Effects of short-chain fatty acid-butyrate supplementation on expression of circadian-clock genes, sleep quality, and inflammation in patients with active ulcerative colitis: a double-blind randomized controlled trial.

BACKGROUND: The regulation of the circadian clock genes, which coordinate the activity of the immune system, is disturbed in inflammatory bowel disease (IBD). Emerging evidence suggests that butyrate, a short-chain fatty acid produced by the gut microbiota is involved in the regulation of inflammatory responses as well as circadian-clock genes. This study was conducted to investigate the effects of sodium-butyrate supplementation on the expression of circadian-clock genes, inflammation, sleep and life quality in active ulcerative colitis (UC) patients. METHODS: In the current randomized placebo-controlled trial, 36 active UC patients were randomly divided to receive sodium-butyrate (600 mg/kg) or placebo for 12-weeks. In this study the expression of circadian clock genes (CRY1, CRY2, PER1, PER2, BMAl1 and CLOCK) were assessed by real time polymerase chain reaction (qPCR) in whole blood. Gene expression changes were presented as fold changes in expression (2^-ΔΔCT) relative to the baseline. The faecal calprotectin and serum level of high-sensitivity C-reactive protein (hs-CRP) were assessed by enzyme-linked immunosorbent assay method (ELIZA). Moreover, the sleep quality and IBD quality of life (QoL) were assessed by Pittsburgh sleep quality index (PSQI) and inflammatory bowel disease questionnaire-9 (IBDQ-9) respectively before and after the intervention. RESULTS: The results showed that sodium-butyrate supplementation in comparison with placebo significantly decreased the level of calprotectin (-133.82 ± 155.62 vs. 51.58 ± 95.57, P-value < 0.001) and hs-CRP (-0.36 (-1.57, -0.05) vs. 0.48 (-0.09-4.77), P-value < 0.001) and upregulated the fold change expression of CRY1 (2.22 ± 1.59 vs. 0.63 ± 0.49, P-value < 0.001), CRY2 (2.15 ± 1.26 vs. 0.93 ± 0.80, P-value = 0.001), PER1 (1.86 ± 1.77 vs. 0.65 ± 0.48, P-value = 0.005), BMAL1 (1.85 ± 0.97 vs. 0.86 ± 0.63, P-value = 0.003). Also, sodium-butyrate caused an improvement in the sleep quality (PSQI score: -2.94 ± 3.50 vs. 1.16 ± 3.61, P-value < 0.001) and QoL (IBDQ-9: 17.00 ± 11.36 vs. -3.50 ± 6.87, P-value < 0.001). CONCLUSION: Butyrate may be an effective adjunct treatment for active UC patients by reducing biomarkers of inflammation, upregulation of circadian-clock genes and improving sleep quality and QoL.

Prevalence of hypertension in Iran: An updated systematic review and meta-analysis of community-based studies.

Background: Hypertension (HTN) is one of the primary risk factors for heart disease and stroke worldwide. The present meta-analysis was aimed to systematically review and statistically estimate the prevalence rate of pre-hypertension (PHTN) and HTN in the Iranian child/adolescent and adult age groups. Methods: In this study, four International databases, including PubMed, Scopus, Web of Science, and Cochrane, as well as three Iranian databases, including SID, Magiran, and IranMedex, were separately investigated for articles published before January 2021. Also, we estimated the pooled effect size for the prevalence of PHTN and HTN in children/adolescent and adult age groups. Stata software (version 14.0) was used for all statistical analyses. Results: From a total of 1185 articles found in database searches, fifty-one were included in the meta-analysis. The prevalence of HTN in the Iranian adult population was 26.26% (25.11 % and 26.22 % for women and men, respectively). Meanwhile, the prevalence of PHTN and HTN in the child/adolescent age group was 8.97% (95% CI 7.33 - 10.61) and 8.98% (95% CI 7.59 - 10.36), respectively. Conclusions: This study provides information which can be used for various purposes, including study designing. Further nationwide surveys should be carried out to obtain accurate information on the HTN prevalence rate, particularly based on the American College of Cardiology /American Heart Association guidelines in the Iranian population.

