Endophytic species of Nigrospora from grasses and shrubs of Shadegan International Wetland, with new species and records from Iran.

The "Shadegan International Wetland" (SIW) is one of the wetlands internationally recognized in the Ramsar convention. The vegetation of this wetland ecosystem consists of mostly grasses and shrubs that host a large number of fungi including endophytes. In this study, Nigrospora isolates were obtained from healthy plants of this wetland and its surrounding salt marshes and identified based on morphological features and multilocus phylogenetic analyses based on three DNA loci, namely the internal transcribed spacer regions 1 and 2 including the intervening 5.8S nuclear ribosomal DNA (ITS), ß-tubulin (tub2), and elongation factor 1-α (tef1-α). Accordingly, the following Nigrospora species were identified: N. lacticolonia, N. oryzae, N. osmanthi, N. pernambucoensis and a novel taxon N. shadeganensis sp. nov., which is described and illustrated. To the best of our knowledge, 10 new hosts for Nigrospora species are here reported, namely Aeluropus lagopoides, Allenrolfea occidentalis, Anthoxanthum monticola, Arthrocnemum macrostachyum, Cressa cretica, Halocnemum strobilaceum, Seidlitzia rosmarinus, Suaeda vermiculata, Tamarix passerinoides, and Typha latifolia. Moreover, the species N. lacticolonia and N. pernambucoensis are new records for the mycobiota of Iran.

Potential role of resveratrol in prevention and therapy of diabetic complications: a critical review.

Background: Diabetes mellitus (DM) is a category of metabolic conditions affecting about 5% of people worldwide. High mortality associated with DM is mostly due to its severe clinical complications, including diabetic nephropathy, retinopathy, neuropathy, and cardiomyopathy. Resveratrol (RSV) is a natural, biologically active polyphenol known to have various health-promoting effects in animal models and humans. Objective: In this review, we have reviewed the preventive and therapeutic role of RSV on diabetes complications with emphasis on its molecular mechanisms of action. Methods: To prepare this review, all the basic and clinical available literatures regarding this topic were gathered through electronic databases, including PubMed, Web of Science, Scopus, and Google Scholar. Therefore, we summarized previous studies that have evaluated the effects of RSV on diabetic complications and their mechanisms. Only English language studies published up to January 2023 were included in this review. Results: RSV improves glucose homeostasis, decreases insulin resistance, induces autophagy, regulates lipid metabolism, protects pancreatic ß-cells, ameliorates metabolic disorders, and increases the GLUT4 expression. These effects induced by RSV are strongly associated with ability of this polyphenol agent to elevation expression/activity of AMP-activated protein kinase and Sirtuin 1 in various organs of diabetic subjects, which leads to prevention and therapy of diabetic complications. In addition, antioxidant and anti-inflammatory properties of RSV were reported to be involved in its action in diabetic complications, such as retinopathy and nephropathy. Conclusion: RSV is a promising compound for improving diabetic complications. However, the exact antidiabetic mechanisms of RSV need to be further investigated.

Screening the critical protein subnetwork to delineate potential mechanisms and protective agents associated with arsenic-induced cutaneous squamous cell carcinoma: A toxicogenomic study.

Recent studies show that complex mechanisms are involved in arsenic-induced malignant transformation of cells. This study aimed to decipher molecular mechanisms associated with arsenic-induced cutaneous squamous cell carcinoma (cSCC) and suggest potential protective factors. RNA-seq-based differentially expressed genes between arsenic-exposed human keratinocytes (HaCaT) and controls were used to construct a protein-protein interaction (PPI) network and discover critical subnetwork-based mechanisms. Protective compounds against arsenic toxicity were determined and their target interactions in the core sub-network were identified by the comparative toxicogenomic database (CTD). The binding affinity between the effective factor and target was calculated by molecular docking. A total of 15 key proteins were screened out as critical arsenic-responsive subnetwork (FN1, IL-1A, CCN2, PECAM1, FGF5, EDN1, FGF1, PXDN, DNAJB9, XBP1, ERN1, PDIA4, DNAJB11, FOS, PDIA6) and 7 effective protective agents were identified (folic acid, quercetin, zinc, acetylcysteine, methionine, catechin, selenium). The GeneMANIA predicted detailed interactions of the subnetwork and revealed terms related to unfolded protein response as the main processes. FN1, IL1A and CCN2, as top significant genes, had good docking affinity with folic acid and quercetin, as selected key compounds. Integration of gene expression and protein-protein interaction related to arsenic exposure in cSCC explored the potential mechanisms and protective agents.

