Association of maternal exposure to endocrine disruptor chemicals with cardio-metabolic risk factors in children during childhood: a systematic review and meta-analysis of cohort studies.

BACKGROUND: In the present systematic review and meta-analysis, the association of maternal exposure to the endocrine disrupting chemicals (EDCs) with cardio-metabolic risk factors in children during childhood for the first time. METHOD: The PubMed, Scopus, EMBASE, and Web of Science databases were systematically searched, up to Feb 2023. In total 30 cohort studies had our inclusion criteria. A random-effects model was used for the variables that had considerable heterogeneity between studies. The Newcastle-Ottawa Scale (NOS) tool was used to classify the quality score of studies. All statistical analyses were conducted using Stata 14 and P-value < 0.05 considered as a significant level. RESULTS: In the meta-analysis, maternal exposure to the EDCs was weakly associated with higher SBP (Fisher_Z: 0.06, CI: 0.04, 0.08), BMI (Fisher_Z: 0.07, CI: 0.06, 0.08), and WC (Fisher_Z: 0.06, CI: 0.03, 0.08) z-scores in children. A significant linear association was found between maternal exposure to the bisphenol-A and pesticides with BMI and WC z-score in children (p < 0.001). Subgroup analysis showed significant linear association of BPA and pesticides, in the urine samples of mothers at the first trimester of pregnancy, with BMI and WC z-score in children from 2-8 years (p < 0.05). CONCLUSION: Prenatal exposure to the EDCs in the uterine period could increase the risk of obesity in children. Maternal exposure to bisphenol-A and pesticides showed the strongest association with the obesity, especially visceral form, in the next generation.

Association between dietary phytochemical index and risk of benign prostatic hyperplasia: a case-control study.

BACKGROUND: Dietary intake of phytochemicals has been associated with a reduced risk of chronic diseases, but research on their relationship with benign prostatic hyperplasia (BPH) is limited. This case-control study aimed to investigate the association between a Dietary Phytochemical Index (DPI) and BPH risk in a Middle-Eastern population. METHODS: The study recruited 112 BPH patients and 112 age-matched healthy controls (40-75 years) from Al-Zahra Hospital Clinic in Isfahan, Iran between 2021 and 2022. Dietary intake was assessed using a validated food-frequency questionnaire, and DPI was calculated as the ratio of energy intake from phytochemical-rich foods to total daily energy intake. Logistic regression analysis was performed, adjusting for potential confounders. RESULTS: In the crude model, participants in the highest DPI tertile had a 70% lower odds of BPH compared to those in the lowest tertile (OR:0.3, 95% CI 0.15-0.61, P-trend = 0.001). After adjusting for confounders, this inverse association remained significant (OR:0.23, 95% CI 0.15-0.63, P-trend = 0.001). Participants with higher DPI consumed more whole grains (p = 0.02), nuts (p < 0.001), legumes (p = 0.02), fruits (p < 0.001), vegetables (p < 0.001), olives and oilve products (p = 0.02), and tomato and its products (p < 0.001) in their diet compared to the lowest tertile. However, red meat (p = 0.03) and refined grains (p < 0.001) were consumed in higher amounts in the lowest tertile compared to the highest DPI tertile. CONCLUSIONS: This study demonstrates a protective association between DPI and BPH risk in the Middle-Eastern population. Encouraging higher intake of phytochemical-rich foods may help reduce the risk of BPH, highlighting the relevance of nutritional science in promoting prostate health.

Relationship between dietary glycemic index and glycemic load and sperm-quality parameters in Iranian men: a cross-sectional study.