Family History of Alzheimer's Disease Increases the Risk of COVID-19 Positivity: A SUMS Employees Cohort-based Study.

Background: Substantial data indicate that genetic and environmental factors play a key role in determining the risk of Alzheimer's disease (AD). Moreover, it is known that having relatives with AD increases the risk of developing this disease. Objective: This study is aimed at investigating whether having a family history of AD, may increase the risk of COVID-19 in a cohort-based study. Material and Methods: Participants of this retrospective cohort study were previously enrolled in the SUMS Employees Cohort (SUMSEC). All participants including those whose SARS-CoV-2 infection was confirmed by positive PCR test and chest CT scan were requested to respond to interviewer-administered questionnaires. Moreover, AD was diagnosed via memory and thinking impairment, concentration problems, confusion with location, and problems in finishing daily tasks. Results: The total numbers of female and male participants with a family history of AD were 463 and 222 individuals, respectively. When all types of family history of AD were considered, a 51.3% increase was found in the relative frequency of the participants with both family history of AD and confirmed COVID-19 compared with those only with a family history of AD. Conclusion: Despite the limitations of our study, and from a broader perspective, our findings can further support the concept that AD risk haplotypes including APOE are linked to the same morbidities from cardiovascular disease and obesity that increase vulnerability to COVID-19. Given this consideration, millions of APOE ε4 carriers around the globe should be advised to take additional precautions to prevent life-threatening diseases such as COVID-19.

Evaluation of Nutritional Status of Intensive Care Unit COVID-19 Patients Based on the Nutritional Risk Screening 2002 Score.

Background: Patients with COVID-19 are susceptible to malnutrition, which is particularly concerning among critically ill patients. We evaluated the Nutritional Risk Screening 2002 (NRS-2002) score in such patients and determined its relationship with the hospitalization outcome. Methods: This cross-sectional study involved COVID-19 patients admitted to the intensive care units (ICUs) of Shahid Faghihi Hospital, Shiraz, Iran, between February and March 2021. We assessed the nutritional status using NRS-2002 and determined disease severity with the APACHE II index. Demographic information, weight, height, clinical signs, previous illness, medications, biochemical test results, and history of anorexia and weight loss were recorded. Data were analyzed using SPSS version 18. Results: The mean age of 100 patients was 55.36 ± 18.86 years. According to NRS-2002, 30%, 29%, and 41% of patients were at low risk, moderate risk, and high risk of malnutrition, respectively. Age and BUN increased significantly with NRS-2002, while albumin and hematocrit followed the opposite trend (P < 0.001). Patients who died had lower albumin and hematocrit levels but higher age, NRS-2002 scores, and BUN/creatinine levels than those who recovered. Multivariable logistic regression revealed that for every unit increase in the NRS-2002 score, the odds of mortality increased by 354% (OR: 4.54, CI: 1.48, 13.95, P=0.008). Conclusion: NRS-2002 is a valuable prognostic tool for critically ill COVID-19 patients, with each unit's rise in the score being associated with a 354% rise in the odds of mortality. Increased malnutrition risk was linked with higher age and BUN and lower albumin and hematocrit levels.

Comparison of nutritional supplements for glycemic control in type 2 diabetes: A systematic review and network meta-analysis of randomized trials.

