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ISSN (Online) 1559-3258
Published by Sage Publications Homepage  [1175 journals]
  • Effect of Diammonium Glycyrrhizinate in Improving Focal Cerebral
           Ischemia-Reperfusion Injury in Rats Through Multiple Mechanisms

    • Authors: Hong Wang, Binbin Zhang, Weiwei Dong, Yuying Li, Liwen Zhao, Ying Zhang
      Abstract: Dose-Response, Volume 20, Issue 4, October-December 2022.
      ObjectiveAcute ischemic stroke is a current major disabling and killer disease worldwide. We aimed to investigate the protective effect and mechanism of diammonium glycyrrhizinate in alleviating acute ischemic stroke.MethodsNinety male Sprague Dawley (SD) rats (weighing 250–300 g) were randomly allocated into three groups: sham operation group (sham group), diammonium glycyrrhizinate group (DG group) and model group (model group) each with 30 individuals. A rat model of focal CIR injury was established by reversible middle cerebral artery occlusion.ResultsZea-Longa scores for the rats in the DG group and model group were 7-fold and 8-fold higher than those of the sham group 2 h post-surgery (2.90 ± 0.99 vs. 0.30 ± 0.53, P < .05; 2.80 ± 0.61 vs. 0.30 ± 0.53, P < .05, respectively). Three days after model establishment, the scores of DG group were 26.92% lower compared with those of the model group (1.90 ± 0.76 vs. 2.60 ± 0.62, P < .05). In addition, compared with the sham group, the number of Nissl bodies and Akt-positive cells in were 27.35% and 30.42% lower in the hippocampus of the DG group (Nissl bodies: 83.40 ± 7.01 vs. 115.60 ± 11.97, p < 0.05; Akt-positive cells: 94.70 ± 8.23 vs. 136.10 ± 10.37, P < .05) and 58.65% and 57.31% lower in the model group (Nissl bodies: 47.80 ± 4.91 vs. 115.60 ± 11.97, P < .05; Akt-positive cells: 58.10 ± 4.98 vs. 136.10 ± 10.37, P < 0.05), respectively. However, the number of Nissl bodies and Akt-positive cells in the hippocampus of DG group were 74.48% and 62.9% higher compared with the model group, respectively (Nissl bodies: 83.40 ± 7.01 vs. 47.80 ± 4, P < 0.05; Akt-positive cells: 94.70 ± 8.23 vs. 58.10 ± 4.98, P < .05). In addition, compared with the sham group, the number of caspase-3-positive cells, the expression level of p38 mitogen-activated protein kinase (MAPK) and the expression of matrix metallopeptidase 9 (MMP-9) were 2-fold, 34.38%, 64.78% higher in the DG group (caspase-3-positive cells: 78.70 ± 6.52 vs. 27.10 ±3.00, P < .05; p-38MAPK: 0.43 ± 0.15 vs. 0.32 ± 0.10, P < .05; MMP-9: 14.83 ± 1.18 vs. 9.00 ± 2.05, P < .05, respectively), and more than 3-fold, 1-fold and 1-fold higher in model group (caspase-3-positive cells: 121.10 ± 11.04 vs. 27.10 ± 3.00, P < .05; p-38MAPK: 0.70 ± 0.12 vs. 0.32 ± 0.10, P < .05; MMP-9: 19.00 ± 1.90 vs. 9.00 ± 2.05, P < .05), respectively. However, the number of caspase-3-positive cells and the expression levels of p-38MAPK and MMP-9 were 35.01%, 38.57% and 28.12% lower in DG group compared with the model group (caspase-3-positive cells: 78.70 ± 6.52 vs. 121.10 ± 11.04, P < .05; p-38MAPK: 0.43 ± 0.15 vs. 0.70 ± 0.12, P < .05; MMP-9: 14.83 ± 1.18 vs. 19.00 ± 1.90, P < .05).ConclusionsOur study showed that diammonium glycyrrhizinate at 20 mg/kg/day had a protective effect on cerebral ischemia-reperfusion injury in rats by promoting formation of Nissl bodies and increasing protein expression of Akt while decreasing that of caspase-3, p38 MAPK and MMP-9, either directly or indirectly, by inhibiting apoptosis and reducing neuroinflammation. All these mechanisms resulted in improved overall neurological function.
      Citation: Dose-Response
      PubDate: 2022-12-01T07:02:04Z
      DOI: 10.1177/15593258221142792
      Issue No: Vol. 20, No. 4 (2022)
  • Hyperbaric Oxygen Therapy-Induced Molecular and Pathway Changes in a Rat
           Model of Spinal Cord Injury: A Proteomic Analysis

