Genomic Structure of Two Kv1.3 Channel Blockers from Scorpion Mesobuthus eupeus and Sea Anemone Stichodactyla haddoni and Construction of their Chimeric Peptide as a Novel Blocker.

Different toxins acting on Kv1.3 channel have been isolated from animal venom. MeuKTX toxin from Mesobuthus eupeus phillipsi scorpion and shtx-k toxin from Stichodactyla haddoni sea anemone have been identified as two effective Kv1.3 channel blockers. In this work, we characterized the genomic organization of both toxins. MeuKTX gene contains one intron and two exons, similar to the most scorpion toxins. There are a few reports of genomic structure of sea anemone toxins acting on Kv channels. The sequence encoding mature peptide of shtx-k was located in an exon separated by an intron from the coding exon of the propeptide and signal region. In order to make a peptide with more affinity for Kv1.3 channel and greater stability, the shtx-k/ MeuKTX chimeric peptide was designed and constructed using splicing by overlap extension-PCR (SOE-PCR) method. MeuKTX, shtx-k, and shtx-k/MeuKTX were cloned and the expression of the soluble proteins in E. coli was determined. Molecular docking studies indicated more inhibitory effect of shtx-k/MeuKTX on Kv1.3 channel compared to shtx-k and MeuKTX toxins. Key amino acids binding channel from both toxins, also involved in interaction of chimeric peptide with channel. Our results showed that the fusion peptide, shtx-k/MeuKTX could be an effective agent to target Kv1.3 channel.

Lycopene Does Not Affect Prostate-Specific Antigen in Men with Non-Metastatic Prostate Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Several randomized controlled trials (RCTs) have investigated the effect of lycopene supplementation on serum levels of prostate-specific antigen (PSA) in patients with prostate cancer. However, results have been inconclusive. We systematically searched PubMed, Embase, and Scopus up to January 2020 to find RCTs investigating the effect of lycopene supplementation on serum levels of PSA in patients with non-metastatic prostate cancer. Using a random-effects model, the reported risk estimates were pooled. A total of six trials were included in the final analysis. we found no significant effect of lycopene on circulating PSA (WMD: -0.60, 95% CI: -2.01, 0.81 µg/L). However, we observed a significant reducing effect when the analysis was confined to studies that included patients with higher baseline levels of PSA (≥6.5 µg/L) (WMD: -3.74 µg/L, 95% CI: -5.15, -2.32, P < 0.001). Subgroup analysis based on the duration of intervention did not result in any significant effect. Non-linear dose-response analysis did not show any significant effects of lycopene dosage (Pnon-linearity = 0.50) and duration of the intervention (Pnon-linearity = 0.63) on serum levels of PSA. Although lycopene supplementation did not produce any reduction in PSA levels overall, a significant reducing effect was observed in patients with higher levels of baseline PSA. Due to the heterogeneity of our results, further high-quality clinical trials with long-term duration are required to determine the efficacy of lycopene in patients with non-metastatic prostate cancer.

Corneal endothelium tissue engineering: An evolution of signaling molecules, cells, and scaffolds toward 3D bioprinting and cell sheets.

Cornea is an avascular and transparent tissue that focuses light on retina. Cornea is supported by the corneal-endothelial layer through regulation of hydration homeostasis. Restoring vision in patients afflicted with corneal endothelium dysfunction-mediated blindness most often requires corneal transplantation (CT), which faces considerable constrictions due to donor limitations. An emerging alternative to CT is corneal endothelium tissue engineering (CETE), which involves utilizing scaffold-based methods and scaffold-free strategies. The innovative scaffold-free method is cell sheet engineering, which typically generates cell layers surrounded by an intact extracellular matrix, exhibiting tunable release from the stimuli-responsive surface. In some studies, scaffold-based or scaffold-free technologies have been reported to achieve promising outcomes. However, yet some issues exist in translating CETE from bench to clinical practice. In this review, we compare different corneal endothelium regeneration methods and elaborate on the application of multiple cell types (stem cells, corneal endothelial cells, and endothelial precursors), signaling molecules (growth factors, cytokines, chemical compounds, and small RNAs), and natural and synthetic scaffolds for CETE. Furthermore, we discuss the importance of three-dimensional bioprinting strategies and simulation of Descemet's membrane by biomimetic topography. Finally, we dissected the recent advances, applications, and prospects of cell sheet engineering for CETE.

