Effect of sesame supplementation on body composition and lipid profile in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.

AIMS: The aim of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) that evaluated the impact of sesame supplementation on body weight (BW), body mass index (BMI), triglycerides (TGs), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C) in patients with type 2 diabetes mellitus (T2DM). DATA SYNTHESIS: PubMed, Scopus, ISI Web of Science, and Embase were searched without any restrictions until September 2023.Only RCTs reporting the effects of sesame supplementation on body composition and lipid profiles were included, while observational studies and animal models were excluded. The methodological quality of the studies was assessed using the Cochrane risk of bias tool. Out of 997 studies identified, 10 were included in the systematic review and meta-analysis. Our meta-analysis suggested a significant association between sesame supplementation and reduction in TG (weighted mean difference (WMD): -37.61 mg/dl, 95 % CI: -61.48, 13.73), TC (WMD: -32.69 mg/dl, 95 % CI: -47.26, 18.12), and LDL-C (WMD: -28.72 mg/dl, 95 % CI: -44.68, 12.76). However, our meta-analysis indicated that the supplementary intake of sesame had no significant effect on HDL-C, BW, and BMI in patients with T2DM. CONCLUSIONS: This study showed that sesame consumption significantly lowered TG, TC, and LDL-C levels, which may have contributed to the improvement of clinical symptoms in T2DM. However, given the limited number of trials included in the analysis, additional large-scale studies are needed to confirm the effects of sesame consumption on the lipid profile and body composition in patients with T2DM. PROSPERO CODE: CRD42023460630.

Effects of chromium supplementation on body composition in patients with type 2 diabetes: A dose-response systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Several randomized controlled trials (RCTs) have demonstrated the beneficial effects of chromium supplementation in managing type 2 diabetes mellitus (T2DM). The current systematic review and meta-analysis aimed to investigate the associations between chromium supplementation and body composition in patients with T2DM. METHODS: To achieve this, PubMed, Scopus, Embase, Cochrane Library, and Web of Science were searched for randomized clinical trials (RCTs) that reported the effects of chromium supplementation on body composition such as body weight (BW), body mass index (BMI), fat mass (FM), and waist circumference (WC) in patients with T2DM from inception until July 2023. Weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated using a fixed-effects model. RESULTS: The meta-analysis included a total of 14 RCTs. The results showed that chromium supplementation did not have any significant effect on FM (WMD = -0.43%; 95% CI -0.94, 0.09), BMI (WMD: 0.09 kg/M2, 95% CI: -0.03, 0.20), WC (WMD: -0.47 cm, 95% CI: -1.10, 0.16), and BW (WMD: -0.26 kg, 95% CI: -0.69, 0.16). However, subgroup analysis revealed that chromium intake decreased FM in subjects aged ≥ 55 years and when chromium picolinate was used as an intervention. Additionally, there was a non-linear association between the dose of chromium supplementation and BW. CONCLUSIONS: The meta-analysis suggests that chromium supplementation does not significantly reduce BW, BMI, WC, and FM in patients with T2DM. Further RCTs with large-scale are required to determine the possible anti-obesity effects of chromium in patients with T2DM.

The effects of alpha lipoic acid (ALA) supplementation on blood pressure in adults: a GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials.

Introduction: There have been various clinical studies on the effect of Alpha lipoic acid (ALA) supplementation on blood pressure (BP), but the findings from these are contradictory. Therefore, we performed a systematic review and dose-response meta-analysis to summarize the relation of ALA supplementation and systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults. Methods: A comprehensive search was conducted in Medline (PubMed), Embase, Scopus, and ProQuest up to July 2023. Randomized controlled trials (RCTs) evaluating the effect of ALA on SBP and DBP were included. The pooled weighted mean difference (WMD) of included trials was estimated using a random-effects model. The dose-dependent effect was also assessed. Results and discussion: A total of 11 RCTs with the participation of 674 patients were included. The result of the meta-analysis indicated that using ALA supplementation significantly reduced the SBP (WMD = -5.46 mmHg; 95% CI: -9.27, -1.65; p < 0.001) and DBP (WMD = -3.36 mmHg, 95% CI: -4.99, -1.74; p < 0.001). The ALA administrations significantly reduced SBP and DBP at the dosages of <800 mg/day, when administered for ≤12 weeks. The present meta-analysis revealed that ALA supplementation could exert favorable effects on SBP and DBP. Further well-designed studies with larger samples are needed to ascertain the long-term effects of ALA on BP. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=447658, identifier PROSPERO: CRD42023447658.