    • Authors: Zhuo Li, Xiaomin Hou, Xuehua Liu, Linlin Ma, Jiewen Tan
      Abstract: Dose-Response, Volume 20, Issue 4, October-December 2022.
      Hyperbaric Oxygen Therapy (HBOT) has definitive therapeutic effects on spinal cord injury (SCI), but its mechanism of action is still unclear. Here, we’ve conducted a systemic proteomic analysis to identify differentially expressed proteins (DEPs) between SCI rats and HBOT + SCI rats. The function clustering analysis showed that the top enriched pathways of DEPs include oxygen transport activity, oxygen binding, and regulation of T cell proliferation. The results of functional and signal pathway analyses indicated that metabolic pathways, thermogenesis, LXR/RXR activation, acute phase response signaling, and the intrinsic prothrombin pathway in the SCI + HBOT group was higher than SCI group.
      Citation: Dose-Response
      PubDate: 2022-11-24T08:40:02Z
      DOI: 10.1177/15593258221141579
      Issue No: Vol. 20, No. 4 (2022)
  • Biophysical Modeling of the Ionizing Radiation Influence on Cells Using
           the Stochastic (Monte Carlo) and Deterministic (Analytical) Approaches

    • Authors: Krzysztof W. Fornalski, Łukasz Adamowski, Ernest Bugała, Rafał Jarmakiewicz, Marek Kirejczyk, Jakub Kopyciński, Julianna Krasowska, Piotr Kukulski, Łukasz Piotrowski, Julia Ponikowska, Joanna Reszczyńska, Iwona Słonecka, Paweł Wysocki, Ludwik Dobrzyński
      Abstract: Dose-Response, Volume 20, Issue 4, October-December 2022.
      This review article describes our simplified biophysical model for the response of a group of cells to ionizing radiation. The model, which is a product of 10 years of studies, acts as (a) a comprehensive stochastic approach based on the Monte Carlo simulation with a probability tree and (b) the thereof derived detailed deterministic models describing the selected biophysical and radiobiological phenomena in an analytical manner. Specifically, the presented model describes effects such as the risk of neoplastic transformation of cells relative to the absorbed radiation dose, the dynamics of tumor development, the priming dose effect (also called the Raper–Yonezawa effect) based on the introduced adaptive response approach, and the bystander effect. The model is also modifiable depending on users’ potential needs.
      Citation: Dose-Response
      PubDate: 2022-11-23T08:59:45Z
      DOI: 10.1177/15593258221138506
      Issue No: Vol. 20, No. 4 (2022)
  • Hepatoprotective Effect of Grape Seed and Skin Extract Against Lithium
           Exposure Examined by the Window of Proteomics

