Folic acid-conjugated dextran-coated Zn0.6Mn0.4Fe2O4 nanoparticles as systemically delivered nano heaters with self-regulating temperature for magnetic hyperthermia therapy of liver tumors.

Successful cancer treatment using magnetic hyperthermia therapy (MHT) strongly depends on biocompatible magnetic nanoparticles (NPs). They can effectively accumulate in tumor tissues after systemic injection and generate heat in the therapeutic temperature range (42-48 °C) by exposure to an AC magnetic field (AMF). For this purpose, folic acid-conjugated dextran-coated Zn0.6Mn0.4Fe2O4 (FA-Dex-ZMF) NPs were synthesized as smart nano heaters with self-regulating temperatures for MHT of liver tumors. Animal studies on BALB/c mice showed that the prepared NPs did not cause acute toxicity upon administration up to 100 mg kg-1. Likewise, no significant changes in hematological and biochemical factors were observed. FA-Dex-ZMF NPs were studied by exposing them to different safe AC magnetic fields (f = 150 kHz, H = 6, 8, and 10 kA m-1). Calorimetric experiments revealed that the NPs reached the desired temperature range (42-48 °C), which was suitable for MHT. Moreover, the efficacy of FA-Dex-ZMF NPs in MHT of liver tumors was investigated in vivo in liver-tumor-bearing mice. The obtained results revealed that the average volume of tumors in the control group increased 2.2 times during the study period. In contrast, the tumor volume remained almost constant during treatment in the MHT group. The results indicated that folic acid-conjugated dextran-coated Zn0.6Mn0.4Fe2O4 NPs with self-regulating temperature could be a promising tool for systemically delivered MHT.

Effects of Calcium and Vitamin D Co-supplementation on the Lipid Profile: A Systematic Review and Meta-analysis.

PURPOSE: Calcium and vitamin D co-supplementation is common and widely used, but randomized, controlled trials (RCTs) have yielded inconclusive results concerning its impact on the serum lipid profile. METHODS: A comprehensive literature search of Medline, Web of Science, Scopus, Embase, Cochrane Central Register of Controlled Trials, and clinical trial registry databases was conducted to identify placebo-controlled RCTs that were published through September 2020 and that evaluated the impact of calcium and vitamin D co-supplementation on total cholesterol (TC), triglycerides (TGs), low- and very-low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C). Standardized mean differences (SMDs) were pooled using random-effects meta-analysis models. FINDINGS: Thirteen studies in a total of 2304 participants met the inclusion criteria. Calcium and vitamin D co-supplementation was associated with significant reductions in both TC (SMD, -0.81; 95% CI, -1.35 to -0.27; I2 = 94.6%) and TGs (SMD, -0.50; 95% CI, -0.91 to -0.08; I2 = 91.5%), and with a significant increase in HDL-C (SMD, 1.22; 95% CI, 0.60 to 1.83; I2 = 95.4%). However, calcium and vitamin D co-supplementation were not found to be associated with significantly decreased low-density lipoprotein cholesterol (SMD, -0.39; 95% CI, -0.78 to 0.01; I2 = 90.1%) or very-low-density lipoprotein cholesterol (SMD, -0.01; 95% CI, -0.70 to 0.69; I2 = 82.3%). IMPLICATIONS: The findings from the present systematic review and meta-analysis suggest that calcium and vitamin D co-supplementation has a beneficial effect on TC, TG, and HDL-C. Larger-scale, well-designed RCTs are needed to clarify the effect of calcium and vitamin D co-supplementation on all lipid-profile components.

The Efficacy of Rosa damascena on Liver Enzymes in Nonalcoholic Fatty Liver Disease: A Randomized Double-Blind Clinical Trial.

