Quercetin may reduce the risk of developing the symptoms of COVID-19.

Objective: Recent evidence reported that some dietary compounds like quercetin and apigenin as the most well-known flavonoids with anti-inflammatory effects may inhibit SARS-CoV-2 main protease. The hypothesis of the promising effects and possible mechanisms of action of quercetin against COVID-19 were assessed in this article. Materials and Methods: Related papers on the inhibitory effects of quercetin against COVID-19 were collected using the following search strategy: "corona or coronavirus or COVID or COVID-19 or viral or virus" AND "nutrient or flavonoid or Quercetin". Results: The findings indicated that quercetin can be considered an effective agent against COVID-19 because of its SARS-CoV-2 main protease and RNA-dependent RNA polymerase inhibitory effects. In addition, quercetin may attenuate angiotensin-converting enzyme-2 (ACE-2) receptors leading to a reduction of SARS-CoV-2 ability to enter host cells. Moreover, the antiviral, anti-inflammatory, and immunomodulatory activities of quercetin have been frequently reported. Conclusion: Quercetin may be an effective agent for managing the complications of COVID-19. Further longitudinal human studies are warranted.

Are resting metabolic rate and clinical symptoms affected by variation of serum thyroid stimulating hormone levels within the normal range in healthy and women with hypothyroidism? A case-control study.

BACKGROUND: It is unclear whether variation in thyroid stimulating hormone (TSH) levels within the reference range affect energy expenditure and clinical symptoms and even within the normal range of TSH levels, resting energy expenditure may alter. The aim of the present study was to determine whether treated hypothyroid subjects and healthy subjects with a low-normal TSH range (0.3-2.3 mIU/L) have better clinical outcomes and increased energy expenditure than those with a high-normal TSH range (2.3-4.3 mIU/L). METHODS: This was a case-control study of 160 overweight/obese women with TSH levels across the reference range of 0.3-4.3 mU/l. Subjects were paired in four groups: healthy subjects with low-normal target TSH (n = 40), healthy subjects with high-normal target TSH (n = 40), subjects with treated hypothyroidism with low-normal target TSH (n = 40), and subjects with treated hypothyroidism with high-normal target TSH (n = 40). Resting energy expenditure (RMR), dietary intake, body composition, physical activity, and biochemical markers were assessed. RESULTS: Subjects with low-normal (≤2.3 mU/L) and high-normal (>2.3 mU/L) TSH levels did not differ in terms of RMR, serum T3 levels, and clinical symptoms except fatigue (P = 0.013). However, serum fT4 levels were found to be significantly different between the study groups (P = 0.002). Serum fT4 concentration was the highest in subjects with treated hypothyroidism with low-normal target TSH. CONCLUSION: Variation in serum TSH levels within the reference range did not significantly affect REE and clinical symptoms except fatigue in healthy and women with hypothyroidism.

Association of phase angle with sarcopenia and muscle function in patients with COPD: a case-control study.

BACKGROUND AND AIMS: The predictive value of phase angle for sarcopenia diagnosis has been discussed for years. The present investigation was conducted to determine the association between phase angle and sarcopenia in patients with COPD. METHODS: In this case-control study, 222 smoker men were divided into healthy and COPD groups. COPD was diagnosed by a pulmonologist through spirometry. Anthropometric indices, phase angle, muscle function, sarcopenia, and dietary intake were assessed. RESULTS: A significant inverse association was observed between phase angle and sarcopenia after adjustment for age and energy intake (OR: 0.31, 95% CI 0.18-0.52) and after adjustment for BMI (OR: 0.31, 95% CI 0.18-0.52). A significant decrease was detected in anthropometric indices and indicators of sarcopenia and muscle function in COPD cases compared to the healthy controls. CONCLUSIONS: Although further studies are suggested, phase angle might be considered an indicator of sarcopenia and muscle function in COPD patients.

A dose-response meta-analysis of randomized clinical trials investigating the effects of omega-3 supplementation on body weight in patients with cancer cachexia.