    • Authors: Ali Mezni, Olfa Khazri, Frédérique Jarnier, Julie Hardouin, Ferid Limam, Thierry Jouenne, Ezzeddine Aouani, Pascal Cosette
      Abstract: Dose-Response, Volume 20, Issue 4, October-December 2022.
      ContextThe liver is the organ by which the majority of substances are metabolized, including psychotropic drugs. Lithium (Li) used as drug for many neurological disorders such as bipolar disorders.ObjectiveThis study aims to assess lithium toxicity and to evaluate the hepatic-protective properties of a grape skin seed and extract (GSSE).Materials and methodsTwenty-four male Wistar rats were exposed for 30 days to either various lithium concentrations, GSSE alone, or lithium supplemented with GSSE. The proteomic analysis revealed alterations of liver protein profiles after lithium treatments that were successfully identified by mass spectrometry.ResultsLithium treatment induced an oxidative damage by the alteration of antioxidant enzymes activities such as superoxide dismutase, CAT, and Gpx. The regulated proteins are mainly involved in the respiratory electron transport chain, detoxification processes, ribosomal stress pathway, glycolysis, and cytoskeleton. Proteins were differentially expressed in a dose-dependent manner. Interestingly, GSSE reversed the situation and restored the level of liver proteins whose abundance was modified after lithium treatment, arguing for its protective activity.ConclusionOur data demonstrated the ability of proteomic analysis to underline the toxicity mechanisms of lithium in animal models. Based on these results, GSSE may be envisaged as a nutritional supplement to weaken the liver toxicity of lithium.
      Citation: Dose-Response
      PubDate: 2022-11-22T05:47:40Z
      DOI: 10.1177/15593258221141585
      Issue No: Vol. 20, No. 4 (2022)
  • Identification of the Constituents in Cnidii Fructus Active Against
           Trichomonas vaginalis Parasites

    • Authors: Chien-Chih Yu, Yi-Ting Chiang, Thau-Ming Cham
      Abstract: Dose-Response, Volume 20, Issue 4, October-December 2022.
      Ethanol extracts of Cnidii Fructus, the dried fruits of Cnidium monnieri (L.) Cusson, have been externally applied in the treatment of Trichomonas vaginalis. However, the precise identity of the major constituents responsible for activity against T. vaginalis is unknown, but there is probability they are coumarin derivatives. In this study, the anti-Trichomonas activity of 4 major coumarin derivative constituents of Cnidii Fructus, namely, osthole, xanthotoxin, isopimpinellin, and bergapten, was characterized in terms of the resulting kinetics of growth and morphology of T. vaginalis upon treatment. The results demonstrated that osthole and xanthotoxol had significant trichomonacidal ability, while isopimpinellin and bergapten displayed low or no inhibitory efficacy toward T. vaginalis parasites. Our study suggests that the coumarin derivatives osthole and xanthotoxol can be potentially used as a basis for the development and design of new drugs for application in alternative or synergistic therapy against T. vaginalis.
      Citation: Dose-Response
      PubDate: 2022-11-11T01:47:15Z
      DOI: 10.1177/15593258221131646
      Issue No: Vol. 20, No. 4 (2022)
  • Characterization of Bioactives and Nutra-Pharmaceutical Potential of
           Supercritical Fluid and Hydro-Distilled Extracted Coriander Leaves
           Essential Oil

    • Authors: Ali Abbas, Farooq Anwar, Naveed Ahmad, Muhammad Shahid, Samiah H. Al-Mijalli, Muhammad Yaseen, Sidra Farooq, Munawar Iqbal
      Abstract: Dose-Response, Volume 20, Issue 4, October-December 2022.
      The volatiles chemical composition and biological attributes of coriander (Coriandrum sativum L.) leaves essential oil obtained by two extraction techniques namely supercritical fluid extraction and hydro-distillation is appraised. The coriander essential oil yield (.12%) by hydro-distillation was slightly higher than that of supercritical fluid extraction (.09%). The physico-chemical variables of the essential oil obtained from both the techniques varied in significantly (P < .05). GC-MS analysis identified 23 different components in supercritical fluid extracted oil and 18 components in hydro-distilled essential oil having linalool as major component (51.32% and 61.78%, respectively) followed by phytol (12.71%). The oil recovered by supercritical fluid extraction exhibited greater DPPH radical scavenging activity as well as reducing power as compared to the essential oil obtained by hydro-distillation technique along with a stronger biofilm inhibition and least hemolysis. The results of antimicrobial activity revealed that super critical fluid extracted essential oil has potent antifungal and antibacterial activity against P. multocida and A alternata, whereas hydro-distilled essential oil displayed better antimicrobial potential against E coli and A niger. Overall, these results depict that supercritical fluid extraction is superior than hydro-distillation with regard to isolation of better-quality coriander essential oil for nutra-pharmaceutical developments.
      Citation: Dose-Response
      PubDate: 2022-11-09T05:33:00Z
      DOI: 10.1177/15593258221130749
      Issue No: Vol. 20, No. 4 (2022)
  • Differential Inhibite Effect of Xanthohumol on HepG2 Cells and Primary

