Subjects -> MEDICAL SCIENCES (Total: 8677 journals)
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MEDICAL SCIENCES (2410 journals)            First | 3 4 5 6 7 8 9 10 | Last

Showing 1201 - 1400 of 3562 Journals sorted alphabetically
Journal of Evidence-Based Integrative Medicine     Open Access   (Followers: 18)
Journal of Evidence-Based Medicine     Partially Free   (Followers: 4)
Journal of Exercise Science & Fitness     Open Access   (Followers: 29)
Journal of Experimental and Clinical Anatomy     Open Access   (Followers: 2)
Journal of Family and Community Medicine     Open Access   (Followers: 3)
Journal of Family Medicine and Primary Care     Open Access   (Followers: 11)
Journal of Foot and Ankle Research     Open Access   (Followers: 5)
Journal of Forensic Science and Research     Open Access   (Followers: 2)
Journal of Gandaki Medical College-Nepal     Open Access  
Journal of Generic Medicines     Hybrid Journal   (Followers: 2)
Journal of Geographical Sciences     Hybrid Journal   (Followers: 1)
Journal of Global Antimicrobial Resistance     Hybrid Journal   (Followers: 3)
Journal of Hand Therapy     Hybrid Journal   (Followers: 19)
Journal of Head & Neck Physicians and Surgeons     Open Access   (Followers: 2)
Journal of Health & Medical Informatics     Open Access   (Followers: 61)
Journal of Health and Biological Sciences     Open Access   (Followers: 1)
Journal of Health Design     Open Access   (Followers: 1)
Journal of Health Economics and Outcomes Research     Open Access   (Followers: 1)
Journal of Health Promotion and Behavior     Open Access  
Journal of Health Research and Reviews     Open Access  
Journal of Health Science and Medical Research     Open Access  
Journal of Health Science Research     Open Access  
Journal of Health Sciences     Open Access   (Followers: 1)
Journal of health sciences     Open Access  
Journal of Health Sciences / Sağlık Bilimleri Dergisi     Open Access  
Journal of Health Sciences and Medicine     Open Access  
Journal of Health Sciences and Medicine     Open Access   (Followers: 2)
Journal of Health Sciences and Surveillance System     Open Access  
Journal of Health Sciences Scholarship     Open Access  
Journal of Health Specialties     Open Access  
Journal of Health Studies     Open Access  
Journal of Healthcare Informatics Research     Hybrid Journal   (Followers: 1)
Journal of Heavy Metal Toxicity and Diseases     Open Access  
Journal of Helminthology     Hybrid Journal   (Followers: 2)
Journal of Herbs Spices & Medicinal Plants     Hybrid Journal  
Journal of HIV for Clinical and Scientific Research     Open Access   (Followers: 2)
Journal of Hospital Medicine     Hybrid Journal   (Followers: 11)
Journal of Huazhong University of Science and Technology [Medical Sciences]     Hybrid Journal  
Journal of Human Hypertension     Hybrid Journal   (Followers: 3)
Journal of Human Rhythm     Open Access  
Journal of Human Transcriptome     Open Access  
Journal of Ideas in Health     Open Access  
Journal of Inflammation     Open Access   (Followers: 2)
Journal of Inflammation Research     Open Access  
Journal of Injury and Violence Research     Open Access   (Followers: 7)
Journal of Innovation in Health Informatics     Open Access   (Followers: 17)
Journal of Institute of Medicine     Open Access  
Journal of Insulin Resistance     Open Access   (Followers: 1)
Journal of Interactional Research in Communication Disorders     Hybrid Journal   (Followers: 5)
Journal of Interferon & Cytokine Research     Hybrid Journal   (Followers: 3)
Journal of International Medical Research     Open Access   (Followers: 3)
Journal of Interventional Medicine     Open Access   (Followers: 1)
Journal of Investigative Medicine     Hybrid Journal   (Followers: 3)
Journal of Islamabad Medical & Dental College     Open Access   (Followers: 2)
Journal of Istanbul Faculty of Medicine     Open Access  
Journal of Karnali Academy of Health Sciences     Open Access   (Followers: 1)
Journal of Kathmandu Medical College     Open Access   (Followers: 1)
Journal of King Abdulaziz University : Medical Sciences     Open Access   (Followers: 2)
Journal of Laboratory Medicine     Hybrid Journal   (Followers: 27)
Journal of Laryngology and Voice     Open Access   (Followers: 11)
Journal of Lasers in Medical Sciences     Open Access  
Journal of Law, Medicine & Ethics     Hybrid Journal   (Followers: 24)
Journal of Legal Medicine     Hybrid Journal   (Followers: 7)
Journal of Limb Lengthening & Reconstruction     Open Access  
Journal of Lumbini Medical College     Open Access   (Followers: 1)
Journal of Mahatma Gandhi Institute of Medical Sciences     Open Access  
Journal of Manipulative and Physiological Therapeutics     Hybrid Journal   (Followers: 6)
Journal of Manmohan Memorial Institute of Health Sciences     Open Access   (Followers: 1)
Journal of Marine Medical Society     Open Access  
Journal of Materials Science : Materials in Medicine     Hybrid Journal   (Followers: 4)
Journal of Maternal and Child Health     Open Access  
Journal of Mechanics in Medicine and Biology     Hybrid Journal  
Journal of Medical and Biological Engineering     Hybrid Journal   (Followers: 4)
Journal of Medical and Biomedical Sciences     Open Access   (Followers: 2)
Journal of Medical Case Reports     Open Access   (Followers: 1)
Journal of Medical Cases     Open Access   (Followers: 6)
Journal of Medical Colleges of PLA     Full-text available via subscription  
Journal of Medical Disorders     Open Access  
Journal of Medical Economics     Hybrid Journal   (Followers: 8)
Journal of Medical Education and Curricular Development     Open Access   (Followers: 6)
Journal of Medical Ethics     Partially Free   (Followers: 25)
Journal of Medical Ethics and History of Medicine     Open Access   (Followers: 17)
Journal of Medical Humanities     Hybrid Journal   (Followers: 21)
Journal of Medical Hypotheses and Ideas     Open Access  
Journal of Medical Imaging and Health Informatics     Full-text available via subscription   (Followers: 1)
Journal of Medical Investigation and Practice     Open Access  
Journal of Medical Laboratory and Diagnosis     Open Access  
Journal of Medical Law and Ethics     Full-text available via subscription   (Followers: 16)
Journal of Medical Microbiology     Full-text available via subscription   (Followers: 6)
Journal of Medical Sciences     Open Access  
Journal of Medical Sciences     Open Access  
Journal of Medical Screening     Hybrid Journal   (Followers: 6)
Journal of Medical Signals and Sensors     Open Access   (Followers: 3)
Journal of Medical Society     Open Access  
Journal of Medical Systems     Hybrid Journal  
Journal of Medical Toxicology     Hybrid Journal   (Followers: 6)
Journal of Medical Ultrasound     Open Access   (Followers: 2)
Journal of Medicinal Botany     Open Access  
Journal of Medicinal Chemistry     Hybrid Journal   (Followers: 203)
Journal of Medicine     Open Access   (Followers: 1)
Journal of Medicine and Biomedical Research     Open Access   (Followers: 1)