OBJECTIVE: This study aimed to appraise the potential effects of Rosa damascena preparation on nonalcoholic fatty liver disease (NAFLD). DESIGN: In the randomized, double-blind placebo-controlled clinical trials, seventy-four patients with NAFLD were prescribed either 1 g Rosa damascena powder or placebo three times in a day for 12 weeks. All patients were provided the lifestyle modification instructions and recommended following them precisely. ALT, AST, FBS, and lipid profiles were measured at the baseline after 12 weeks of studying. The Mann-Whitney U test was correctly used to compare the changes of variables among the groups. RESULTS: Seventy-two patients completed the study in two groups. Sixty-seven patients were men, and the mean ± standard deviation of age was 40.11 ± 9.05 years. The Rosa damascena group showed a considerable decrease in the serum ALT (23.83 ± 24.82 vs. 16.19 ± 27.41, p=0.042), waist circumference (99.73 ± 10.01 vs. 101.52 ± 8.84, p=0.003), triglyceride (TG) (186.29 ± 76.75 vs. 184.47 ± 73.05, p=0.001), cholesterol (167.47 ± 34.48 vs. 184.11 ± 33.54, p=0.001), low-density lipoprotein (LDL) (99.17 ± 28.66 vs. 107.52 ± 25.42, p=0.001), and elevation in serum high-density lipoprotein (HDL) (41.85 ± 6.56 vs. 39.20 ± 5.00, p < 0.007) compared to the control group. Improving fatty liver degree due to liver ultrasound was higher in the Rosa damascena group than the control group (p=0.001). CONCLUSION: Rosa damascena meaningfully improves liver function in NAFLD. Hence, it can be recommended along with lifestyle modification for these patients. Further studies are recommended with a larger sample size.

Molecular mechanisms underlying curcumin-mediated microRNA regulation in carcinogenesis; Focused on gastrointestinal cancers.

Curcumin is a bioactive ingredient found in the Rhizomes of Curcuma longa. Curcumin is well known for its chemopreventive and anti-cancer properties. Recent findings have demonstrated several pharmacological and biological impacts of curcumin, related to the control and the management of gastrointestinal cancers. Mechanistically, curcumin exerts its biological impacts via antioxidant and anti-inflammatory effects through the interaction with various transcription factors and signaling molecules. Moreover, epigenetic modulators such as microRNAs (miRNAs) have been revealed as novel targets of curcumin. Curcumin was discovered to regulate the expression of numerous pathogenic miRNAs in gastric, colorectal, esophageal and liver cancers. The present systematic review was performed to identify miRNAs that are modulated by curcumin in gastrointestinal cancers.

Effect of omega-3 fatty acids supplementation on cardio-metabolic and oxidative stress parameters in patients with chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Omega-3 fatty acids (FAs) have been suggested as a beneficial supplement in chronic kidney disease (CKD) patients, but the results of randomized clinical trials (RCTs) are controversial. We conducted a systematic review and meta-analysis to evaluate all the RCTs about the impact of omega-3 FAs supplementation on cardiometabolic outcomes and oxidative stress parameters in patients with CKD. METHODS: We performed a systematic database search in PubMed/MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Central, up to May 2020. We included all placebo-controlled randomized trials that assessed the effect of omega-3 FAs supplementation on any cardiometabolic outcomes: blood pressure, total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) or triglycerides (TG) and oxidative stress parameters. Data were pooled using DerSimonian-Laird's random-effects model. RESULTS: Finally, thirteen articles met the inclusion criteria for this review omega-3 FAs supplementation significantly decrease TC (SMD: -0.26; 95% CI: - 0.51, - 0.02; I2 = 52.7%), TG (SMD: -0.22; 95% CI: - 0.43, - 0.02; I2 = 36.0%) and Malondialdehyde (MDA) levels (SMD: -0.91; 95% CI: - 1.29, - 0.54; I2 = 00.0%) and also significantly increase superoxide dismutase (SOD) (SMD: 0.58; 95% CI: 0.27, 0.90; I2 = 00.0%) and Glutathione peroxidase (GPx) (SMD: 0.50; 95% CI: 0.14, 0.86; I2 = 00.0%) activities. However our results show that omega-3 FAs supplementation have no significant effects on HDL, LDL and blood pressure. Conclusion This systematic review and meta-analysis supports current evidence for the clinical benefit of omega-3 FAs intake to improve cardiometabolic parameters in CKD patients. However, well-designed RCTs still needed to provide a conclusive picture in this field.

A randomized controlled trial on the coloprotective effect of coenzyme Q10 on immune-inflammatory cytokines, oxidative status, antimicrobial peptides, and microRNA-146a expression in patients with mild-to-moderate ulcerative colitis.

