfunction in Parkinson’s disease, especially oscillatory neuronal activities and how stem cell technologies may transform our abilities to understand the pathophysiology of Parkinson’s disease.Impact statementResearch on the pathophysiology of Parkinson’s disease (PD) has generated effective therapies such as deep brain stimulation. A better understanding of PD pathophysiology calls for patient-specific materials amenable for invasive mechanistic studies. In this minireview, I discuss our recent work on oscillatory neuronal activities in midbrain neurons differentiated from induced pluripotent stem cells (iPSCs) of PD patients with parkin mutations. These patient-specific neurons enable a variety of studies previously not feasible in the human system. Further development in stem cell technologies may generate more realistic models for us to decipher PD pathophysiology. These new developments will transform research and development in Parkinson’s disease.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-25T06:35:05Z
      DOI: 10.1177/1535370220961788
       
  • Secondary hemophagocytic lymphohistiocytosis versus cytokine release
           syndrome in severe COVID-19 patients
    • Authors: Nausheen N Hakim, Jeffrey Chi, Coral Olazagasti, Johnson M Liu
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      COVID-19 or SARS-CoV-2 infection can lead to severe acute respiratory distress syndrome/pneumonia with features of cytokine storm reminiscent of secondary hemophagocytic lymphohistiocytosis (HLH), which can be diagnosed by the calculated HScore. Recent reports have suggested favorable responses to the interleukin-1 receptor antagonist, anakinra in patients with COVID-19 associated secondary HLH. In our single institution study, we compared 14 COVID-19 cytokine storm patients with 10 secondary HLH patients seen immediately prior to the pandemic (non-COVID-19), to determine whether diagnostic features of secondary HLH were typically seen in COVID-19 patients presenting with cytokine storm. Although most of our COVID-19 patients did not fulfill diagnostic criteria for HLH, we hypothesize that identification of HLH may relate to the severity or timing of cytokine release. Based on our observations, we would suggest distinguishing between cytokine release syndrome and secondary HLH, reserving the latter term for cases fulfilling diagnostic criteria.Impact statementSevere COVID-19 associated pneumonia and acute respiratory distress syndrome has recently been described with life-threatening features of cytokine storm and loosely referred to as hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS). Although a recent report indicated favorable responses to the interleukin-1 receptor antagonist, anakinra in eight patients with COVID-19 secondary HLH diagnosed using the HScore calculation, others have suggested that the diagnosis of secondary HLH is uncommon and that the use of the HScore has limited value in guiding immunomodulatory therapy for COVID-19. Here, we provide additional perspective on this important controversy based upon comparisons between 14 COVID-19 cytokine storm patients and 10 secondary HLH patients seen immediately prior to the pandemic. We hypothesize that identification of HLH may relate to the severity or timing of cytokine release and suggest distinguishing between cytokine release syndrome and secondary HLH, reserving the latter term for cases fulfilling diagnostic criteria.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-25T06:10:09Z
      DOI: 10.1177/1535370220962043
       
  • Role of age and neuroinflammation in the mechanism of cognitive deficits
           in sickle cell disease
    • Authors: Raven A Hardy, Noor Abi Rached, Jayre A Jones, David R Archer, Hyacinth I Hyacinth
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      This study aims to determine whether sickle cell mice could recapitulate features of cognitive and neurobehavioral impairment observed in sickle cell patients and whether neuroinflammation could be a potential therapeutic target as in other non-sickle cell disease-related cognitive dysfunction. Cognitive (learning and memory) and behavioral (anxiety) deficits in 13- and later 6-month-old male Townes humanized sickle cell (SS) and matched control (AA) mice were evaluated using novel object recognition (NOR) and fear conditioning tests. Immunohistochemistry was performed to quantify peripheral immune cell (CD45+) and activated microglia (Iba1+) as markers of neuroinflammation in the dentate and peri-dentate gyrus areas. We evaluated cell fate by measuring 5'-bromodeoxyuridine and doublecortin fluorescence and phenotyped proliferating cells using either glial fibrillary acid protein (GFAP+), neuronal nuclei (NeuN+), CD45+, and Iba1+. In addition, Golgi-Cox staining was used to assess markers of neuroplasticity (dendritic spine density and morphology and density of dendrite arbors) on cortical and hippocampal pyramidal neurons. Compared to matched AA controls, 13-month-old SS mice showed significant evidence of cognitive and behavioral deficit on NOR and fear conditioning tests. Also, SS mice had significantly higher density of CD45+ and activated microglia cells (i.e. more evidence of neuroinflammation) in the dentate and peri-dentate gyrus area. Additionally, SS mice had significantly lower dendritic spine density, but a higher proportion of immature dendritic spines. Treatment of 13-month-old SS mice with minocycline resulted in improvement of cognitive and behavioral deficit compared to matched vehicle-treated SS mice. Also, treated SS mice had significantly fewer CD45+ and activated microglia cells (i.e. less evidence of neuroinflammation) in the dentate and peri-dentate gyrus, as well as a significant improvement in markers of neuroplasticity.Impact statementThis study provides crucial information that could be helpful in the development of new or repurposing of existing therapies for the treatment of cognitive deficit in individuals with sickle cell disease (SCD). Its impact is in demonstrating for the first time that neuroinflammation and along with abnormal neuroplasticity are among the underlying mechanism of cognitive and behavioral deficits in SCD and that drugs such as minocycline which targets these pathophysiological mechanisms could be repurposed for the treatment of this life altering complication of SCD.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-23T04:09:30Z
      DOI: 10.1177/1535370220958011
       
  • Prevalence and correlation of human papillomavirus genotypes with clinical
           factors in cervical samples from Mexican women
    • Authors: Fabiola Hernández-Rosas, Erika Orozco-Hernández, Liliana Maza-Sánchez, Pamela Citlalli Salgado-García, Enrique Navarro-Vidal, Mercedes Piedad de León-Bautista
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      In the last decade, the inclusion of HPV DNA testing in cervical cancer screening has provided one of the best strategies for the prevention and timely detection of HPV. We conducted a high-throughput HPV genotyping study based on MALDI-TOF mass spectrometry to determine the prevalence of 24 HPV genotypes, including oncogenic genotypes, in Mexican women and correlated the results with cytological findings and clinical variables. We likewise identified the risk factors in patients with the HPV infection. Our study included 1000 women from Sonora, Mexico, who participated in cervical cancer screening campaigns and who underwent a Pap smear and HPV DNA test. The results showed that the overall prevalence of HPV was 27.2%, 18.5% with single, and 8.7% multiple infections. The low-risk HPV genotype 6 (8.5%) and oncogenic genotypes 31 (8.1%) and 53 (4.4%) were the most prevalent in the study population. The number of lifetime sexual partners, previous STIs, and age at first intercourse was significantly associated with HPV infection (P ≤ 0.05). Smoking (OR = 1.5609; 95% IC 1.062–2.292) and more than three lifetime sexual partners (OR = 1.609; 95% IC = 1.124–2.303) represented risk factors for HPV infection. Cytological abnormalities were found in 3.4% of the HPV-positive samples. CIN 1–3 occurred in 0.6% of high-risk HPV cases. In general, the prevalence of the HPV genotypes is high in Mexican women with normal cytological findings. This issue highlights the importance of HPV research in seemingly healthy women and could help guide screening strategies for cervical cancer prevention in Mexico.Impact statementWe are submitting data regarding the prevalence and type distribution of the HPV infection and the risk factors associated with it, which may provide a valuable reference to reinforce screening strategies, and to maintain HPV genotype surveillance in Mexico. We discuss the overall prevalence of HPV infection as detected in normal cytological samples stratified by age, different types of infection, and oncogenic capacity. One of the most important findings was that common HPV genotypes detected in healthy women were the genotype numbers: 6, 31, 16, and 56, likewise, smoking and having a history of more than three sexual partners over their lifetime, represented the main risk factors in this study. Furthermore, we found a low frequency of cytological abnormalities and CIN 1–3 in women with HR-HPV.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-23T04:09:30Z
      DOI: 10.1177/1535370220959747
       
  • ADMA (asymmetric dimethylarginine) and angiogenic potential in patients
           with type 2 diabetes and prediabetes
    • Authors: Radosław Wieczór, Anna M Wieczór, Arleta Kulwas, Danuta Rość
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Asymmetric dimethylarginine is an endogenous competitive inhibitor of nitric oxide synthase and marker of endothelial dysfunction, but the question remains as to whether asymmetric dimethylarginine is a marker of cardiovascular episodes or their independent risk factor. ADMA/DDAH (dimethylaminohydrolase) pathway regulates vascular endothelial growth factor (VEGF)-mediated angiogenesis due to its impact on the NO formation. The aim of the study was to assess the concentrations of asymmetric dimethylarginine and the angiogenic potential in the blood of subjects with type 2 diabetes (T2DM, n = 33) and patients with prediabetes (n = 32)—impaired fasting glycemia and/or impaired glucose tolerance (WHO criteria). The study found that both the prediabetes group and subjects with T2DM had significantly elevated concentrations of asymmetric dimethylarginine, significantly high levels of VEGF-A, low ratio of sVEGF-R1/VEGF-A, and sVEGF-R2/VEGF-A. This may suggest endothelial damage at early stages of carbohydrate metabolism dysfunction—before T2DM is diagnosed. Higher proangiogenic potential in prediabetes and T2DM patients than in healthy subjects, is not only the effect of an increase in VEGF-A levels, but also reduced inhibition of circulating receptors.Impact statementOur research provided new insight into the mechanisms governing vascular complications in prediabetes and type 2 diabetes. Unfortunately, most studies focus on angiogenesis markers (VEGF-A, sVEGF-R1, sVEGF-R2) and endothelial dysfunction marker (ADMA) separately. Our findings reported for the first time that endothelial damage and angiogenic potential at early stage of carbohydrate dysfunction appear in prediabetes before type 2 diabetes is diagnosed.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-22T07:03:06Z
      DOI: 10.1177/1535370220959738
       