AIMS: Direct and indirect evidence were combined in this systematic-review and network meta-analysis (NMA) to assess and compare the effect of nutritional supplements on glycemic control, and rank the supplements accordingly. METHODS: PubMed, Scopus, and Web of Science were searched up to April 2021. We included randomized controlled trials that investigated the effect of vitamins D, C, and E, magnesium, zinc, calcium, selenium, and omega-3 on at least one glycemic marker, including glycated hemoglobin (HbA1c), fasting blood sugar (FBS), homeostasis model assessment-estimated insulin resistance (HOMA-IR), HOMA-B, and insulin, in adults with type 2 diabetes. To estimate effectiveness of supplements, a random-effects NMA in the Bayesian framework was applied. To assess risk of bias, Cochrane Collaboration Tool was used. RESULTS: Analysis of 178 studies indicated that zinc, vitamin D, omega-3, vitamin C, and vitamin E were effective in reducing HbA1c with low certainty. For reduction of FBS, zinc, vitamin D, and vitamin C, and for HOMA-IR, vitamin D were effective with low certainty. None of the supplements were effective in the reduction of insulin and HOMA-B with low certainty. After excluding poor-quality studies, only vitamin D was significantly effective in reducing all of the markers. Consistently, when the analysis was restricted to studies with a duration of ≥12-weeks, vitamin D reduced HbA1c, FBS, and HOMA-IR. CONCLUSIONS: Vitamin D supplementation was more effective compared to other supplements in improving HbA1c, FBS, and HOMA-IR, albeit with low certainty of evidence. This result was confirmed by low-risk of bias studies. REGISTRATION: CRD42021240691.

The Association between Energy-Adjusted Dietary Inflammatory Index, Body Composition, and Anthropometric Indices in COVID-19-Infected Patients: A Case-Control Study in Shiraz, Iran.

Background and Aims: Inflammation is strongly associated with the severity and mortality rate of SARS-CoV-2 disease (COVID-19). Dietary factors have a crucial role in preventing chronic and systemic inflammation. This study aimed to evaluate the association between energy-adjusted dietary inflammatory index (E-DII) scores and body composition parameters in COVID-19-infected patients compared to noninfected controls. Methods: A total of 133 COVID-19-infected patients and 322 noninfected controls were selected and enrolled from the Cohort Study of Employees of Shiraz University of Medical Sciences. E-DII score was calculated based on a validated food frequency questionnaire (FFQ) and body composition was measured using In-Body 770 equipment. Logistic regression models were utilized to estimate the odds ratio (OR). Results: In the control group, the mean E-DII score was significantly lower than the case group (-2.05 vs. -0.30, P ≤ 0.001), indicating that the diet of COVID-19-infected subjects was more proinflammatory than the controls. For every 1 unit increase in E-DII score, the odds of infection with COVID-19 was nearly triple (OR: 2.86, CI: 2.30, 3.35, P ≤ 0.001). Moreover, for each unit increase in body mass index (BMI), the odds of infection to COVID-19 increased by 7% (OR: 1.07, CI: 1.01, 1.13, P = 0.02). No significant difference was observed for other anthropometric parameters. Conclusion: The findings revealed that obese people and those consuming a more proinflammatory diet were more susceptible to coronavirus infection. Therefore, maintaining ideal body weight and consuming a more anti-inflammatory diet can decrease the probability of COVID-19 infection.

Protection by pure and genistein fortified extra virgin olive oil, canola oil, and rice bran oil against acetic acid-induced ulcerative colitis in rats.

Genistein is a major isoflavone with antioxidant and anti-inflammatory activities and hydrophobic features. To increase its bioavailability, researchers supplemented genistein with dietary oils. The present study aims to compare the effectiveness of genistein supplementation with water solution or oils and find the best possible dietary oil for fortification. A total of 135 male Sprague-Dawley rats were randomly assigned to nine groups, including one control group and eight acetic acid-induced colitis groups. The rats in the intervention groups were treated with 5 ml per kg body weight of oral pure and genistein fortified forms of extra virgin olive oil (EVOO), canola oil (CaO), and rice bran oil (RBO); the Genistein group (G) received 100 mg per kg body weight of genistein in aqueous solution orally. The colitis and control groups did not receive any treatment. The levels of colonic MDA (malondialdehyde), MPO (myeloperoxidase) activity, and IL-1ß (interleukin-1ß) were evaluated and a stereological analysis of colonic tissues was performed. All of the dietary oils (EVOO, CaO, and RBO) were effective at ameliorating the rats' oxidative and inflammatory status (p < 0.05); however, EVOO (with or without genistein) prescription resulted in slightly better results, especially with regard to the inflammatory profile. Additionally, delivering genistein via an oil vehicle was more efficient at reducing MDA formation, MPO activity, and IL-1ß concentration than genistein in aqueous solution. The quantitative analysis of colonic tissue was consistent with the biochemical analysis. Our findings suggest that the oral administration of EVOO, canola oil, and rice bran oil can attenuate the elevated IL-1ß levels and oxidative damage in induced colitis. Moreover, genistein fortified oils, especially EVOO, showed more beneficial effects in decreasing these markers in comparison with the pure oils or genistein (aqueous solution).