Journal of Medicine and Philosophy     Hybrid Journal   (Followers: 8)
Journal of Medicine and the Person     Hybrid Journal  
Journal of Medicine in Scientific Research     Open Access  
Journal of Medicine in the Tropics     Open Access  
Journal of Medicine Research and Development     Open Access   (Followers: 3)
Journal of Medicine, Physiology and Biophysics     Open Access   (Followers: 5)
Journal of Medicines Development Sciences     Open Access   (Followers: 1)
Journal of Metabolomics & Systems Biology     Open Access   (Followers: 2)
Journal of Mind and Medical Sciences     Open Access   (Followers: 1)
Journal of Molecular Medicine     Hybrid Journal   (Followers: 11)
Journal of Movement Disorders     Open Access   (Followers: 2)
Journal of Muscle Research and Cell Motility     Hybrid Journal   (Followers: 1)
Journal of Nanotechnology in Engineering and Medicine     Full-text available via subscription   (Followers: 6)
Journal of Nanotheranostics     Open Access   (Followers: 1)
Journal of Natural Medicines     Hybrid Journal  
Journal of Natural Science, Biology and Medicine     Open Access   (Followers: 3)
Journal of Nature and Science of Medicine     Open Access   (Followers: 4)
Journal of Negative and No Positive Results     Open Access  
Journal of Nepalgunj Medical College     Open Access  
Journal of Neurocritical Care     Open Access  
Journal of Neurodegenerative Diseases     Open Access   (Followers: 2)
Journal of Neurorestoratology     Open Access  
Journal of Neuroscience and Neurological Disorders     Open Access  
Journal of Nobel Medical College     Open Access  
Journal of Obesity and Bariatrics     Open Access   (Followers: 1)
Journal of Occupational Health     Open Access  
Journal of Occupational Therapy Education     Open Access   (Followers: 11)
Journal of Ocular Biology, Diseases, and Informatics     Hybrid Journal  
Journal of Oral Biology and Craniofacial Research     Full-text available via subscription  
Journal of Oral Health and Craniofacial Science     Open Access  
Journal of Orofacial Sciences     Open Access  
Journal of Otorhinolaryngology, Hearing and Balance Medicine     Open Access   (Followers: 1)
Journal of Ovarian Research     Open Access  
Journal of Ozone Therapy     Open Access  
Journal of Palliative Medicine     Hybrid Journal   (Followers: 47)
Journal of Paramedical Sciences & Rehabilitation     Open Access  
Journal of Parkinsonism and Restless Legs Syndrome     Open Access   (Followers: 2)
Journal of Parkinson’s Disease and Alzheimer’s Disease     Open Access   (Followers: 1)
Journal of Participatory Medicine     Open Access  
Journal of Patan Academy of Health Sciences     Open Access  
Journal of Pathogens     Open Access   (Followers: 1)
Journal of Patient Experience     Open Access  
Journal of Patient Safety and Risk Management     Hybrid Journal   (Followers: 2)
Journal of Patient-Centered Research and Reviews     Open Access  
Journal of Patient-Reported Outcomes     Open Access  
Journal of Periodontal Research     Hybrid Journal  
Journal of Personalized Medicine     Open Access   (Followers: 3)
Journal of Pest Science     Hybrid Journal   (Followers: 1)
Journal of Pharmaceutical Policy and Practice     Open Access   (Followers: 4)
Journal of Physiobiochemical Metabolism     Hybrid Journal   (Followers: 2)
Journal of Physiology-Paris     Hybrid Journal   (Followers: 2)
Journal of Pioneering Medical Sciences     Open Access  
Journal of Postgraduate Medicine     Open Access  
Journal of Pregnancy     Open Access   (Followers: 4)
Journal of Prevention & Intervention Community     Hybrid Journal   (Followers: 6)
Journal of Preventive Medicine and Public Health     Open Access  
Journal of Primary Prevention     Hybrid Journal   (Followers: 7)
Journal of Prosthodontic Research     Full-text available via subscription   (Followers: 1)
Journal of Prosthodontics     Hybrid Journal   (Followers: 2)
Journal of Receptor, Ligand and Channel Research     Open Access   (Followers: 1)
Journal of Regenerative Medicine     Partially Free   (Followers: 4)
Journal of Research in Medical Sciences     Open Access   (Followers: 2)
Journal of Science and Applications : Biomedicine     Open Access   (Followers: 1)
Journal of Science and Technology (Ghana)     Open Access   (Followers: 3)
Journal of Scientific Innovation in Medicine     Open Access  
Journal of Scientific Perspectives     Open Access   (Followers: 1)
Journal of Sensory Studies     Hybrid Journal   (Followers: 4)
Journal of Shaheed Suhrawardy Medical College     Open Access  
Journal of Shoulder and Elbow Arthroplasty     Open Access  
Journal of Sleep Disorders : Treatment & Care     Hybrid Journal   (Followers: 10)
Journal of South American Earth Sciences     Hybrid Journal   (Followers: 5)
Journal of Spinal Cord Medicine     Hybrid Journal   (Followers: 4)
Journal of Spinal Disorders & Techniques     Hybrid Journal   (Followers: 2)
Journal of Sports Medicine and Allied Health Sciences : Official Journal of the Ohio Athletic Trainers Association     Open Access   (Followers: 1)
Journal of Stem Cell Therapy and Transplantation     Open Access   (Followers: 1)
Journal of Stomal Therapy Australia     Full-text available via subscription  
Journal of Strength and Conditioning Research     Hybrid Journal   (Followers: 77)
Journal of Substance Use     Hybrid Journal   (Followers: 15)
Journal of Surgical Academia     Open Access   (Followers: 1)
Journal of Surgical and Clinical Research     Open Access  
Journal of Surgical Case Reports     Open Access  
Journal of Surgical Education     Full-text available via subscription   (Followers: 3)
Journal of Surgical Technique and Case Report     Open Access  
Journal of Systemic Therapies     Full-text available via subscription   (Followers: 3)
Journal of Taibah University Medical Sciences     Open Access  
Journal of Telemedicine and Telecare     Hybrid Journal   (Followers: 12)
Journal of The Academy of Clinical Microbiologists     Open Access  
Journal of the American Association for Laboratory Animal Science     Full-text available via subscription   (Followers: 9)
Journal of the American College of Certified Wound Specialists     Hybrid Journal   (Followers: 2)
Journal of the American College of Clinical Wound Specialists     Hybrid Journal   (Followers: 2)
Journal of the American Medical Directors Association     Hybrid Journal   (Followers: 5)
Journal of the American Medical Informatics Association : JAMIA     Hybrid Journal   (Followers: 36)
Journal of the American Podiatric Medical Association     Full-text available via subscription   (Followers: 7)
Journal of the Anatomical Society of India     Full-text available via subscription  
Journal of the Anus, Rectum and Colon     Open Access  
Journal of The Arab Society for Medical Research     Open Access  
Journal of the Australasian College of Nutritional and Environmental Medicine     Full-text available via subscription  
Journal of the Australasian Society of Aerospace Medicine     Open Access   (Followers: 1)
Journal of the Ceylon College of Physicians     Open Access  