Fluorescence anisotropy cytosensing of folate receptor positive tumor cells using 3D polyurethane-GO-foams modified with folic acid: molecular dynamics and in vitro studies.

Integrated polyurethane (PU)-based foams modified with PEGylated graphene oxide and folic acid (PU@GO-PEG-FA) were developed with the goal of capturing and detecting tumor cells with precision. The detection of the modified PU@GO-PEG surface through FA against folate receptor-overexpressed tumor cells is the basis for tumor cell capture. Molecular dynamics (MD) simulations were applied to study the strength of FA interactions with the folate receptor. Based on the obtained results, the folate receptor has intense interactions with FA, which leads to the reduction in the FA interactions with PEG, and so decreases the fluorescence intensity of the biosensor. The synergistic interactions offer the FA-modified foams a high efficiency for capturing the tumor cell. Using a turn-off fluorescence technique based on the complicated interaction of FA-folate receptor generated by target recognition, the enhanced capture tumor cells could be directly read out at excitation-emission wavelengths of 380-450 nm. The working range is between 1×10 2 to 2×10 4 cells mL -1 with a detection limit of 25 cells mL -1 and good reproducibility with relative standard deviation of 2.35%. Overall, findings demonstrate that the fluorescence-based biosensor has a significant advantage for early tumor cell diagnosis.

Targeting and ultrabroad insight into molecular basis of Resistance-nodulation-cell division efflux pumps.

Resistance-nodulation-cell devision (RND) efflux pump variants have attracted a great deal of attention for efflux of many antibiotic classes, which leads to multidrug-resistant bacteria. The present study aimed to discover the interaction between the RND efflux pumps and antibiotics, find the conserved and hot spot residues, and use this information to target the most frequent RND efflux pumps. Protein sequence and 3D conformational alignments, pharmacophore modeling, molecular docking, and molecular dynamics simulation were used in the first level for discovering the function of the residues in interaction with antibiotics. In the second level, pharmacophore-based screening, structural-based screening, multistep docking, GRID MIF, pharmacokinetic modeling, fragment molecular orbital, and MD simulation were utilized alongside the former level information to find the most proper inhibitors. Five conserved residues, containing Ala209, Tyr404, Leu415, Asp416, and Ala417, as well as their counterparts in other OMPs were evaluated as the crucial conserved residues. MD simulation confirmed that a number of these residues had a key role in the performance of the efflux antibiotics; therefore, some of them were hot spot residues. Fourteen ligands were selected, four of which interacted with all the crucial conserved residues. NPC100251 was the fittest OMP inhibitor after pharmacokinetic computations. The second-level MD simulation and FMO supported the efficacy of the NPC100251. It was exhibited that perhaps OMPs worked as the intelligent and programable protein. NPC100251 was the strongest OMPs inhibitor, and may be a potential therapeutic candidate for MDR infections.

Graphene oxide quantum dot-chitosan nanotheranostic platform as a pH-responsive carrier for improving curcumin uptake internalization: In vitro & in silico study.

