Knocking down the expression of the molecular motors, myosin A, C and F genes in Toxoplasma gondii to decrease the parasite virulence.

Toxoplasmosis is a serious parasitic infection and novel therapeutic options are highly demanded to effectively eliminate it. In current study, Toxoplasma gondii myosin A, C and F genes were knocked down using small interference RNA (siRNA) method and the parasite survival and virulence was evaluated in vitro and in vivo. The parasites were transfected with specific siRNA, virtually designed for myosin mRNAs, and co-cultured with human foreskin fibroblasts. The transfection rate and the viability of the transfected parasites were measured using flow cytometry and methyl thiazole tetrazolium (MTT) assays, respectively. Finally, the survival of BALB/c mice infected with siRNAs-transfected T. gondii was assessed. It was demonstrated that a transfection rate of 75.4% existed for siRNAs, resulting in 70% (P = 0.032), 80.6% (P = 0.017) and 85.5% (P = 0.013) gene suppression for myosin A, C and F in affected parasites, respectively, which was subsequently confirmed by Western blot analysis. Moreover, lower parasite viability was observed in those with knocked down myosin C with 80% (P = 0.0001), followed by 86.15% (P = 0.004) for myosin F and 92.3% (P = 0.083) for myosin A. Considerably higher mouse survival (about 40 h) was, also, demonstrated in mice challenged with myosin siRNA-transfected T. gondii, in comparison with control group challenged with wild-type parasites. In conclusion, myosin proteins knock down proposes a promising therapeutic strategy to combat toxoplasmosis.

Effect of dietary approaches to stop hypertension, and standard diets with and without curcumin on interleukin-1 alpha, 5-alpha reductase gene expressions, and androgenic and glycemic profile in polycystic ovary syndrome women undergoing in vitro fertilization treatment: A study protocol.

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases with major reproductive and metabolic complications with an impact on public health. Hyperandrogenism and chronic inflammation have been suggested as the leading cause of pathophysiology and clinical manifestations associated with PCOS. It seems that the altered expression of genes involved in the synthesis of pro-inflammatory cytokine and androgens contribute to the promotion of PCOS. Objective: This trial aims to determine the effects of dietary approaches to stop hypertension (DASH) and standard diets with and without curcumin supplementation on the gene expression of interleukin -1 alpha(IL1α), 5α reductase and androgenic and glycemic profile among PCOS patients, who are candidates for in vitro fertilization. Materials and Methods: 96 infertile women with PCOS, aged 18-40 yr, will participate in this randomized, placebo-controlled clinical trial. Based on treatment conditions and body mass index, the participants will be randomly divided into 4 equal groups using a randomized block design. They will receive a DASH or standard diet containing 52% carbohydrate, 18% protein, and 30% total fat, with the same prescribed sodium, plus 500 mg twice daily curcumin or placebo for 12 wk. The mRNA expression of IL-1α, 5α reductase, and androgenic and glycemic profiles will be measured at baseline and at the end of the study. Conclusion: Concomitant administration of DASH diet and curcumin supplementation may reduce IL-1α, 5α reductase gene expressions, and improve glycemic and androgenic profiles.

The addition of exercise to a weight loss diet on inflammatory markers: a systematic review and Meta-analysis of controlled clinical trials.

This systematic review and meta-analysis of controlled clinical trials was performed to evaluate the effects of weight-loss diets plus exercise compared with weight-loss diets alone on inflammatory biomarkers in adults. PubMed, Scopus, EMBASE, Web of Science (ISI), and Google Scholar were searched up to April 2021. Overall effects were derived using a random effects model. The overall quality of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Twenty-nine trials were included in this systematic review and meta-analysis. The meta-analysis showed no significant difference in serum high sensitivity C-reactive protein (hs-CRP) [weighted mean difference (WMD) = -0.004 mg/l, 95% CI: -0.140, 0.132, P = 0.954], interleukin-6 (IL-6) (WMD = -0.039 pg/ml, 95% CI: -0.233 to 0.156, P = 0.696), and tumor necrosis factor-α (TNF-α) (WMD = 0.405 ng/ml, 95% CI: -1.036 to 0.226, P = 0.209) after adding exercise to a weight-loss diet compared with a weight-loss diet alone. Subgroup analysis revealed that exercise plus a weight-loss diet significantly reduced TNF-α in studies greater than 16 weeks in duration (WMD = -0.742 ng/ml, 95% CI: -1.384 to -0.1, P = 0.024). This systematic review and meta-analysis indicate that exercise in addition to a weight-loss diet does not have a significant effect on further reducing inflammatory markers compared to a weight loss diet alone.

Dietary total anti-oxidant capacity is inversely related to the prevalence of depression in adolescent girls.