  • Contrast effects of autophagy in the treatment of bladder cancer
    • Authors: Ece Konac, Yener Kurman, Sümer Baltaci
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Bladder cancer is a disease that negatively affects patients’ quality of life, but treatment options have remained unchanged for a long time. Although promising results have been achieved with current bladder cancer treatments, cancer recurrence, progression, and therapy resistance are the most severe problems preventing the efficiency of bladder cancer treatments. Autophagy refers to an evolutionarily conserved catabolic process in which proteins, damaged organelles, and cytoplasmic components are degraded by lysosomal enzymes. Autophagy regulates the therapeutic response to the chemotherapy drugs, thus determining the effect of therapy on cancer cells. Autophagy is a stress-induced cell survival mechanism and its excessive stimulation can cause resistance of tumor cells to therapeutic agents. Depending on the conditions, an increase in autophagy may cause treatment resistance or autophagic cell death, and it is related to important anti-cancer mechanisms, such as apoptosis. Therefore, understanding the roles of autophagy under different conditions is important for designing effective anti-cancer agents. The dual role of autophagy in cancer has attracted considerable attention in respect of bladder cancer treatment. In this review, we summarize the basic characteristics of autophagy, including its mechanisms, regulation, and functions, and we present examples from current studies concerning the dual role of autophagy in bladder cancer progression and therapy.Impact statementAutophagy acts as an intracellular recycling system. Infection and mitochondrial damage, maintaining cellular homeostasis, orchestrating nutrient stress, hypoxia, and oxidative stress are some of the physiological roles associated with autophagy. Autophagy has also context-dependent roles in cancer. Autophagy has a significant impact on tumor initiation and promotion, with both tumor-suppressive and tumor-promoting roles. Unfortunately, conventional systemic chemotherapy for cancer therapy has been reported to have primary limitations such as chemo-resistance of targeted cells. The cytoprotective role of autophagy has been postulated as one of the causes of this resistance. Hence, combination therapy using autophagy inhibitors has recently started to emerge as a noteworthy strategy in the treatment of cancer. Therefore, targeting the autophagy pathways may be a potential therapeutic strategy for addressing cancer progression or therapy resistance in the near future. This review will provide a novel insight to understanding the paradoxical roles of autophagy in tumor suppression and tumor promotion.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-21T06:03:43Z
      DOI: 10.1177/1535370220959336
       
  • Microengineered systems with iPSC-derived cardiac and hepatic cells to
           evaluate drug adverse effects
    • Authors: Keri Dame, Alexandre JS Ribeiro
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Hepatic and cardiac drug adverse effects are among the leading causes of attrition in drug development programs, in part due to predictive failures of current animal or in vitro models. Hepatocytes and cardiomyocytes differentiated from human induced pluripotent stem cells (iPSCs) hold promise for predicting clinical drug effects, given their human-specific properties and their ability to harbor genetically determined characteristics that underlie inter-individual variations in drug response. Currently, the fetal-like properties and heterogeneity of hepatocytes and cardiomyocytes differentiated from iPSCs make them physiologically different from their counterparts isolated from primary tissues and limit their use for predicting clinical drug effects. To address this hurdle, there have been ongoing advances in differentiation and maturation protocols to improve the quality and use of iPSC-differentiated lineages. Among these are in vitro hepatic and cardiac cellular microsystems that can further enhance the physiology of cultured cells, can be used to better predict drug adverse effects, and investigate drug metabolism, pharmacokinetics, and pharmacodynamics to facilitate successful drug development. In this article, we discuss how cellular microsystems can establish microenvironments for these applications and propose how they could be used for potentially controlling the differentiation of hepatocytes or cardiomyocytes. The physiological relevance of cells is enhanced in cellular microsystems by simulating properties of tissue microenvironments, such as structural dimensionality, media flow, microfluidic control of media composition, and co-cultures with interacting cell types. Recent studies demonstrated that these properties also affect iPSC differentiations and we further elaborate on how they could control differentiation efficiency in microengineered devices. In summary, we describe recent advances in the field of cellular microsystems that can control the differentiation and maturation of hepatocytes and cardiomyocytes for drug evaluation. We also propose how future research with iPSCs within engineered microenvironments could enable their differentiation for scalable evaluations of drug effects.Impact statementCardiac and hepatic adverse drug effects are among the leading causes of attrition in preclinical and clinical drug development programs as well as marketing withdrawals. The insufficiency of animal testing models has led to considerable interest in the employment of cardiac and hepatic models using human-induced pluripotent stem cells (iPSCs) for drug toxicity testing. However, current batches of iPSC-derived cardiomyocytes and hepatocytes are variable and not matured as adult primary tissues, which limit their prediction of drug effects. This article discusses how the use of microfluidics can create microenvironments to better control differentiation protocols and increase the physiological relevance of iPSC-derived cardiomyocytes and hepatocytes. Development and standardization of technologies will enable evaluation of the potential value of cellular microsystems to improve the in vitro models used in drug development programs. Future steps in this field include controlled connections of organ systems to better recreate clinical metabolism and pharmacokinetics.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-17T08:36:41Z
      DOI: 10.1177/1535370220959598
       
  • Liquiritigenin decreases tumorigenesis by inhibiting DNMT activity and
           increasing BRCA1 transcriptional activity in triple-negative breast cancer
           
    • Authors: Fang Liang, Hao Zhang, Hui Gao, Duo Cheng, Nan Zhang, Jie Du, Junmin Yue, Peng Du, Beibei Zhao, Lu Yin
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      As a selective estrogen receptor β agonist, the natural flavonoid liquiritigenin reportedly inhibits invasiveness of breast cancer cells, but its specific role and mechanism remain largely unclear. In this study, cells from the triple negative breast cancer lines MDA-MB-231 and BT549 were incubated with different concentrations of liquiritigenin. The results indicated that low concentrations had no significant cytotoxic effect, whereas high concentrations decreased viability of both MDA-MB-231 and BT549 cells. Liquiritigenin treatment also resulted in increased apoptosis and enhanced Caspase3 activity. After liquiritigenin treatment, we observed decreased invasive and migratory capacities of cells, as well as upregulated E-cadherin and downregulated N-cadherin, vimentin, and MMP9. Interestingly, liquiritigenin increased the mRNA and protein expression of breast cancer 1 (BRCA1). It also increased p21 and growth arrest and DNA-damage-inducible 45 alpha (GADD45A) levels, accompanied by decreased cellular DNA methyltransferase (DNMT) activity and downregulation of DNMT1, DNMT3a, and DNMT3b. These findings suggest that liquiritigenin can inhibit malignant behavior of triple negative breast cancer cells by inhibiting DNMT activity and increasing BRCA1 expression and its transcriptional activity. Liquiritigenin thus may be a promising candidate for the treatment of breast cancer.Impact statementTriple negative breast cancer (TNBC) is an aggressive cancer with a poor prognosis and higher metastatic rates and relapse frequencies than other breast cancers. Natural flavonoid liquiritigenin reportedly inhibits invasiveness of TNBC MDA-MB-231 cells, but its specific role and mechanism remain unclear. This study administered different doses of liquiritigenin into TNBC cell lines MDA-MB-231 and BT549, and found that it hindered cell proliferation, increased apoptosis, and repressed cell invasion and migration. BRCA1 exerts multiple functions and is closely related to the occurrence and development of breast cancer. Interestingly, the mRNA and protein expression of BRCA1 increased after liquiritigenin administration. Liquiritigenin also upregulated two downstream genes of BRCA1 (p21 and DNA-damage-inducible 45 alpha), decreased cellular DNA methyltransferase (DNMT) activity, and reduced BRCA1 promoter methylation. Thus, liquiritigenin may be a promising candidate for the treatment of TNBC due to its inhibition of DNMT activity and upregulation of BRCA1.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-17T08:36:40Z
      DOI: 10.1177/1535370220957255
       
  • Role of GATA3 exon 6 germline mutations in breast cancer progression in
           Egyptian female patients
    • Authors: Iman H Ibrahim, Heba G Abdel-Aziz, Fatema EM Hassan, Hesham SA El-Sameea
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Several mutations act as driver mutations in breast cancer, including GATA3 mutations. Reports of the relation between GATA3 mutations and breast cancer prognosis remain conflicting. Also, the role of GATA3 germline mutations is not well studied. We hypothesize that different mutation types could have different effects. Also, this study aims to assess effect of GATA3 mutations on GATA3 protein function as a transcription factor, and target pathways affected. DNA from de novo breast cancer female patients was sequenced to detect exon 6 GATA3 mutation. Sequence analysis was performed along with clinical and prognostic parameters and disease-free survival. Public datasets were analyzed for differentially expressed genes and pathways with mutant GATA3 patients. Mutations in GATA3 exon 6 were detected in 56.1% of patients (including 2 novel, Lys368fs, Pro354Lys). Intronic mutations were significantly higher in long disease-free survival group, while frameshift mutations were significantly higher in short DFS group. Patients with tumor size ≥20 had significantly higher protein coding and lower intronic mutations compared to patients with tumor size
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-17T08:36:40Z
      DOI: 10.1177/1535370220958610
       
  • A novel microRNA-based signature predicts prognosis among nasopharyngeal
           cancer patients
    • Authors: Tianyu Wang, Jian Wu, Yun Wu, Yin Cheng, Yue Deng, Jianchun Liao, Huanhai Liu, Hu Peng
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Nasopharyngeal cancer is one of the most common malignant tumors in the head and neck. Identification of promising miRNA biomarkers might benefit a lot to the detection of nasopharyngeal carcinoma. miRNA expression profile and clinical information were obtained from two microarray profiling data sets from the Gene Expression Omnibus (GEO) database. miRNA signature model was constructed via univariate Cox survival analysis, multivariate Cox survival analysis, and least absolute shrinkage and selection operator Cox regression analysis. Kaplan–Meier curve, area under the curve (AUC), decision curve analysis, Box plot, and nomogram were used to evaluate the prognosis of the model to patients. 67 up-regulated and 93 down-regulated miRNAs were identified from GEO microarray data sets (P 
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-17T05:30:58Z
      DOI: 10.1177/1535370220958680
       