We herein fabricated a cancer nanotheranostics platform based on Graphene Oxide Quantum Dot-Chitosan-polyethylene glycol nanoconjugate (GOQD-CS-PEG), which were targeted with MUC-1 aptamer towards breast and colon tumors. The interaction between aptamer and MUC-1 receptor on the desired cells was investigated utilizing molecular docking. The process of curcumin release was investigated, as well as the potential of the produced nanocomposite in targeted drug delivery, specific detection, and photoluminescence imaging. The fluorescence intensity of GOQD-CS-PEG was reduced due to transferred energy between (cytosine-guanin) base pairs in the hairpin structure of the aptamer, resulting in an "on/off" photoluminescence bio-sensing. Interestingly, the integration of pH-responsive chitosan nanoparticles in the nanocomposite results in a smart nanocomposite capable of delivering more curcumin to desired tumor cells. When selectively binds to the MUC-1 receptor, the two strands of aptamer separate in acidic conditions, resulting in a sustained drug release and photoluminescence recovery. The cytotoxicity results also revealed that the nanocomposite was more toxic to MUC-1-overexpressed tumor cells than to negative control cell lines, confirming its selective targeting. As a result, the proposed nanocomposite could be used as an intelligent cancer nanotheranostic platform for tracing MUC-1-overexpressed tumor cells and targeting them with great efficiency and selectivity.

Rational design of a new variant of Reteplase with optimized physicochemical profile and large-scale production in Escherichia coli.

Structural engineering of the recombinant thrombolytic drug, Reteplase, and its cost-effective production are important goals in the pharmaceutical industry. In this study, a single-point mutant of the protein was rationally designed and evaluated in terms of physicochemical characteristics, enzymatic activity, as well as large-scale production settings. An accurate homology model of Reteplase was used as the input to appropriate tools to identify the aggregation-prone sites, while considering the structural stability. Selected variants underwent extensive molecular dynamic simulations (total 540 ns) to assess their solvation profile and their thermal stability. The Reteplase-fibrin interaction was investigated by docking. The best variant was expressed in E. coli, and Box-Behnken design was used through response surface methodology to optimize its expression conditions. M72R mutant demonstrated appropriate stability, enhanced enzymatic activity (p < 0.05), and strengthened binding to fibrin, compared to the wild type. The optimal conditions for the variant's production in a bioreactor was shown to be 37 ºC, induction with 0.5 mM IPTG, for 2 h of incubation. Under these conditions, the final amount of the produced enzyme was increased by about 23 mg/L compared to the wild type, with an increase in the enzymatic activity by about 2 IU/mL. This study thus offered a new Reteplase variant with nearly all favorable properties, except solubility. The impact of temperature and incubation time on its large-scale production were underlined as well.

Psychological impact of COVID-19 on health-care workers: A multicenter cross-sectional study.

BACKGROUND: Health-care workers (HCWs) as frontline soldiers are involved in the war against COVID-19. Not only their protection from COVID-19 is important but also their mental health is a concern. This study aimed to measure the psychological distress among HCWs in the time of COVID-19 in Isfahan, Iran. MATERIALS AND METHODS: A cross-sectional study was conducted in the 2nd month of the spread of COVID-19 in Isfahan, Iran (March 16 to April 3). A total of 321 HCWs participated in an online survey and answered the General Health Questionnaire, the Insomnia Severity Index, and the Medical Outcomes Study Social Support Survey. t-test and ANOVA were used for comparing variables between groups. Multiple linear regression was used to evaluate the predictive factors of psychological distress. RESULTS: About 34% of our HCWs suffer from some levels of psychological distress. The result of multiple linear regression (R 2: 0.41) shows that the predictive variables with the highest value were insomnia, working as a medical resident, and lack of social support (standardized coefficient of beta: 0.51, 0.25, and 0.16, respectively; P < 0.05). CONCLUSION: The result of our study shows that about one-third of HCWs in COVID-19 special hospitals have some psychological problems. Being a medical resident, suffering from insomnia, and lack of social support are predictive variables.

Investigation of Supercharging as A Strategy to Enhance the Solubility and Plasminogen Cleavage Activity of Reteplase.