    • Authors: Xiuli Zhang, Tao Wang, Haihong Zhou, Yonghui Li, Hongyun Guo, Haixiang Su
      Abstract: Dose-Response, Volume 20, Issue 4, October-December 2022.
      Xanthohumol (XN) is the major prenylated chalcone of the female inflorescences (cone) of the hop plant (Humulus lupulus). It is also a constituent of beer, the major dietary source of prenylated flavonoids. It has shown strong antitumorigenic activity towards various types of cancer cells. In the present study, we show the impact on human hepatocarcinoma cell line HepG2 cell and potential adverse effects on rat primary hepatocytes. Cell growth/viability assay (MTT) demonstrated that HepG2 cells are highly sensitive to XN at a concentration range of 25-100 μM. The primary mode of tumor cell destruction was apoptosis as demonstrated by the binding of Annexin Ⅴ-FITC, we show that XN at a concentration of 25 μM induced apoptosis in HepG2. Further evidence that XN kills HepG2 by inducing apoptosis was provided by the impact of XN on the cleavage of PARP-1 and caspases-3. In contrast, XN concentrations up to 100 μM did not affect viability of primary rat hepatocytes in vitro, meanwhile, XN did not induce the apoptosis of primary rat hepatocytes in vitro. In summary, our data provide a rationale for clinical evaluation of XN for the treatment of liver cancer.
      Citation: Dose-Response
      PubDate: 2022-11-09T02:19:06Z
      DOI: 10.1177/15593258221136053
      Issue No: Vol. 20, No. 4 (2022)
  • Differentially Expressed mRNAs and Potential Mechanisms of
           Radiation-Induced TUT4−/− Esophageal Cell Injury

    • Authors: Zhiqiang Sun, Jiaqi Zhang, Fanye Zeng, Shuyu Zhang, Zhifang Chai, Judong Luo, Jianping Cao
      Abstract: Dose-Response, Volume 20, Issue 4, October-December 2022.
      Radiation-induced esophageal injury remains a limitation for the process of radiotherapy for lung and esophageal cancer patients. Esophageal epithelial cells are extremely sensitive to irradiation, nevertheless, factors involved in the radiosensitivity of esophageal epithelial cells are still unknown. Terminal uridyl transferase 4 (TUT4) could modify the sequence of miRNAs, which affect their regulation on miRNA targets and function. In this study, we used transcriptome sequencing technology to identify mRNAs that were differentially expressed before and after radiotherapy in esophageal epithelial cells. We further explored the mRNA expression profiles between wild-type and TUT4 knockout esophageal epithelial cells. Volcano and heatmap plots unsupervised hierarchical clustering analysis were performed to classify the samples. Enrichment analysis on Gene Ontology functional annotations and Kyoto Encyclopedia of Genes and Genomes pathways was performed. We annotated differential genes from metabolism, genetic information processing, environmental information processing, cellular processes, and organismal systems human diseases. The aberrantly expressed genes are significantly enriched in irradiation-related biological processes, such as DNA replication, ferroptosis, and cell cycle. Moreover, we explored the distribution of transcription factor family and its target genes in differential genes. These mRNAs might serve as therapeutic targets in TUT4-related radiation-induced esophageal injury.
      Citation: Dose-Response
      PubDate: 2022-10-28T01:49:48Z
      DOI: 10.1177/15593258221136810
      Issue No: Vol. 20, No. 4 (2022)
  • Antihypertensive Potential of Tartaric Acid and Exploration of Underlying
           Mechanistic Pathways