BACKGROUND: Infertility is a major clinical problem with psychological, financial and medical costs. Male infertility has recently been linked to 50% of childless couples. It is worth mentioning that diet and its components can be manipulated and applied in counseling meetings of infertile men as a modifiable factor. The goal of this study was to determine the correlation of dietary glycemic index (GI) and glycemic load (GL) with sperm-quality parameters in Iranian men. MATERIALS AND METHODS: In this cross-sectional study which was carried from Aug to Nov 2023, after excluding smokers, 322 men who were attending the IVF clinic of Ayatollah Mousavi Hospital for seminal analysis were enrolled. Dietary intake was completed by an expert dietitian through face-to-face interviews with a validated 168-item food frequency questionnaire (FFQ). In the present study, sperm-quality parameters, including motility, concentration, normal morphology, vitality, DNA fragmentation index (DFI), and chromatin maturation of sperm, were analyzed. The relationship between dietary GI and CL and these parameters was assessed. RESULTS: Adjusting for the baseline variables, dietary GI and GL showed positive and negative associations with sperm progressive motility, respectively (p = 0.01 and p < 0.001). Higher dietary GI was associated with lower (p = 0.03); however, a higher dietary GL was associated with higher immotile sperm (p < 0.001). A higher dietary GI was associated with a 77% higher sperm count (p = 0.003). In contrast, higher dietary GL was associated with a lower count (p < 0.001). Higher dietary GI and GL were associated with higher and lower percentages of sperm with normal morphology by 70% and 40%, respectively (p < 0.001 in both). A higher dietary GL was associated with an increase in sperm vitality and DFI of 33% and 53%, respectively (p < 0.001). Higher dietary GI showed a significant negative effect on sperm DFI (p = 0.009). Dietary GI and GL showed significant positive and negative effects on SCMA, respectively (p = 0.002 and p < 0.001). CONCLUSION: A diet with a higher GI showed beneficial effects on more parameters of sperm; however, higher dietary GL showed deleterious effects, except sperm vitality and SCMA. More studies are needed to obtain a concise result.

A low-carb diet increases fecal short-chain fatty acids in feces of obese women following a weight-loss program: randomized feeding trial.

To compare fecal level of short-chain fatty acid (SCFA) and some serum inflammatory markers between the low-carbohydrate (LCD) and the habitual (HD) diet, subjects were enrolled from our previous study on the effect of LCD vs. HD on gut microbiota in obese women following an energy-restricted diet. Serum interleukin-6 (IL-6) significantly increased in the HD group (p < 0.001). Adjusted for the baseline parameters, fecal level of butyric, propionic, and acetic acid were significantly different between the LCD and HD groups (p < 0.001, p = 0.02, and p < 0.001, respectively). Increase in serum insulin level correlated with decrease in fecal propionic acid by 5.3-folds (95% CI = - 2.7, - 0.15, p = 0.04). Increase in serum high sensitive C-reactive protein (hs-CRP) correlated with decrease in the percentage of fecal butyric acid by 25% (p = 0.04). Serum fasting blood sugar (FBS) and insulin showed a significant effect on fecal acetic acid (p = 0.009 and p = 0.01, respectively). Elevated serum FBS and insulin correlated with increase in fecal acetic acid by 2.8 and 8.9-folds (95%CI = 0.34, 1.9 and 1.2, 9.2), respectively. The LCD increased fecal SCFAs and a significant correlation was seen between serum IL-6 and fecal propionic acid level. More studies are needed to reach a concise correlation. Trial registration number: The trial was registered in Iranian ClinicalTrials.gov IRCT20200929048876N3.

Correlation of Dietary Macro- and Micro-Mineral Intake with Seminal Plasma Quality/Quantity and Oxidant/Antioxidant Status in Infertile Compared to the Normal Men: a Case-Control Study.