Effect of weight-loss diet combined with taurine supplementation on body composition and some biochemical markers in obese women: a randomized clinical trial.

Taurine (Tau), an endogenous non-protein and sulfuric-amino acid, is involved in various biological pathways including anti-inflammatory, anti-oxidation, insulin resistance inhibition, and lipid profile improvement. According to some experimental and clinical studies, insulin resistance and excess body weight are associated with reduced serum level of Tau. Therefore, this study was aimed to evaluate Tau supplementation and a diet-induced weight-loss intervention on body composition and some biochemical indices of obese women. Participants were divided randomly into the intervention (standard weight-loss group + cap Tau 3 g/day for 8 weeks, n = 20) and control (standard weight-loss group + cap placebo for 8 weeks, n = 18) groups. To achieve weight loss, all participants received an individualized diet that included a 30% reduction in their total energy intake. Chi-square test was applied to compare categorical variables between two groups at baseline. Paired t test and independent-sample t test were also used to analyze the parametric continuous data within and between the two groups, respectively. Analysis of covariance was run for controlling the confounding variables. At the post-intervention, the mean changes of total cholesterol (p = 0.03), low-density lipoprotein cholesterol (p = 0.03), leptin (p = 0. 006), total adiponectin (p = 0.04), and high sensitivity C-reactive protein (p = 0.03) decreased significantly in Tau group compared with the control group. No significant results were found in the mean changes of high-density lipoprotein cholesterol, anthropometric measurements, glycemic indices, and liver enzymes between the two groups (p > 0.05). The findings showed that Tau supplementation along with a weight-loss diet may be more effective in improving the lipid profile and metabolic risk factors compared with a weight-loss diet alone.

The effects of soy isoflavones on total testosterone and follicle-stimulating hormone levels in women with polycystic ovary syndrome: a systematic review and meta-analysis.

OBJECTIVES: The aims of this systematic review and meta-analysis were to evaluate the effectiveness of soy isoflavones on serum levels of total testosterone (TT) and follicle-stimulating hormone (FSH) in women with polycystic ovary syndrome (PCOS). METHODS: A meta-analysis was performed by searching for relevant randomised controlled trials (RCTs) in several databases. Of the four trials found, the eligibility criteria to evaluate the efficacy of soy isoflavones on serum levels of FSH were met by three trials and of TT by four trials. The Cochrane scale was used to evaluate the risk of bias. Fixed-effects and random-effects models were used to evaluate overall effect. The χ 2 test (Cochran's Q test) and the I 2 index were used to assess the heterogeneity of RCTs. RESULTS: Our results showed that soy isoflavones significantly decreased TT (weighted mean difference [WMD] - 0.14; 95% confidence interval [CI] - 0.2, -0.02; p = 0.016; I 2 = 89%, p < 0.001) but had no significant effect on FSH levels (WMD -0.25; 95% CI -0.54, 0.02; p = 0.06; I 2 = 0%, p = 0.85). CONCLUSION: Although the results of this meta-analysis showed that soy isoflavones in women with PCOS decreased TT and had no significant effect on FSH, better and more valid studies are needed to confirm these results.

A systematic review of effectiveness and economic evaluation of Cardiohelp and portable devices for extracorporeal membrane oxygenation (ECMO).