PURPOSE: Coenzyme Q10 (CoQ10), having potent antioxidant and anti-inflammatory pharmacological properties, has recently been shown to be a safe and promising agent in maintaining remission of ulcerative colitis (UC). This trial was, therefore, designed to determine CoQ10 efficacy on inflammation and antioxidant status, antimicrobial peptides, and microRNA-146a expression in UC patients. METHODS: In this randomized double-blind controlled trial, 88 mild-to-moderate UC patients were randomly allocated to receive CoQ10 (200 mg/day) or placebo (rice flour) for 2 months. At the baseline and at an 8-week follow-up, serum levels of Nrf2, cathelicidin LL-37, ß-defensin 2, IL-10, IL-17, NF-κB p65 activity in peripheral blood mononuclear cells (PBMCs), simple clinical colitis activity index questionnaire (SCCAIQ), and quality of life (IBDQ-32 score), as well as an expression rate of microRNA-146a were measured. RESULTS: A significant reduction was detected in the serum IL-17 level, activity of NF-κB p65 in PBMCs, and also SCCAI score in the CoQ10 group compared to the placebo group, whereas IL-10 serum concentrations and IBDQ-32 score of the CoQ10 group considerably increased versus the control group; the changes of these variables were also significantly different within and between groups at the end of the study. Furthermore, CoQ10 remarkably increased serum levels of cathelicidin LL-37. A significant change in serum cathelicidin LL-37 levels was also observed between the two groups. No statistical difference, however, was seen between the two groups in terms of the serum levels of Nrf2 and ß-defensin 2 and the relative expression of microRNA-146a. CONCLUSIONS: Our results indicate that CoQ10 supplementation, along with drug therapy, appears to be an efficient reducer of inflammation in patients with mild-to-moderate UC at a remission phase. TRIAL REGISTRATION: The research has also been registered at the Iranian Registry of Clinical Trials (IRCT): IRCT20090822002365N17.

Effect of Probiotic, Prebiotic, and Synbiotic Supplementation on Cardiometabolic and Oxidative Stress Parameters in Patients With Chronic Kidney Disease: A Systematic Review and Meta-analysis.

PURPOSE: Chronic kidney disease (CKD) is a major health problem worldwide. Evidence supporting the use of probiotic, prebiotic, and synbiotic supplementation in the management of CKD is mixed, although some studies suggest they may be useful. A systematic review and meta-analysis was performed to evaluate the effectiveness of probiotic, prebiotic, and synbiotic supplementation for improving cardiometabolic and oxidative stress parameters in patients with CKD. METHODS: A comprehensive key word search was performed in EMBASE, Medline, Scopus, Cochrane Central, and Web of Science until April 2020. Randomized controlled trials investigating the effectiveness of probiotic, synbiotic, and prebiotic supplementation for the management of adults with CKD were included. Primary outcomes were measures of cardiometabolic parameters such as cholesterol and fasting blood glucose. Secondary outcomes were measures of oxidative stress (eg, malondialdehyde levels) and body mass index. Random effects meta-analyses were used to estimate mean treatment effects. Results are reported as standardized mean differences (SMDs) and 95% CIs. FINDINGS: Fourteen articles were included. In patients with CKD, probiotic, prebiotic, and synbiotic supplementation significantly reduced total cholesterol (SMD, -0.25; 95% CI, -0.46 to -0.04; I2 = 00.0%), fasting blood glucose (SMD, -0.41; 95% CI, -0.65 to -0.17; I2 = 00.0%), homeostatic model assessment of insulin resistance (SMD, -0.63; 95% CI, -0.95 to -0.30; I2 = 43.3%), insulin levels (SMD, -0.49; 95% CI, -0.90 to -0.08; I2 = 65.2%), high-sensitivity C-reactive protein levels (SMD, -0.52; 95% CI, -0.81 to -0.22; I2 = 52.7%), and malondialdehyde levels (SMD, -0.79; 95% CI, -1.22 to -0.37; I2 = 69.8%) compared with control interventions. Supplementation significantly increased the quantitative insulin sensitivity check index (SMD, 0.78; 95% CI, 0.51 to 1.05; I2 = 00.0%), total antioxidant capacity (SMD, 0.42; 95% CI, 0.18 to 0.66; I2 = 00.0%), and glutathione levels (SMD, 0.52; 95% CI, 0.19 to 0.86; I2 = 37.0%). IMPLICATIONS: Probiotic, prebiotic, and synbiotic supplementation seems to be a promising intervention for improving cardiometabolic and oxidative stress parameters in patients with CKD.

Effect of ginger (Zingiber officinale) supplementation on oxidative stress parameters: A systematic review and meta-analysis.