BACKGROUND: Cachexia is one of the side effects of cancer diseases that can be reduced weight, and lower overall survival. Weight loss has been associated with adverse outcomes in both cancer patients and patients with benign diseases. There is no definitive treatment for fully reverse cachexia. studies showed higher levels of inflammatory markers in patient with cachectic cancer. Therefore, this study aimed to investigate the dose-response effects of omega-3 as an anti-inflammatory supplement on body weight in patients with cancer cachexia. METHODS: Online databases including PubMed, Scopus, and Web of Science were systematically searched by relevant keywords up to January 2022. Random effect analysis was applied to perform meta-analysis. Subgroup analyses were performed to find heterogeneity sources. Quality assessment was conducted using Revised Cochrane Collaboration's tool II. Trim and fill analysis were also carried out in case of the presence of publication bias. The certainty in the evaluations was assessed by the GRADE approach. RESULTS: Omega-3 supplementation resulted in a significant increase of body weight in patients with cancer cachexia when the age of study participants was ≥67 years and the baseline weight of them was ≤60 kg (WMD = 0.99; 95 % CI: 0.06, 1.92 and WMD = 1.22; 95 % CI: 0.14, 2.30, respectively). Also, there was a non-significant linear relationship between the dosage of omega-3 supplementation and body weight in patients with cancer cachexia. CONCLUSION: Omega-3 supplementation may be a promising agent to increase body weight in patients with cancer cachexia. Also, a non-significant linear relationship between the dosage of omega-3 supplementation and body weight was found in these patients.

Effects of oleoylethanolamide supplementation on the expression of lipid metabolism-related genes and serum NRG4 levels in patients with non-alcoholic fatty liver disease: A randomized controlled trial.

BACKGROUND: This study investigated the effects of oleoylethanolamide (OEA) supplementation on the expression levels of SIRT1, AMPK, PGC-1α, PPAR-γ, CEBP-α and CEBP-ß genes and serum neuregulin 4 (NRG4) levels in patients with non-alcoholic fatty liver diseases (NAFLD). METHODS: Sixty obese patients with NAFLD were equally allocated into either OEA or placebo group for 12 weeks. The mRNA expression levels of genes were determined using the reverse transcription polymerase chain reaction (RT-PCR) technique. Serum NRG4 level was also assessed using an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: At the endpoint, mRNA expression levels of SIRT1(p = 0.001), PGC-1α (p = 0.011) and AMPK (p = 0.019) were significantly higher in the OEA group compared to placebo group. However, no significant differences were observed in the expression levels of PPAR-γ, CEBP-α and CEBP-ß between the two groups. Serum NRG4 levels significantly increased in the OEA group compared with the placebo group after controlling for confounders (p = 0.027). In the OEA group, significant relationships were found between percent of changes in the expression levels of the SIRT1, AMPK and PGC-1α as well as serum NRG4 level with percent of changes in some anthropometric measures. Moreover, in the intervention group, percent of changes in high-density lipoprotein cholesterol was positively correlated with percent of changes in the expression levels of the SIRT1 and AMPK. While, percent of changes in triglyceride was inversely correlated with percent of changes in the expression levels of SIRT1. CONCLUSION: OEA could beneficially affect expression levels of some lipid metabolism-related genes and serum NRG4 level. "REGISTERED UNDER IRANIAN REGISTRY OF CLINICAL TRIALS IDENTIFIER NO: IRCT20090609002017N32".

The Association between Total Protein, Animal Protein, and Animal Protein Sources with Risk of Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis of Cohort Studies.

We aimed to conduct this dose-dependent meta-analysis to examine the relation between total protein, animal protein, and its sources with inflammatory bowel disease (IBD). We searched databases, comprising PubMed/Medline, Web of Science (ISI), Embase, and Google Scholar, for the published studies up to 28 March 2023. Prospective cohort study designs that investigated associations between dietary intake of various animal protein sources and with risk of IBD in the general population were identified. Eleven prospective cohort studies with 4,302,554 participants and 8067 cases were considered eligible. Findings indicated that higher intake of dairy was significantly associated with a lower risk of IBD (relative risk [RR]: 0.81; 95% confidence interval [CI]: 0.72, 0.90), Crohn disease (RR: 0.69; 95% CI: 0.56, 0.86), and ulcerative colitis (RR: 0.84; 95% CI: 0.75, 0.94). There was no association between different sources of animal protein and the risk of IBD. The dose-response analysis suggested that each 100 g/d increment in dietary total meat consumption was associated with a 38% greater risk of IBD. Moreover, a positive linear association was found between total meat intake and risk of IBD (Pnonlinearity = 0.522, Pdose-response = 0.005). Overall, among the dietary sources of protein, the risk of IBD increased only with increasing total meat intake, and the consumption of protein from dairy products was found to be a protective factor against the IBD risk. This trial was registered at PROSPERO as CRD42023397719.