  First | 3 4 5 6 7 8 9 10 | Last

Similar Journals
Journal Cover
Journal of Molecular Medicine
Journal Prestige (SJR): 2.177
Citation Impact (citeScore): 5
Number of Followers: 11  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1432-1440 - ISSN (Online) 0946-2716
Published by Springer-Verlag Homepage  [2626 journals]
  • Fetal programming effects of pentaerythritol tetranitrate in a rat model
           of superimposed preeclampsia
    • Abstract: Preeclampsia is a common medical condition during pregnancy and a major cause of maternal and prenatal mortality. The present study was conducted to investigate the effects of maternal treatment with pentaerythritol tetranitrate (PETN) in Dahl salt-sensitive rats (DSSR), a model of superimposed preeclampsia. F0 parental DSSR were treated with PETN (50 mg/kg) from the time point of mating to the end of lactation. Maternal PETN treatment improved fetal growth and had no effect on blood pressure in DSSR offspring fed with normal chow or high-salt diet. Upon high-fat diet (HFD) feeding, offspring from PETN-treated mother showed improved glucose tolerance despite similar weight gain. Unexpectedly, maternal PETN treatment significantly potentiated the HFD-induced blood pressure elevation in male DSSR offspring. Endothelium-derived hyperpolarization factor (EDHF)-mediated vasodilation was similar between NCD-fed and HFD-fed control offspring but was markedly reduced in HFD-fed PETN offspring. EDHF genes were downregulated in the vasculature of HFD-fed PETN offspring, which was associated with epigenetic changes in histone modifications. In conclusion, maternal PETN treatment in DSSR shows both beneficial and unfavorable effects. It improves fetal growth and ameliorates glucose tolerance in the offspring. Although maternal PETN treatment has no effect on blood pressure in offspring fed with normal chow or high-salt diet, the offspring is at higher risk to develop HFD-induced hypertension. PETN may potentiate the blood pressure response to HFD by epigenetic modifications of EDHF genes. Key messages The core findings of this article suggest that maternal PETN treatment of DSSR, a rat model of a spontaneous superimposed preeclampsia, leads to • Improvement of fetal growth; • No changes of maternal blood pressure or markers of preeclampsia; • Amelioration of HFD-induced glucose intolerance in adult offspring; • No changes in blood pressure development of the offspring on normal chow or high salt-diet; • Potentiation of blood pressure elevation of the offspring on HFD.
      PubDate: 2020-08-03
       
  • Sars-Cov-2 interference in HEME production: is it the time for an early
           predictive biomarker'
    • PubDate: 2020-08-01
       
  • TCF21: a critical transcription factor in health and cancer
    • Abstract: Abstract Transcription factor 21 (TCF21) is a member of the basic helix-loop-helix (bHLH) transcription factors that mediate cell fate and differentiation by orchestrating temporal and spatial gene expression during the development of various organs. It plays a crucial role in a wide spectrum of biological processes, including organogenesis, epithelial-mesenchymal transition (EMT), cell cycle, autophagy, proliferation, differentiation, specification, maturation, and survival of cells, as well as invasion and metastasis of cancer cells. Controlled expression and activity of TCF21 provide a balanced transcriptional program that guarantees appropriate growth and maturation during embryogenesis and organ development. Its dysregulation is closely correlated with a variety of diseases, including cancer. Its function is mainly regulated by non-coding RNAs (ncRNAs), post-translational modifications (PTMs), and protein–protein interactions. However, the exact mechanisms of TCF21 dysregulation in disease progression are still elusive. This review summarizes the regulatory mechanisms of TCF21 expression and activity and highlights its critical role in health and disease. This information may contribute to the development of better diagnostics and treatments for cancer and other developmental diseases.
      PubDate: 2020-08-01
       