BACKGROUND: Reteplase, the recombinant form of tissue plasminogen activator, is a thrombolytic drug with outstanding characteristics, while demonstrating limited solubility and reduced plasminogen activation. Previously, we in silico designed a variant of Reteplase with positively supercharged surface, which showed promising stability, solubility and activity. This study was devoted to evaluation of the utility of supercharging technique for enhancing these characteristics in Reteplase. OBJECTIVE: To test the hypothesis that reinforced surface charge of a rationally-designed Reteplase variant will not compromise its stability, will increase its solubility, and will enhance its plasminogen cleavage activity. MATERIALS AND METHODS: Supercharged Reteplase coding sequence was cloned in pDest527 vector and expressed in E. coli BL21 (DE3). The expressed protein was extracted by cell disruption. Inclusion bodies were solubilized using guanidine hydrochloride, followed by dialysis for protein refolding. After confirmation with SDS-PAGE and western blotting, extracted proteins were assayed for solubility and tested for bioactivity. RESULTS: SDS-PAGE and western blot analysis confirmed the successful expression of Reteplase. Western blot experiments showed most of Reteplase expressed in the insoluble form. Plasminogen cleavage assay showed significantly higher activity of the supercharged variant than the wild type protein (P < 0.001). The stability of the supercharged variant was also comparable to the wild type. CONCLUSION: Our findings, i.e. the contribution of the surface supercharging technique to retained stability, enhanced plasminogen cleavage activity, while inefficiently changed solubility of Reteplase, contain implications for future designs of soluble variants of this fibrinolytic protein drug.

Investigation of the Association between 5-Hydroxytryptamine Transporter Gene-Linked Polymorphic Region with Type 2 Diabetes Mellitus, Obesity and Biochemical Profiles of Serum in Iranian Population.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is a serious problem in the world. 5-Hydroxytryptamine (5-HT, serotonin) plays an important role in obesity, glucose control and insulin resistance. The polymorphism of the serotonin transporter gene linked promoter region (5-HTTLPR) might influence 5-HTT expression and serotonin uptake. The polymorphism results in two alleles of L (Long) and S (Short). The aim of the present study was to evaluate the association between 5-HTTLPR genotypes in type 2 diabetes mellitus (T2DM), obesity as well as serum biochemical profiles in Iranian population from 2012 until 2015. METHODS: 180 patients with T2DM and 180 controls were selected and the frequency of S and L alleles was determined by PCR. Then, the relationship between genotypes, body mass index (BMI) and serum biochemical variables was investigated. RESULTS: The frequency of S and L alleles in experimental and control groups was the same [for the L allele p=0.754, OR (95%CI)=1.103 (0.597 to 2.041) and for the S allele p=0.906, OR (95%CI)=(0.490 to 1.676)]. However, the mean triglyceride, cholesterol, LDL-C, systolic and diastolic blood pressure levels in the diabetic subjects with LL genotype were significantly higher than LS and SS genotypes (p<0.001) in this population. CONCLUSION: The L allele of 5-HTTLPR was related to the increased serum lipids and blood pressure in the diabetic patients. However, there was no relationship between the polymorphism of 5-HTTLPR L/S and T2DM in Iranian population.

Reteplase: Structure, Function, and Production.

Thrombolytic drugs activate plasminogen which creates a cleaved form called plasmin, a proteolytic enzyme that breaks the crosslinks between fibrin molecules. The crosslinks create blood clots, so reteplase dissolves blood clots. Tissue plasminogen activator (tPA) is a well-known thrombolytic drug and is fibrin specific. Reteplase is a modified nonglycosylated recombinant form of tPA used to dissolve intracoronary emboli, lysis of acute pulmonary emboli, and handling of myocardial infarction. This protein contains kringle-2 and serine protease domains. The lack of glycosylation means that a prokaryotic system can be used to express reteplase. Therefore, the production of reteplase is more affordable than that of tPA. Different methods have been proposed to improve the production of reteplase. This article reviews the structure and function of reteplase as well as the methods used to produce it.