A wide variety of antioxidant properties are attributed to ginger (Zingiber officinale) and several randomized controlled trials (RCTs) have investigated the effect of ginger intake on major oxidative stress (OS) parameters. We conducted a systematic review and meta-analysis to evaluate the effects of using ginger to improve OS levels. Medline, Scopus, ISI Web of Science, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched up until March 2020 to gather RCTs that evaluated the impact of ginger intake on the levels and activity of OS parameters in adult subjects. Means and standard deviations for relevant OS variables were extracted and evaluated to assess the quality of the trials based on the Cochrane risk-of-bias tool for randomized trials. The gathered data were pooled and expressed as standardized mean difference (SMD) with 95% Confidence Intervals (95% CI). Twelve trials were included in this review. Ginger intake was shown to significantly increase glutathione peroxidase (GPx) activity (SMD: 1.64; 95% CI: 0.43, 2.85; I2  = 86.8%) and total antioxidant capacity (TAC) (SMD: 0.40; 95% CI: 0.06, 0.73; I2  = 42.8%) and significantly decrease malondialdehyde (MDA) levels (SMD: -0.69; 95% CI: -1.26, -0.12; I2  = 85.8%) compared to control groups. Ginger supplementation also non-significantly associated with an increase in CAT activity (SMD: 1.09; 95% CI: -0.07, 2.25; I2  = 87.6%). This systematic review and meta-analysis presents convincing evidence supporting the efficacy of ginger supplementation on improving OS levels. PRACTICAL IMPLICATIONS: In health sciences, OS, due to its pivotal role in the pathophysiology of several chronic diseases, is a subject with a long history. Recent research strives for a safe, ideal, and effective antioxidant. Ginger is herbal medicine, which has been widely used in traditional and complementary medicine. Proving the antioxidant effect and potential benefit of ginger has positive clinical implications for the application of this practical herb.

Formulation, Standardization, and a Preliminary Before-After Clinical Trial on Effect of a Traditional Herbal Formula (Maqliasa) on Manifestations of Ulcerative Colitis.

BACKGROUND: Ulcerative Colitis (UC) is a chronic condition that represents a group of intestinal disorders causing prolonged inflammation of the digestive tract. Nowadays, efforts to investigate new remedies have led to a committed movement toward the integration of traditional and complementary medicine into mainstream medicine. In Traditional Persian Medicine (TPM), Maqliasa is one of the most frequent gastrointestinal prescriptions which is claimed to be effective in both remission and recurrent phases of UC. OBJECTIVE: The aim of this pilot study was to examine the effect of Maqliasa on UC symptoms. METHODS: Through a non-randomized before-after uncontrolled clinical trial, 13 outpatients with active UC were enrolled in the study. They continued their conventional drug regimens plus Maqliasa capsules (2 capsules t.i.d.) for 28 days. Three visits were arranged for each patient- the first admission, day 14th admission and day 28th admission. The patients were evaluated by Lichtiger Colitis Activity Index. Wilcoxon signed-rank test was used for statistical analysis. RESULTS: The Lichtiger colitis activity index improved in the study group was compared to the corresponding baseline values: baseline score: 7.8 ± 0.5; after two weeks: 5.9 ± 0.6 (P=0.002); after four weeks: 3.6 ± 0.5 (P=0.001). CONCLUSIONS: This study showed the promising effect of Maqliasa in the treatment of active UC. However, due to some of the limitations of the study, conducting future high-quality randomized clinical trials would be crucial.

Glutamine Supplementation Enhances the Effects of a Low FODMAP Diet in Irritable Bowel Syndrome Management.

Background and Aims: Although irritable bowel syndrome is one of the most common gastrointestinal disorders presented to gastroenterologists, therapeutic strategies are not yet well-established. Accordingly, we conducted a randomized, double-blind, placebo-controlled, clinical trial to evaluate the possible superiority of adding glutamine supplement to low fermentable oligo- di- monosaccharides and polyols (FODMAP) diet in patients with irritable bowel syndrome (IBS). Methods: Eligible adults were randomized to receive a low FODMAP diet either with glutamine (15 g/day) or a placebo for 6 weeks. The primary endpoint was a significant reduction in IBS-symptom severity score (IBS-SSS). Secondary endpoints were changes in IBS symptoms, stool frequency, consistency, and quality of life. Results: The study group enrolled 50 patients, among which 22 participants from each group completed the study protocol. The glutamine group had significant changes in total IBS-severity score, dissatisfaction of bowel habit and interference with community function (58% reduction; P < 0.001, 57% reduction; P < 0.001, 51% reduction; P = 0.043, respectively). Improvement in IBS-severity score of more than 45% was observed in 22 of 25 participants (88%) in the glutamine group, while it was only 15 of 25 participants (60%) in the control group (p = 0.015). No serious adverse events were observed. Conclusions: Our findings indicated the superiority of adding glutamine supplementation to a low FODMAP diet in amelioration of IBS symptoms while confirming the beneficial effects of a low FODMAP diet in IBS management.