Therapeutic Potential of Resveratrol and Atorvastatin Following High-Fat Diet Uptake-Induced Nonalcoholic Fatty Liver Disease by Targeting Genes Involved in Cholesterol Metabolism and miR33.

The present study was designed to evaluate the effects of resveratrol, atorvastatin, and a combination of resveratrol and atorvastatin on expression levels of genes involved in the cholesterol metabolic pathway in the fatty liver of C57/BL6 mice. A high-fat diet was used to induce fatty liver in C57/BL6 mice treated with resveratrol, atorvastatin, or a combination of resveratrol and atorvastatin. Pathological and biochemical studies were performed. In addition, hepatic gene expressions of ATP-binding cassette transporter A1 (ABCA1), ABCG1, liver X receptor (LXR)α, scavenger receptor B1 (SR-B1), low-density lipoprotein receptor (LDLR), and miR33 were evaluated by the real-time PCR method, and the Western blot method was used to measure the ABCA1, ABCG1, and LXRα protein levels. Resveratrol and atorvastatin reduced fat accumulation in the liver of mice with fatty liver, and this effect was correlated with decreased blood glucose levels, triglyceride, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol blood levels compared with the positive control (PC) group. In contrast to the animals of the PC group, fatty liver groups that received resveratrol and atorvastatin had a significant effect on the mRNA levels of the ABCA1, ABCG1, LXRα, SR-B1, LDLR, and miR33 genes. Moreover, resveratrol and atorvastatin administration elevated ABCA1 and ABCG1 and reduced LXRα protein expression. Obtained results showed that resveratrol and atorvastatin combination therapy can improve nonalcoholic fatty liver disease by targeting genes involved in cholesterol metabolism and miR33.

Metabolomic study of serum in patients with invasive ductal breast carcinoma with LC-MS/MS approach.

BACKGROUND: Invasive ductal carcinoma (IDC) is the most common type of breast cancer so its early detection can lead to a significant decrease in mortality rate. However, prognostic factors for IDC are not adequate and we need novel markers for the treatment of different individuals. Although positron emission tomography and magnetic resonance imaging techniques are available, they are based on morphological features that do not provide any clue for molecular events accompanying cancer progression. In recent years, "omics" approaches have been extensively developed to propose novel molecular signatures of cancers as putative biomarkers, especially in biofluids. Therefore, a mass spectrometry-based metabolomics investigation was performed to find some putative metabolite markers of IDC and potential metabolites with prognostic value related to the estrogen receptor, progesterone receptor, lymphovascular invasion, and human epidermal growth factor receptor 2. METHODS: An untargeted metabolomics study of IDC patients was performed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The multivariate principal component analysis by XCMS online built a model that could separate the study groups and define the significantly altered m/z parameters. The most important biological pathways were also identified by pathway enrichment analysis. RESULTS: The results showed that the significantly altered metabolites in IDC serum samples mostly belonged to amino acids and lipids. The most important involved pathways included arginine and proline metabolism, glycerophospholipid metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. CONCLUSIONS: Significantly altered metabolites in IDC serum samples compared to healthy controls could lead to the development of metabolite-based potential biomarkers after confirmation with other methods and in large cohorts.

Mass Spectrometry-Based Proteomics Research to Fight COVID-19: An Expert Review on Hopes and Challenges.