Male infertility is a global public health issue, but studies on the correlation between the dietary components and sperm quality showed inconclusive results due to the heterogeneous population with different dietary habits and environmental stimuli. Herein, the correlation of dietary macro- and micro-mineral intake was evaluated with quality/quantity and oxidant/antioxidant status of seminal fluid in infertile compared to the healthy men. One hundred twenty men attending to the infertility clinic of Ayatollah Mousavi Hospital in Zanjan City were enrolled. Seminal fluid was extracted, and groups were categorized into the infertile (non-standard) and normal (standard) groups based on the WHO, 2020 criteria. Food frequency questionnaire was completed. Seminal malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured by ELISA kit based on the manufacture's instruction. An independent sample t-test was used to determine differences between the two groups, and linear regression model was used to determine the effect of each dietary macro/micro mineral intake on these parameters. Adjusting for all parameters, dietary selenium increased 3.7-folds the seminal TAC level (p=0.04) and decreased sperm with non-progressive motility by 2.4-folds (p=0.04). Higher manganese intake increased the sperm count by 7.8-folds (p=0.005). Dietary copper decreased sperm vitality and increased sperm with slow motility (OR= -1.7, 95% CI= -59.8, -9.9; p=0.007). Dietary zinc (OR=1.24, p=0.01) and iron (OR=1.5, p=0.02) showed a positive effect on sperm vitality. None of macro and micro minerals showed a significant effect on the seminal MDA level. Daily intake of adequate amounts of micro and macro minerals improves sperm quality and increases the antioxidant capacity of the seminal fluid; however, copper showed a negative correlation that must be evaluated in future studies.

Association of Leptin and Retinol Binding Protein 4 with the Risk of Gestational Diabetes: A Systematic Review and Meta-Analysis of Observational Studies.

The positive correlation between serum levels of retinol binding protein 4 (RBP4) and gestational diabetes (GDM) has been proven in the previous meta-analysis on case-control studies. However, its association with serum levels of leptin is not studied in any meta-analysis. Therefore, we performed an updated systematic review of observational studies evaluating the association between serum RBP4 and leptin with the risk of GDM. A systematic search was performed on four databases, including PubMed, Scopus, Web of Science, and Google Scholar, up to March 2021. After screening and deleting duplicates, nine articles met our inclusion criteria. Studies had case-control and cohort design, and included 5074 participants with a mean age range between 18 and 32.65 years (2359 participants for RBP4 and 2715 participants for leptin). Interestingly, this meta-analysis revealed higher levels of RBP4 (OR=2.04; 95% CI: 1.37, 3.04) and leptin (OR=2.32; 95% CI: 1.39, 3.87) are significantly associated with the increased risk of overall GDM. The subgroup analysis approved the results based on the study design, trimester of pregnancy and serum/plasms to investigate the source of heterogeneity. The present meta-analysis determines serum leptin and RBP4 levels as predictors of GDM occurrence. However, studies included in this meta-analysis showed significant heterogeneity.

Rescuing fertility during COVID-19 infection: exploring potential pharmacological and natural therapeutic approaches for comorbidity, by focusing on NLRP3 inflammasome mechanism.

The respiratory system was primarily considered the only organ affected by Coronavirus disease 2019 (COVID-19). As the pandemic continues, there is an increasing concern from the scientific community about the future effects of the virus on male and female reproductive organs, infertility, and, most significantly, its impact on the future generation. The general presumption is that if the primary clinical symptoms of COVID-19 are not controlled, we will face several challenges, including compromised infertility, infection-exposed cryopreserved germ cells or embryos, and health complications in future generations, likely connected to the COVID-19 infections of parents and ancestors. In this review article, we dedicatedly studied severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virology, its receptors, and the effect of the virus to induce the activation of inflammasome as the main arm of the innate immune response. Among inflammasomes, nucleotide oligomerization domain-like receptor protein, pyrin domain containing 3 (NLRP3) inflammasome pathway activation is partly responsible for the inflicted damages in both COVID-19 infection and some reproductive disorders, so the main focus of the discussion is on NLRP3 inflammasome in the pathogenesis of COVID-19 infection alongside in the reproductive biology. In addition, the potential effects of the virus on male and female gonad functions were discussed, and we further explored the potential natural and pharmacological therapeutic approaches for comorbidity via NLRP3 inflammasome neutralization to develop a hypothesis for averting the long-term repercussions of COVID-19. Since activation of the NLRP3 inflammasome pathway contributes to the damage caused by COVID-19 infection and some reproductive disorders, NLRP3 inflammasome inhibitors have a great potential to be considered candidates for alleviating the pathological effects of the COVID-19 infection on the germ cells and reproductive tissues. This would impede the subsequent massive wave of infertility that may threaten the patients.