  • Translation of curative therapy concepts with T cell and cytokine antibody
           combinations for type 1 diabetes reversal in the IDDM rat
    • Abstract: Proinflammatory cytokines released from the pancreatic islet immune cell infiltrate in type 1 diabetes (T1D) cause insulinopenia as a result of severe beta cell loss due to apoptosis. Diabetes prevention strategies targeting different cytokines with antibodies in combination with a T cell antibody, anti-TCR, have been assessed for therapy success in the LEW.1AR1-iddm (IDDM) rat, an animal model of human T1D. Immediately after diabetes manifestation, antibody combination therapies were initiated over 5 days with anti-TNF-α (tumour necrosis factor), anti-IL-1β (interleukin), or anti-IFN-γ (interferon) together with anti-TCR for the reversal of the diabetic metabolic state in the IDDM rat. Anti-TCR alone showed only a very limited therapy success with respect to a reduction of immune cell infiltration and beta cell mass regeneration. Anti-TCR combinations with anti-IL-1β or anti-IFN-γ were also not able to abolish the increased beta cell apoptosis rate and the activated immune cell infiltrate leading to a permanent beta cell loss. In contrast, all anti-TCR combinations with anti-TNF-α provided sustained therapy success over 60 to 360 days. The triple combination of anti-TCR with anti-TNF-α plus anti-IL-1β was most effective in regaining sustained normoglycaemia with an intact islet structure in a completely infiltration-free pancreas and with a normal beta cell mass. Besides the triple combination, the double antibody combination of anti-TCR with anti-TNF-α proved to be the most suited therapy for reversal of the T1D metabolic state due to effective beta cell regeneration in an infiltration free pancreas. Key messages Anti-TCR is a cornerstone in combination therapy for autoimmune diabetes reversal. The combination of anti-TCR with anti-TNF-α was most effective in reversing islet immune cell infiltration. Anti-TCR combined with anti-IL-1β was not effective in this respect. The combination of anti-TCR with anti-TNF-α showed a sustained effect over 1 year.
      PubDate: 2020-08-01
       
  • Molecular karyotyping and gene expression analysis in childhood cancer
           patients
    • Abstract: The genetic etiology of sporadic childhood cancer cases remains unclear. We recruited a cohort of 20 patients who survived a childhood malignancy and then developed a second primary cancer (2N), and 20 carefully matched patients who survived a childhood cancer without developing a second malignancy (1N). Twenty matched cancer-free (0N) and additional 1000 (0N) GHS participants served as controls. Aiming to identify new candidate loci for cancer predisposition, we compared the genome-wide DNA copy number variations (CNV) with the RNA-expression data obtained after in vitro irradiation of primary fibroblasts. In 2N patients, we detected a total of 142 genes affected by CNV. A total of 53 genes of these were not altered in controls. Six genes (POLR3F, SEC23B, ZNF133, C16orf45, RRN3, and NTAN1) that we found to be overexpressed after irradiation were also duplicated in the genome of the 2N patients. For the 1N collective, 185 genes were affected by CNV and 38 of these genes were not altered in controls. Five genes (ZCWPW2, SYNCRIP, DHX30, DHRS4L2, and THSD1) were located in duplicated genomic regions and exhibited altered RNA expression after irradiation. One gene (ABCC6) was partially duplicated in one 1N and one 2N patient. Analysis of methylation levels of THSD1 and GSTT2 genes which were detected in duplicated regions and are frequently aberrantly methylated in cancer showed no changes in patient’s fibroblasts. In summary, we describe rare and radiation-sensitive genes affected by CNV in childhood sporadic cancer cases, which may have an impact on cancer development. Key messages • Rare CNV’s may have an impact on cancer development in sporadic, non-familial, non-syndromic childhood cancer cases. • In our cohort, each patient displayed a unique pattern of cancer-related gene CNVs, and only few cases shared similar CNV. • Genes that are transcriptionally regulated after radiation can be located in CNVs in cancer patients and controls. • THSD1 and GSTT2 methylation is not altered by CNV.
      PubDate: 2020-08-01
       
  • Transcriptional signature of resting-memory CD4 T cells differentiates
           spontaneous from treatment-induced HIV control
    • Abstract: The HIV reservoir is the main barrier to eradicating HIV infection, and resting memory CD4 T (Trm) cells are one of the most relevant cellular component harboring latent proviruses. This is the first study analyzing the transcriptional profile of Trm cells, in two well-characterized groups of HIV patients with distinct mechanisms of viral replication control (spontaneous versus treatment-induced). We use a systems biology approach to unravel subtle but important differences in the molecular mechanisms operating at the cellular level that could be associated with the host’s ability to control virus replication and persistence. Despite the absence of significant differences in the transcriptome of Trm cells between Elite Controllers (ECs) and cART-treated (TX) patients at the single gene level, we found 353 gene ontology (GO) categories upregulated in EC compared with TX. Our results suggest the existence of mechanisms at two different levels: first boosting both adaptive and innate immune responses, and second promoting active viral replication and halting HIV latency in the Trm cell compartment of ECs as compared with TX patients. These differences in the transcriptional profile of Trm cells could be involved in the lower HIV reservoir observed in ECs compared with TX individuals, although mechanistic studies are needed to confirm this hypothesis. Combining transcriptome analysis and systems biology methods is likely to provide important findings to help us in the design of therapeutic strategies aimed at purging the HIV reservoir. Key messages HIV-elite controllers have the lowest HIV-DNA content in resting memory CD4 T cells. HIV-ECs show a particular transcriptional profile in resting memory CD4 T cells. Molecular mechanisms of enhanced adaptative and innate immune response in HIV-ECs. High viral replication and low viral latency establishment associate to the EC status.
      PubDate: 2020-08-01
       