  • At the dawn of the transcriptomic medicine
    • Authors: Gea Koks, Abigail L Pfaff, Vivien J Bubb, John P Quinn, Sulev Koks
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Impact statementThis review describes the impact of transcriptomics on experimental biology and its integration into medical practice. Transcriptomics is an essential part of modern biomedical research based on highly sophisticated and reliable technology. Transcriptomics can aid clinical practice and improve the precision of clinical diagnoses and decision-making by complementing existing clinical best practice. The power of which will be increased when combined with genomic variation from genome wide association studies and next generation sequencing. We are witnessing the implementation of RNA-based technologies in clinical practice that will eventually lead to the establishment of transcriptional medicine as a routine tool in diagnosis.Progress in genomic analytical technologies has improved our possibilities to obtain information regarding DNA, RNA, and their dynamic changes that occur over time or in response to specific challenges. This information describes the blueprint for cells, tissues, and organisms and has fundamental importance for all living organisms. This review focuses on the technological challenges to analyze the transcriptome and what is the impact of transcriptomics on precision medicine. The transcriptome is a term that covers all RNA present in cells and a substantial part of it will never be translated into protein but is nevertheless functional in determining cell phenotype. Recent developments in transcriptomics have challenged the fundamentals of the central dogma of biology by providing evidence of pervasive transcription of the genome. Such massive transcriptional activity is challenging the definition of a gene and especially the term “pseudogene” that has now been demonstrated in many examples to be both transcribed and translated. We also review the common sources of biomaterials for transcriptomics and justify the suitability of whole blood RNA as the current optimal analyte for clinical transcriptomics. At the end of the review, a brief overview of the clinical implications of transcriptomics in clinical trial design and clinical diagnosis is given. Finally, we introduce the transcriptome as a target for modern drug development as a tool for extending our capacity for precision medicine in multiple diseases.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-11T05:01:31Z
      DOI: 10.1177/1535370220954788
       
  • The protective effects of C16 peptide and angiopoietin-1 compound in
           lipopolysaccharide-induced acute respiratory distress syndrome
    • Authors: Dingqian Wu, Xiaoxiao Fu, Yuanyuan Zhang, Qiang Li, Ligang Ye, Shu Han, Mao Zhang
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      C16 peptide and angiopoietin-1 (Ang-1) have been found to have anti-inflammatory activity in various inflammation-related diseases. However, their combined role in acute respiratory distress syndrome (ARDS) has not been investigated yet. The objective of this study was to investigate the effects of C16 peptide and Ang-1 in combination with lipopolysaccharide (LPS)-induced inflammatory insult in vitro and in vivo. Human pulmonary microvascular endothelial cells and human pulmonary alveolar epithelial cells were used as cell culture systems, and an ARDS rodent model was used for in vivo studies. Our results demonstrated that C16 and Ang-1 in combination significantly suppressed inflammatory cell transmigration by 33% in comparison with the vehicle alone, and decreased the lung tissue wet-to-dry lung weight ratio to a maximum of 1.53, compared to 3.55 in the vehicle group in ARDS rats. Moreover, C  +  A treatment reduced the histology injury score to 60% of the vehicle control, enhanced arterial oxygen saturation (SO2), decreased arterial carbon dioxide partial pressure (PCO2), and increased oxygen partial pressure (PO2) in ARDS rats, while also improving the survival rate from 47% (7/15) to 80% (12/15) and diminishing fibrosis, necrosis, and apoptosis in lung tissue. Furthermore, when C  +  A therapy was administered 4 h following LPS injection, the treatment showed significant alleviating effects on pulmonary inflammatory cell infiltration 24 h postinsult. In conclusion, our in vitro and in vivo studies show that C16 and Ang-1 exert protective effects against LPS-induced inflammatory insult. C16 and Ang-1 hold promise as a novel agent against LPS-induced ARDS. Further studies are needed to determine the potential for C16 and Ang-1 in combination in treating inflammatory lung diseases.Impact statementThe mixture of C16 peptide and Ang-1 is a novel therapeutic agent, which has been confirmed as effective in several inflammatory diseases of central nervous system in previous studies. Since this compound medicine has a general role in protecting against inflammation and edema, its acting mechanisms may be not tissue- or organ-specific, and it may provide a valuable clue to the potential clinical application in the prevention and treatment of inflammatory lung diseases like ARDS. The experimental research of the novel therapeutic agent’s potential protective effects in different animal models will be beneficial for the future drug transformation and clinical trial.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-11T05:01:29Z
      DOI: 10.1177/1535370220953791
       
  • IL-17A is involved in diabetic inflammatory pathogenesis by its receptor
           IL-17RA
    • Authors: Ao-Wang Qiu, Xin Cao, Wei-Wei Zhang, Qing-Huai Liu
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Interleukin (IL)-17A, a proinflammatory cytokine produced by T-helper (Th)17 cells, has been associated with autoimmune diseases. Type 1 diabetes (T1D) is caused either due to mutation of insulin gene or developed as an autoimmune disease. Studies have shown that IL-17A expression is upregulated in the pancreas in T1D patients and animal models. However, role or importance of IL-17A in T1D pathogenesis needs elucidation. Particularly, evidence for a direct injury of IL-17A to pancreatic β cells through activating IL-17 receptor A (IL-17RA) is lacking. Ins2Akita (Akita) mouse, a T1D model with spontaneous mutation in insulin 2 gene leading to β-cell apoptosis, was crossed with IL-17A-knockout mouse and male IL-17A-deficient Akita mice were used. Streptozotocin, a pancreatic β-cell-specific cytotoxin, was employed to induce a diabetic model in MIN6 cells, a mouse insulinoma cell line. IL-17A expression in the pancreas was upregulated in both Akita and streptozotocin-induced diabetic mice. IL-17A-knockout Akita mice manifested reduced blood glucose concentration and raised serum insulin level. IL-17A deficiency also decreased production of the proinflammatory cytokines tumor necrosis factor (TNF)-α, IL-1β, and interferon (IFN)-γ in Akita mice. IL-17RA expression in MIN6 cells was upregulated by IL-17A. IL-17A enhanced expression of TNF-α, IL-1β, IFN-γ, and inducible nitric oxide synthase (iNOS) and further increased streptozotocin-induced expression of the inflammatory factors in MIN6 cells. IL-17A exacerbated streptozotocin-induced MIN6 cell apoptosis and insulin secretion impairment. Blocking IL-17RA with anti-IL-17RA-neutralizing antibody reduced all these deleterious effects of IL-17A on MIN6 cells. Collectively, IL-17A deficiency alleviated hyperglycemia, hypoinsulinemia, and inflammatory response in Akita mice that are characteristic for T1D. IL-17A exerted an alone and synergistic destruction with streptozotocin to pancreatic β cells through IL-17RA pathway. Thus, the data suggest that targeting IL-17A and/or IL-17RA is likely to preserve remaining β-cell function and treat T1D.Impact statementThe participation of interleukin (IL)-17A in diabetic pathogenesis is suggested in animal models of autoimmune diabetes and in patients with type 1 diabetes (T1D), but with some contradictory results. Particularly, evidence for a direct injury of IL-17A to pancreatic β cells is lacking. We showed that IL-17A deficiency alleviated diabetic signs including hyperglycemia, hypoinsulinemia, and inflammatory response in Ins2Akita (Akita) mice, a T1D model with spontaneous mutation in insulin 2 gene leading to β-cell apoptosis. IL-17A enhanced inflammatory reaction, oxidative stress, and cell apoptosis but attenuated insulin level in mouse insulin-producing MIN6 cells. IL-17A had also a synergistic destruction to MIN6 cells with streptozotocin (STZ), a pancreatic β-cell-specific cytotoxin. Blocking IL-17 receptor A (IL-17RA) reduced all these deleterious effects of IL-17A on MIN6 cells. The results demonstrate the role and the importance of IL-17A in T1D pathogenesis and suggest a potential therapeutic strategy for T1D targeting IL-17A and/or IL-17RA.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-09T06:37:23Z
      DOI: 10.1177/1535370220956943
       
  • Orally administered emu oil attenuates disease in a mouse model of
           Crohn’s-like colitis
    • Authors: Chloe J Mitchell, Gordon S Howarth, Lauren C Chartier, Debbie Trinder, Ian C Lawrance, Li San Huang, Suzanne Mashtoub
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Crohn’s disease is a severe, incurable inflammatory bowel disease. Orally administered emu oil has demonstrated anti-inflammatory properties in previous models of gastrointestinal disease. We aimed to determine whether orally administered emu oil could attenuate disease in a mouse model of Crohn’s-like colitis. Female ARC(s) mice (CD-1 equivalent, n = 10/group) were intra-rectally administered water (120 μL) or trinitrobenzene sulfonic acid (TNBS; 3 mg in 50% ethanol; 120 μL bolus) on day 0. Mice were orally administered water (80 μL) or emu oil (80 μL or 160 μL) daily for five days and euthanized on day six. Bodyweight and disease activity were recorded daily. Colonoscopy, burrowing activity, facial grimace, histological parameters (damage severity, small intestinal villus height/crypt depth and colonic crypt depth), myeloperoxidase activity and intestinal permeability were assessed. P 
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-09T06:37:22Z
      DOI: 10.1177/1535370220951105
       
  • Mechanisms of aging, age-associated diseases, and lifespan determination
    • Authors: Shigemi Matsuyama
      Abstract: Experimental Biology and Medicine, Ahead of Print.