Effects of oleoylethanolamide supplementation on inflammatory biomarkers, oxidative stress and antioxidant parameters of obese patients with NAFLD on a calorie-restricted diet: A randomized controlled trial.

Background: Oxidative stress is considered a major factor in the pathophysiology of non-alcoholic liver disease (NAFLD). A growing body of evidence indicates that oleoylethanolamide (OEA), a bioactive lipid mediator, has anti-inflammatory and antioxidant properties. This trial investigated the effects of OEA administration on inflammatory markers, oxidative stress and antioxidant parameters of patients with NAFLD. Methods: The present randomized controlled trial was conducted on 60 obese patients with NAFLD. The patients were treated with OEA (250 mg/day) or placebo along with a low-calorie diet for 12 weeks. Inflammatory markers and oxidative stress and antioxidant parameters were evaluated pre-and post-intervention. Results: At the end of the study, neither the between-group changes, nor the within-group differences were significant for serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-1 beta (IL-1ß), IL-6, IL-10, and tumor necrosis-factor α (TNF-α). Serum levels of total antioxidant capacity (TAC) and superoxide dismutase (SOD) significantly increased and serum concentrations of malondialdehyde (MDA) and oxidized-low density lipoprotein (ox-LDL) significantly decreased in the OEA group compared to placebo at study endpoint (p = 0.039, 0.018, 0.003 and 0.001, respectively). Although, no significant between-group alterations were found in glutathione peroxidase and catalase. There were significant correlations between percent of changes in serum oxidative stress and antioxidant parameters with percent of changes in some anthropometric indices in the intervention group. Conclusion: OEA supplementation could improve some oxidative stress/antioxidant biomarkers without any significant effect on inflammation in NAFLD patients. Further clinical trials with longer follow-up periods are demanded to verify profitable effects of OEA in these patients. Clinical Trial Registration: www.irct.ir, Iranian Registry of Clinical Trials IRCT20090609002017N32.

Association between animal protein sources and risk of neurodegenerative diseases: a systematic review and dose-response meta-analysis.

CONTEXT: Current findings about the differential effects of various sources of dietary animal protein on the risk of neurodegenerative diseases are contradictory. OBJECTIVE: The current meta-analysis was conducted to investigate the associations between intake of dietary animal protein sources and the risk of neurodegenerative diseases. DATA SOURCES: PubMed, Scopus, Web of Science, and Google Scholar databases were searched systematically until October 2021. DATA EXTRACTION: Prospective cohort studies exploring the association between consumption of animal protein sources and risk of neurodegenerative diseases in the general population were included. Among 10 571 identified studies, 33 prospective cohort studies met the eligibility criteria. DATA ANALYSIS: Dietary fish consumption was associated with a reduced risk of Alzheimer's disease (RR = 0.75; 95%CI, 0.57-0.97), dementia (RR = 0.84; 95%CI, 0.75-0.93), and cognitive impairment (RR = 0.85; 95%CI, 0.81-0.95). The risk of developing Parkinson's disease was significantly higher among those in the highest vs the lowest intake categories of total dairy (RR = 1.49; 95%CI, 1.06-2.10) and milk (RR = 1.40; 95%CI, 1.13-1.73). Moreover, dietary intake of total dairy (RR = 0.89; 95%CI, 0.80-0.99), total meat (RR = 0.72; 95%CI, 0.57-0.90), and poultry (RR = 0.82; 95%CI, 0.68-0.99) was significantly associated with a lower risk of cognitive impairment. A linear dose-response meta-analysis revealed that each 200-g increase in total daily dairy intake was associated with an 11% higher risk of Parkinson's disease and a 12% lower risk of cognitive impairment. Furthermore, there was a strong linear association between fish consumption and reduced risk of dementia. CONCLUSION: Dairy consumption is associated with an increased risk of Parkinson's disease, but a higher intake of fish may be associated with lower risk of neurodegenerative disease. Future well-controlled, randomized clinical trials are essential to validate the present findings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021281887.