The COVID-19 pandemic caused by the severe acute respiratory syndrome (SARS)-CoV-2 infection is a systemic disease and a major planetary health burden. While SARS-CoV-2 impacts host biology extensively, our knowledge of these alterations from a systems perspective remains incomplete. Moreover, there is currently only a limited description of this systemic disease. For precision diagnosis and treatment of SARS-CoV-2, multiomics technologies and systems science research offer significant prospects. This expert review offers a critical analysis of the prospects and challenges of the emerging mass spectrometry-based proteomics approaches to the study of COVID-19 as seen through a systems medicine lens. We also discuss the ways in which proteomics is poised to offer hope for diagnostics and therapeutics innovation on SARS-CoV-2 infection as the disease transitions from a pandemic to an endemic disease, and thus further challenging the health systems and services worldwide in the coming decade. Proteomics is an important high-throughput technology platform to achieve a functional overview of the ways in which COVID-19 changes host biology, and hence, can help identify possible points of entry for innovation in medicines and vaccines, among others.

Serum cortisol concentration and COVID-19 severity: a systematic review and meta-analysis.

The novel COVID-19 outbreak is a major health threat to human beings with multiorgan injuries. However, its endocrine system manifestations are much less studied. In this study, we aimed to reassess the available findings on the association between cortisol level and severity of COVID-19 infection. We conducted a systematic search on Medline/PubMed, Scopus, Web of Science, and Cochrane Library databases. To pool data, a random-effects model was performed depending on the heterogeneity among studies. Sensitivity analysis was also carried out by removing each study systematically. In addition, subgroup and meta-regression analyses were performed depending on the presence of the variables of sex and age. Subsequently, 11 studies (5 observational studies and 6 case reports) were included in the meta-analysis. Pooled analysis on the observational studies showed significantly higher levels of cortisol in patients with severe COVID-19 in comparison with those with mild-to-moderate COVID-19 (standardized mean difference: 1.48 µg/dL; 95% CI (0.51 to 2.46); p=0.003). Assessment of the results of case reports revealed that the patients with severe COVID-19 demonstrated higher cortisol levels than the patients with mild-to-moderate COVID-19. No publication bias was observed using the Begg's (p=0.08) and Egger's tests (p=0.09). Meta-regression illustrated a significant correlation between cortisol levels with sex. The serum cortisol level seems to be higher in patients with severe COVID-19 infection. This finding could be helpful to detect patients with poor prognosis at early stages of the disease, although age and sex may modify this level.

Metformin reduces lipid accumulation in HepG2 cells via downregulation of miR-33b.

INTRODUCTION: Here, we aimed to investigate whether the beneficial effects of metformin on lipid accumulation is mediated through regulation of miR-33b. METHODS: The expression of the genes and miRNAs and protein levels were evaluated using real-time PCR and western blot, respectively. To investigate the potential role of miR-33b in lipid accumulation, the mimic of the miR-33b was transfected into HepG2 cells. RESULTS: We found that metformin reduces high glucose-induced lipid accumulation in HepG2 cells through inhibiting of SREBP1c and FAS and increasing the expression of CPT1 and CROT. Overexpression of miR-33b significantly prevented the decreasing effect of metformin on lipid content and intra and extra triglyceride levels. Importantly, miR-33b mimic inhibited the increasing effects of metformin on the expression of CPT1 and CROT. CONCLUSION: These findings suggest that metformin attenuates high glucose-induced lipid accumulation in HepG2 cell by downregulating the expression of miR-33b.

Association between circulating visfatin and pre-eclampsia: a systematic review and meta-analysis.