      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-09T06:37:18Z
      DOI: 10.1177/1535370220955146
       
  • SNHG1 represses the anti-cancer roles of baicalein in cervical cancer
           through regulating miR-3127-5p/FZD4/Wnt/β-catenin signaling
    • Authors: Xiaolan Yu, Jiyi Xia, Yong Cao, Li Tang, Xiaoping Tang, Zhengyu Li
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      As a flavonoid, baicalein exhibits remarkable anti-cancer roles in several cancers. However, the factors regulating the antitumorigenic roles of baicalein in cervical cancer remain undefined. Here, we revealed that long noncoding RNA SNHG1 is implicated in the tumor-suppressive roles of baicalein. Functional assays demonstrated that ectopic expression of SNHG1 attenuates the roles of baicalein in repressing cervical cancer cell viability, inducing apoptosis, and repressing migration. SNHG1 silencing promotes the tumor-suppressive roles of baicalein in cervical cancer cell viability, apoptosis, and migration. Xenograft assays showed that SNHG1 reverses the tumor-suppressive roles of baicalein in repressing cervical cancer growth in vivo. Mechanistic investigations revealed that SNHG1 directly binds miR-3127-5p and up-regulates FZD4, a target of miR-3127-5p. Via regulating miR-3127-5p/FZD4, SNHG1 activates Wnt/β-catenin signaling. Moreover, SNHG1 reverses the repressive role of baicalein on Wnt/β-catenin signaling. The effect of SNHG1 on the antitumorigenic process of baicalein was abolished by Wnt/β-catenin signaling inhibitor ICG-001. Together, our observations demonstrated that SNHG1 represses the tumor-suppressive roles of baicalein in cervical cancer through regulating miR-3127-5p/FZD4/Wnt/β-catenin axis, and suggested that targeting SNHG1 represents a potential strategy to enhance the tumor-suppressive roles of baicalein in cervical cancer.Impact statementBaicalein exhibits anti-cancer roles in several cancers. However, the factors influencing the antitumorigenic efficiencies of baicalein in CC remain largely unclear. Here, we provide convincing evidences that lncRNA SNHG1 attenuates the tumor-suppressive roles of baicalein in CC cell viability, apoptosis, migration, and CC tumor growth. This study further demonstrates that the influences of SNHG1 in the antitumorigenic process of baicalein are achieved through modulating the miR-3127-5p/FZD4Wnt/β-catenin axis. SNHG1 attenuates the repressive role of baicalein on Wnt/β-catenin. Therefore, SNHG1 is a novel modulator of the tumor-suppressive roles of baicalein and SNHG1 represents a therapeutic intervention target to reinforce the tumor-suppressive roles of baicalein in CC.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-04T04:36:22Z
      DOI: 10.1177/1535370220955139
       
  • RASL11B gene enhances hyaluronic acid-mediated chondrogenic
           differentiation in human amniotic mesenchymal stem cells via the
           activation of Sox9/ERK/smad signals
    • Authors: Yi Luo, Ai-Tong Wang, Qing-Fang Zhang, Ru-Ming Liu, Jian-Hui Xiao
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      This study aimed to elucidate the molecular mechanisms, whereby hyaluronic acid, a main extracellular matrix component of articular cartilage, promotes the chondrogenic differentiation of human amniotic mesenchymal stem cells (hAMSCs). Our previous findings indicated that hyaluronic acid combined with hAMSCs showed a marked therapeutic effect against rat osteoarthritis. In the present study, hyaluronic acid markedly enhanced the expression of chondrocyte-specific markers including Col2α1, Acan, and Sox9 in hAMSCs, with strong synergistic effects on chondrogenic differentiation, in combination with the commonly used inducer, transforming growth factor β3 (TGF-β3). Microarray analysis showed that Ras-like protein family member 11B (RASL11B) played a pivotal role in the process of hyaluronic acid-mediated chondrogenesis of hAMSCs. This directional differentiation was significantly inhibited by RASL11B knockdown, but RASL11B overexpression dramatically promoted the expression of Sox9, a master chondrogenesis transcriptional factor, at the levels of transcription and translation. Increased Sox9 expression subsequently resulted in high expression levels of Col2α1 and Acan and the accumulation of cartilage-specific matrix components, such as type 2 collagen and glycosaminoglycans. Moreover, we observed that RASL11B activated the signal molecules such as ERK1/2, and Smad2/3 in the presence of hyaluronic acid during TGF-β3-induced chondrogenesis of hAMSCs. Taken together, these findings suggest that hyaluronic acid activates the RASL11B gene to potentiate the chondrogenic differentiation of hAMSCs via the activation of Sox9 and ERK/Smad signaling, thus providing a new strategy for cartilage defect repairing by hyaluronic acid-based stem cell therapy.Impact statementRASL11B, a member of the small GTPase superfamily, has high similarity to RAS proteins, and involves some pathophysiological processes, such as inflammation, arteriosclerosis, and cancer. However, there is no available information regarding the role of RASL11B in chondrogenic differentiation. We show that RASL11B is activated in the process of HA-mediated chondrogenesis of hAMSCs, and RASL11B regulates the differentiation of hAMSCs into chondrocytes through the activation of Sox9 and ERK/Smad signals. The results of this study support that RASL11B may be used as a target in the chondroinductive differentiation of hAMSCs in the presence of HA and even in the cartilage defect repairing by HA-based stem cell therapy.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-03T04:43:59Z
      DOI: 10.1177/1535370220944375
       
  • Acupuncture reduces pain in rats with osteoarthritis by inhibiting
           MCP2/CCR2 signaling pathway
    • Authors: Bocun Li, Li Jing, Li Jia, Tan Qian, Chen Jianyi, Huang Zhongsheng, Zhou Xiaohong, Cai Guowei
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Acupuncture is an emerging alternative therapy that has been beneficial for the pain of osteoarthritis (OA). However, the underlying mechanism of protective effect remains unclear. MCP1/CCR2 axis can be stimulated in various periods of OA, and we hypothesize that acupuncture may treat OA by regulating the MCP1/CCR2 axis. This study aimed to explore the effect of acupuncture at points ST35 and ST36 on the effects of hyperalgesia and cartilage in OA rats including the expression of chemokines, nerve growth factor (NGF), and inflammatory-related proteins. OA was induced in male Sprague–Dawley rats by anterior cruciate ligament transection at the right knee. The first acupuncture intervention was performed on the seventh day after surgery and once a day for seven weeks. The knee-pain-related behaviors, histology, and related protein were examined in this study. We have found that electroacupuncture at ST35 and ST36 can significantly alleviate the hyperalgesia and cartilage degeneration as well as reducing nerve sprouting in OA knee joint. Moreover, acupuncture treatment may inhibit the MCP1/CCR2 axis as well as down-regulate inflaming factor and NGF in cartilage and synovial tissue. The data presented here indicate that acupuncture exerts a protective effect against hyperalgesia and cartilage degeneration, and the mechanism might involve in chemokines and NGF pathway.Impact statementOsteoarthritis (OA) is the most common form of arthritis, affecting an estimated 302 million people worldwide, but the mechanism of OA is far away understood. Acupuncture has been widely used in treating with chronic pain, but how does acupuncture work is still unclear. In this essay, we investigated the molecular target of acupuncture and found new mechanism of the pathogenesis in knee OA. Our results could provide new analgesic mechanisms and find new targets for acupuncture analgesia in OA. In a word, the study can help further understanding and provides more evidence of the clinical use of acupuncture in treating OA.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-03T04:43:58Z
      DOI: 10.1177/1535370220952342
       
  • Hsa-miR-30e-3p inhibits influenza B virus replication by targeting viral
           NA and NP genes
    • Authors: Kritsada Khongnomnan, Suthat Saengchoowong, Oraphan Mayuramart, Pattaraporn Nimsamer, Trairak Pisitkun, Yong Poovorawan, Sunchai Payungporn
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Influenza B virus is a member of the Orthomyxoviridae family which can infect humans and causes influenza. Although it is not pandemic like influenza A virus, it nevertheless affects millions of people worldwide annually. MicroRNAs are small non-coding RNAs regulating gene expression at posttranscriptional level. They play various important roles in cellular processes including response to viral infection. MiRNA profiles from our previous study suggested that miR-30e-3p was one of the upregulated miRNAs that responded to influenza B virus infection. In this study, in silico prediction and in vitro investigation proved that this miRNA can directly target NA and NP genes of the influenza B virus and inhibit its replication. This finding might be useful for using miRNA as an alternative therapeutics for influenza virus infection.Impact statementThis is the first study to investigate the function of human miRNA in influenza B virus infection. The hsa-miR-30e-3p was computationally predicted and in vitro studies proved that this miRNA can directly target viral NA and NP genes and inhibit influenza B virus replication. Thus, it is the first report suggesting that human miRNA can directly target influenza B virus and inhibit viral replication. It also proved the concept that in response to viral infection, some host miRNAs are upregulated and miRNA can be used as a silencing strategy to inhibit viral replication at the early stage of viral infection.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-03T04:43:57Z
      DOI: 10.1177/1535370220953151
       
  • CD248+CD8+ T lymphocytes suppress pathological vascular remodeling in
           human thoracic aortic aneurysms
    • Authors: Xiaojuan Hu, Ting Wu, Chenxi Wang, Jun Li, Chunmei Ying
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Aortic aneurysms are characterized by vascular inflammation, neovascularization, and extracellular matrix destruction of the aortic wall. Although experimental studies indicate a potential role of CD248 in microvessel remodeling, the functions of CD248 in human vascular pathologies remain unexplored. Here we aimed to study how CD248 interferes with pathological vascular remodeling of human aortic aneurysms. Immunofluorescent staining showed that CD248 expression was mainly localized in the CD8+ T cells infiltrating in the adventitia and media of aortic walls of patients with ascending thoracic aortic aneurysms. qPCR and immunofluorescent staining analyses revealed increased aortic CD248 expression and infiltrating CD248+CD8+ T cells in aortic aneurysms than in nonaneurysmal aortas. Flow cytometry analysis of human peripheral blood further identified a fraction of circulating CD248+ cells which was confined in the CD8+ T-cell compartment. The increased infiltrating of CD248+CD8+ T cells was coincident with reduced circulating CD248+CD8+ T cells in patients with ascending TAA when compared with patients with coronary artery diseases and healthy donors. The CD248+CD8+ T cells were characterized by upregulated IL-10 and downregulated IL-1β/INF-γ expression when compared with CD248-CD8+ T cells. Moreover, when co-cultured with human aortic endothelial cells, the CD248+CD8+ T cells not only downregulated endothelial expression of ICAM1/VCAM1 and MMP2/3 but also suppressed endothelial migration. This study shows that CD248 reduces pathological vascular remodeling via anti-inflammatory CD248+CD8+ T cells, revealing a CD248-mediated cellular mechanism against human aortic aneurysms.Impact statementIn spite of recent evidence indicating that CD248 is linked to microvasculature remodeling, immune response, and MMP activity, the functions of CD248 in human TAA remain unexplored. In this work, by analyzing cellular components of in situ as well as of blood circulation of human TAA, we have identified a novel T cell subset, the CD248+CD8+ T cells, which exhibits anti-inflammatory properties, and that we have also provided the first evidence that these cells not only suppress endothelial expression of ICAM1/VCAM1 and MMP2/3, but also inhibit endothelial migration, thus uncovering a CD248-mediated cellular mechanism against pathological vascular remodeling in human aortic aneurysms.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-01T05:47:19Z
      DOI: 10.1177/1535370220953386
       