BACKGROUND: Oxidative stress is considered to be a contributory factor for depression, and is affected by the dietary intake of pro-and anti-oxidants. Dietary total antioxidant capacity (DTAC) is an index which is applied to estimate the cumulative power of antioxidants in the whole diet. The aim of this study was to determine the relationship between DTAC and prevalence of depression in adolescent girls. METHODS: A total of 741 Iranian adolescent girls aged 12-18 years were recruited into this cross-sectional study. Dietary intake and depression severity score were assessed using a food frequency questionnaire and Beck's depression inventory, respectively. To estimate the DTAC, the oxygen radical absorbance capacity method was used for selected foods. To explore the associations between DTAC and depression, logistic regression was applied using crude and adjusted models. RESULTS: Individuals in the greatest adherence to high DTAC had more intakes of whole grains, legumes, fruits, dried fruits, low fat dairy products, cruciferous vegetables, fiber, magnesium, vitamin C, folate, potassium, zinc, ß-carotene, lutein, thiamin, riboflavin, niacin and vitamin B-6 and lower consumption of refined grains. Subjects in the highest quartile of DTAC had a 39% lower odds of depression compared to those in the first quartile (OR = 0.61; 95% CI: 0.38-0.97, P for trend = 0.012); these associations remained significant after adjustments in first, second and third (OR = 0.5; 95% CI: 0.28-0.92, P for trend < 0.001) adjusted models. CONCLUSIONS: An inverse association was observed between the DTAC and the prevalence of depression in our population sample of adolescent girls. Further research needs to be conducted in different areas, including longitudinal studies with larger sample sizes.

Effect of exercise as adjuvant to energy-restricted diets on quality of life and depression outcomes: a meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Obesity and related co-morbidities lead to a decrease in health-related quality of life (HRQOL) and mood. Lifestyle strategies may improve these outcomes. However, the efficacy of exercise in conjunction with a weight-loss diet on HRQOL and mood is unclear. The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to examine whether the addition of exercise to energy-restricted dietary programs improves HRQOL and mood status when compared with energy-restricted diets alone in overweight and obese adults. METHODS: Eligible RCTs were identified by searching PubMed/MEDLINE, EMBASE, ISI (Web of sciences), Scopus, and Google Scholar up to April 2021. Summary effects were derived using a random-effects model. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. RESULTS: The meta-analysis revealed that an energy-restricted diet plus exercise compared with an energy-restricted diet alone had no significant effects on depression (n = 6, hedges'g = - 0.04, 95% CI: - 0.28,0.20), MOS 36-Item Short-Form Health Survey (SF-36)-physical component summary scores (n = 8, weighted mean difference (WMD) = 1.51, 95% CI: - 0.16, 3.18), SF36-mental component summary scores (n = 7, WMD = 0.64, 95% CI: - 1.00, 2.28), and HRQOL disease-specific questionnaire scores (n = 5, hedges'g = 0.16, 95% CI: - 0.09, 0.40). The GRADE revealed that the quality of evidence was low for disease-specific HRQOL scores, and depression status; and high for physical and mental health assessed by SF-36. CONCLUSION: In our sample of overweight and obese adults, no beneficial effect of adding exercise to an energy-restricted diet was found in terms of HRQOL and Depression.

Phenylalanine gold nanoclusters as sensing platform for π-π interfering molecules: a case study of iodide.

The photo-physical properties of metal nano clusters are sensitive to their surrounding medium. Fluorescence enhancement, quenching, and changes in the emitted photon properties are usual events in the sensing applications using these nano materials. Combining this sensitivity with unique properties of self-assembled structures opens new opportunities for sensing applications. Here, we synthesized gold nanoclusters by utilizing phenylalanine amino acid as both capping and reducing molecule. Phenylalanine is able to self-assemble to rod-shaped nano structure in which the π-π interaction between the aromatic rings is a major stabilizing force. Any substance as iodide anion or molecule that is able to weaken this interaction influence the fluorescence of metal nano-clusters. Since the building blocks of the self-assembled structure are made through the reaction of gold ions and phenylalanine, the oxidized products and their effect of sensing features are explored.

Does exercise beneficially affect sex hormones when added to hypo-caloric diets in adults with overweight or obesity? A systematic review and meta-analysis of controlled clinical trials.