    • Authors: Mubeen Kousar, Umme Salma, Taous Khan, Abdul Jabbar Shah
      Abstract: Dose-Response, Volume 20, Issue 4, October-December 2022.
      Tartaric acid is capable of balancing blood pressure. It is the main constituent of antihypertensive agents (grapes and wine) and has not been scientifically explored as an antihypertensive remedy. This study aimed to investigate the antihypertensive effect of a low-dose tartaric acid in vivo and explore underlying mechanisms in vitro. Intravenous administration of tartaric acid at the dose of 50 µg/kg caused a % fall in mean arterial pressure (MAP) in normotensive and hypertensive rats [51.5 ± 1.7 and 63.5 ± 2.9% mmHg]. This hypotensive effect was partially inhibited by atropine (1 mg/kg) and L-NAME (100 µg/kg) pretreatment. In hypertensive rats, oral administration of tartaric acid (.1, .5, 1, 5, and 10 mg/kg) for 2 weeks resulted in 65 ± 7.3 mmHg MAP at 10 mg/kg. This antihypertensive effect was comparable to the orally administered verapamil (10 mg/kg) for 2 weeks which caused a decrease in MAP 60.4 ± 3.8 mmHg. Tartaric acid relaxed phenylephrine (PE) and High K+-induced contractions with EC50 values of .157 (.043-.2) and 1.93 (.07-2) µg/mL in vitro. This endothelium-dependent relaxation was inhibited with atropine (1 µM) and L-NAME (10 µM) pretreatment. Tartaric acid also suppressed phenylephrine contractions in Ca+2 free/EGTA medium and on voltage-dependent calcium channels, causing the concentration–response curves toward right. Tartaric acid induced negative inotropic and chronotropic effects with EC50 values of .26 (.14-.4) and .60 (.2-.8) in rat atria. It showed its effect by complete blockade against atropine and partially in propranolol pretreatment. These findings provide scientific basis to low-dose tartaric acid as an antihypertensive and vasodilatory remedy through muscarinic receptor-linked nitric oxide (NO) pathway and Ca+2 channel antagonist.
      Citation: Dose-Response
      PubDate: 2022-10-22T12:24:27Z
      DOI: 10.1177/15593258221135728
      Issue No: Vol. 20, No. 4 (2022)
  • Antibacterial, Antibiofilm, and Anti-Quorum Sensing Potential of Novel
           Synthetic Compounds Against Pathogenic Bacteria Isolated From Chronic
           Sinusitis Patients

    • Authors: Muhammad Asif Rafiq, Muhammad Shahid, Kashif Jilani, Muhammad Aamir Aslam
      Abstract: Dose-Response, Volume 20, Issue 4, October-December 2022.
      Quorum sensing (QS) is a major controller of virulence and biofilm formation in pathogenic bacteria. The aim of the research was to screen novel synthetic compounds (18) from 2 series (Pyrazole and Diene dione) for quorum sensing and biofilm inhibitory potential against resistant pathogens isolated from patients with chronic sinusitis. Most of the compounds have documented zone of inhibition against Gram positive strains Staphylococcus aureus, Enterococcus faecalis and moderate activity against Gram negative Klebseilla pneumoniae and Proteus mirabilis in comparison with standard antibiotic. Compounds Q1 and Q7 have given the maximum zone of inhibition 18 and 20 mm with MICs 0.312 mg/mL and .156 mg/mL against S aureus and E faecalis, respectively. Some compounds were equally potent at inhibiting the formation of biofilm which later established by phase contrast microscopy. Regarding quorum sensing inhibition, the tested concentration of synthetic compound UA3 0.313 mg/mL inhibited violacein production without decreasing Chromobacterium pseudoviolaceum count which was significantly lower than determined MIC’s. It was depicted from the results that selected compounds exhibited low level of cytotoxicity toward human red blood cells. Hence, these findings revealed that most novel compounds were effective antibacterial, whereas compound UA3 has shared significant anti-quorum sensing potential against Chromobacterium pseudoviolaceum.
      Citation: Dose-Response
      PubDate: 2022-10-22T03:43:59Z
      DOI: 10.1177/15593258221135731
      Issue No: Vol. 20, No. 4 (2022)
  • Corrigendum to Trans-Generational Impacts of Paternal Irradiation in a
           Cricket: Damage, Life-History Features and Hormesis in F1 Offspring

    • Abstract: Dose-Response, Volume 20, Issue 4, October-December 2022.