In recent years, there have been substantial advancements in the development of different technologies for extracorporeal membrane oxygenation (ECMO) for in-hospital and out of hospital applications. However the effectiveness of these devices is not clearly known. The objective of this study was to evaluate the cost-effectiveness of Cardiohelp compared to other portable ECMO devices. In this systematic review, we searched Medline (via Ovid), Embase, Pubmed, Cochrane Library, SCOPUS, CRD and NICE. Articles were assessed by two independent reviewers for eligibility and quality of the evidence. Studies which compared Cardiohelp to other ECMO devices were included. Seven out of 1316 publication were included in this review, three of them were clinical trials and four were observational studies. The majority of the studies had limited quality. According to the measures of safety, Cardiohelp had safer technological features, but on the other hand, was more complex to use. Considering the effectiveness, Cardiohelp was not statistically different from other technologies. Cardiohelp showed slightly better performance than Centrimag in terms of cost per patient and cost-effectiveness. However, when clinical criteria were used to select the patients with good prognosis to administer the ECMO, incremental cost utility ratios (ICURs) for both Cardiohelp and Centrimag were below the level of willingness-to-pay threshold. According to the measures of safety and effectiveness, ECMO with Cardiohelp was not considerably different from other evaluated technologies. Moreover, ECMO with Cardiohelp or Centrimag can be considered cost-effective, provided that the patients are selected carefully in terms of neurological outcomes.

SARS-CoV-2 mechanisms of cell tropism in various organs considering host factors.

A critical step in the drug design for SARS-CoV-2 is to discover its molecular targets. This study comprehensively reviewed the molecular mechanisms of SARS-CoV-2, exploring host cell tropism and interaction targets crucial for cell entry. The findings revealed that beyond ACE2 as the primary entry receptor, alternative receptors, co-receptors, and several proteases such as TMPRSS2, Furin, Cathepsin L, and ADAM play critical roles in virus entry and subsequent pathogenesis. Additionally, SARS-CoV-2 displays tropism in various human organs due to its diverse receptors. This review delves into the intricate details of receptors, host proteases, and the involvement of each organ. Polymorphisms in the ACE2 receptor and mutations in the spike or its RBD region contribute to the emergence of variants like Alpha, Beta, Gamma, Delta, and Omicron, impacting the pathogenicity of SARS-CoV-2. The challenge posed by mutations raises questions about the effectiveness of existing vaccines and drugs, necessitating consideration for updates in their formulations. In the urgency of these critical situations, repurposed drugs such as Camostat Mesylate and Nafamostat Mesylate emerge as viable pharmaceutical options. Numerous drugs are involved in inhibiting receptors and host factors crucial for SARS-CoV-2 entry, with most discussed in this review. In conclusion, this study may provide valuable insights to inform decisions in therapeutic approaches.

AI-based histopathology image analysis reveals a distinct subset of endometrial cancers.

Endometrial cancer (EC) has four molecular subtypes with strong prognostic value and therapeutic implications. The most common subtype (NSMP; No Specific Molecular Profile) is assigned after exclusion of the defining features of the other three molecular subtypes and includes patients with heterogeneous clinical outcomes. In this study, we employ artificial intelligence (AI)-powered histopathology image analysis to differentiate between p53abn and NSMP EC subtypes and consequently identify a sub-group of NSMP EC patients that has markedly inferior progression-free and disease-specific survival (termed 'p53abn-like NSMP'), in a discovery cohort of 368 patients and two independent validation cohorts of 290 and 614 from other centers. Shallow whole genome sequencing reveals a higher burden of copy number abnormalities in the 'p53abn-like NSMP' group compared to NSMP, suggesting that this group is biologically distinct compared to other NSMP ECs. Our work demonstrates the power of AI to detect prognostically different and otherwise unrecognizable subsets of EC where conventional and standard molecular or pathologic criteria fall short, refining image-based tumor classification. This study's findings are applicable exclusively to females.

3D printed pH-responsive tablets containing N-acetylglucosamine-loaded methylcellulose hydrogel for colon drug delivery applications.