  • Gut microbiota and atherosclerosis: role of B cell for atherosclerosis
           focusing on the gut-immune-B2 cell axis
    • Abstract: Atherosclerosis is the leading cause of cardiovascular mortality and morbidity worldwide and is described as a complex disease involving several different cell types and their molecular products. Recent studies have revealed that atherosclerosis arises from a systemic inflammatory process, including the accumulation and activities of various immune cells. However, the immune system is a complicated network made up of many cell types, hundreds of bioactive cytokines, and millions of different antigens, making it challenging to readily define the associated mechanism of atherosclerosis. Nevertheless, we previously reported a potential persistent inflammatory process underlying atherosclerosis development, centered on a pathological humoral immune response between commensal microbes and activated subpopulations of substantial B cells in the vicinity of the arterial adventitia. Accumulating evidence has indicated the importance of gut microbiota in atherosclerosis development. Commensal microbiota are considered important regulators of immunity and metabolism and also to be possible antigenic sources for atherosclerosis development. However, the interplay between gut microbiota and metabolism with regard to the modulation of atherosclerosis-associated immune responses remains poorly understood. Here, we review the mechanisms by which the gut microbiota may influence atherogenesis, with particular focus on humoral immunity and B cells, especially the gut-immune-B2 cell axis. Graphical abstract Under high-fat and high-calorie conditions, signals driven by the intestinal microbiota via the TLR signaling pathway cause B2 cells in the spleen to become functionally active and activated B2 cells then modify responses such as antibody production (generation of active antibodies IgG and IgG3), thereby contributing to the development of atherosclerosis. On the other hand, intestinal microbiota also resulted in recruitment and ectopic activation of B2 cells via the TLR signaling pathway in perivascular adipose tissue (PVAT), and, subsequently, an increase in circulating IgG and IgG3 led to the enhanced disease development. This is a potential link between microbiota alterations and B cells in the context of atherosclerosis.
      PubDate: 2020-07-31
       
  • Microparticles expressing myeloperoxidase as potential biomarkers in
           
    • Abstract: To investigate presence of circulating myeloperoxidase-positive microparticles (MPO+MPs) in relation to disease activity in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Forty-six patients with AAV and 23 age- and sex-matched healthy controls were included. Vasculitis disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). MPs were analyzed in citrate plasma by flow cytometry and phenotyped based on MPO expression and co-expression of pentraxin-3 (PTX3), high mobility group box 1 protein (HMGB1), and tumor necrosis factor-like weak inducer of apoptosis (TWEAK). Serum levels of PTX3, sTWEAK, and HMGB1 were also determined. Twenty-three patients had active vasculitis (BVAS ≥ 1). Concentrations of MPO+MPs expressing PTX3, HMGB1, and TWEAK were significantly higher in patients compared to healthy controls (p < 0.001, p < 0.01, p < 0.001, respectively), while concentrations of PTX3+ and HMGB1+MPO+MPs were significantly higher in active AAV compared to patients in remission. MPO+MPs expressing either PTX3 or HMGB1 were associated with BVAS (r = 0.5, p < 0.001; r = 0.3, p = 0.04, respectively). Significantly higher serum PTX3 levels were found in active- than in inactive AAV (p < 0.001), correlating strongly with BVAS (r = 0.7, p < 0.001). Serum levels of sTWEAK and HMGB1 did not differ between patients and controls. Concentration of MPO+MPs is increased in plasma from AAV patients compared to healthy individuals. PTX3 in serum as well as PTX3 and HMGB1 expressed on MPO+MPs were associated with disease activity in the investigated patients. Key messages Myeloperoxidase-positive microparticles (MPO+MPs) are increased in plasma from patients with ANCA-associated vasculitis. Concentrations of MPO+MPs expressing PTX3, HMGB1, and TWEAK were significantly higher in patients compared to healthy controls. MPO+MPs expressing PTX3 and HMGB1 are associated with disease activity in ANCA-associated vasculitis.
      PubDate: 2020-07-30
       
  • Interaction with p53 explains a pro-proliferative function for VHL in
           cancer
    • Abstract: The von Hippel-Lindau (VHL) protein binds and degrades hypoxia-inducible factors (HIF) hydroxylated by prolyl-hydroxylases under normoxia. Although originally described as a tumor suppressor, there is growing evidence that VHL may paradoxically promote tumor growth. The significance of its described interactions with many other proteins remains unclear. We found that VHL interacts with p53, preventing its tetramerization, promoter binding and expression of its target genes p21, PUMA, and Bax. VHL limited the decrease in proliferation and increase in apoptosis caused by p53 activation, independent of prolyl-hydroxylation and HIF activity, and its presence in tumors caused a resistance to p53-inducing chemotherapy in vivo. We propose that VHL has both anti-tumor function, via HIF degradation, and a new pro-tumor function via p53 target (p21, PUMA, Bax) inhibition. Because p53 plays a critical role in tumor biology, is activated by many chemotherapies, and because VHL levels vary among different tumors and its function can even be lost by mutations in some tumors, our results have important clinical applications. Key messages VHL and p53 physically interact and VHL inhibits p53 activity by limiting the formation of p53 tetramers. VHL attenuates the expression of p53 target genes in response to p53 stimuli. The inhibition of p53 by VHL is independent of HIF and prolyl-hydroxylation.
      PubDate: 2020-07-28
       