  • Angiogenic and anti-inflammatory properties of azadirachtin A improve
           random skin flap survival in rats
    • Authors: Ji-Bing He, Miao-Jie Fang, Xin-Yi Ma, Wen-Jie Li, Ding-Sheng Lin
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Random skin flaps are widely used to repair tissue defects. However, the distal flap regions are prone to ischemic necrosis, limiting clinical applications. Azadirachtin A, a fruit extract from the neem, improves tissue blood supply and metabolism, reduces cell swelling, promotes tissue healing, and prevents venous thrombosis. We explored whether it enhances random skin flap survival. Fifty-four Sprague-Dawley rats were divided into control, low-dose, and high-dose Azadirachtin A-treated groups using a random number table. We used an improved version of the McFarlane technique to create flaps. On day 2, superoxide dismutase and malondialdehyde levels were measured. Tissue slices prepared on day 7 were stained with hematoxylin and eosin. The expression levels of vascular endothelial growth factor (VEGF), toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-kB), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were immunohistochemically assayed. Microcirculatory blood flow was measured via laser Doppler blood flowmetry. Flap angiography was performed using the lead-oxide gelatin injection technique. And the azadirachtin A groups exhibited a greater mean flap survival area, an improved mean blood vessel density, a greater blood flow, and higher superoxide dismutase and VEGF levels, especially at the high dose. Azadirachtin A markedly reduced the levels of TNF-α, IL-6, IL-1β, TLR4, and NF-kB. These findings suggest that azadirachtin A promotes random skin flap survival by improving the blood supply, reducing tissue inflammation, and inhibiting flap ischemia reperfusion injury.Impact statementIn plastic and reconstructive surgery, skin flap necrosis often occurs. How to improve the clinical application of skin flaps is a problem that people now look forward to solving. Drug therapy is one of the research focuses to improve skin flap survival. Our research found that Azadirachtin A promotes random skin flap survival by improving the blood supply, reducing tissue inflammation, and inhibiting flap ischemia reperfusion injury. These findings suggest that Azadirachtin A is a potential therapeutic agent for random skin flap necrosis in clinical application.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-01T05:44:20Z
      DOI: 10.1177/1535370220951896
       
  • Short-term enhancement of motor neuron synaptic exocytosis during early
           aging extends lifespan in Caenorhabditis elegans
    • Authors: Tsui-Ting Ching, Yen-Chieh Chen, Guang Li, Jianfeng Liu, XZ Shawn Xu, Ao-Lin Hsu
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Age-related mobility decline is often associated with negative physical and psychological outcomes, such as frailty, in the elderly population. In C. elegans, during the early stage of the aging process, a progressive deficit of synaptic exocytosis in the motor neurons results in a functional decline at the neuromuscular junctions, which eventually leads to degeneration of both neurons and muscles. This age-dependent functional decline can be ameliorated by pharmacological interventions, such as arecoline, a muscarinic AChR agonist known to promote synaptic exocytosis at the neuromuscular junctions. In this study, we found that a short-term treatment of arecoline during the early stage of aging, when the NMJ functional decline begins, not only slows muscle tissue aging, but also extends lifespan in C. elegans. We have also demonstrated that arecoline acts on the GAR-2/PLCβ pathway in the motor neurons to increases longevity. Together, our findings suggest that synaptic transmission in aging motor neurons may serve as a potential target for pharmacological interventions to promote both health span and lifespan, when applied at the early stage aging.Impact statementThe functional decline of motor activity is a common feature in almost all aging animals that leads to frailty, loss of independence, injury, and even death in the elderly population. Thus, understanding the molecular mechanism that drives the initial stage of this functional decline and developing strategies to increase human healthspan and even lifespan by targeting this process would be of great interests to the field. In this study, we found that by precisely targeting the motor neurons to potentiate its synaptic releases either genetically or pharmacologically, we can not only delay the functional aging at NMJs but also slow the rate of aging at the organismal level. Most importantly, we have demonstrated that a critical window of time, that is the early stage of NMJs functional decline, is required for the beneficial effects. A short-term treatment within this time period is sufficient to extend the animals’ lifespan.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-08-28T05:04:16Z
      DOI: 10.1177/1535370220950639
       
  • Imaging depth extension of optical coherence tomography in rabbit eyes
           using optical clearing agents
    • Authors: Ruiming Kong, Wenjuan Wu, Rui Qiu, Lei Gao, Fengxian Du, Ailin Liu, Xuan Cai, Cuixia Dai
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Optical coherence tomography has become an indispensable diagnostic tool in ophthalmology for imaging the retina and the anterior segment of the eye. However, the imaging depth of optical coherence tomography is limited by light attenuation in tissues due to optical scattering and absorption. In this study of rabbit eye both ex vivo and in vivo, optical coherence tomography imaging depth of the anterior and posterior segments of the eye was extended by using optical clearing agents to reduce multiple scattering. The sclera, the iris, and the ciliary body were clearly visualized by direct application of glycerol at an incision on the conjunctiva, and the posterior boundary of sclera and even the deeper tissues were detected by submerging the posterior segment of eye in glycerol solution ex vivo or by retro-bulbar injection of glycerol in vivo. The ex vivo rabbit eyes recovered to their original state in 60 s after saline-wash treatment, and normal optical coherence tomography images of the posterior segment of the sample eyes proved the self-recovery of in vivo performance. Signal intensities of optical coherence tomography images obtained before and after glycerol treatment were compared to analysis of the effect of optical clearing. To the best of our knowledge, this is the first study for imaging depth extension of optical coherence tomography in both the anterior and posterior segments of eye by using optical clearing agents.Impact statementImaging depth of optical coherence tomography in ophthalmology is limited by light attenuation in tissues due to inherent optical scattering and absorption. In this study, imaging depth of the anterior and posterior segments of rabbit eyes was extended by using optical clearing agents to reduce multiple scattering. This study may provide a potential method for ophthalmic research, such as accommodation, ocular growth, and biometry of the eye, and for diagnosis of posterior scleritis and intra-orbital tumor, such as orbital cavernous hemangioma, optic nerve glioma, and inflammatory pseudotumor.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-08-14T06:24:04Z
      DOI: 10.1177/1535370220949834
       
  • An overview of neuroblastoma cell lineage phenotypes and in vitro models
    • Authors: Sheron Campos Cogo, Thatyanne Gradowski Farias da Costa do Nascimento, Fernanda de Almeida Brehm Pinhatti, Nilton de França Junior, Bruna Santos Rodrigues, Luciane Regina Cavalli, Selene Elifio-Esposito
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      This review was conducted to present the main neuroblastoma (NB) clinical characteristics and the most common genetic alterations present in these pediatric tumors, highlighting their impact in tumor cell aggressiveness behavior, including metastatic development and treatment resistance, and patients’ prognosis. The distinct three NB cell lineage phenotypes, S-type, N-type, and I-type, which are characterized by unique cell surface markers and gene expression patterns, are also reviewed. Finally, an overview of the most used NB cell lines currently available for in vitro studies and their unique cellular and molecular characteristics, which should be taken into account for the selection of the most appropriate model for NB pre-clinical studies, is presented. These valuable models can be complemented by the generation of NB reprogrammed tumor cells or organoids, derived directly from patients’ tumor specimens, in the direction toward personalized medicine.Impact statementThis review provides an update on the mostly used cell line in vitro models for neuroblastoma (NB), a heterogeneous disease with high metastatic potential and resistance to treatment. The genetic and phenotypic profiles of the most used NB cell lines in the last 10 years are presented, considering the molecular markers that are involved in the distinct NB tumor phenotypes, including distinct core regulatory circuitries and non-coding RNAs. This gathered information can assist in the selection of the most appropriate NB in vitro model, based on the specific goals and objectives of each study.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-08-13T04:26:24Z
      DOI: 10.1177/1535370220949237
       
  • Retraction Notice: “Jinshui He, Xu Zhang, Chaowei Lian, Jinzhi Wu,
           Yanling Fang, Xiaoling Ye. Exendin-4 prevented pancreatic beta cells from
           apoptosis in (Type I) diabetic mouse via keap1-Nrf2 signaling”
    • Abstract: Experimental Biology and Medicine, Ahead of Print.