      Citation: Dose-Response
      PubDate: 2022-10-20T02:36:57Z
      DOI: 10.1177/15593258221134746
      Issue No: Vol. 20, No. 4 (2022)
  • Antibiofilm and Quorum Sensing Inhibition (QSI) Potential of Lagerstroemia
           speciosa Leaves Extract

    • Authors: Farzana Zafar, Muhammad Shahid, Hina Fatima, Muhammad Riaz, Fozia Anjum, Zahid Mushtaq, Saadiya Zia, Muhammad Muzammil Jahangir, Muhammad Amir Aslam
      Abstract: Dose-Response, Volume 20, Issue 4, October-December 2022.
      Disruption of quorum sensing pathway of pathogenic microbes is considered as novel approach to fight against infectious diseases. The current study was planned to evaluate the antibiofilm and quorum sensing inhibitory potential of Lagerstroemia speciosa. Antibacterial and antibiofilm potential of L. speciosa extracts was determined through agar well diffusion and crystal violet assay against sinusitis isolates, that is, Staphylococcus aureus, Enterococcus faecalis, Proteus mirabilis, and Klebsiella pneumoniae, while quorum sensing inhibition efficacy of L. speciosa extracts was determined through violacein inhibition assay using Chromobacterium pseudoviolaceum as bacterial model. The methanolic extract of L. speciosa presented the highest antimicrobial activity against E. faecalis and antibiofilm activity against K. pneumoniae (77.42 ± 1.51%), while n-hexane extract was found to be least active against all tested bacterial strains. Quorum sensing inhibition activity of L. speciosa extracts against C. pseudoviolaceum showed significant dose-dependent inhibition in violacein production by different concentrations of methanolic extract. Furthermore, none of the extracts of L. speciosa showed any hemolytic activity against human RBCs and hold considerable thrombolytic potential in comparison to streptokinase (75.9 ± .46%). In conclusion, findings suggest that L. speciosa leaves are excellent source of phytochemicals with potent antibiofilm and quorum sensing inhibition potential.
      Citation: Dose-Response
      PubDate: 2022-10-13T12:39:49Z
      DOI: 10.1177/15593258221132080
      Issue No: Vol. 20, No. 4 (2022)
  • Trypsin Inhibitor Isolated From Glycine max (Soya Bean) Extraction,
           Purification, and Characterization

    • Authors: Sabir Khan, Shafia Arshad, Amina Arif, Rida Tanveer, Zeemal Seemab Amin, Saba Abbas, Amna Maqsood, Muhammad Raza, Arooj Munir, Amara Latif, Maryam Habiba, Muhammad Afzal
      Abstract: Dose-Response, Volume 20, Issue 4, October-December 2022.
      The current study aims to isolate, purify, and characterize the trypsin inhibitor protein from seeds of soya beans, scientifically known as Glycine max. Its seeds were ground, and the powder was soaked several times using n-hexane. It was added to phosphate buffer saline (PBS) followed by filtration and centrifugation of the PBS dissolved extract. The supernatant was subjected to ammonium sulfate precipitation and about six fractions, 30% to 80% were prepared. The centrifuged pellets obtained from each fraction were dialyzed and run on SDS-PAGE. The trypsin inhibitor protein was precipitated and characterized in 30% pellet and molecular weight was 21.5 kDa compared to protein ladder (ThermoFisher 10-170 kDa). GC-MS analysis revealed the steroid derivatives such as stigmasterol, campesterol, beta-sitosterol, and gamma-tocopherol. Glycine max trypsin inhibitor could be used as a plant-derived drug to overcome the over-activation of trypsin without its real substrate (proteins) becoming activated and start auto digestion leading to pancreatitis.
      Citation: Dose-Response
      PubDate: 2022-10-13T05:54:16Z
      DOI: 10.1177/15593258221131462
      Issue No: Vol. 20, No. 4 (2022)
  • The Effect of α-lipoic Acid on C-Reactive Protein Level: A Meta-analysis
           of Randomized, Double-Blind, and Placebo-Controlled Studies