  • Phenotypic characteristics of commonly used inbred mouse strains
    • Abstract: Abstract The laboratory mouse is the most commonly used mammalian model for biomedical research. An enormous number of mouse models, such as gene knockout, knockin, and overexpression transgenic mice, have been created over the years. A common practice to maintain a genetically modified mouse line is backcrossing with standard inbred mice over several generations. However, the choice of inbred mouse for backcrossing is critical to phenotypic characterization because phenotypic variabilities are often observed between mice with different genetic backgrounds. In this review, the major features of commonly used inbred mouse lines are discussed. The aim is to provide information for appropriate selection of inbred mouse lines for genetic and behavioral studies.
      PubDate: 2020-07-25
       
  • SCFAs induce autophagy in intestinal epithelial cells and relieve colitis
           by stabilizing HIF-1α
    • Abstract: Hypoxia-inducible factor-1α (HIF-1α) is a critical regulator of barrier integrity during colonic mucosal injury. Previous works have shown that the absence of autophagy is implicated in the development of inflammatory bowel disease (IBD). Additionally, changes in bacterial profiles in the gut are intimately associated with IBD. Although HIF-1α, autophagy, microbiota, and their metabolites are all involved in the pathogenesis of IBD, their roles are not known. In this study, we investigated the relationship between HIF-1α and autophagy in healthy and inflammatory states using transgenic mice, colitis models, and cell culture models. We confirmed that the absence of intestinal epithelial HIF-1α changed the composition of the intestinal microbes and increased the susceptibility of mice to dextran sodium sulfate (DSS)-induced colitis. In addition, autophagy levels in the intestinal epithelial cells (IECs) were significantly reduced in IEC-specific HIF-1α-deficient (HIF-1α∆IEC) mice. Moreover, in the cell culture models, butyrate treatment significantly increased autophagy in HT29 cells under normal conditions, whereas butyrate had little effect on autophagy after HIF-1α ablation. Furthermore, in the DSS-induced colitis model, butyrate administration relieved the colonic injury and suppressed inflammation in Cre-/HIF-1α- (HIF-1αloxP/loxP) mice. However, the butyrate-mediated protection against colonic injury was considerably diminished in the HIF-1α∆IEC mice. These results show that HIF-1α, autophagy, and intestinal microbes are essential for the maintenance of intestinal homeostasis. Butyrate can alleviate DSS-induced colitis by regulating autophagy via HIF-1α. These insights may have important implications for the development of therapeutic strategies for IBD. Key messages • The absence of intestinal epithelial HIF-1α leads to downregulation of autophagy in mice. • The absence of intestinal epithelial HIF-1α exacerbates DSS-induced colitis. • Short-chain fatty acids (SCFAs) can alleviate DSS-induced colitis by regulating autophagy via HIF-1α.
      PubDate: 2020-07-22
       
  • TNFSF13 upregulation confers chemotherapeutic resistance via triggering
           autophagy initiation in triple-negative breast cancer
    • Abstract: Since chemotherapy is a main strategy to treat triple-negative breast cancer (TNBC) patients currently, identifying a biomarker to predict chemotherapeutic responses is urgently needed for patients to avoid suffering through unnecessary chemotherapeutic treatments. Here, we found that the endogenous expression of TNFSF13 in a panel of TNBC cell lines highly correlates with paclitaxel (PTX) and doxorubicin IC50 concentrations. Whereas knocking down TNFSF13 enhances PTX effectiveness in PTX-insensitive MDA-MB231 cells, recombinant TNFSF13 (recTNFSF13) desensitizes PTX-sensitive HCC1806 cells to PTX treatment. Moreover, Kaplan-Meier analysis revealed that higher TNFSF13 mRNA expression significantly predicts an increased risk for cancer recurrence in estrogen receptor (ER)-negative breast cancer patients receiving an anthracycline-based treatment. Accordingly, immunohistochemistry experiments indicated that higher levels of TNFSF13 protein are detected in TNBC patients who do not respond to an anthracycline-based treatment. The in silico analysis and Western blotting demonstrated that TNFSF13 expression inversely associates with the activity of the Akt-mTOR pathway, which acts as a negative regulator of autophagy activity. Significantly, the pharmaceutical inhibition of autophagy activity restores the therapeutic effectiveness of PTX in TNFSF13-treated HCC1806 cells. These findings suggest that TNFSF13 can serve as a predictive biomarker for TNBC patients, who can use it to decide whether to receive chemotherapy. Key messages TNFSF13 upregulation correlates with a poor response to chemotherapy in TNBCs. TNFSF13 promotes autophagy initiation in chemotherapeutic resistant TNBCs. Therapeutic targeting of autophagy initiation overcomes the TNFSF13-related chemoresistance. TNFSF13 could be a predictive biomarker for TNBC patients receiving chemotherapy.
      PubDate: 2020-07-15
       
  • Metabolism of N-nitrosodimethylamine, methylation of macromolecules, and
           development of hepatic fibrosis in rodent models
    • Abstract: Abstract Hepatic fibrosis and cirrhosis are chronic diseases affecting liver and a major health problem throughout the world. The hallmark of fibrosis and cirrhosis is inordinate synthesis and deposition of fibril forming collagens in the extracellular matrix of the liver leading to nodule formation and loss of normal architecture. Hepatic stellate cells play a crucial role in the pathogenesis and progression of liver fibrosis through secretion of several potent fibrogenic factors that trigger hepatocytes, portal fibrocytes, and bone marrow–derived fibroblasts to synthesize and deposit several connective tissue proteins, especially collagens between hepatocytes and space of Disse. Regulation of various events involved in the activation and transformation of hepatic stellate cells seems to be an appropriate strategy for the arrest of hepatic fibrosis and liver cirrhosis. In order to unravel the molecular mechanisms involved in the pathogenesis and progression of hepatic fibrosis, to determine proper and potent targets to arrest fibrosis, and to discover powerful therapeutic agents, a quick and reproducible animal model of hepatic fibrosis and liver cirrhosis that display all decompensating features of human condition is required. This review thoroughly evaluates the biochemical, histological, and pathological features of N-nitrosodimethylamine-induced model of liver injury, hepatic fibrosis, and early cirrhosis in rodents.
      PubDate: 2020-07-14
       