OBJECTIVE: Pre-eclampsia (PE) is a serious pregnancy status characterized by high blood pressure. Although visfatin is usually associated with PE. Observational studies evaluating the relationship between circulating visfatin and pre-eclampsia have reported inconsistent results. We conducted this systematic review and meta-analysis to summarize published data on the association between visfatin and pre-eclampsia. METHODS: Electronic databases PubMed, ISI web of science, EMBASE, Scopus and the Cochrane library were comprehensively searched for selection of eligible studies until January 5, 2020. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. The assessment of study quality was performed using the e Newcastle-Ottawa scale and the Agency for Healthcare Research and Quality. Sensitivity analyses and prespecified subgroup were conducted to evaluate potential heterogeneity. Random-effects meta-regression was conducted to assess the impact of potential confounders on the estimated effect sizes. The protocol for this study was registered in PROSPERO (No. CRD42018105861) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: Thirteen studies comprising a total of 536 subjects were included in this meta-analysis. We observed that the pre-eclampsia risk is associated with a statistically significant elevation of visfatin level [SMD (1.33 µg/l) (95% CI 0.37, 2.2) p = .007]. No significant publication bias was observed in the meta-analysis. Subgroup and sensitivity analyses indicated that the pooled effects size were affected by systolic blood pressure [SMD (1.82 µg/l) 95% CI (0.94, 2.7), p < .05], gestational age [SMD (2.01 µg/l) 95% CI (0.57, 3.4), p = .006], body mass index [SMD (1.6 µg/l) 95% CI (0.37, 3), p < .05] and pregnancy trimesters[SMD (2.3 µg/l) 95% CI (0.95, 3.7), p = .001]. Random-effects meta-regression showed a significant association of visfatin level with potential confounders including systolic blood pressure, gestational age and birth weight at delivery of pre-eclampsia patients. CONCLUSIONS: Collectively, our data revealed that the increase of visfatin level can be associated with the risk of pre-eclampsia. However, further studies on pre-eclampsia populations are warranted for corroboration of our findings.

Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets.

Deciphering the molecular downstream consequences of severe acute respiratory syndrome coronavirus (SARS-CoV)- 2 infection is important for a greater understanding of the disease and treatment planning. Furthermore, greater understanding of the underlying mechanisms of diagnostic and therapeutic strategies can help in the development of vaccines and drugs against COVID-19. At present, the molecular mechanisms of SARS-CoV-2 in the host cells are not sufficiently comprehended. Some of the mechanisms are proposed considering the existing similarities between SARS-CoV-2 and the other members of the ß-CoVs, and others are explained based on studies advanced in the structure and function of SARS-CoV-2. In this review, we endeavored to map the possible mechanisms of the host response following SARS-CoV-2 infection and surveyed current research conducted by in vitro, in vivo and human observations, as well as existing suggestions. We addressed the specific signaling events that can cause cytokine storm and demonstrated three forms of cell death signaling following virus infection, including apoptosis, pyroptosis, and necroptosis. Given the elicited signaling pathways, we introduced possible pathway-based therapeutic targets; ADAM17 was especially highlighted as one of the most important elements of several signaling pathways involved in the immunopathogenesis of COVID-19. We also provided the possible drug candidates against these targets. Moreover, the cytokine-cytokine receptor interaction pathway was found as one of the important cross-talk pathways through a pathway-pathway interaction analysis for SARS-CoV-2 infection.

Effects of Imunit Insecticide on Biological Characteristics and Life Table Parameters of Spodoptera cilium (Lepidoptera: Noctuidae).

Imunit is a mixture of alpha-cypermethrin + teflubenzuron, and has been launched for controlling caterpillars. In this study, the effects of Imunit at LC50 and LC30 were investigated on parental and offspring generation of S. cilium, according to age-stage, two-sex life table. The experiments were conducted by leaf dipping method at 25 °C and 60 ± 5% relative humidity, under a cycle of 16 h fluorescent light and 8 h darkness. LC30 and LC50 concentrations of Imunit increased the immature developmental time of S. cilium in the offspring generation, while the LC50 of Imunit significantly reduced the developmental time of adults. The adult pre-oviposition period and total pre-oviposition period considerably increased when offspring were treated with LC50 of Imunit. In offspring of S. cilium exposed to LC50 and LC30 concentrations of Imunit, the gross reproductive rate (GRR), net reproduction rate (R0), the intrinsic rate of population increase (r), and the finite rate of population increase (λ) significantly reduced compared to the control. This study showed that the application of Imunit at LC50 could suppress the S. cilium population and can be used in the integrated management program of this pest.

Identification of differential protein expression and putative drug target in metacyclic stage of Leishmania major and Leishmania tropica: A quantitative proteomics and computational view.