Soy isoflavone intake and risk of cardiovascular disease in adults: A systematic review and dose-response meta-analysis of prospective cohort studies.

We examined the association between soy isoflavone intake and risk of cardiovascular disease (CVD) outcomes in adults. We searched the online databases for relevant studies published up to September 2021. In total, 13 publications were included in the systematic review and 12 in the meta-analysis. We found that a high intake of soy isoflavones was significantly associated with a lower risk of coronary heart disease (CHD) among whole populations (Pooled RR: 0.92, 95% CI: 0.85-0.99, I2 = 41.0%, Pheterogeneity = 0.10) and a lower risk of overall CVD (Pooled RR: 0.91, 95% CI: 0.84-0.98, I2 = 30.7%, Pheterogeneity = 0.19) and CHD (Pooled RR: 0.89, 95% CI: 0.83-0.96, I2 = 14.4%, Pheterogeneity = 0.32) among Western population. In the linear dose-response analysis, a 3 mg/day increase in soy isoflavone intake was associated with 16% and 14% lower risks of overall CVD and CHD, respectively, among Western population. In conclusion, we found that soy isoflavone intake was associated with a lower risk of overall CVD and CHD in adults, particularly among Western population.

Effects of collagen peptide supplementation on cardiovascular markers: a systematic review and meta-analysis of randomised, placebo-controlled trials.

Previous studies have advocated that collagen peptide supplementation (CPS) can positively affect cardiovascular health. However, the widespread impact of CPS on CVD-related markers is not fully resolved. Consequently, the current systematic review and meta-analysis aimed to assess the efficacy of CPS on CVD-related markers. A systematic search in the Scopus, PubMed and ISI Web of Science databases were completed to identify relevant randomised, placebo-controlled trials (RCT) published up to November 2021. Mean Differences were pooled using a random-effects model, while publication bias, sensitivity analyses and heterogeneity were assessed using previously validated methods. Twelve RCT, comprising of a total of eleven measured markers, were selected for the quantitative analysis. Pooled data revealed that CPS significantly decreased fat mass (-1·21 kg; 95 % CI: -2·13, -0·29; I2 = 0·0 %; P = 0·010) and increased fat-free mass, based on body mass percentage (1·49 %; 95 % CI: 0·57, 2·42; I2 = 0·0 %; P = 0·002). Moreover, collagen peptide supplementation led to a significant decrease in serum LDL (-4·09 mg/dl; 95 % CI: -8·13, -0·04; I2 = 93·4 %; P = 0·048) and systolic blood pressure (SBP) (-5·04 mmHg; 95 % CI: -9·22, -0·85; I2 = 98·9 %; P = 0·018). Our analysis also indicated that CPS did not affect glycemic markers. Our outcomes indicate that CPS reduces fat mass, LDL and SBP while increasing fat-free mass. Future investigations with longer CPS duration are needed to expand on our results.

Yogurt consumption and risk of mortality from all causes, CVD and cancer: a comprehensive systematic review and dose-response meta-analysis of cohort studies.

OBJECTIVES: To quantify the dose-response relation between yogurt consumption and risk of mortality from all causes, CVD and cancer. DESIGN: Systematic review and meta-analysis. SETTING: We conducted a comprehensive search of PubMed/Medline, ISI Web of Science and Scopus databases through August 2022 for cohort studies reporting the association of yogurt consumption with mortality from all causes, CVD and cancer. Summary relative risks (RR) and 95 % CI were calculated with a random-effects model. PARTICIPANTS: Seventeen cohort studies (eighteen publications) of 896 871 participants with 75 791 deaths (14 623 from CVD and 20 554 from cancer). RESULTS: High intake of yogurt compared with low intake was significantly associated with a lower risk of deaths from all causes (pooled RR 0·93; 95 % CI: 0·89, 0·98, I2 = 47·3 %, n 12 studies) and CVD (0·89; 95 % CI: 0·81, 0·98, I2 = 33·2 %, n 11), but not with cancer (0·96; 95 % CI: 0·89, 1·03, I2 = 26·5 %, n 12). Each additional serving of yogurt consumption per d was significantly associated with a reduced risk of all-cause (0·93; 95 % CI: 0·86, 0·99, I2 = 63·3 %, n 11) and CVD mortality (0·86; 95 % CI: 0·77, 0·99, I2 = 36·6 %, n 10). There was evidence of non-linearity between yogurt consumption and risk of all-cause and CVD mortality, and there was no further reduction in risk above 0·5 serving/d. CONCLUSION: Summarising earlier cohort studies, we found an inverse association between yogurt consumption and risk of all-cause and CVD mortality; however, there was no significant association between yogurt consumption and risk of cancer mortality.