The pH-responsive drug release approach in combination with three-dimensional (3D) printing for colon-specific oral drug administration can address the limitations of current treatments such as orally administered solid tablets. Such existing treatments fail to effectively deliver the right drug dosage to the colon. In order to achieve targeted drug release profiles, this work aimed at designing and producing 3D printed tablet shells using Eudragit® FS100 and polylactic acid (PLA) where the core was filled with 100 µl of N-acetylglucosamine (GlcNAc)-loaded methyl cellulose (MC) hydrogel. To meet the requirements of such tablets, the effects of polymer blending ratios and MC concentrations on physical, thermal, and material properties of various components of the tablets and most importantly in vitro drug release kinetics were investigated. The tablets with 80/20 wt% of Eudragit® FS100/PLA and the drug-loaded hydrogel with 30 mg/ml GlcNAc and 3% w/v MC showed the most promising results having the best printability, processability, and drug release kinetics besides being non-cytotoxic. Manufacturing of these tablets will be the first milestone in shifting from the conventional "one size fits all" approach to personalized medicine where different dosages and various combinations of drugs can be effectively delivered to the inflammation site.

Harnessing the Power of CAR-NK Cells: A Promising Off-the-Shelf Therapeutic Strategy for CD38-Positive Malignancies.

Background: CD38 is highly expressed on multiple myeloma (MM) cells and has been successfully targeted by different target therapy methods. This molecule is a critical prognostic marker in both diffuse large B-cell lymphoma and chronic lymphocytic leukemia. Objective: We have designed and generated an anti-CD38 CAR-NK cell applying NK 92 cell line. The approach has potential application as an off-the-shelf strategy for treatment of CD38 positive malignancies. Methods: A second generation of anti-CD38 CAR-NK cell was designed and generated, and their efficacy against CD38-positive cell lines was assessed in vitro. The PE-Annexin V and 7-AAD methods were used to determine the percentage of apoptotic target cells. Flow cytometry was used to measure IFN-γ, Perforin, and Granzyme-B production following intracellular staining. Using in silico analyses, the binding capacity and interaction interface were evaluated. Results: Using Lentivirus, cells were transduced with anti-CD38 construct and were expanded. The expression of anti-CD38 CAR on the surface of NK 92 cells was approximately 25%. As we expected from in silico analysis, our designed CD38-chimeric antigen receptor was bound appropriately to the CD38 protein. NK 92 cells that transduced with the CD38 chimeric antigen receptor, generated significantly more IFN-γ, perforin, and granzyme than Mock cells, and successfully lysed Daudi and Jurkat malignant cells in a CD38-dependent manner. Conclusion: The in vitro findings indicated that the anti-CD38 CAR-NK cells have the potential to be used as an off-the-shelf therapeutic strategy against CD38-positive malignancies. It is recommended that the present engineered NK cells undergo additional preclinical investigations before they can be considered for subsequent clinical trial studies.

Oral contraceptive pill and metabolic syndrome: Fasa Persian Cohort Study (Descriptive study).

BACKGROUND AND AIMS: The contraceptive use is 56% and prevalence of metabolic syndrome (MetS) is 30% in Iran. The aim of this study investigates relationship between oral contraceptive pills (OCP) use and MetS in women in the cohort population of Fasa city. METHODS: In a cross-sectional study, 5489 women aged 35-70 years were studied for 5 years in the Sheshdeh area in 2016. MetS were calculated using adult treatment panel III (ATP III) and international diabetes federation (IDF) methods. The odds ratio (OR) with a 95% confidence interval (CI) was reported. Linear regression was used to eliminate the confounding effect. RESULTS: The OR of developing MetS in the OCP recipients was estimated as higher than the non-recipients. The OR of developing MetS using IDF criteria in OCP recipients was (OR = 0.896,95% CI:0.800-1.004). that increased to (OR = 1.230,95% CI:1.084-1.395) after adjusting for confounding variables. Also, the odds ratio using ATP (III) criteria was (OR = 0.900,95% CI:0.804-1.009). that increased to (OR = 1.245,95% CI:1.098-1.413) after adjusting for confounding variables. Also, the OR of developing MetS in OCP recipients decreased with increasing the number of MetS components from 1.199 to 0.812,95% CI:0.771-1.864,0.467-1.413, but after adjustment, increased from 1.151 to 1.747,95% CI:0.733-1.805,0.815-3.746. CONCLUSION: The results of the present study showed that the OR of developing MetS in OCP recipients using both IDF and ATP (III) methods was higher after adjusting by confounder effects so it is recommended monitoring by physicians.