Cutaneous leishmaniasis (CL) is an infectious disease that commonly caused by Leishmania (L.) major and L.tropica. Recently there has been a growing interest in proteomics analysis on Leishmania for drug target discovery. Therefore, we aimed to distinguish proteins which might be characteristic for each of the species from those shared by both to the detection of drug targets, which may become helpful for designing new drugs for CL. To identify differences in protein profiles of L. major and L. tropica, we conducted a Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) analysis. Totally 67 differentially expressed proteins (DEPs) (fold change> 2 and p < 0.05) were identified between species. Of these, 42 and 25 proteins were up-regulated in L. major and L. tropica, respectively. Several enriched GO terms were identified via biological process of up-regulated proteins. Furthermore, the small molecule metabolic process and translation were detected as significant biological processes for up-regulated proteins in L. major, while translation was identified for L. tropica. Also, KEGG analysis has revealed glycolysis/gluconeogenesis and translation as the top pathways in the proteins up-regulated in L. major and L. tropica, respectively. Finally glycosomal malate dehydrogenase was identified as putative drug target using network and homology analyses. The DEPs between the species are essential in host-pathogen interactions and parasite survival in the macrophage. Furthermore, L. major and L. tropica possibly uses different pathogenicity mechanisms that leads to anthroponotic or zoonotic CL. Our results may help in the drug discovery and chemotherapeutic interventions.

Increased the circulating levels of malondialdehyde in patients with obstructive sleep apnea: a systematic review and meta-analysis.

PURPOSE: Obstructive sleep apnea (OSA) is a prevalent sleep disorder associated with increased risk of cardiovascular disease. Several studies have demonstrated elevated oxidative stress in patients with OSA. This oxidative stress is a direct inducer of lipid peroxidation. Malondialdehyde (MDA), a robust marker of lipid peroxidation, has been evaluated in patients with OSA but results have been inconsistent. The present systematic review and meta-analysis was performed to quantify the circulating levels of MDA in patients with OSA compared to controls. METHODS: Search was performed in data bases of PubMed, Scopus, EMBASE, Web of Science, and Cochrane library, to find out those studies that measured MDA in patients with OSA compared to controls. RESULTS: The search produced 563 records and after removing duplicates, 383 records remained. Screening by title and abstract and the evaluation of the full text resulted in the selection of 14 articles, which were included in the meta-analysis. Pooled analysis demonstrated higher levels of MDA in the patients compared to the controls (SMD (95% CI): 1.18 (0.68, 1.68), p < 0.0001). CONCLUSION: The results of this meta-analysis demonstrated considerable elevation of MDA in patients with OSA compared to controls. The meta-analysis also indicated a positive association of MDA levels with the degree of severity of OSA. These results suggest a state of increased lipid peroxidation in patients with OSA.

Evaluating the effect of a mixture of two main conjugated linoleic acid isomers on hepatic steatosis in HepG2 cellular model.

Hepatic steatosis is an early form of non-alcoholic fatty liver disease (NAFLD), caused by abnormal fat deposition in the hepatocytes. Conjugated linoleic acid (CLA) is a group of positional and geometric dienoic isomers of linoleic acid that attract significant attention because of its beneficial effects on chronic diseases such as cancer, obesity, and metabolic syndrome. This study examined the influence of a mixture of two main CLA isomers (CLA-mix) on lipid accumulation and lipid metabolism-related genes using HepG2 cells treated with palmitic acid (PA) as an in vitro model for hepatic steatosis. Methods and Results: HepG2 cells were treated for 24 h: control (BSA), model (BSA + PA), and treated groups (BSA-PA + non-toxic concentrations of CLA-mix). Intracellular lipid deposition, triglyceride (TG), total cholesterol (TC) and gene expression were measured by Oil-Red O staining, colorimetric assay kits and real-time PCR, respectively. CLA-mix at high concentrations had significantly decreased intracellular total lipid and TG deposition compared to the model group. However, none of the CLA-mix concentrations had a significant effect on the intracellular TC level. CLA-mix significantly increased the expression of some genes mainly regulated by PPARα but did not alter the expression of lipogenesis-related genes. Conclusions: These results demonstrate that high concentrations of CLA-mix protect against hepatic steatosis and play a role in regulating fatty acid oxidation and bile excretion through the PPARα pathway. It is suggested that the effect of different ratios of two main CLA isomers on the amount and ratio of bile compounds be investigated in future studies.