Association of dietary phytochemical index with metabolically unhealthy overweight/obesity phenotype among Iranian women: A cross-sectional study.

Background: Phytochemicals have been recently studied as adjuvants for the treatment of obesity. No study has investigated the association of phytochemical-rich foods with metabolically unhealthy overweight/obesity phenotype (MUOW/O). This study aimed to determine the association of dietary phytochemical index (DPI) with MUOW/O based on Karelis criteria among Iranian female adults. Methods: In this cross-sectional study, a total of 228 overweight and obese women aged 18-48 years were included. Anthropometric measurements were evaluated for all participants. A validated 147-item Food Frequency Questionnaire (FFQ) was used for dietary assessment. DPI was calculated as [dietary energy derived from phytochemical-rich foods (kcal)/total daily energy intake (kcal)] × 100. Participants' body composition and biochemical parameters of Karelis criteria [triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), insulin, and high-sensitivity C-reactive protein (hs-CRP)] were determined. Results: The mean age of the study participants was 36.69 ± 9.20, and the mean DPI score was 26.23 ± 9.48 among participants with MUOW/O phenotype. After controlling for potential confounders, women in the highest tertile of DPI had lower odds for MUOW/O phenotype [odds ratio (OR): 0.23, 95% confidence interval (CI): 0.07-0.68, P = 0.008] compared to the lowest tertile. Among the components of Karelis criteria, homeostatic model assessment for insulin resistance (HOMA-IR) was significantly associated with MUOW/O phenotype in the fully adjusted model (OR: 0.29, 95% CI: 0.10-0.79, P = 0.01). Conclusion: We found a significant association between DPI and MUOW/O phenotype in Iranian women. Prospective studies are needed to confirm these findings.

The effect of grape products on liver enzymes: A systematic review and meta-analysis of randomized controlled trials.

The favorable influence of grape consumption on metabolic diseases has previously been shown in studies. We sought to assess the effects of grape intake on liver enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), in adults. We performed literature search in online databases, to find eligible randomized controlled trials (RCTs). we considered RCTs that met the following criteria: RCTs consisted of use of grape products on ALT, AST, and ALP in adults (≥18 years) with at least 2 weeks intervention duration. Pooling data from 11 trials showed that grape products intake significantly reduced ALP (p = .010), without any significant changes in ALT (p = .234) and AST (p = .300). In subgroup analysis, we found a significant reduction in ALP, ALT, and AST when the duration of intervention was ≥12 weeks, and when grape seed extract (GSE) was administered. The variable duration and dosage of intervention was one of the sources of bias in our meta-analysis. Additionally, participants involved in included studies had different physiological status and various age groups. Grape products administration may significantly improve ALT, AST, and ALP in adults in long-term interventions and/or when GSE is administered. It should be noted that the favorable effects of grape consumption were small and may not reach clinical importance.

Study protocol for a pilot randomised controlled trial evaluating the effectiveness of oral trehalose on inflammatory factors, oxidative stress, nutritional and clinical status in traumatic head injury patients receiving enteral nutrition.