Effect of melatonin supplementation on oxidative stress parameters: A systematic review and meta-analysis.

BACKGROUND: Oxidative stress, defined as an imbalance between pro-oxidants and neutralizing antioxidants within the body, is a growing public health concern. Oxidative stress is involved in the progression of nearly all chronic diseases. Melatonin has been suggested to reduce oxidative stress by its potential radical scavenging properties. OBJECTIVE: To determine the efficacy and safety of melatonin as a therapy for the improvement of oxidative stress parameters in randomized controlled trials. METHODS: A systematic database search using Scopus, PubMed/Medline, EMBASE, Web of Science, the Cochrane Controlled Register of Trials and clinicaltrials.gov (https://clinicaltrials.gov) for studies published up to July 2020 was conducted. We included studies which investigated the effect of supplemental melatonin compared to placebo on oxidative stress parameters in unhealthy patients. Quantitative data synthesis was conducted using a random-effects model with standard mean difference (SMD) and 95 % confidence intervals (CI). Cochrane's Q and I2 values were used to evaluate heterogeneity. RESULTS: A total of 12 randomized controlled trials (RCTs) were eligible. The meta-analysis indicated an association between melatonin intake and a significant increase in total antioxidant capacity (TAC) (SMD: 0.76; 95 % CI: 0.30, 1.21; I2 = 80.1 %), glutathione (GSH) levels (SMD: 0.57; 95 % CI: 0.32, 0.83; I2 = 15.1 %), superoxide dismutase (SOD) (SMD: 1.38; 95 % CI: 0.13, 2.62; I2 = 86.9 %), glutathione peroxidase (GPx) (SMD: 1.36; 95 % CI: 0.46, 2.30; I2 = 89.3 %), glutathione reductase (GR) (SMD: 1.21; 95 % CI: 0.65, 1.77; I2 = 00.0 %) activities, and a significant reduction in malondialdehyde (MDA) levels (SMD: -0.79; 95 % CI: -1.19, -0.39; I2 = 73.1 %). Melatonin intake was not shown to significantly affect nitric oxide (NO) levels (SMD: -0.24; 95 % CI: -0.61, 0.14; I2 = 00.0 %) or catalase (CAT) activity (SMD: -1.38; 95 % CI: -1.42, 4.18; I2 = 96.6 %). CONCLUSION: Melatonin intake was shown to have a significant impact on improving Oxidative stress parameters. However, future research through large, well-designed randomized controlled trials are required to determine the effect of melatonin on oxidative stress parameters in different age groups and different disease types.

Effects of vitamin D3 supplementation on clinical symptoms, quality of life, serum serotonin (5-hydroxytryptamine), 5-hydroxy-indole acetic acid, and ratio of 5-HIAA/5-HT in patients with diarrhea-predominant irritable bowel syndrome: A randomized clinical trial.

Vitamin D deficiency, common in the population with irritable bowel syndrome (IBS), can induce the main factors that lead to IBS clinical symptoms, such as depression, anxiety, and inflammation. Serotonin (5-HT) plays an important role in the pathophysiology of IBS, and its production and secretion are increased from the lumen due to stress and inflammation. The aim of this study was to evaluate the effect of vitamin D3 supplementation on the pathogenesis of diarrhea-predominant IBS (IBS-D). Seventy-four IBS-D patients (age: 18-65 y) participated in a randomized, double-blind, placebo-controlled trial study from February 2017 to May 2018, at Rasoul-e-Akram Hospital, Tehran, Iran. Subjects were allocated into two groups receiving 50,000 IU/week of vitamin D3 or placebo for 9 weeks. IBS severity score system (IBS-SSS), IBS-quality of life questionnaire (QoL), hospital anxiety and depression Scale (HADs), visceral sensitivity index (VSI) and serum 25(OH) vitamin D3, serotonin, 5-hydroxy-indole acetic acid and ratio of 5-HIAA/5-HT were evaluated before and after the interventions. Symptoms severity, QoL, HADs-depression, and VSI score improved significantly in the vitamin D group as compared to the placebo group (P-values: <0.001, 0.049, 0.023, and 0.008; respectively). There were no significant differences in abdominal bloating, HADs-anxiety, serum 5-HT, 5-HIAA, and 5-HIAA/5-HT between the two groups at the end of the study. Based on our results, we recommend serum vitamin D be evaluated in the process of treatment of these patients to ameliorate symptoms and quality life of IBS-D patients with vitamin D deficiency and/or insufficiency.