Hepatic cell-sheet fabrication of differentiated mesenchymal stem cells using decellularized extracellular matrix and thermoresponsive polymer.

PURPOSE: Liver tissue engineering via cell sheet technology would open new doors for treatment of patients with liver failure. Decellularized tissues could provide sufficient extracellular matrix (ECM) to support development of hepatocytes in in vivo niches. Besides, with the potential of temperature responsive polymer (pNIPAAm) as an intelligent surface for controlling the attachment/detachment of cell, we set out to generate three in vitro microenvironments models including I: pNIPAAm hydrogel (pN hydrogel), II: decellularized ECM incorporated into pNIPAAm hydrogel (dECM + pN hydrogel) and III: decellularized ECM scaffold (dECM scaffold) to investigate the structural and function cues of hepatocyte-like cells after differentiation of adipose tissue-derived mesenchymal stem cells (AT-MSCs) on the surface of these models. METHOD: dECM scaffold was obtained after decellularization of rat liver, and its efficiency was analyzed. pN hydrogel and dECM + pN hydrogel (1:3 and 2:3 ratios) of were fabricated, and scaffold architecture was characterized. Each well of culturing plates was coated separately with these three constructs and AT-MSCs were instructed to differentiate into hepatocyte-like cells (HLCs). After recellularization, patterns of differentiation, and expression of hepatogenic markers were investigated via biochemical assays and qRT-PCR at different time points. RESULTS: Multipotency of AT-MSCs, after their ability for osteogenesis and adipogenesis was documented. Production of dense and intact cell sheets was reported in dECM + pN hydrogel, as opposed to pN hydrogel and dECM scaffold. Also, statistically significant difference of HLCs functionality in dECM + pN hydrogel was confirmed after evaluation of the expression of hepatocyte markers including, alpha-fetoprotein, cytokeratin 18, cytochrome P450-2E1 and phosphoenolpyruvate carboxykinase. CONCLUSION: Our results proved dECM + pN hydrogel were able to preserve hepatocyte function in cell sheets owing to the high level of albumin, urea, hepatogenic markers, and glycogenesis potential of HLCs. Accordingly, dECM incorporated in pN hydrogel could remodel microenvironments to guide the AT-MSCs into conducive differentiation and proliferation to give rise to multilayer sheets of cells in their own ECM.

Liver bioengineering: Recent trends/advances in decellularization and cell sheet technologies towards translation into the clinic.

Development of novel technologies provides the best tissue constructs engineering and maximizes their therapeutic effects in regenerative therapy, especially for liver dysfunctions. Among the currently investigated approaches of tissue engineering, scaffold-based and scaffold-free tissues are widely suggested for liver regeneration. Analogs of liver acellular extracellular matrix (ECM) are utilized in native scaffolds to increase the self-repair and healing ability of organs. Native ECM analog could improve liver repairing through providing the supportive framework for cells and signaling molecules, exerting normal biomechanical, biochemical, and physiological signal complexes. Recently, innovative cell sheet technology is introduced as an alternative for conventional tissue engineering with the advantage of fewer scaffold restrictions and cell culture on a Thermo-Responsive Polymer Surface. These sheets release the layered cells through a temperature-controlled procedure without enzymatic digestion, while preserving the cell-ECM contacts and adhesive molecules on cell-cell junctions. In addition, several novelties have been introduced into the cell sheet and decellularization technologies to aid cell growth, instruct differentiation/angiogenesis, and promote cell migration. In this review, recent trends, advancements, and issues linked to translation into clinical practice are dissected and compared regarding the decellularization and cell sheet technologies for liver tissue engineering.