Beneficial effects of Ginkgo biloba leaf extract on inflammatory markers: A systematic review and meta-analysis of the clinical trials.

The beneficial effects of Ginkgo biloba on cardio-metabolic markers have been reported. However, its effect on inflammation is not assessed in any meta-analysis. We performed a systematic review of randomized controlled trials evaluating the effects of Ginkgo biloba leaf extract (GBLE) on serum C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels. A systematic search was performed on four databases, including PubMed, Scopus, Web of Science, and Google Scholar, up to October 2021. After screening, 17 trials met our inclusion criteria. Trials were of 1-24 weeks of duration and included 1,104 participants. In the meta-analysis, the weighted mean differences (WMD) in change for serum CRP were -1.5 mg/L (95% CI: -2.16, -0.85, p < 0.001). Moreover, WMD for serum IL-6 and TNF-α were in favor of the GBLE compared to the placebo [(-16.86 pg/mL, 95% CI: -19.38, -14.34, p < 0.001); and (-4.19 pg/mL, 95%CI: -5.14, -3.23, p < 0.001), respectively]. Subgroup analysis showed that GBLE has a beneficial effect on serum CRP at the baseline levels≥3 mg/L and doses<500 mg/day. This meta-analysis showed that the GBLE could reduce serum inflammatory markers. Therefore, this medicinal herb might be a possible strategy for inflammation control.

Effects of a Mediterranean Diet Compared with the Low-Fat Diet on Patients with Knee Osteoarthritis: A Randomized Feeding Trial.

Objectives: Knee osteoarthritis is a common global problem, especially in overweight and obese people. It is not clear that weight loss is a factor for pain reduction in these patients or dietary components are important. Herein, we compared the effects of Mediterranean (MD) and low-fat diet on pain, stiffness, and physical function in patients with knee osteoarthritis. Subjects: /. Methods: In this randomized feeding trial, 129 patients with knee osteoarthritis were enrolled. Participants were randomly allocated to the MD (n = 43), low-fat diet (n = 43), and control group (regular diet) (n = 43) for 12 weeks by the blocked randomization method. Total Western Ontario and McMaster Universities Arthritis Index (WOMAC) score and its subscales and anthropometric indices were compared among the groups at the baseline and end of the study. Results: Weight and waist circumference reduction was significantly higher in the MD and low-fat diet groups compared with the regular group (p < 0.001 and p < 0.001, respectively), but there was no significant difference between the MD and low-fat diet groups (p = 0.2). Pain was significantly decreased in the Mediterranean-style compared with the low-fat (p = 0.04) and regular (p = 0.002) diet groups. Physical function was significantly improved in the MD compared with the regular diet group (p = 0.01), but had no significant difference with the low-fat one. Stiffness had no significant difference among the dietary groups. Conclusions: Pain severity was reduced in the MD group, but no significant change was reported in patients on low-fat and regular diets. It seems that dietary components in the MD, regardless of weight loss effect, are effective on pain reduction in patients with KOA. The present study was registered in the IRCT under the code of IRCT20200929048876N1.

Dietary Pattern or Weight Loss: Which One Is More Important to Reduce Disease Activity Score in Patients with Rheumatoid Arthritis? A Randomized Feeding Trial.

Objectives: Herein, disease activity score 28 (DAS 28) was compared between patients with rheumatoid arthritis (RA) receiving the Mediterranean dietary pattern (MD) and low-fat diet. Subjects/Methods. Overweight and obese RA patients aged 15-75 y participated in this randomized feeding trial. Participants were randomized to MD (n = 51) and low-fat high-carbohydrate diet (n = 53) for 12 weeks. The control group followed their regular diet (n = 50). Participants completed the form of tender and swollen joint counts before the study enrollment and after 12 weeks to compute DAS 28. Results: Weight loss was not statistically significant between the MD and LF-HC groups. DAS 28 significantly decreased in MD compared to the LF-HC group (p=0.02) and controls (p=0.001). Adjusting for the baseline variables, MD reduced DAS 28 by 76% (95% CI = -0.45, -0.2; p=0.03) after 12 weeks of intervention. The baseline serum ESR level showed 99.8% effect on DAS 28 score at the end (95% CI = 0.014, 0.035; p < 0.001). Conclusions: The MD showed beneficial effects on DAS 28 compared to the LF-HC diet in patients with RA, regardless of weight loss. It is a better dietary choice for pain reduction in patients with RA. The trial is registered at Iranian Registry of Clinical Trials (IRCT20200929048876N2).