      Citation: Experimental Biology and Medicine
      PubDate: 2020-08-13T01:57:13Z
      DOI: 10.1177/1535370220952051
       
  • Analysis of epigenetic aging in vivo and in vitro: Factors controlling the
           speed and direction
    • Authors: Mieko Matsuyama, Arne Søraas, Sarah Yu, Kyuhyeon Kim, Evi X Stavrou, Paolo F Caimi, David Wald, Marcos deLima, John A Dahl, Steve Horvath, Shigemi Matsuyama
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      The mechanism of aging is not yet fully understood. It has been recognized that there are age-dependent changes in the DNA methylation pattern of the whole genome. To date, there are several DNA methylation-based estimators of the chronological age. A majority of the estimators use the DNA methylation data from a single tissue type, such as blood. In 2013, for the first time, Steve Horvath reported the DNA methylation-based age estimator (353 CpGs were used) that could be applied to multiple tissues. A refined, more sensitive version that uses 391 CpGs was subsequently developed and validated in human cells, including fibroblasts. In this review, the age predicted by DNA methylation-based age estimator is referred to as DNAmAge, and the biological process controlling the progression of DNAmAge is referred to as the epigenetic aging in this minireview. The concepts of DNAmAge and epigenetic aging provide us opportunities to discover previously unrecognized biological events controlling aging. In this article, we discuss the frequently asked questions regarding DNAmAge and the epigenetic aging by introducing recent studies of ours and others. We focus on addressing the following questions: (1) Is there any synchronization of DNAmAge between cells in a human body', (2) Can we use in vitro (cell culture) systems to study the epigenetic aging', (3) Is there an age limit of DNAmAge', and (4) Is it possible to change the speed and direction of the epigenetic aging' We describe our current understandings to these questions and outline potential future directions.Impact statementAging is associated with DNA methylation (DNAm) changes. Recent advancement of the whole-genome DNAm analysis technology allowed scientists to develop DNAm-based age estimators. A majority of these estimators use DNAm data from a single tissue type such as blood. In 2013, a multi-tissue age estimator using DNAm pattern of 353 CpGs was developed by Steve Horvath. This estimator was named “epigenetic clock”, and the improved version using DNAm pattern of 391 CpGs was developed in 2018. The estimated age by epigenetic clock is named DNAmAge. DNAmAge can be used as a biomarker of aging predicting the risk of age-associated diseases and mortality. Although the DNAm-based age estimators were developed, the mechanism of epigenetic aging is still enigmatic. The biological significance of epigenetic aging is not well understood, either. This minireview discusses the current understanding of the mechanism of epigenetic aging and the future direction of aging research.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-08-07T04:35:05Z
      DOI: 10.1177/1535370220947015
       
  • Fluid shear stress modulates endothelial inflammation by targeting LIMS2
    • Authors: Junyao Wang, Shiyanjin Zhang
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Mechanosensitive genes regulate multiple cardiovascular pathophysiological processes and disorders; however, the role of flow-sensitive genes in atherosclerosis is still unknown. In this study, we identify LIM Zinc Finger Domain Containing 2 (LIMS2) that acts as a mechanosensitive gene downregulated by disturbed flow (d-flow) both in human endothelial cells (ECs) in vitro and in mice in vivo. Mechanistically, d-flow suppresses LIMS2 expression, which leads to endothelial inflammation by upregulating typical inflammatory factors, VCAM-1, and ICAM-1 in human ECs. The findings indicate that LIMS2, the new flow-sensitive gene, may help us to find a new insight to explain how d-flow caused endothelial inflammation and provide a new therapeutic approach for atherosclerosis in the future.Impact statementWhereas we all know that atherosclerosis is the most main common reason of death all over the world, the mechanism of atherosclerosis is still unclear. Recently, more and more evidence indicate that atherosclerosis is a kind of flow-dependent disease, and plenty of mechanosensitive genes have been mentioned in it. Here, we identified for the first time that LIMS2 is a novel flow-sensitive gene and inhibits inflammation by modulating inflammatory factors, VCAM-1, and ICAM-1 in endothelial cells. It will help us to understand the connection between endothelial shear stress and endothelial inflammation deeply; certainly, LIMS2 may also act as a potential target for flow-dependent atherosclerosis.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-08-05T06:37:02Z
      DOI: 10.1177/1535370220943837
       
  • Histone deacetylases in modulating cardiac disease and their clinical
           translational and therapeutic implications
    • Authors: Zhengke Wang, Yu Tina Zhao, Ting C Zhao
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Cardiovascular diseases are the leading cause of mortality and morbidity worldwide. Histone deacetylases (HDACs) play an important role in the epigenetic regulation of genetic transcription in response to stress or pathological conditions. HDACs interact with a complex co-regulatory network of transcriptional regulators, deacetylate histones or non-histone proteins, and modulate gene expression in the heart. The selective HDAC inhibitors have been considered to be a critical target for the treatment of cardiac disease, especially for ameliorating cardiac dysfunction. In this review, we discuss our current knowledge of the cellular and molecular basis of HDACs in mediating cardiac development and hypertrophy and related pharmacologic interventions in heart disease.Impact statementHistone deacetylases (HDACs) have recently been recognized as one of the most important regulated mechanism(s) in mediating cardiovascular development, myocardial injury, and hypertrophy. This detailed review of the functional role(s) and molecular mechanism(s) of histone deacetylase will provide the current view by which HDACs induce different biological signaling in the regulation of cardiac physiology and disease. More importantly, HDACs could be targeted to develop a new therapeutic strategy in treating cardiovascular disorders. Further studies of the specific roles and targets of HDACs will extend our knowledge of the biological impact and clinical implications of HDACs.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-07-30T06:17:23Z
      DOI: 10.1177/1535370220944128
       
  • Redox and mTOR-dependent regulation of plasma lamellar calcium influx
           controls the senescence-associated secretory phenotype
    • Authors: Akshaya Chandrasekaran, May Y Lee, Xuexin Zhang, Shaheen Hasan, Haban Desta, Scott A Tenenbaum, J Andrés Melendez
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Cellular senescence has evolved as a protective mechanism to arrest growth of cells with oncogenic potential but is accompanied by the often pathologically deleterious senescence-associated secretory phenotype (SASP). Here we demonstrate an H2O2-dependent functional disruption controlling senescence-associated Ca2+ homeostasis and the SASP. Senescent cells fail to respond to H2O2-dependent plasma lamellar Ca2+ entry when compared to pre-senescent cells. Limiting exposure to senescence-associated H2O2 restores H2O2-dependent Ca2+ entry as well as transient receptor potential cation channel subfamily C member 6 (TRPC6) function. SA-TRPC6 and SASP expression is blocked by restoring Ca2+ entry with the TRP channel antagonist SKF-96365 or by the mTOR inhibitors rapamycin and Ku0063794. Together, our findings provide compelling evidence that redox and mTOR-mediated regulation of Ca2+ entry through TRPC6 modulates SASP gene expression and approaches which preserve normal Ca2+ homeostasis may prove useful in disrupting SASP activity.Impact statementThrough its ability to evoke responses from cells in a paracrine fashion, the senescence-associated secretory phenotype (SASP) has been linked to numerous age-associated disease pathologies including tumor invasion, cardiovascular dysfunction, neuroinflammation, osteoarthritis, and renal disease. Strategies which limit the amplitude and duration of SASP serve to delay age-related degenerative decline. Here we demonstrate that the SASP regulation is linked to shifts in intracellular Ca2+ homeostasis and strategies which rescue redox-dependent calcium entry including enzymatic H2O2 scavenging, TRP modulation, or mTOR inhibition block SASP and TRPC6 gene expression. As Ca2+ is indispensable for secretion from both secretory and non-secretory cells, it is exciting to speculate that the expression of plasma lamellar TRP channels critical for the maintenance of intracellular Ca2+ homeostasis may be coordinately regulated with the SASP.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-07-20T05:52:43Z
      DOI: 10.1177/1535370220943122
       
  • High atherogenic index of plasma and cardiovascular risk factors among
           Ghanaian breast cancer patients
    • Authors: Emmanuel A Tagoe, Eric Dwamena-Akoto, Josephine Nsaful, Anastasia R Aikins, Joe-Nat Clegg-Lamptey, Osbourne Quaye
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Comorbidities impact negatively on breast cancer prognosis, especially in developing countries where cases are usually presented to clinics at advanced stages. This study aimed to determine the atherogenic index of plasma (AIP) and cardiovascular risk factors among Ghanaian women diagnosed with breast cancer. A total of 52 breast cancer patients were age-matched with 52 healthy controls. Sociodemographics of participants were obtained using a well-structured questionnaire. Pathological data of patients were obtained from medical records, and all clinical and anthropometric measurements were done using standard instruments. Lipid profile was determined from serum using enzymatic assays, and cardiovascular risk factors were calculated from estimated lipid parameters. Blood pressure, AIP, total cholesterol (T. chol), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c) were significantly elevated (P 
      Citation: Experimental Biology and Medicine
      PubDate: 2020-07-09T05:42:20Z
      DOI: 10.1177/1535370220940992
       
  • Metabolic alterations caused by the mutation and overexpression of the
           Tmem135 gene
    • Authors: Wei-Hua Lee, Vijesh J Bhute, Hitoshi Higuchi, Sakae Ikeda, Sean P Palecek, Akihiro Ikeda
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Mitochondria are dynamic organelles that undergo fission and fusion. While they are essential for cellular metabolism, the effect of dysregulated mitochondrial dynamics on cellular metabolism is not fully understood. We previously found that transmembrane protein 135 (Tmem135) plays a role in the regulation of mitochondrial dynamics in mice. Mice homozygous for a Tmem135 mutation (Tmem135FUN025/FUN025) display accelerated aging and age-related disease pathologies in the retina including the retinal pigment epithelium (RPE). We also generated a transgenic mouse line globally overexpressing the Tmem135 gene (Tmem135 TG). In several tissues and cells that we studied such as the retina, heart, and fibroblast cells, we observed that the Tmem135 mutation causes elongated mitochondria, while overexpression of Tmem135 results in fragmented mitochondria. To investigate how abnormal mitochondrial dynamics affect metabolic signatures of tissues and cells, we identified metabolic changes in primary RPE cell cultures as well as heart, cerebellum, and hippocampus isolated from Tmem135FUN025/FUN025 mice (fusion > fission) and Tmem135 TG mice (fusion  fission) and over-fragmented (fusion 
      Citation: Experimental Biology and Medicine
      PubDate: 2020-06-09T12:29:24Z
      DOI: 10.1177/1535370220932856
       