Investigation of olfactory receptor family 51 subfamily j member 1 (OR51J1) gene susceptibility as a potential breast cancer-associated biomarker.

Among cancer treatment methods, targeted therapy using cancer-associated biomarkers has minimum side effects. Recently olfactory receptor (OR) family attracts the researcher's attention as a favorable biomarker of cancer. Here, a statistical approach using complete data from the human protein atlas database was used to evaluate the potential of OR51J1 gene as a cancer-associated biomarker. To confirm the findings of statistical analysis, the OR51J1 mRNA and protein expression levels in breast tumor and normal tissue were measured using quantitative Real Time PCR (qRT-PCR) and immunohistochemistry (IHC) techniques. The association with clinicopathological factors was analyzed. Statistical analysis revealed that OR51J1 has a high expression level in more than 20 types of cancer tissues without any expression in 44 normal tissues. In 15 cancer types, including breast cancer, expression score was more than 90%. The qRT-PCR analysis in breast cancer showed OR51J1 have significantly higher expression level in tumors than normal tissues (2.91 fold). The IHC results showed OR51J1 expression on other cellular subtypes than tumor and normal cells, including myoepithelium, fibroblast, and lymphocytes. OR51J1 protein expression in invasive cells, as well as its overall score, showed a significant correlation with ER and PR expression and breast cancer (BC) subtypes. Results revealed the potential of OR51J1 as a cancer-associated biomarker for the diagnosis of breast cancer at the mRNA level.

The effect of l-carnitine supplementation on lipid profile and glycaemic control in adults with cardiovascular risk factors: A systematic review and meta-analysis of randomized controlled clinical trials.

BACKGROUND & AIMS: Several randomized clinical trials (RCTs) have investigated the effect of l-carnitine supplementation on lipid profile and glycaemic control in adults with cardiovascular risk factors; however, the results were conflicting. Therefore, a meta-analysis was performed to assess the effect of l-carnitine on lipid profile and glycaemic control in adults with cardiovascular risk factors. METHODS: We searched PubMed, Scopus, Cochrane Databases, Google Scholar, ProQuest, Web of Science and Embase for randomized, placebo-controlled human trials that investigated the effect of l-carnitine supplementation on lipid profile and glycaemic control up to April 2017. From the eligible trials, 24 articles were selected for the meta-analysis. The meta-analysis was performed in a random-effects model. Heterogeneity was determined by I2 statistics and Cochrane Q test. RESULTS: The result showed significant effect of l-carnitine on TC (WMD: -13.73 [95% CI: -22.28, -5.17] mg/dL; P < 0.001), LDL-C (WMD = - 7.70 [95% CI: - 11.80, -3.61]mg/dL; p < 0.001), HDL-C (WMD = 0.82 [95% CI: 0.44, 1.21] mg/dL; P > 0.001), Lp(a) (WMD = - 7.13 [95% CI: -9.82,- 4.43]mg/dL; P < 0.001), FPG (WMD = -6.25 [95% CI: -10.35, -2.16] mg/dL; P < 0.001), HbA1C (WMD (%) = - 0.35 [95% CI: -0.65,- 0.05]; p = 0.02) and HOMA-IR (WMD (%) = - 0.94 [95% CI: -1.89, -0.00]; P = 0.05). No effect of l-carnitine was detected in TG, Apo A-I and Apo B 100 on pooled effect size. Additionally, sensitivity analysis showed l-carnitine supplementation could improve glycaemic control, particularly along with hypocaloric diet. CONCLUSION: This meta-analysis showed that l-carnitine supplementation could improve lipid profile levels, particularly in doses more than 1500 mg/day. More RCTs with large sample sizes, focusing on gut microbiome profiles and dietary patterns are needed to better understand the effect of l-carnitine on patients with cardiovascular risk factors.