Effect of Atkins versus a low-fat diet on gut microbiota, and cardiometabolic markers in obese women following an energy-restricted diet: Randomized, crossover trial.

BACKGROUND AND AIMS: There is controversy about effects of the Atkins diet on cardiometabolic markers in previous studies. No study compared effects of Atkins versus a low-fat diet on gut microbiota in obese women during a weight-loss program up to date. METHODS AND RESULTS: A 6-week, randomized, crossover trial was conducted. Twenty-four healthy women with obesity (BMI≥30 kg/m2) were randomly assigned to receive the Atkins (55%, 25%, and 20% of total daily calories from fat, protein, and carbohydrates), or low-fat (20%, 15%, and 65% of total daily calories from fat, protein, and carbohydrates) diets while following a weight-loss program. Vegetable oils were used as the main source of dietary fat. Dietary groups were switched after two weeks of washout period with a weight maintenance low-fat diet. The effects of the two diets did not differ for the most endpoints. However, Gut Actinobacteria residency and serum total antioxidant capacity significantly increased in the Akins diet group compared with the low-fat one (p = 0.02 and p = 0.04). Adjusting for all parameters, gut Actinobacteria residency 1.48- and 2.5-folds decreased the serum LDL.C/HDL.C ratio and non-HDL.C levels (95%CI: 3.1, -0.22; p = 0.03 and -0.07, -0.002; p = 0.04), respectively. Decrease in gut Proteobacteria residency showed a significant reduction in serum total oxidant status (95%CI: 7.4, -0.07; p = 0.04). CONCLUSIONS: The Atkins diet, based on vegetable oils, alters gut microbiota composition, atherogenic and antioxidant parameters. REGISTRATION NUMBER FOR CLINICAL TRIAL: IRCT20200929048876N3.

Design of a new light curable starch-based hydrogel drug delivery system to improve the release rate of quercetin as a poorly water-soluble drug.

In spite of quercetin advantages, its utilization as a cancer drug is confined due to its very low water solubility and bioavailability. Accordingly, we prepared a biodegradable starch-based hydrogel, using a new technique to control and improve quercetin release and bioavailability. For this purpose, the molecular structure of starch was modified by polyethylene glycol/acrylate and Fe3O4 nanoparticles were used to enhance mechanical properties of hydrogel. In order to prepare the final hydrogel drug carrier, the modified starch was directly mixed with quercetin and other additives in different ratios and cured under blue light. Synthesis confirmation and structural properties of the modified starch, silanized and pure Fe3O4 nanoparticles and final hydrogel were studied using 1H NMR, FT-IR, SEM, XRD, TGA, VSM and DLS analyses. We improved in vitro drug release to 56.62%, while the maximum release of quercetin from the starch-based hydrogel in our previous study was only 27% (Doosti et al., 2019).

Effects of Ramadan and Non-ramadan Intermittent Fasting on Gut Microbiome.