  • Genetic contribution of endoplasmic reticulum aminopeptidase 1
           polymorphisms to liver fibrosis progression in patients with HCV infection
           
    • Abstract: The endoplasmic reticulum aminopeptidase ERAP1 regulates innate and adaptive immune responses, trimming peptides and loading onto HLA class I molecules. Coding single nucleotide polymorphisms within ERAP1 are associated with autoimmune diseases, viral infections, and cancer development. Our purpose was to analyze the influence of ERAP1 variants on fibrogenesis in hepatitis C virus (HCV)–infected patients. A range of ERAP1 polymorphisms were genotyped in 722 unrelated Caucasian patients diagnosed with chronic HCV from two Spanish cohorts. Patients were classified according to their fibrosis stage. Paraffin-embedded tissue microarrays were constructed to assess ERAP1 expression (HCV = 38; alcoholic = 20) by immunohistochemistry. A statistical algorithm was applied to derive a fibrogenesis prediction model. The ERAP1 variants rs30187/T (K528, pc < 0.001) and rs27044/G (Q730, pc < 0.001) were related with severe fibrosis. These results were validated in the two independent cohorts. Furthermore, patients with the rs30187/T allele had stronger ERAP1 protein expression than those with the rs30187/C (p < 0.05). The statistical model showed that patients with rs30187 C/T and T/T genotypes took 15.58 years (median) to develop advanced fibrosis, but this value was 32.08 years in patients carrying C/C genotype (p < 0.005). ERAP1 variants may influence the clinical course of fibrogenesis in HCV-infected patients. These polymorphisms could be exploited as constitutive new markers of fibrosis evolution. The results highlight the possibility of using modulators of ERAP1 to generate a protective immune response against chronic HCV infection. Key messages What is known Several ERAP1 polymorphisms are associated with autoimmune diseases and cancer. ERAP1 trims peptides to HLA class I presentation. What is new here ERAP1 polymorphisms are associated with fibrogenesis. The ERAP1 polymorphisms genotype could help us in clinical management of patients. Potential translational impact The use of modulators of ERAP1 could generate a protective response depending on SNPs.
      PubDate: 2020-07-09
       
  • Synergistic effects of pazopanib and hyperthermia against uterine
           leiomyosarcoma growth mediated by downregulation of histone
           acetyltransferase 1
    • Abstract: Pazopanib—a multitargeted tyrosine kinase inhibitor with prominent antiangiogenic effects—has shown promise in the treatment of soft-tissue sarcomas. Hyperthermia has been also applied as an adjunctive treatment to chemotherapy for these malignancies. Here, we show that pazopanib and hyperthermia act synergistically in inhibiting uterine leiomyosarcoma (LMS) cell growth. Compared with either treatment alone, the combination of pazopanib and hyperthermia exerted the highest antitumor activity in a xenograft model. Mechanistically, we found that combined treatment with pazopanib and hyperthermia inhibited histone acetyltransferase 1 (HAT1) expression in LMS cells. The Clock element on the HAT1 promoter was critical for pazopanib- and hyperthermia-induced HAT1 downregulation. Inhibition of HAT1—either by pazopanib and hyperthermia or through HAT1 silencing—was mediated by suppression of Clock. Accordingly, Clock protein reconstitution rescued both HAT1 levels and HAT1-mediated histone acetylation. Immunohistochemistry revealed a higher expression of HAT1 in uterine LMS than in leiomyomas (p = 0.007), with high HAT1 expression levels being associated with poor clinical outcomes (p = 0.007). We conclude that pazopanib and hyperthermia exert synergistic effects against LMS growth by inhibiting HAT1. Further preclinical studies on HAT1 as a potential drug target in uterine LMS are warranted, especially in combination with hyperthermia. Key messages Pazopanib and hyperthermia inhibit the growth of leiomyosarcoma. Their combined use inhibits HAT1 expression in leiomyosarcoma cells. The promoter Clock element is required for HAT1 downregulation. HAT1 expression is higher in leiomyosarcoma than in leiomyomas. An increased HAT1 expression is associated with poor clinical outcomes.
      PubDate: 2020-07-07
       
  • Vascular K ATP channels protect from cardiac dysfunction and preserve
           cardiac metabolism during endotoxemia
    • Abstract: KATP channels in the vasculature composed of Kir6.1 regulate vascular tone and may contribute to the pathogenesis of endotoxemia. We used mice with cell-specific deletion of Kir6.1 in smooth muscle (smKO) and endothelium (eKO) to investigate this question. We found that smKO mice had a significant survival disadvantage compared with their littermate controls when treated with a sub-lethal dose of lipopolysaccharide (LPS). All cohorts of mice became hypotensive following bacterial LPS administration; however, mean arterial pressure in WT mice recovered to normal levels, whereas smKO struggled to overcome LPS-induced hypotension. In vivo and ex vivo investigations revealed pronounced cardiac dysfunction in LPS-treated smKO, but not in eKO mice. Similar results were observed in a cecal slurry injection model. Metabolomic profiling of hearts revealed significantly reduced levels of metabolites involved in redox/energetics, TCA cycle, lipid/fatty acid and amino acid metabolism. Vascular smooth muscle-localised KATP channels have a critical role in the response to systemic infection by normalising cardiac function and haemodynamics through metabolic homeostasis. Key messages • Mice lacking vascular KATP channels are more susceptible to death from infection. • Absence of smooth muscle KATP channels depresses cardiac function during infection. • Cardiac dysfunction is accompanied by profound changes in cellular metabolites. • Findings from this study suggest a protective role for vascular KATP channels in response to systemic infection.
      PubDate: 2020-07-06
       