The impact of empowerment model-based education on quality of life of transgender people under hormone therapy: A randomized clinical trial.

INTRODUCTION: Gender identity disorder is a complex psychological problem and people with this disorder are at risk of many problems, including reduced quality of life. Empowerment intervention is one of the methods that can be used to improve the quality of life of people. The present study aimed to investigate the effect of empowerment model-based training on the quality of life of transgender people undergoing hormone therapy. METHODS: The present study is a randomized clinical trial that was conducted in 2012 on 81 transgender people at Tehran Welfare Center. The study samples were randomly assigned into two groups of intervention and control. The intervention group received training based on the empowerment model (threat perception, problem-solving, educational participation, and evaluation) and the control group received routine treatment. RESULTS: According to the findings, after the intervention, a statistically significant difference was found between the two groups in terms of the mean level of overt anxiety (P = 0.045) and aspects of emotional health (P = 0.030), the general perception of health (P = 0.007), mental health (P = 0.008), and overall quality of life (P = 0.005). Also, although there was a statistically significant difference in the aspect emotional well-being in the intervention group before and after the intervention (P = 0.034), this difference was not significant between the two groups (P = 0.274). CONCLUSION: The results showed that the empowerment-based training program had a significant relationship with the improvement in aspects of emotional health, the overall perception of health, mental health, emotional well-being and overall quality of life.

The effect of melatonin supplementation on liver indices in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized clinical trials.

Several randomized clinical trials (RCTs) evaluated the effect of melatonin supplementation on liver enzymes in patients with non-alcoholic fatty liver disease (NAFLD) and reported conflicting results. To meet these discrepancies, a meta-analysis was conducted to evaluate the eff ;ect of melatonin on liver indices in patients with NAFLD. To collect the required data, a thorough search was conducted through Web of science, Pubmed, Cochrane database, Embase, Google Scholar, ProQuest, and Scopus databases. The aim was to find clinical trials over the effect of melatonin supplementation on liver indices up to 16 May 2019. As a result, five eligible articles were selected and analysed in this meta-analysis using a fixed-effects model. Heterogeneity test was performed by I2 statistics and Cochrane Q test. The results showed that melatonin had a significant effect on aspartate aminoteransferase (AST) (WMD = 2.29, [95 %CI: 1.14, 3.43] IU/L, p = <0.001), alkaline phosphatase (ALP) (WMD = -8.40, [95 %CI -11.33, -5.48] IU/L, p < 0.001), and gamma-glutamyltransferase (GGT) (WMD = -33.37, [95 %CI: -37.24, -29.49] IU/L, p= < 0.001). Melatonin had no significant effect on alanine aminotransferase (ALT) regarding the overall effect size. Based on this meta-analysis, melatonin supplementation can improve liver indices. However, more RCTs are required with larger sample sizes and better control of confounding variables such as weight, body mass index, and gender to determine the effect of melatonin on patients with non-alcoholic fatty acid disease.

Circulating vitamin D and the risk of gestational diabetes: a systematic review and dose-response meta-analysis.

PURPOSE: Several meta-analyses of observational studies revealed a modest increase in the risk of gestational diabetes (GDM) among pregnant women with low levels of serum vitamin D. However, no study examined a dose-response meta-analysis as well as a high versus low analysis in this regard. METHODS: We systematically searched PubMed, Embase, ISI Web of Science, and Scopus up to August 2019 to find prospective observational studies investigating the association of serum 25(OH)D with the risk of developing GDM. Using a random-effects model, the reported risk estimates were pooled. RESULTS: Nine cohort studies and six nested case-control studies were included in the final analysis (40,788 participants and 1848 cases). Considering linear analysis, each 10 nmol/L increase in circulating 25(OH)D was associated with a 2% lower risk of GDM (effect size (ES): 0.98; 95% CI: 0.98, 0.99; I2 = 85.0%, P < 0.001). highest compared with the lowest category of circulating 25(OH)D was associated with a 29% lower risk of GDM, with low evidence of heterogeneity (I2 = 45.0%, P = 0.079). CONCLUSIONS: In conclusion, lower levels of serum 25(OH)D were associated with a higher chance of GDM. Differential results existed between the overall and subgroup analysis, either based on vitamin D detection methods or based on maternal age, although these subgroups partially lowered the heterogeneity.