  • NAD metabolism in aging and cancer
    • Authors: John WR Kincaid, Nathan A Berger
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      NAD+ and its derivatives NADH, NADP+, and NADPH are essential cofactors in redox reactions and electron transport pathways. NAD serves also as substrate for an extensive series of regulatory enzymes including cyclic ADP-ribose hydrolases, mono(ADP-ribosyl)transferases, poly(ADP-ribose) polymerases, and sirtuin deacetylases which are O-acetyl-ADP-ribosyltransferases. As a result of the numerous and diverse enzymes that utilize NAD as well as depend on its synthesis and concentration, significant interest has developed in its role in a variety of physiologic and pathologic processes, and therapeutic initiatives have focused both on augmenting its levels as well as inhibiting some of its pathways. In this article, we examine the biosynthesis of NAD, metabolic processes in which it is involved, and its role in aging, cancer, and other age-associated comorbidities including neurodegenerative, cardiovascular, and metabolic disorders. Therapeutic interventions to augment and/or inhibit these processes are also discussed.Impact statementNAD is a central metabolite connecting energy balance and organismal growth with genomic integrity and function. It is involved in the development of malignancy and has a regulatory role in the aging process. These processes are mediated by a diverse series of enzymes whose common focus is either NAD’s biosynthesis or its utilization as a redox cofactor or enzyme substrate. These enzymes include dehydrogenases, cyclic ADP-ribose hydrolases, mono(ADP-ribosyl)transferases, poly(ADP-ribose) polymerases, and sirtuin deacetylases. This article describes the manifold pathways that comprise NAD metabolism and promotes an increased awareness of how perturbations in these systems may be important in disease prevention and/or progression.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-06-05T12:23:00Z
      DOI: 10.1177/1535370220929287
       
  • Retinoid analogs and polyphenols as potential therapeutics for age-related
           macular degeneration
    • Authors: Tanu Parmar, Joseph T Ortega, Beata Jastrzebska
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Progressive retinal degeneration manifesting as age-related macular degeneration (AMD) in the elderly affects millions of individuals worldwide. Among various blinding diseases, AMD is the leading cause of central vision impairment in developed countries. Poor understanding of AMD etiology hampers the development of therapeutics against this devastating ocular disease. Currently, daily intravitreal injections of anti-angiogenic drugs, preventing abnormal vessel growth are the only treatment option for wet AMD. However, for dry AMD associated with retinal atrophy, at present there is no cure available. Recent clinical research has demonstrated beneficial effects of plant-derived compounds for various eye disorders. Thus, the ongoing efforts toward discovering efficient treatments preventing or delaying AMD progression focus on implementing a healthy diet rich in vitamins, including vitamin A, E, and C, minerals and carotenoids, in particular lutein and zeaxanthin, to reduce the disease burden. In addition, studies in cell culture and animal models indicated therapeutic potential of dietary polyphenolic compounds present in fruits and vegetables. These natural compounds protect visual function and retinal morphology likely due to their anti-oxidant and anti-inflammatory properties. Although understanding of the exact mechanism of these compounds’ positive effects requires further investigation, they provide non-invasive alternative to battle AMD-like condition. Additionally, studies carried in animal models mimicking AMD-like pathology, examining the pharmacological potential of particular retinoid analogs, demonstrated promising results for their use, and thus they should be considered as an option in developing therapies for AMD. In here, we summarize the most current knowledge regarding developments of therapeutic options to maintain ocular health and prevent vision loss associated with aging.Impact statementAge-related macular degeneration (AMD) is a devastating retinal degenerative disease. Epidemiological reports showed an expected increasing prevalence of AMD in the near future. The only one existing FDA-approved pharmacological treatment involves an anti-vascular endothelial growth factor (VEGF) therapy with serious disadvantages. This limitation emphasizes an alarming need to develop new therapeutic approaches to prevent and treat AMD. In this review, we summarize scientific data unraveling the therapeutic potential of the specific retinoid and natural compounds. The experimental results reported by us and other research groups demonstrated that retinoid analogs and compounds with natural product scaffolds could serve as lead compounds for the development of new therapeutic agents with potential to prevent or slow down the pathogenesis of AMD.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-05-22T04:40:02Z
      DOI: 10.1177/1535370220926938
       
  • Current perspectives on the cellular and molecular features of epigenetic
           ageing
    • Authors: Kenneth Raj, Steve Horvath
      Abstract: Experimental Biology and Medicine, Ahead of Print.

      Citation: Experimental Biology and Medicine
      PubDate: 2020-04-11T06:49:31Z
      DOI: 10.1177/1535370220918329
       
  • Cytoplasmic mislocalization and mitochondrial colocalization of TDP-43 are
           common features between normal aged and young mice
    • Authors: Pichet Termsarasab, Thananan Thammongkolchai, Ju Gao, Luwen Wang, Jingjing Liang, Xinglong Wang
      Abstract: Experimental Biology and Medicine, Ahead of Print.

      Citation: Experimental Biology and Medicine
      PubDate: 2020-03-26T04:23:24Z
      DOI: 10.1177/1535370220914253
       
  • Is periodontal disease a risk factor for developing severe Covid-19
           infection' The potential role of Galectin-3
    • Authors: Cankat Kara, Kübra Çelen, Figen Öngöz Dede, Ceren Gökmenoğlu, Nihal Beldüz Kara
      First page: 1425
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Impact statementThere could be a close relationship between periodontal diseases (PDs) severity and Covid-19 infections. This relationship could be caused by Galectin-3-mediated increased immune response and increased viral attachment. Keeping PDs under control and maintaining rigorous oral hygiene during this troubled Covid-19 pandemic period is very important.Patients with older age and pre-existing conditions like cardiovascular disease, hypertension, diabetes, and obesity are in the higher risk group for developing severe Covid-19 infections. The inflammatory pathways that are involved in these conditions are the same pathways that we see in periodontal diseases (PDs). This raises a significant question: Is PD a pre-existing condition that can increase the risk of developing severe Covid-19 infection' Several studies have shown that Galectins play a key role in the homeostasis of immune cells, and recently, a relationship was found between Covid-19 and Galectin-3 (Gal-3).It has been determined that an important area in the spike protein of Coronavirus-19 is almost exactly the same as the morphology of Gal-3, and these spike proteins are critical for the entry of the virus into host cells. We suspect that there is enough evidence to support a close relationship between PDs severity and Covid-19 infections. There is accumulating evidence to suggest a relationship between the severity of PD and the risk of infection with Covid-19, which requires further investigation. This relationship could be caused by Gal-3-mediated increased immune response and increased viral attachment. In this context, we want to emphasize the importance of keeping PD under control by maintaining rigorous oral hygiene during this troubled Covid-19 pandemic period. We would also like to point out the possibility that having PD may be a pre-disposition toward developing a severe Covid-19 infection.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-08-25T04:56:41Z
      DOI: 10.1177/1535370220953771
       
  • Circulating serum exosomal miR-20b-5p and miR-3187-5p as efficient
           diagnostic biomarkers for early-stage non-small cell lung cancer
    • Authors: Zhi-Jun Zhang, Xing-Guo Song, Li Xie, Kang-Yu Wang, You-Yong Tang, Miao- Yu, Xiao-Dong Feng, Xian-Rang Song
      First page: 1428
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Circulating exosomal microRNAs (ExmiRNAs) provide an ideal non-invasive method for cancer diagnosis. In this study, we evaluated two circulating ExmiRNAs in NSCLC patients as a diagnostic tool for early-stage non-small lung cancer (NSCLC). The exosomes were characterized by qNano, transmission electron microscopy, and Western blot, and the ExmiRNA expression was measured by microarrays. The differentially expressed miRNAs were verified by RT-qPCR using peripheral blood specimens from NSCLC patients (n = 276, 0 and I stage: n = 104) and healthy donors (n = 282). The diagnostic values were measured by receiver operating characteristic (ROC) analysis. The results show that the expression of both ExmiR-20b-5p and ExmiR-3187-5p was drastically reduced in NSCLC patients. The area under the ROC curve (AUC) was determined to be 0.818 and 0.690 for ExmiR-20b-5p and ExmiR-3187-5p, respectively. When these two ExmiRNAs were combined, the AUC increased to 0.848. When the ExmiRNAs were administered with either carcinoembryonic antigen (CEA) or cytokeratin-19-fragment (CYFRA21-1), the AUC was further improved to 0.905 and 0.894, respectively. Additionally, both ExmiR-20b-5p and ExmiR-3187-5p could be used to distinguish early stages NSCLC (0 and I stage) from the healthy controls. The ROC curves showed that the AUCs were 0.810 and 0.673, respectively. Combination of ExmiR-20b-5p and ExmiR-3187-5p enhanced the AUC to 0.838. When CEA and CYFRA21-1 were administered with the ExmiRNAs, the AUCs were improved to 0.930 and 0.928, respectively. In summary, circulating serum exosomal miR-20b-5p and miR-3187-5p could be used as effective, non-invasive biomarkers for the diagnosis of early-stage NSCLC, and the effects were further improved when the ExmiRNAs were combined.Impact statementThe high mortality of non-small cell lung cancer (NSCLC) is mainly because the cancer has progressed to a more advanced stage before diagnosis. If NSCLC can be diagnosed at early stages, especially stage 0 or I, the overall survival rate will be largely improved by definitive treatment such as lobectomy. We herein validated two novel circulating serum ExmiRs as diagnostic biomarkers for early-stage NSCLC to fulfill the unmet medical need. Considering the number of specimens in this study, circulating serum exosomal miR-20b-5p and miR-3187-5p are putative NSCLC biomarkers, which need to be further investigated in a larger randomized controlled clinical trial.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-08-02T11:19:53Z
      DOI: 10.1177/1535370220945987
       
  • Alternative splicing of leptin receptor overlapping transcript in
           osteosarcoma
    • Authors: Emel Rothzerg, Xuan D Ho, Jiake Xu, David Wood, Aare Märtson, Katre Maasalu, Sulev Kõks
      First page: 1437
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Alternative splicing of RNA is an essential mechanism that increases proteomic diversity in eukaryotic cells. Aberrant alternative splicing is often associated with various human diseases, including cancer. We conducted whole-transcriptome analysis of 18 osteosarcoma bone samples (paired normal—tumor biopsies). Using RNA-seq, we identified statistically significant (FDR
      Citation: Experimental Biology and Medicine
      PubDate: 2020-08-13T04:26:24Z
      DOI: 10.1177/1535370220949139
       