OBJECTIVE: There is no consensus of opinion if exercise beneficially affects sex hormones if added to weight-loss diets. The purpose of this study was to perform a systematic review and meta-analysis of controlled clinical trials to evaluate the effect of adding exercise to a hypo-caloric diet during a weight-loss program, on serum testosterone, estradiol, and sex hormone-binding globulin (SHBG) in adults with overweight/obesity. DESIGN: Systematic review and meta-analysis of the literature. METHODS: Online databases including PubMed/MEDLINE, EMBASE, Scopus, ISI Web of Science, and Google Scholar were searched up to April 2021. A random-effects model was applied to compare mean changes in sex hormones and SHBG between participants undergoing a hypo-caloric diet with or without exercise. RESULTS: In total, 9 eligible clinical trials with 462 participants were included. Out of these, seven, three, and four studies illustrated changes in testosterone, estradiol, and SHBG, respectively. The meta-analysis revealed that exercise had no significant effect on circulating testosterone (WMD = -0.03 nmol/L, 95% CI: -0.11, 0.06, P = 0.51), estradiol (WMD = -0.46 pg/mL, 95% CI: -1.57, 0.65, P = 0.42), and SHBG (WMD = 0.54 nmol/L, 95% CI: -2.63, 3.71, P = 0.74) when added to low-calorie diets. CONCLUSION: The addition of exercise to a hypo-caloric diet provided no additional improvement in sex hormone profiles. Further, well-designed randomized controlled trials with longer follow-up periods in both sexes are recommended to confirm and expand the current results.

Does exercise affect bone mineral density and content when added to a calorie-restricted diet? A systematic review and meta-analysis of controlled clinical trials.

The effects of exercise in conjunction with weight-loss diets on bone health are mixed. Our objective was to systematically review and meta-analyze controlled clinical trials in adults investigating the addition of exercise to a weight-loss diet compared with a calorie-matched weight-loss diet without exercise on bone measures. Online databases including PubMed/MEDLINE, EMBASE, ISI (Web of Science), Scopus, and Google Scholar were searched up to April 2021 with no restriction. A random effects model was used to calculate the overall estimates. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Fourteen eligible controlled clinical trials were included in the systematic review. The meta-analysis revealed that, compared to weight-loss diets alone, the addition of exercise did not improve total body bone mineral density (BMD) [weighted mean difference (WMD) = 0.002 g/cm2, P = 0.62, n = 8], lumbar BMD (WMD = 0.007 g/cm2, P = 0.44, n = 9), total hip BMD (WMD = 0.015 g/cm2, P = 0.14, n = 4) and total bone mineral content (BMC) (WMD = - 11.97 g, P = 0.29, n = 7). Subgroup analysis revealed that resistance exercise in conjunction with hypocaloric diets positively affects total BMD compared to an energy restrictive diet alone (WMD = 0.01 g/cm2, P = 0.003, n = 3). Overall, it appears that only resistance exercise beneficially affects total BMD during a calorie-restricted diet in adults. Further well-controlled and long-term clinical trials are still needed to confirm these results. PROSPERO registration number: CRD42020173434.

The effects of exercise and low-calorie diets compared with low-calorie diets alone on health: a protocol for systematic reviews and meta-analyses of controlled clinical trials.

BACKGROUND: Exercise and weight loss diets are two independent non-pharmaceutical strategies used to improve several aspects of body composition and health. We plan to systematically review controlled clinical trials investigating weight loss diets alone compared to weight loss diets in conjunction with exercise on energy intake, body weight, body composition, cardiometabolic risk factors, sex hormones, and mental health. METHODS AND ANALYSIS: PubMed/MEDLINE, EMBASE, ISI (Web of Science), Scopus, and Google Scholar will be searched to retrieve potential controlled clinical trials investigating the effects of exercise in conjunction with weight loss diets compared with weight loss diets alone on energy intake, body weight and composition (fat mass, fat-free mass), anthropometrics (waist circumference), cardiometabolic markers, sex hormones [testosterone, estradiol, and sex hormone binding globulin (SHBG)], liver and kidney enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), uric acid, blood urea nitrogen (BUN), glomerular filtration rate (GFR), quality of life, and depression in adults. The weighted mean difference (WMD) and its corresponding 95% confidence intervals (CIs) will be derived using random effects model. Several subgroup analyses based on follow-up duration, the health status of the participants, the diet used for weight loss, the exercise protocol, participants' sex, and other possible variables will be conducted to explore possible sources of heterogeneity. Publication bias will be explored by inspecting funnel plots and by conducting asymmetry tests. Overall quality of the evidence will be assessed by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. DISCUSSION: We envisage that this systematic review and meta-analysis will provide valuable information regarding the effectiveness of adding exercise to weight loss diets. No primary data is going to be collected; therefore, ethical approval is not required. The resulting manuscripts will be disseminated in peer-reviewed journals and at international and national conferences. SYSTEMATIC REVIEW REGISTRATION: The study protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO, Registration ID: CRD42020173434 ).

Ternary Nanocomplexes of Metallic Nanoclusters and Recombinant Peptides for Fluorescence Imaging and Enhanced Gene Delivery.