INTRODUCTION: In traumatic brain injury (TBI) patients, inflammatory processes and oxidative stress have been linked to the development of neurodegenerative diseases, disability, increased rate of muscle catabolism, malnutrition, hospital stay and mortality. Previous in vitro and in vivo studies have shown that trehalose can decrease inflammatory and oxidative factors. Therefore, the present study was designed to evaluate the effect of oral trehalose consumption on this marker in critically ill TBI patients at intensive care unit (ICU). METHODS AND ANALYSIS: This study is a pilot randomised, prospective and double-blind clinical trial. The study sample size is of 20 (10 patients in each group) TBI patients aged 18-65 years at ICU. Randomisation is performed by permuted block randomisation method. The allocation ratio is 1:1. An intervention group will receive 30 g of trehalose instead, as a part of the carbohydrate of daily bolus enteral feeding and the control group will receive standard isocaloric hospital bolus enteral feeding for 12 days. The inflammatory factors (C reactive protein, interleukin 6) and oxidative stress markers (glutathione, malondialdehyde, superoxide dismutase, pro-oxidant-antioxidant balance, total antioxidant capacity) will be measured at the baseline, at the 6th day, and at the end of the study (12th day). Sequential Organ Failure Assessment, Acute Physiology and Chronic Health Evaluation II, Nutrition Risk in the Critically ill scores, 28-day mortality, anthropometric assessments and the clinical and nutritional status will be measured. Each patient's nutritional needs will be calculated individually. The statistical analysis would be based on the intention to treat. ETHICS AND DISSEMINATION: The vice-chancellor of the research centre of Mashhad University of Medical Sciences is sponsoring this study. IR.MUMS.MEDICAL.REC.1400.113. TRIAL REGISTRATION NUMBER: Iranian Registry of Clinical Trials (IRCT) Id: IRCT20210508051223N1, Registration date: 26 July 2021.

The therapeutic effects and mechanisms of action of resveratrol on polycystic ovary syndrome: A comprehensive systematic review of clinical, animal and in vitro studies.

Polycystic ovary syndrome (PCOS) is one of the most important and common polygenic endocrine disorders among women of reproductive age. Resveratrol, a natural phenol, is involved in various biological activities, including antioxidant, antiseptic, anti-inflammatory, anti-ageing and anti-cancer effects. This systematic review aimed to investigate the therapeutic effects and mechanisms of actions of resveratrol in PCOS. The present study was conducted according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis statements. We searched PubMed, Science Direct, Google Scholar, Scopus, ISI Web of Science, ProQuest and Embase databases up to August 2021 by using the relative keywords. Original studies published in the English language that assessed the effects of resveratrol on PCOS and its associated complications were considered. Out of 417 records screened, only 24 articles met the inclusion criteria: 10 in vitro, 10 animal and 4 human studies. The results obtained in the present study showed that resveratrol supplementation might be effective in improving PCOS-related symptoms by reducing insulin resistance, alleviating dyslipidaemia, improving ovarian morphology and anthropometric indices, regulating the reproductive hormones and reducing inflammation and oxidative stress by affecting biological pathways. According to the available evidence, resveratrol may reduce the complications of PCOS. However, further studies are recommended for a comprehensive conclusion on the exact mechanism of resveratrol in PCOS patients.

Nano-curcumin supplementation in critically ill patients with sepsis: a randomized clinical trial investigating the inflammatory biomarkers, oxidative stress indices, endothelial function, clinical outcomes and nutritional status.

Sepsis is a severe reaction and excessive immune response to infection, which can lead to organ dysfunction, and death. This study aimed to investigate the protective effect of nano-curcumin (NC) on inflammatory biomarkers, endothelial function, oxidative stress indices, biochemical factors, nutritional status, and clinical outcomes in patients with sepsis. In the present double-blind placebo-controlled randomized clinical trial, 40 ICU-admitted patients were randomly allocated into either NC or placebo group for 10 days. Both nano-curcumin (160 mg) and placebo were administered via a nasogastric tube twice a day. The mRNA expression of nuclear-related factor 2 (Nrf-2), BCL2 associated X (BAX), B-cell lymphoma 2 (BCL-2), and toll-like receptor 4 (TLR-4) genes in the peripheral blood mononuclear cells (PBMCs), and the serum levels of primary, secondary, tertiary, and exploratory outcomes were assessed before the baseline and on days 5 and 10. There were significant improvements in the primary outcomes, including inflammatory markers (IL-6, IL-18, IL-1ß, IL-10, TLR-4, BCL-2 and BAX), markers of endothelial function (ICAM-1 and VCAM-1), and oxidative stress indices (malondialdehyde (MDA), nuclear-related factor 2 (Nrf-2), catalase, superoxide dismutase (SOD), and TAC) (p < 0.005) in the NC group compared to the placebo group after 10 days, while no significant increase was observed in the glutathione peroxidase (GPx) level between the two groups. However, no significant decrease was observed in the levels of secondary outcomes, including biochemical factors (creatinine, fasting blood sugar (FBS), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin, triglycerides (TG) and total cholesterol (TC)) (P > 0.05). Our results showed that in the tertiary outcome (nutritional status), there was no significant increase (P > 0.05) except for TLC (P = 0.003). NC supplementation also resulted in a significant decrease in the exploratory outcomes including the SOFA score and the duration of mechanical ventilation (P < 0.05). Supplementation with NC may be a promising treatment strategy for critically ill patients with sepsis. However, further experiments are suggested to investigate the effects of nano-curcumin on biochemical pathways involved in sepsis.