Background: In recent years, intermittent fasting (IF) has gained popularity in the health and wellness in the world. There are numerous types of IF, all of which involve fasting periods that last longer than an overnight fast and involve limited meal time-windows, with or without calorie restriction. The objective of this review is to summarize the current evidence for the effects of Ramadan and non-Ramadan IF on gut microbiome. Methods: We explored PubMed, Scopus, Web of Science, and Google Scholar according to the PRISMA criteria (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). Animal and human studies were screened and reviewed separately by two researchers. Results: Twenty-eight studies were selected after screening. Some of the studies were performed on animal models and some on humans. The results of these studies indicate a significant shift in the gut microbiota, especially an increase in the abundance of Lactobacillus and Bifidobacteria following fasting diets. The results of some studies also showed an increase in the bacterial diversity, decrease inflammation and increased production of some metabolites such as short-chain fatty acids (SCFAs) in individuals or samples under fasting diets. Moreover, Ramadan fasting, as a kind of IF, improves health parameters through positive effects on some bacterial strains such as Akkermansia muciniphila and Bacteroide. However, some studies have reported adverse effects of fasting diets on the structure of the microbiome. Conclusion: In general, most studies have seen favorable results following adherence from the fasting diets on the intestinal microbiome. However, because more studies have been done on animal models, more human studies are needed to prove the results.

Deletion allele of Apo B gene is associated with higher inflammation, oxidative stress and dyslipidemia in obese type 2 diabetic patients: an analytical cross-sectional study.

BACKGROUND: We decided to compare some inflammatory, and oxidative stress markers, as well as lipid profiles between the obese and non-obese patients with type 2 diabetes considering ApoB gene polymorphism. METHODS: one-hundred sixty two patients with type 2 diabetes were included in this study. ApoB genotyping was conducted by the polymerase chain reaction. Serum interleukin-(IL-18), pentraxin-3 (PTX-3), and high sensitive- C reactive protein (hs-CRP) was measured as the inflammatory markers. Moreover, copper-zinc superoxide dismutase (Cu/Zn-SOD), total antioxidant capacity (TAC) and 8-isoprostane F2α were analyzed for oxidative stress assessment. Anthropometric indices and lipid profiles were measured. RESULTS: Adjusted for confounders, serum hs-CRP (p = 0.04), LDL-C (p = 0.01), LDL-C/HDL-C (p = 0.04), and TG (p = 0.02) were significantly lower at the Homozygous Insertion (Ins)/Ins vs. deletion (Del) allele carriers in the obese patients. Serum TAC was significantly lower at the obese Del allele carriers than Ins/Ins Homozygous (p = 0.03). Serum hs-CRP (p = 0.006), and 8-IsoprostanF2α (P = 0.04) were significantly higher in the obese Del allele carriers than non-obese. Serum Cu/Zn-SOD was significantly higher in the non-obese Del allele carriers than obese (p = 0.04). CONCLUSION: Inflammation, dyslipidemia, and oxidative stress are higher in the Obese Del allele carriers with type 2 diabetes which prone them to other chronic disorders.

Co-Administration of Vitamin E and Atorvastatin Improves Insulin Sensitivity and Peroxisome Proliferator-Activated Receptor-γ Expression in Type 2 Diabetic Patients: A Randomized Double-Blind Clinical Trial.

Background: Negative effects of statins on glucose metabolism have been reported. The present study aimed to investigate the effects of co-administration of vitamin E and atorvastatin on glycemic control in hyperlipidemic patients with type 2 diabetes mellitus (T2DM). Methods: A randomized double-blind clinical trial was conducted at Vali-e-Asr Teaching Hospital (Zanjan, Iran) from July 2017 to March 2018. A total of 30 T2DM female patients were allocated to two groups, namely atorvastatin with placebo (n=15) and atorvastatin with vitamin E (n=15). The patients received daily 20 mg atorvastatin and 400 IU vitamin E or placebo for 12 weeks. Anthropometric and biochemical measures were recorded pre- and post-intervention. Peroxisome proliferator-activated receptor-γ (PPAR-γ) expression was measured in peripheral blood mononuclear cells (PBMCs). Independent sample t test and paired t test were used to analyze between- and within-group variables, respectively. The analysis of covariance (ANCOVA) was used to adjust the effect of baseline variables on the outcomes. P<0.05 was considered statistically significant. Results: After baseline adjustment, there was a significant improvement in homeostatic model assessment for insulin resistance (HOMA-IR) (P=0.04) and serum insulin (P<0.001) in the atorvastatin with vitamin E group compared to the atorvastatin with the placebo group. In addition, co-administration of vitamin E with atorvastatin significantly upregulated PPAR-γ expression (OR=5.4, P=0.04) in the PBMCs of T2DM patients. Conclusion: Co-administration of vitamin E and atorvastatin reduced insulin resistance and improved PPAR-γ mRNA expression. Further studies are required to substantiate our findings. Trial registration number: IRCT 20170918036256N.