    • Authors: Ljiljana Đukić, Lazar Trajković, Tamara Knežević, Jelena Dimitrijević, Danijela Krstić, Marko Stojanović
      Abstract: Dose-Response, Volume 20, Issue 4, October-December 2022.
      The C-reactive protein is generally considered a marker of inflammation, and it is widely used in clinical practice as a minimally invasive index of any ongoing inflammatory response. Alpha-lipoic acid (ALA) supplementation can be beneficial for human health, especially in the sense of its anti-inflammatory action. The aim of this meta-analysis was to, based on the currently available highest level of evidence (prospective, randomized, double-blind, and placebo-controlled data), investigate the effect of ALA supplementation on CRP levels. Prospective, randomized, double-blind, and placebo-controlled clinical trials were extracted after a systematic search of PubMed, the Cochrane Library, the Web of Science, EMBASE, and the Scopus databases. A random effect model was used in this meta-analysis to investigate the influence of ALA on the blood CRP level. The subgroup analysis and meta-regression were used to identify the source of heterogeneity. This meta-analysis provided evidence of the positive effect of ALA on the reduction of the blood CRP level. The subgroup analysis and meta-regression results indicated that ALA can reduce the CRP level when administrated at a 600 mg dose, and not in higher or lower doses. Also, a shorter duration of study positively correlates with the reduction of CRP after ALA supplementation.
      Citation: Dose-Response
      PubDate: 2022-10-13T04:10:30Z
      DOI: 10.1177/15593258221126827
      Issue No: Vol. 20, No. 4 (2022)
  • Garmultin-A Incites Apoptosis in CB3 Cells Through miR-17-5p by
           Attenuating Poly (ADP-Ribose) Polymerase-1

    • Authors: Jianfei Qiu, Li Chen, Jue Yang, Krishnapriya M. Varier, Babu Gajendran, Yao Yao, Wuling Liu, Jingrui Song, Qing Rao, Qun Long, Chunmao Yuan, Xiaojiang Hao, Yanmei Li
      Abstract: Dose-Response, Volume 20, Issue 4, October-December 2022.
      BackgroundLeukemia accounts for a large number of deaths, worldwide, every year. Treating this ailment is always a challenging job. Recently, oncogenic miRNA leading to apoptosis are highly promising targets of many natural products. In this study, Garmultin-A (GA), isolated from the bark of Garcinia multiflora, was elucidated for its anti-leukemic effect in CB3 cells.MethodsThe effect of the compound on CB3 cell viability was detected by MTT assay and apoptosis by FITC Annexin V/PI and Hochest 33258 staining. The western blot analysis assessed the BAX, BCL2, cMYC, pERK, and PARP-1 protein levels. Autodock analysis predicted the ligand–protein interactions. q-RT-PCR quantified the miR-17-5p expression. Luciferase assay confirmed the interaction between PARP-1 and miR-17-5p.ResultsWe uncover that GA leads to apoptosis by inducing overexpression of miR-17-5p and significantly downregulate PARP-1 protein levels in CB3 cells. The overexpression of miR-17-5p promotes apoptosis, and the miR-17-5p antagomirs restore GA-triggered apoptosis. Notably, we disclose that PARP-1 is a direct target of miR-17-5p. Increased pro-apoptotic and reduced anti-apoptosis protein levels were also observed in GA-treated CB3 cells.ConclusionThese results provide critical insights that GA could induce apoptosis in CB3 cells through targeting miR-17-5p by attenuating PARP-1. Thus, GA could act as a novel therapeutic agent for erythroleukemia.
      Citation: Dose-Response
      PubDate: 2022-10-11T05:45:47Z
      DOI: 10.1177/15593258221130681
      Issue No: Vol. 20, No. 4 (2022)
  • Bleomycin-Induced Damage in Rat Lung: Protective Effect of Grape Seed and
           Skin Extract