The effects of all trans retinoic acid, vitamin D3 and their combination on plasma levels of miRNA-125a-5p, miRNA-34a, and miRNA-126 in an experimental model of diabetes.

OBJECTIVE: The purpose of this study was to evaluate the effects of ATRA (all trans retinoic acid), vitamin D3, and their combination on circulating levels of miR (MicroRNA) -125a-5p, miR-126, and miR-34ain diabetic rats. MATERIALS AND METHODS: Total miRNA was extracted from plasma samples. miRNA expression profiles of 30 rats in five groups were analyzed after 4-week intervention. The expression levels of miRNAs were measured using qRT-PCR. RESULTS: We analyzed the expression of miR-126, miR-125a-5p, and miR-34a in serum among all five groups (p=0.268). The levels of miRNA-126 (p=0.004) and miR-125a-5p (p=0.014) showed a significant difference among our experimental groups. The circulating levels of miR-126 decreased in DC (Diabetic control) group compared to the HC (Healthy control) group (p=0.009). In addition, vitamin D3+ATRA supplementation increased miR-126 expression (p=0.014). Moreover, the levels of miR-125a-5p decreased in the DC group compared to the HC group (p=0.019). CONCLUSION: The expression of miR-126 and miR-125a-5p decreased in diabetic rats. Also, vitamin D3+ATRA can be considered a new therapeutic agent that can elevate miR-126 expression and prevent diabetes-related cardiovascular complications.

Does nano-curcumin supplementation improve hematological indices in critically ill patients with sepsis? A randomized controlled clinical trial.

Sepsis is the final common pathway to death for severe infectious diseases worldwide. The present trial aimed to investigate the effects of nano-curcumin supplementation on hematological indices in critically ill patients with sepsis. Fourteen ICU-admitted patients were randomly allocated into either nano-curcumin or placebo group for 10 days. The blood indices, serum levels of inflammatory biomarker and presepsin as well as nutrition status, and clinical outcomes were assessed before the intervention and on days 5 and 10. White blood cells, neutrophils, platelets, erythrocyte sedimentation rate (ESR), and the levels of interleukin-8 significantly decreased in the nano-curcumin group compared to the placebo after 10 days of intervention (p = .024, p = .045, p = .017, p = .041, and p = .004, respectively). There was also a marginal meaningful decrease in serum presepsin levels in the intervention group compared to the placebo at the end of the study (p = .054). However, total lymphocyte count showed a significant increase in the nano-curcumin group compared to the placebo at the end-point (p = .04). No significant differences were found in the level of lymphocyte and the ratios of neutrophil/lymphocyte and platelet/lymphocyte between the study groups. Moreover, no significant between-group differences were observed for other study outcomes, post-intervention. Collectively, nano-curcumin may be a useful adjuvant therapy in critically ill patients with sepsis. However, further trials are suggested to examine the effects of nano-curcumin in the management of sepsis and its complications. PRACTICAL APPLICATIONS: Curcumin (1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5- dione) or diferuloylmethane is widely used in medicine due to its several biological properties. Recent evidence has shown that curcumin possesses multiple pharmacological activities including immune-modulatory, antioxidant, anti-inflammatory, anti-cancer, and anti-microbial effects. In this study, it was observed that nano-curcumin at a dose of 160 mg for 10 days, without side effects, reduced some inflammatory factors and regulated the immune responses in sepsis patients. For the first time, this trial was conducted to determine the effect of nano-curcumin on hematological indices and the serum levels of presepsin and IL-8.