Effect of rosiglitazone on circulating malondialdehyde (MDA) level in diabetes based on a systematic review and meta-analysis of eight clinical trials.

Patients with type 2 diabetes have high levels of malondialdehyde (MDA), and clinical data suggest a reducing effect of rosiglitazone (RSG) on the level of MDA in these patients. However, the results of available studies on the level of MDA in RSG-treated patients are not univocal. This meta-analysis aimed to assess the impact of RSG on the level of MDA. We performed a comprehensive search of PubMed, the Institute for Scientific Information Web of Science, Embase, Scopus, and Cochrane Library for related controlled trials until July 2020. Eligible studies were selected based on the inclusion criteria. Extracted data from each study were combined using a random-effects model. Sensitivity and subgroup analyses were conducted to explore potential heterogeneity. Eight trials with 456 subjects met the inclusion criteria. The results significantly showed the reducing effect of RSG on circulating MDA level (-0.47 µmol/mL; 95% CI -0.93 to -0.01; p=0.04; I2=82.1%; p heterogeneity=0.00) in individuals with T2D. No publication bias was observed with Begg's rank correlation (p=0.71) and Egger's linear regression (p=0.52) tests. Subgroup analyses showed that an intervention dose of 8 mg/day in serum samples was found to have a reducing effect on the level of MDA (-0.56 µmol/mL; 95% CI -0.98 to -0.14; p=0.008; I2=11.4%; p heterogeneity=0.32). Random-effects meta-regression did not show any significant association between the level of MDA and potential confounders including RSG dose, treatment duration, and sex. In conclusion, we found a significant reduction in MDA concentration in subjects with T2D who received a dose of 8 mg of RSG daily.

Effect of Metformin on Circulating Levels of Inflammatory Markers in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Emerging evidence indicates that metformin has anti-inflammatory effect; however, the results differ concerning randomized controlled trails of the effect of metformin on inflammatory markers in type 2 diabetes (T2D) patients. OBJECTIVE: This study reassessed the data on the effect of metformin treatment on inflammatory markers in T2D patients through a systematic review and meta-analysis. METHODS: A systematic search was performed in the PubMed, ISI Web of Science, EMBASE, Cochrane Library and Scopus databases to collect relevant published data up to September 2020. Data of each study was combined using random-effects model. Subgroup analysis was performed based on subgroups of the treatment duration, dose and target population. RESULTS: Thirteen RCTs including 1776 participants with T2D were analyzed. Although CRP levels significantly decreased [SMD: -0.76 mg/L; 95% CI (-1.48, -0.049); P = 0.036] in patients with T2D following metformin treatment, circulating levels of TNF-α [SMD: -0.17 pg/mL; 95% CI (-0.55, 0.20); P = 0.37] and IL-6 [SMD: -0.06 pg/mL; 95% CI (-0.38, 0.25); P = 0.69] were insignificant after metformin treatment. Compared to treatment duration of less than 24 weeks, longer treatment duration (more than 24 weeks) was associated with reduced level of CRP. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Based on available evidence from RCTs in this meta-analysis, metformin decreased CRP level. However, strategies for the treatment of inflammation should focus on metformin in patients with T2D. CONCLUSION: The present study evidences that therapy with metformin can reduce CRP level significantly in T2D patients compared to other inflammatory markers.

Prognostic value of microRNA-125a/b family in patients with gastric cancer: a meta-analysis.