Synthesis of a green bigel using cottonseed oil/cannabis oil/alginate/ferula gum for quercetin release: Synergistic effects for treating infertility in rats.

Although therapeutic effect of quercetin (Quer) was reported on non-alcoholic fatty liver disease (NAFLD), destructive effects have been shown on male fertility due to its pro-oxidative properties. On the other hand, NAFLD impairs germ cells to produce sperm and leads to male infertility. Herein, a biocompatible and green bigel was designed for Quer delivery to prevent infertility induced by NAFLD as the increasing complications. Bigels were prepared using cottonseed oil/cannabis oil/alginate/ferula gum and optimized by the mixture design method. NAFLD was induced by 58% of dietary calorie as lard and 42 g/l fructose for 16 weeks in Sprague-Dawley rats. So on animals received 2 mg/kg Quer loaded on bigels, free bigels, or free Quer for 45 days as daily gavage. Semen was analyzed, followed by the assessment of DNA integrity. Count, motility, and normal morphology reached the healthy control group at the bigel-Quer-treated one. Moreover, all of these parameters were significantly higher in the bigel-Quer group than the Quer and bigel, alone. The percent of sperms with head and tail abnormality decreased considerably in the bigel-Quer group compared with the Quer, free bigel, and NAFLD groups. Serum testosterone levels significantly increased and reached the healthy control group in the bigel-Quer group. DNA fragmentation of sperm significantly decreased in the bigel-Quer group (p < 0.05). The bigel showed synergistic effects with Quer for treating infertility in rats with NAFLD.

Daily parenteral selenium therapy in critically ill patients: An updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Patients hospitalized at the intensive care unit (ICU) are more prone to oxidative stress. Antioxidants such as selenium (Se) may have beneficial effects on outcomes in these patients. Studies and systematic reviews in this field have inconclusive results. METHODS: An updated systematic search was done to find clinical trials published in PubMed, Cochrane's library, ISI web of Science, Scopus, and Ovid databases from January 1980 up to April 2020, to assess the effects of daily Se supplementation on patient's survival, hospital and ICU stay, duration of mechanical ventilation, infection, acute renal failure (ARF) occurrence and serum creatinine levels. RESULTS: From 1394 papers found in the first step of the search, after deleting duplicate findings, 24 studies were included in this meta-analysis. Results of the pooled random-effect size analysis of 24 trials showed no remarkable effect of daily parenteral Se administration on patient's hospital and ICU stay, duration of mechanical ventilation, infectious complications, ARF, survival and serum creatinine levels (p > 0.05). The subgroup analysis showed that daily parenteral Se administration (in doses higher than 1000 µg/d) increased the length of ICU stay by 4.48-folds (95%CI: -0.5, 9.46, p = 0.07). Parenteral Se supplementation at the first and following dose of ≤1000 µg reduced the number of ARF at the hospitalized patients by 76% and 45%, respectively (p = 0.02, and p = 0.05). CONCLUSIONS: High doses of Se increases days of ICU stay, but low doses decreases the number of ARF occurrence in ICU patients. More trials are needed to assess its effect on ARF occurrence.

Effect of vitamin D supplementation on CREB-TrkB-BDNF pathway in the hippocampus of diabetic rats.