  • Overdosing on iron: Elevated iron and degenerative brain disorders
    • Authors: Santosh R D’Mello, Mark C Kindy
      First page: 1444
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      All cells in organisms ranging from yeast to humans utilize iron as a cofactor or structural element of proteins that function in diverse and critical cellular functions. However, deregulation of the homeostatic mechanisms regulating iron metabolism resulting in a reduction or excess of iron within the cell or outside of it can have serious effects to the health of cells and the organism. This review provides a brief overview of the molecular and cellular mechanisms regulating iron physiology, including the molecules and processes regulating iron uptake, its storage and utilization, its recycling, and its release from the cell, such that the cellular iron levels are sufficient to meet metabolic demand but below those that cause permanent damage. The major focus of review is on the pathological consequences of dysregulation of these homeostatic mechanisms, focusing on the brain. Current advances on the role of iron accumulation to the pathogenesis of rare neurological disorders caused by genetic mutations as well as to the more prevalent and age-associated neurodegenerative diseases are described.Impact statementBrain degenerative disorders, which include some neurodevelopmental disorders and age-associated diseases, cause debilitating neurological deficits and are generally fatal. A large body of emerging evidence indicates that iron accumulation in neurons within specific regions of the brain plays an important role in the pathogenesis of many of these disorders. Iron homeostasis is a highly complex and incompletely understood process involving a large number of regulatory molecules. Our review provides a description of what is known about how iron is obtained by the body and brain and how defects in the homeostatic processes could contribute to the development of brain diseases, focusing on Alzheimer’s disease and Parkinson’s disease as well as four other disorders belonging to a class of inherited conditions referred to as neurodegeneration based on iron accumulation (NBIA) disorders. A description of potential therapeutic approaches being tested for each of these different disorders is provided.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-09-03T04:43:56Z
      DOI: 10.1177/1535370220953065
       
  • Ferrotoxicity and its amelioration by endogenous vitamin D in experimental
           acute kidney injury
    • Authors: Chandrashekar Annamalai, Rajesh N Ganesh, Pragasam Viswanathan
      First page: 1474
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Acute kidney injury causes significant morbidity and mortality. This experimental animal study investigated the simultaneous impact of iron and vitamin D on acute kidney injury induced by iohexol, an iodinated, non-ionic monomeric radiocontrast agent in Wistar rats. Out of 36 healthy male Wistar rats, saline was injected into six control rats (group 1) and iohexol into the remaining 30 experimental rats (groups 2 to 6 comprising six rats each). Biochemical, renal histological changes, and gene expression of iron-regulating proteins and 1 α-hydroxylase were analyzed. Urinary neutrophil gelatinase-associated lipocalin (NGAL), serum creatinine, urine protein, serum and urine catalytic iron, 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, and tissue lipid peroxidation were assayed. Rats injected with iohexol showed elevated urinary NGAL (11.94 ± 6.79 ng/mL), serum creatinine (2.92 ± 0.91 mg/dL), and urinary protein levels (11.03 ± 9.68 mg/mg creatinine) together with histological evidence of tubular injury and iron accumulation. Gene expression of iron-regulating proteins and 1 α-hydroxylase was altered. Serum and urine catalytic iron levels were elevated (0.57 ± 0.17; 48.95 ± 29.13 µmol/L) compared to controls (0.49 ± 0.04; 20.7 ± 2.62 µmol/L, P 
      Citation: Experimental Biology and Medicine
      PubDate: 2020-08-02T11:19:53Z
      DOI: 10.1177/1535370220946271
       
  • Calliandra portoricensis ameliorates ovarian and uterine
           oxido-inflammatory responses in N-methyl-N-nitrosourea and
           benzo[a]pyrene-treated rats
    • Authors: Adedoyin O Adefisan, Judith C Madu, Solomon E Owumi, Oluwatosin A Adaramoye
      First page: 1490
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Reproductive dysfunction stemming from chemical agents may lead to infertility. We examined the protective effects of Calliandra portoricensis (CP) extract on benzo[a]pyrene (BaP) and N-methyl-N-nitrosourea (NMU)-induced ovarian and uterine toxicity in rat, treated as follows: control (group 1), NMU + BaP (group 2), groups 3 and 4 received (NMU + BaP), and CP (50 and 100 mg/kg), respectively. Group 5: CP (100 mg/kg) alone, group 6: (NMU + BaP) and vincristine (VIN: 0.5 mg/kg) and group 7: VIN alone. Rats were injected at age 7, 10, and 13 weeks with single doses of NMU and BaP for 10 consecutive weeks. NMU + BaP significantly (P 
      Citation: Experimental Biology and Medicine
      PubDate: 2020-08-04T05:41:42Z
      DOI: 10.1177/1535370220947387
       
  • Endothelin-1 in portal hypertension: The intricate role of hepatic
           stellate cells
    • Authors: Devaraj Ezhilarasan
      First page: 1504
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Portal hypertension is one of the most important cirrhosis-associated complications of chronic liver disease, leading to significant morbidity and mortality. After chronic liver injury, hepatic stellate cells reside in the perisinusoidal space activted and acquire a myofibroblast-like phenotype. The activated hepatic stellate cells act as both sources as well as the target for a potent vasoconstrictor endothelin-1. Activation of hepatic stellate cells plays a vital role in the onset of cirrhosis by way of increased extracellular matrix production and the enhanced contractile response to vasoactive mediators such as endothelin-1. In fibrotic/cirrhotic liver, activated hepatic stellate cells produce endothelin-1 leading to an imbalance between pro and antifibrotic factors responsible for enormous extracellular matrix synthesis. Thus, extracellular matrix deposition in the perisinusoidal space further augments liver stiffness and elevates the vascular tone and portal hypertension. Portal hypertension is a complex process modulated by several cell types like hepatic stellate cells, liver sinusoidal endothelial cells, Kupffer cells, injured hepatocytes, immune cells, and biliary epithelial cells. Therefore, targeting a single cell type may not be useful for regression of cirrhosis and portal hypertension. Nevertheless, numerous findings indicate that functionally liver sinusoidal endothelial cells and hepatic stellate cells closely regulate the sinusoidal blood flow via synthesis of several vasoactive molecules including endothelin-1, and hence targeting these cells with novel pharmacological agents may offer promising results.Impact statementPortal hypertension is pathologically defined as increase of portal venous pressure, mainly due to chronic liver diseases such as fibrosis and cirrhosis. In fibrotic liver, activated hepatic stellate cells increase their contraction in response to endothelin-1 (ET-1) via autocrine and paracrine stimulation from liver sinusoidal endothelial cells and injured hepatocytes. Clinical studies are limited with ET receptor antagonists in cirrhotic patients with portal hypertension. Hence, studies are needed to find molecules that block ET-1 synthesis. Accumulation of extracellular matrix proteins in the perisinusoidal space, tissue contraction, and alteration in blood flow are prominent during portal hypertension. Therefore, novel matrix modulators should be tested experimentally as well as in clinical studies. Specifically, tumor necrosis factor-α, transforming growth factor-β1, Wnt, Notch, rho-associated protein kinase 1 signaling antagonists, and peroxisome proliferator-activated receptor α and γ, interferon-γ and sirtuin 1 agonists should be tested elaborately against cirrhosis patients with portal hypertension.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-08-14T06:24:05Z
      DOI: 10.1177/1535370220949148
       
  • Concentration standardization improves the capacity of drainage CRP and
           IL-6 to predict surgical site infections
    • Authors: Xiaoqin Bi, Yan Li, Jie Lin, Chunjie Li, Jiping Li, Yubin Cao
      First page: 1513
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      The early detection of surgical site infection (SSI) remains an unsolved problem. Inflammatory factors in fluids drained from surgical sites may be a promising tool for predicting SSI. Previous attempts to predict SSI via such factors have not taken baseline concentrations into account. However, this may have comprised predictive efficacy. In the current study, concentrations of C-reactive protein (CRP) and interleukin 6 (IL-6) in fluid samples drained from surgical sites in 20 patients with SSI and 60 matched controls were assessed, and concentrations from day 2 to day 4 were divided by the concentration at day 1 to achieve concentration standardization. There were no significant differences of CRP or IL-6 concentrations at day 1 or day 2 (p > 0.05), but there were significant differences at day 3 and day 4 (p 
      Citation: Experimental Biology and Medicine
      PubDate: 2020-07-27T05:39:52Z
      DOI: 10.1177/1535370220945290
       
  • Chemokine-like factor 1: A promising therapeutic target in human diseases
    • Authors: Xiaopeng Cai, Jingwen Deng, Qianqian Ming, Huiqiang Cai, Zhi Chen
      First page: 1518
      Abstract: Experimental Biology and Medicine, Ahead of Print.
      Chemokines are a family of small molecular-weight proteins, being well-known with their important roles in the process of allergic response, immune regulation, cell proliferation, and differentiation. Almost two decades ago, a novel member of this family, chemokine-like factor 1 (CKLF1) was identified. In recent years, it draws much attention of researchers because of its key roles in many types of tissues and its potential implications in a large number of diseases. Up to now, CKLF1 has been shown to have two main functions: broad-spectrum chemotactic activity, and proliferation- and differentiation-promoting abilities. In this review, we would introduce the basic structural features of CKLF1 and its biological functions, and then elaborate the relationships between CKLF1 and human diseases. The cell signaling pathways CKLF1 may be involved in would be discussed and summarized in details. Furthermore, we present the trials of CKLF1-targeted treatments in animal disease models, hoping to provide a few important insights about CKLF1 to both medical researchers and pharmacy, and finally conclude that CKLF1 is a potent, and very promising, therapeutic target.Impact statementCKLF1, a recently identified chemokine, has been reported by a number of studies to play important roles in quite many diseases. However, the potential pathways that CKLF1 may be involved are not manifested well yet. In our review, we showed the basic molecular structure and major functions of this novel chemokine, and implication in human diseases, such as tumors. To attract more attention, we summarized its signaling pathways and clearly present them in a set of figures. With the overview of the experimental trial of CKLF1-targeting medicines in animal models, we hope to provide a few important insights about CKLF1 to both medical researchers and pharmacy.
      Citation: Experimental Biology and Medicine
      PubDate: 2020-07-27T05:39:53Z
      DOI: 10.1177/1535370220945225
       
 
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