AIM: This meta-analysis was designed to reassess the prognostic and clinicopathologic values of the microRNA-125 family in GC patients. BACKGROUND: The miR-125 family (including miR-125a, miR-125b) has been reported as being pivotal prognostic biomarkers of gastric cancer (GC). However, there is controversy about the role of the miR-125 family in predicting the progression of GC. METHODS: The miR-125 family (including miR-125a, miR-125b) has been reported as being pivotal prognostic biomarkers of gastric cancer (GC). However, there is controversy about the role of the miR-125 family in predicting the progression of GC. RESULTS: The electronic databases of PubMed, ISI Web of Science, Scopus, and Cochrane Library were systematically searched for relevant studies. Overall survival (OS) rate as the primary outcome from each study was extracted. The overall hazard ratio (HR or survival rate in patients with GC) and odds ratio (OR) with 95% confidence interval (CI) was calculated to evaluate the association between miR-125 family expression and prognosis and susceptibility to gastric cancer. The quality of evidence was evaluated using the Newcastle-Ottava Scale (NOS). The extracted data was combined based on the random-effects model. CONCLUSION: The low expression of miR-125 family predicts poor OS in GC patients. Thus, the miR-125 family may be helpful as a potential biomarker for the prognosis of gastric cancer.

Discovery of Novel Pyruvate Kinase Inhibitors Against Leishmania major Among FDA Approved Drugs Through System Biology and Molecular Docking Approach.

OBJECTIVES: Leishmaniasis is one of the common forms of neglected parasitic diseases that cause a worldwide disease burden without any effective therapeutic strategy. Control of the disease currently relies on chemotherapy because most of the available drugs have toxic side-effects and drug-resistant strains have emerged. Therefore, the development of new therapeutic strategies to treat patients for leishmaniasis has become a priority. The first step in drug discovery is to identify an effective drug target by methods such as system biology. Protein kinases are a promising drug target for different diseases. Due to lack of a functional krebs cycle in Leishmania species, they use glycolysis as the only source of ATP generation. Pyruvate kinase is the enzyme involved in the last step of glycolysis and considered as essential enzyme for the Leishmania survival. MATERIALS AND METHODS: This study sought to discover FDA approved compounds against the leishmanial pyruvate kinase protein. Our approach involved using quantitative proteomics, protein interaction networks and docking to detect new drug targets and potent inhibitors. RESULTS: Pyruvate kinase was determined as the potential drug target based on protein network analysis. The docking studies suggested trametinib and irinotecan with high binding energies of -10.4 and -10.3 kcal/mol, respectively, as the potential chemotherapeutic agents against L. major. CONCLUSION: This study demonstrated the importance of integrating protein network analysis and molecular docking to identify new anti-leishmanial drugs. These potential inhibitors constitute novel drug candidates that should be tested in vitro and in vivo to determine their potential as an alternative chemotherapy in the treatment of leishmaniasis.

Effect of garlic intake on inflammatory mediators: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Garlic is a species in the onion genus, Allium. Data have shown that garlic has anti-inflammatory activity; however, the findings are inconclusive and inconsistent. We aimed to evaluate the impact of garlic intake on inflammatory mediators through systematic review and meta-analysis of existing data. METHODS: Electronic databases were completely investigated using databases of ISI Web of Science, Medline, Scopus, Cochrane Library and EMBASE until October 2019. A random effects model and the generic reverse variance procedure were used for quantitative data production. Sensitivity analyses and prespecified subgroup were done to evaluate potential heterogeneity. Random effect meta-regression was conducted to investigate the effects of possible confounders on the assessed effect size. RESULTS: Ten trials with one observational study, including 530 participants, met the eligibility criteria. The findings showed reduction in the tumour necrosis factor alpha (TNF-α) (-0.31 pg/mL, 95% CI -1.07 to 0.46) and C reactive protein (CRP) levels (-0.20 mg/L, 95% CI -1.4 to 1.05) following supplementation with garlic, although it had no marked impact on the interleukin 6 (IL-6) level (0.37 pg/mL, 95% CI -0.58 to 1.33). In the subgroup analysis, we found that garlic supplementation significantly decreased TNF-α, highly sensitive CRP and IL-6 levels in subgroups of >8, >6 and ≥4 weeks of intervention duration, respectively, and dose of garlic consumption between 2 and 2.4 g/day. CONCLUSION: These findings suggested that current evidence may support garlic as an adjunct to pharmacological management of metabolic diseases. PROSPERO REGISTRATION NUMBER: CRD42018108816.