    • Authors: Olfa Khazri, Ali Mezni, Ferid Limam, Ezzeddine Aouani
      Abstract: Dose-Response, Volume 20, Issue 4, October-December 2022.
      IntroductionBleomycin is an effective chemotherapeutic agent with main side effects including lung fibrosis which limited its clinical use. The aim of this study is to evaluate the protective effect of grape seed and skin extract (GSSE) against bleomycin-induced oxidative damage and inflammation in rat lung, by assessing respiratory index (RI), oxidative and nitrosative stress (SOD and XO activity, NO), fibrotic mediators (hydroxyproline and collagen), apoptosis (cytochrome C and LDH), inflammation (IL-6, TNF-α and TGF-β1), and histological disturbances.MethodsRats were pre-treated during three weeks with vehicle [ethanol 10% control] or GSSE (4 g/kg) and then administered with a single dose of bleo (15 mg/kg bw) at the 7th day.Results: Bleo disturbed lung function through the accumulation of hydroxyproline and collagen, decreased SOD activity but increased XO activity as well as GSH and NO levels. Bleo also increased the pro-inflammatory cytokines IL-6, TNF-α, and TGF-β1, and pro-apoptotic cytochrome C factor and induced severe histological alterations of lung parenchyma. Interestingly GSSE pre-treatment efficiently counteracted most of the bleo-induced lung tissue damages.ConclusionData suggest that GSSE exerts anti-oxidant, ant-inflammatory, and anti-fibrosis properties that could find potential application in the protection against bleo-induced lung fibrosis.
      Citation: Dose-Response
      PubDate: 2022-10-10T06:01:30Z
      DOI: 10.1177/15593258221131648
      Issue No: Vol. 20, No. 4 (2022)
  • Evaluation of Renessans (Iodine Complex Molecule) Safety in Human Beings:
           An Open-Labeled Clinical Study

    • Authors: Ahmad Kamal, Asif Mahmood, Muhammad Zaman, Muhammad Farooq, Bilal Nasir, Nasir Islam, Rai Muhammad Sarfraz, Nadiah Zafar, Ghulam Murtaza, Abdul-Basit Raheel, Areeba Shahid, Zahra Abid, Sajjad Ahmed
      Abstract: Dose-Response, Volume 20, Issue 4, October-December 2022.
      Extensive studies on evaluation of effectiveness/toxicity of different oral doses of iodine have not been explored yet. An open-labeled phase I clinical studies were conducted using iodine complex based research compound called Renessans. Study groups were observed for development of any adverse/serious adverse events and alteration in laboratory values of vital organs, TSH and T4 hormones before and after the administration of the products. Out of 31 consented individuals, 24 healthy individuals participated in the study. Rate of occurrence of mild Adverse Events (AEs) in group A was 8.3% while in Group B it was 33.33% but these Adverse Events were self-resolving. After completion of study treatment blood serum iodine was reported to 3522.88 µg/l while mean urine iodine concentration (MUIC) was greater than 2000 µg/l. Hormonal and vital organ’s testing revealed that all parameters of TSH and T4, LFT, CBC, RFT remained unaltered except from ALT-SGPT (P-value = .006) and AST-SGOT (P-value = .02). From all of these findings, it can be inferred that the use of Renessans formulations did not pose any sort of risk to human body and can be considered safe through this pilot study.
      Citation: Dose-Response
      PubDate: 2022-10-10T05:39:55Z
      DOI: 10.1177/15593258221129777
      Issue No: Vol. 20, No. 4 (2022)
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