OBJECTIVES: Cyclic AMP (adenosine monophosphate) response element-binding protein (CREB) and Brain-derived neurotrophic factor (BDNF) are reported to broadly involve in learning capacity and memory. BDNF exerts its functions via tropomyosin receptor kinase B (TrkB). BDNF transcription is regulated by stimulating CREB phosphorylation. The CREB-TrkB-BDNF pathway is reported to be affected by diabetes, which may contribute to its cognitive deficits. This study was conducted to investigate the effect of vitamin D supplementation on the hippocampal fraction of this pathway in an animal model of type-1 diabetes mellitus (T1DM). MATERIALS AND METHODS: Thirty-six adult male Sprague-Dawley rats were randomly divided into 4 groups as follows: Group 1: normal healthy rats (n=8); group 2: normal healthy rats receiving sesame oil supplementation as placebo (n=8); Group 3: diabetic rats receiving sesame oil (n=10); and Group 4: diabetic rats treated with 4300 IU/kg/week vitamin D dissolved in sesame oil (n=10). Diabetes was induced by intraperitoneal (IP) injection of streptozotocin. Blood and hippocampal samples were acquired at the end of the experiment. RNA was extracted from the hippocampus, and real-time PCR (polymerase chain reaction) was performed for BDNF and TrkB gene expression. RESULTS: Administration of vitamin D (4300 IU/kg/week) in a T1DM animal model increased CREB phosphorylation in the hippocampus, but the serum and hippocampal BDNF levels and TrkB and BDNF gene expression did not change significantly. CONCLUSION: Vitamin D increased hippocampal CREB phosphorylation in a T1DM animal model. Our findings showed that vitamin D might be protective against central nervous system complications in diabetes. However, future studies are warranted.

Enhancing quercetin bioavailability by super paramagnetic starch-based hydrogel grafted with fumaric acid: An in vitro and in vivo study.

Application of Quercetin (Quer) as a natural flavonoid is confined because of limited solubility in water and stability in the body. Herein, we prepared a biodegradable super paramagnetic starch-based hydrogel grafted onto fumaric acid for increasing Quer bioavailability and controlling its release. The molecular structure of starch was modified by using fumaric acid to increase hydrophilicity of hydrogel, and iron oxide nanoparticles is used to strengthen its physical and mechanical properties. The structural, morphological and magnetic properties of the optimized hydrogel were characterized. Application of the synthesized hydrogel was assessed in the in vitro and in vivo studies. In vitro release curve was nicely fitted to the Higuchi model. Stability and bioavailability of Quer were significantly increased at the plasma and liver of rats which received 100 mg kg-1 Quer- loaded on synthetic hydrogel compared with 100 mg kg-1 free Quer (p < 0.05).

Reduction of Some Atherogenic Indices in Patients with Non-Alcoholic Fatty Liver by Vitamin D and Calcium Co-Supplementation: A Double Blind Randomized Controlled Clinical Trial.

The role of non-alcoholic fatty liver disease (NAFLD) as a potential independent cardiovascular disease (CVD) risk factor has recently gained considerable attention because CVD is the common cause of death in NAFLD patients. We aimed to estimate the effects of vitamin D supplementation alone or in combination with calcium on atherogenic indices, liver function tests, and grade of disease in patients with NAFLD. One-hundred twenty NAFLD patients were randomized in a double-blind, placebo-controlled clinical trial as follows: D (1000 IU vitamin D), CaD (500 mg as calcium carbonate plus 1000 IU vitamin D) or P (placebo), once daily with meals over 12 weeks. Adjusted for all the baseline measures, reduction in serum ALT, AST, LDL-C/HDL-C, TC/HDL-C, and non-HDL-C were significantly higher in the CaD compared with the P group (p < 0.001, p = 0.03, p < 0.001, p < 0.001, p < 0.001 and p < 0.001, respectively). Also, mean difference of serum ALT, LDL-C/HDL-C, TC/HDL-C, and TG/HDL-C were significantly higher in the CaD than D group (p < 0.001, p = 0.006, p < 0.001 and p = 0.03, respectively). Serum non-HDL-C was marginally decreased in the CaD compared with the D group (p = 0.06). With considering the BMI changes as covariate, reduction in the grade of fatty liver was significantly higher in the CaD and D groups than the P (p < 0.001). The present study suggests that supplemental calcium combined with vitamin D, but not vitamin D alone, may reduce serum atherogenic indices, liver function tests, and grade of disease in patients with NAFLD.