Alpha-lipoic acid (ALA) supplementation effect on glycemic and inflammatory biomarkers: A Systematic Review and meta- analysis.

BACKGROUND & AIMS: Several randomized clinical trials (RCTs) have investigated the effect of Alpha - Lipoic Acid (ALA) supplementation on metabolic parameters, with conflicting results. Therefore, the present study assessed the effect of ALA on some glycemic and inflammatory parameters. METHODS: A comprehensive literature search was conducted up from inception to July 2018 on PubMed, Scopus, Cochrane databases, Google Scholar, ProQuest, Web of Science, and Embase. From among eligible trials, 41 articles were selected for the meta-analysis. Two reviewers independently assessed the risk of bias and extracted data from the included studies. Meta-analyses using the random-effects model were performed to analyze the data. RESULTS: Based on the Cochrane risk of bias tool, 19 articles had a good quality, 16 trials had a poor quality and 6 trials had a fair quality. The results demonstrated the significant effect of ALA on Fasting Blood Sugar (FBS) (weighted mean difference (WMD)) = -6.57, 95% confidence interval (CI: -11.91 to -1.23, P = 0.016), Hemoglobin A1c (HbA1c) (WMD = -0.35, 95% CI: -0.55 to -0.15, P = 0.004), Tumor Necrosis Factor Alpha (TNF-α) (WMD = -1.57, 95% CI: -2.29 to -0.85, P < 0.05), Interleukin 6 levels (IL-6) (WMD = -1.15, 95% CI: -1.58 to -0.72, P < 0.001), and C-reactive protein (CRP) (WMD = -0.31, 95% CI: -0.47 to -0.16, P > 0.001). No effect was detected for ALA on insulin and the homeostatic model assessment of insulin resistance (HOMA-IR). CONCLUSIONS: These findings suggest that ALA is a viable supplement to improve some of the glycemic and inflammatory biomarkers.

Evaluation of the effect of oral taurine supplementation on fasting levels of fibroblast growth factors, ß-Klotho co-receptor, some biochemical indices and body composition in obese women on a weight-loss diet: a study protocol for a double-blind, randomized controlled trial.

BACKGROUND: Taurine (Tau) is involved in many biochemical functions such as regulation of glucose and lipid metabolism, enhancement of energy expenditure, anti-inflammatory effects and appetite control. The most important effect of Tau in obesity is its direct effect on adipose tissue. Some evidence has shown an impaired FGF (fibroblast growth factor) 19 and 21 biosyntheses in obesity. Besides the effects of eicosapentaenoic acid on serum FGF concentrations, the effect of other nutrients on FGFs is not clear. Since obesity as an important health problem is rising around the world and on the other side, Tau biosynthesis is reduced by adipose-tissue-derived factors in obesity, the effects of Tau and a weight-loss diet on obesity need to be investigated further. METHODS: We will conduct an 8-week. double-blind, parallel-group, randomized controlled clinical trial to investigate the effect of Tau supplementation on fasting serum levels of FGFs, ß-Klotho co-receptor, some biochemical indices and body composition in 50 obese women aged between 18 and 49 years on a weight-loss diet. DISCUSSION: We will determine the other advantages of a weight-loss diet on new metabolic risk factors. Since Tau may regulate adipose-tissue-derived factors and a weight-loss diet can promote the useful effects of Tau supplementation; for the first time, the effects of a weight-loss diet along with Tau supplementation on these variables will be assessed. TRIAL REGISTRATION: Iran Clinical Trials Registry, ID: IRCT20131125015542N2 . Registered on 24 November 2018.