The efficient carrier design for transferring therapeutic genes into target cells as well as tracking the delivered agents has attracted lots of attention in the field of DNA-based therapeutics. Here, we demonstrate this concept by a fast and facilitated method using BSA gold nanocluster (BSA AuNcs) conjugated with chimeric peptide with ability of DNA binding/packaging, endosome disruption and cell nuclear localization. An extensive characterization of photoluminescence properties, electrophoresis mobility and size distribution of the nanocarrier demonstrating the stable complexes composed of plasmid DNA, chimeric peptide and BSA AuNcs were successfully formed through electrostatic interactions. In the hybrid complexes, chimeric peptide could effectively decrease the cytotoxicity of AuNcs as well as enhance internalization of plasmid harboring firefly luciferase gene into HEK 293 T. The designed nanocarrier could be a promising vector in gene delivery systems for improved theranostics applications.

Diphenylalanin nanofibers-inspired synthesis of fluorescent gold nanoclusters for screening of anti-amyloid drugs.

Protein misfolding and aggregation into amyloid structures is linked with a number of pathophysiological disorders. In the past decade, significant progresses have been made in the drug discovery strategies against toxic aggregates. Although lack of specificity and high sensitivity for in vitro screening system still seen. Here we demonstrate a new targeting probe based on FF diphenylalanine peptide -protected gold nanoclusters (FF AuNCs). Diphenylalanine peptide has previously been shown to self-assemble into well-ordered fiber like the fibers that are observed in amyloid aggregates. We used of the self-assembly properties along with the ability of FF dipeptide in reduction of gold ions for synthesis of novel Au nanoclusters. We used FF AuNCs for monitoring of effectiveness of anti-amyloid drugs. Fluorescence was considerably diminished when drugs at different concentrations added, due to destruction of the amyloid fibers. Furthermore, the analysis of several components demonstrates significant selectivity against the amyloid disrupting molecules. Prepared FF AuNCs will gain possible strategy for in vitro screening of amyloid disrupting molecules.

Knocking down of the DHFR-TS gene in Toxoplasma gondii using siRNA and assessing the subsequences on toxoplasmosis in mice.

Toxoplasma gondii (T. gondii), an obligatory intracellular parasite, is the etiologic agent of toxoplasmosis. Dihydrofolate reductase-thymidylate synthase (DHFR-TS) is one of the most important enzymes in toxoplasma folic acid cycle. Due to the emergence of resistance in RH strain of T. gondii against pyrimethamine that acts via DHFR-TS inhibition and also the crucial role of small interference RNA (siRNA) technology in gene silencing, we aimed to use siRNA to knock down DHFR-TS gene expression in T. gondii as a therapeutic target against toxoplasmosis in a mouse model. Based on the DHFR-TS gene sequence, siRNA was designed. The siRNAs were transfected into the parasites by electroporation. Total RNA was extracted using RNX-Plus kit. The viability of parasite was assessed by methylthiazole tetrazolium (MTT). The survival time of mice challenged with siRNA-treated T.gondii were compared to the control group infected with the same amount of wild-type tachyzoites. The viability of siRNA-embedded parasites was 70.7% (29.3% decreased) compared to the wild-type parasite as control (P = 0.0001). The transcription level of siRNA-transfected parasites was reduced to 17.4% (82.6% inhibition) (P = 0.016). The in vivo assessment showed that the mean survival time of the mice inoculated with modified parasites was increased about 2 days after the death of all mice in the control group. The designed siRNAs in the current study were able to silence the DHFR-TS gene efficiently. This silencing led to a decrease in viability of the parasites and an increase in the survival time of the parasites-treated mice.

Diphenylalanine peptide nanotubes self-assembled on functionalized metal surfaces for potential application in drug-eluting stent.

This study focuses on the potential of diphenylalanine self-assembled peptide nanotubes (FF Nts) for delivery of flufenamic acid (FA) from metal implants. Self-assembly of FF Nts was studied in solution and on surfaces of glass, silicone and gold substrates. FA was loaded inside the shell of FF Nts and subsequently FF/FA Nts were attached to gold surfaces. The substrate were characterized by Field Emission Scanning Electron Microscopy (FESEM), fluorescence microscopy, confocal microscopy, and UV-vis spectroscopy. Release of FA from FF Nts were investigated by immersing coated metal substrates in phosphate-buffered saline for 12 days. Self-assembly of FF in water and solvent resulted in formation of nanotubes, which efficiently loaded 98% of FA with concentration of 20 µg/mL. FESEM images confirmed successful attachment of FF/FA Nts to functionalized gold substrates. In vitro release studies indicated using FF Nts has prolonged the release rate of FA for several days. Biocompatibility studied confirmed more than 50% of the cells were alive in concentration of 250-1000 µg/mL of FF Nts thus suggesting the potential of peptide based self-assemble nanostructures as an alternate system for polymer coating in drugs eluting stents. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2280-2290, 2016.