Effects of naringenin supplementation on cardiovascular risk factors in overweight/obese patients with nonalcoholic fatty liver disease: a pilot double-blind, placebo-controlled, randomized clinical trial.

OBJECTIVE: Although several experimental models have suggested promising pharmacological effects of naringenin in the management of obesity and its related disorders, the effects of naringenin supplementation on cardiovascular disorders as one of the main complications of nonalcoholic fatty liver disease (NAFLD) are yet to be examined in humans. METHODS: In this double-blind, placebo-controlled, randomized clinical trial, 44 overweight/obese patients with NAFLD were equally allocated into either naringenin or placebo group for 4 weeks. Cardiovascular risk factors including atherogenic factors, hematological indices, obesity-related parameters, blood pressure, and heart rate were assessed pre- and postintervention. RESULTS: The atherogenic index of plasma value, serum non-HDL-C levels as well as total cholesterol/high-density lipoprotein cholesterol (HDL-C), triglyceride/HDL-C, low-density lipoprotein cholesterol/HDL-C, and non-HDL-C/HDL-C ratios were significantly reduced in the intervention group, compared to the placebo group post intervention (P < 0.05). Moreover, there was a significant reduction in BMI and visceral fat level in the intervention group when compared with the placebo group (P = 0.001 and P = 0.039, respectively). Furthermore, naringenin supplementation could marginally reduce systolic blood pressure (P = 0.055). Mean corpuscular hemoglobin increased significantly in the naringenin group compared to the placebo group at the endpoint (P = 0.023). Supplementation with naringenin also resulted in a marginally significant increase in the mean corpuscular hemoglobin concentration when compared with the placebo group (P = 0.050). There were no significant between-group differences for other study outcomes post intervention. CONCLUSION: In conclusion, these data indicate that naringenin supplementation may be a promising treatment strategy for cardiovascular complications among NAFLD patients. However, further trials are warranted.

Effects of naringenin supplementation in overweight/obese patients with non-alcoholic fatty liver disease: study protocol for a randomized double-blind clinical trial.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of chronic liver disease worldwide. Flavonoids, a group of natural compounds, have garnered a great deal of attention in the management of NAFLD because of their profitable effects on glucose and lipid metabolism, inflammation, and oxidative stress which are the pivotal pathophysiological pathways in NAFLD. Naringenin is a citrus-derived flavonoid with a broad spectrum of potential biological effects including anti-inflammatory and antioxidant properties, which may exert protective effects against NAFLD. The present clinical trial aims to examine the efficacy of naringenin supplementation on plasma adiponectin and neurogulin-4 (NRG-4) concentrations, metabolic parameters, and liver function indices in overweight/obese patients with NAFLD. METHODS AND ANALYSIS: This is a double-blind, randomized, placebo-controlled clinical study that will investigate the impacts of naringenin supplementation in overweight/obese patients with NAFLD. Liver ultrasonography will be applied to diagnose NAFLD. Forty-four eligible overweight/obese subjects with NAFLD will be selected and randomly assigned to receive naringenin capsules or identical placebo (each capsule contains 100 mg of naringenin or cellulose), twice daily for 4 weeks. Participants will be asked to remain on their usual diet and physical activity. Safety of naringenin supplementation was confirmed by the study pharmacist. The primary outcome of this study is changes in adiponectin circulating levels. The secondary outcomes include changes in NRG-4 levels, liver function indices, metabolic parameters, body weight, body mass index (BMI), waist circumference (WC), blood pressure, and hematological parameters. Statistical analysis will be conducted using the SPSS software (version 25), and P value less than 0.05 will be regarded as statistically significant. DISCUSSION: We hypothesize that naringenin administration may be useful for treating NAFLD by modulating energy balance, glucose and lipid metabolism, oxidative stress, and inflammation through different mechanisms. The current trial will exhibit the effects of naringenin, whether negative or positive, on NAFLD status. ETHICAL ASPECTS: The current trial received approval from the Medical Ethics Committee of Tehran University of Medical Sciences, Tehran, Iran (IR.TUMS.MEDICNE.REC.1399.439). TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT201311250155336N12 . Registered on 6 June 2020.