  • The novel protein homeostatic modulator BTX306 is active in myeloma and
           overcomes bortezomib and lenalidomide resistance
    • Abstract: Small molecules targeting the cereblon-containing E3 ubiquitin ligase including thalidomide, lenalidomide, and pomalidomide modulate turnover of downstream client proteins and demonstrate pre-clinical and clinical anti-myeloma activity. Different drugs that engage with cereblon hold the potential of unique phenotypic effects, and we therefore studied the novel protein homeostatic modulator (PHM™) BTX306 with a unique thiophene-fused scaffold bearing a substituted phenylurea and glutarimide. This agent much more potently reduced human-derived myeloma cell line viability, with median inhibitory concentrations in the single nanomolar range versus micromolar values for lenalidomide or pomalidomide, and more potently activated caspases 3/8/9. While lenalidomide and pomalidomide induced greater degradation of Ikaros and Aiolos in myeloma cells, BTX306 more potently reduced levels of GSPT1, eRF1, CK1α, MCL-1, and c-MYC. Suppression of cereblon or overexpression of Aiolos or Ikaros induced relative resistance to BTX306, and this agent did not impact viability of murine hematopoietic cells in an in vivo model, demonstrating its specificity for human cereblon. Interestingly, BTX306 did show some reduced activity in lenalidomide-resistant cell line models but nonetheless retained its nanomolar potency in vitro, overcame bortezomib resistance, and was equipotent against otherwise isogenic cell line models with either wild-type or knockout TP53. Finally, BTX306 demonstrated strong activity against primary CD138-positive plasma cells, showed enhanced anti-proliferative activity in combination with bortezomib and dexamethasone, and was effective in an in vivo systemic model of multiple myeloma. Taken together, the data support further translational studies of BTX306 and its derivatives to the clinic for patients with relapsed and/or refractory myeloma. Key messages BTX306 has a unique thiophene-fused scaffold bearing phenylurea and glutarimide. BTX306 is more potent against myeloma cells than lenalidomide or pomalidomide. BTX306 overcomes myeloma cell resistance to lenalidomide or bortezomib in vitro. BTX306 is active against primary myeloma cells, and shows efficacy in vivo.
      PubDate: 2020-07-06
       
  • A comprehensive review of genetic alterations and molecular targeted
           therapies for the implementation of personalized medicine in acute myeloid
           leukemia
    • Abstract: Abstract Acute myeloid leukemia (AML) is an extremely heterogeneous disease defined by the clonal growth of myeloblasts/promyelocytes not only in the bone marrow but also in peripheral blood and/or tissues. Gene mutations and chromosomal abnormalities are usually associated with aberrant proliferation and/or block in the normal differentiation of hematopoietic cells. So far, the combination of cytogenetic profiling and molecular and gene mutation analyses remains an essential tool for the classification, diagnosis, prognosis, and treatment for AML. This review gives an overview on how the development of novel innovative technologies has allowed us not only to detect the genetic alterations as early as possible but also to understand the molecular pathogenesis of AML to develop novel targeted therapies. We also discuss the remarkable advances made during the last decade to understand the AML genome both at primary and relapse diseases and how genetic alterations might influence the distinct biological groups as well as the clonal evolution of disease during the diagnosis and relapse. Also, the review focuses on how the persistence of epigenetic gene mutations during morphological remission is associated with relapse. It is suggested that along with the prognostic and therapeutic mutations, the novel molecular targeted therapies either approved by FDA or those under clinical trials including CART-cell therapy would be of immense importance in the effective management of AML.
      PubDate: 2020-07-03
       
  • Genetically programmed changes in transcription of the novel progranulin
           regulator
    • Abstract: Progranulin is a glycoprotein marking chronic inflammation in obesity and type 2 diabetes. Previous studies suggested PSRC1 (proline and serine rich coiled-coil 1) to be a target of genetic variants associated with serum progranulin levels. We aimed to identify potentially functional variants and characterize their role in regulation of PSRC1. Phylogenetic module complexity analysis (PMCA) prioritized four polymorphisms (rs12740374, rs629301, rs660240, rs7528419) altering transcription factor binding sites with an overall score for potential regulatory function of Sall > 7.0. The effects of these variants on transcriptional activity and binding of transcription factors were tested by luciferase reporter and electrophoretic mobility shift assays (EMSA). In parallel, blood DNA promoter methylation of two regions was tested in subjects with a very high (N = 100) or a very low (N = 100) serum progranulin. Luciferase assays revealed lower activities in vectors carrying the rs629301-A compared with the C allele. Moreover, EMSA indicated a different binding pattern for the two rs629301 alleles, with an additional prominent band for the A allele, which was finally confirmed with the supershift for the Yin Yang 1 transcription factor (YY1). Subjects with high progranulin levels manifested a significantly higher mean DNA methylation (P < 1 × 10−7) in one promoter region, which was in line with a significantly lower PSRC1 mRNA expression levels in blood (P = 1 × 10−3). Consistently, rs629301-A allele was associated with lower PSRC1 mRNA expression (P < 1 × 10−7). Our data suggest that the progranulin-associated variant rs629301 modifies the transcription of PSRC1 through alteration of YY1 binding capacity. DNA methylation studies further support the role of PSRC1 in regulation of progranulin serum levels. Key messages PSRC1 (proline and serine rich coiled-coil 1) SNPs are associated with serum progranulin levels. rs629301 regulates PSRC1 expression by affecting Yin Yang 1 transcription factor (YY1) binding. PSRC1 is also epigenetically regulated in subjects with high progranulin levels.
      PubDate: 2020-07-03
       
  • Correction to: Signaling lipids as diagnostic biomarkers for ocular
           surface cicatrizing conjunctivitis
    • Abstract: The correct name of the 11th Author and the missing Acknowledgment is presented in this paper.
      PubDate: 2020-06-10
       
 
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