The Healing Effects of Hydroalcoholic Extract of Carum copticum L. on Experimental Colitis in Rats.

BACKGROUND: Ulcerative colitis is an inflammatory disease with indefinite treatment. The present study aimed to assess the anti-inflammatory and antioxidant effects of Carum copticum L. (CC) extract on induced colitis in rats. METHODS: Sixty male rats were randomly divided into six groups (n=10 per group). Acetic acid-induced colitis rats were orally administered with doses of 100, 200, and 400 mg/kg CC extract, and 100 mg/kg sulfasalazine for seven consecutive days, respectively. Colonic biopsies were taken to measure histopathological parameters as well as the tumor necrosis factor (TNF-α), interleukin-6 (IL-6), myeloperoxidase (MPO), malondialdehyde (MDA), and glutathione (GSH). Data analysis was performed using the one-way ANOVA and Tukey's test for normally distributed data. Kruskal-Wallis test followed by Dunn's test was used for non-normally distributed data. The analysis was performed at P≤0.05 using SigmaStat software (version 10.0). RESULTS: The control colitis group had a significantly higher total colitis index (P=0.01), TNF-α (P=0.01), IL-6 (P=0.01), MPO (P=0.01), and MDA (P=0.01); and lower GSH (P=0.01) than those of the sham group. The colitis group receiving a dose of 200 mg/kg/day CC extract had a significantly lower total colitis index (P=0.01), TNF-α (P=0.01), IL-6 (P=0.01), MPO (P=0.01), and MDA (P=0.01); and higher GSH (P=0.01) than those of the control colitis group. The colitis group receiving a dose of 200 mg/kg/day CC extract had a significantly lower total colitis index (P=0.04), TNF-α (P=0.03), IL-6 (P=0.04), MPO (P=0.03), and MDA (P=0.03); and higher GSH (P=0.01) than those of the colitis group receiving sulfasalazine. CONCLUSION: The present study revealed that CC extract had healing effects on colitis, possibly due to its antioxidant and anti-inflammatory properties.

Effects of supplementation with quercetin on plasma C-reactive protein concentrations: a systematic review and meta-analysis of randomized controlled trials.

Promising experimental studies suggest that quercetin has potential anti-inflammatory effects. However, the results of current clinical trials on quercetin's effects on the C-reactive protein (CRP), a sensitive inflammatory biomarker, are ambiguous. We conducted a meta-analysis of available randomized controlled trials (RCTs) to resolve this inconsistency and quantify the net effect of quercetin on circulating CRP concentrations. A systematic search was performed in several databases including SCOPUS, PubMed-Medline and Google Scholar until 16 June 2016. We used a random-effects model in combination with weight mean difference (WMD) and 95% confidence intervals (CI) for data analysis. Standard methods were used for the assessment of heterogeneity, meta-regression, sensitivity analysis and publication bias. The meta-analysis of seven RCTs (10 treatment arms) showed a significant reduction of circulating CRP levels (WMD: -0.33 mg/l; 95% CI: -0.50 to -0.15; P<0.001) following quercetin supplementation. In the subgroup analysis, a significant reducing effect was observed in trials with ⩾500 mg/day dosage (WMD: -0.34 mg/l; 95% CI: -0.52, -0.16; P⩽0.001) and in those with CRP <3 mg/l (WMD: -0.34 mg/l; 95% CI: -0.51, -0.18; P⩽0.001). In meta-regression, there was no association between changes in CRP concentrations, dose of supplementation and CRP baseline values. Our findings showed a significant effect of quercetin supplementation on the C-reactive protein-especially at doses above 500 mg/day and in patients with CRP <3 mg/l.