The effect of saffron supplementation on some inflammatory and oxidative markers, leptin, adiponectin, and body composition in patients with nonalcoholic fatty liver disease: A double-blind randomized clinical trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is characterized by oxidative stress and inflammation in the hepatocytes. Saffron and its constituents are reported to have several properties such as anti-inflammatory and anti-diabetic effects. MATERIALS AND METHODS: In a randomized double-blind placebo-controlled trial with two parallel groups including 76 eligible men and female patients with NAFLD aged 18-65, recruited from Hazrat Rasul Akram Hospital in Tehran, Iran. NAFLD was defined by a Gastroenterologist based on the American Gastrointestinal and Liver Association standards. Participants were randomly assigned to two groups receiving daily supplementation of either one tablet of 100 mg saffron (n = 38) or one placebo (n = 38) for 12 weeks. The primary outcome was high sensitive C-reactive protein (hs-CRP) and secondary outcomes were alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor alpha (TNF-α), malondialdehyde (MDA), total anti-oxidant capacity (TAC), leptin, adiponectin, anthropometric, and body composition Both groups were assigned similar diet and physical activity. RESULTS: In the treatment group, significant decreases in hs-CRP (-1.80 ng/ml, 95% CI = -2.97, -0.63, p = .032), leptin (-0.27 ng/ml, 95% CI = -0.65, -0.10, p = .040), MDA (-1.01 ng/ml, 95% CI = -1.89, -0.14, p = .023) and significant increase in TAC (0.34 µmol/L, 95% CI = 0.08, 0.61, p = .011) were observed compared to the placebo group. However, there were no significant changes in serum alanine aminotransferase, AST, TNF-α, body composition, and anthropometric indexes (p > .05). CONCLUSION: In the present study, 12 weeks of 100 mg of saffron supplementation indicated beneficial effects on serum levels of some inflammatory, oxidative stress, and adipokines biomarkers but it had no significant effect on serum concentrations of liver enzymes, anthropometric, and body composition measurements.

Effect of ginger (Zingiber officinale) on inflammatory markers: A systematic review and meta-analysis of randomized controlled trials.

The aim of this systematic review and meta-analysis was to investigate the efficacy of ginger supplementation on circulating levels of C-reactive protein (CRP), high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), soluble intercellular adhesion molecule (sICAM), and interleukin-6 (IL-6) concentrations in randomized controlled trials (RCTs). The search included PubMed-Medline, EMBASE, Scopus, Web of Science and Cochrane Library databases to identify randomized clinical trials on the effect of ginger supplementation on circulation levels of CRP, hs-CRP, IL-6, sICAM, and TNF-α published up until February 1st, 2020. We did not restrict articles based on language of publication. Standard mean differences and 95% confidence intervals were calculated for net changes in inflammatory mediators using a random-effects model. Sixteen RCTs comprising 1010 participants were found to be eligible for this meta-analysis. There was a significant reduction of circulating CRP (SMD: -5.11, 95% CI: -7.91, -2.30, I2 = 98.1%), hs-CRP (SMD: -0.88, 95% CI: -1.63, -0.12, I2 = 90.8%) and TNF-α levels (SMD: -0.85, 95% CI: -1.48, -0.21, I2 = 89.4%) following ginger supplementation. However, meta-analysis results did not show any significant impact of ginger supplementation on IL-6 (SMD: -0.45, 95% CI: -1.29, 0.38, I2 = 89.2%), and sICAM levels (SMD: -0.05, 95% CI: -0.36, 0.26, I2 = 00.0%). This systematic review and meta-analysis of RCTs demonstrates a significant impact of ginger in lowering circulating CRP, hs-CRP and TNF-α levels. Large-scale RCTs are still needed to draw concrete conclusions about the effect of ginger on other inflammatory mediators.

Improvement of Patient Satisfaction and Anorectal Manometry Parameters After Biofeedback Therapy in Patients with Different Types of Dyssynergic Defecation.

Biofeedback is a well-known and effective treatment for patients with fecal evacuation disorder (FED). The main purpose of this study was to investigate the outcome and the effects of biofeedback therapy on physiological parameters as assessed by manometry in patients with FED. Data from 114 consecutive patients with FED who underwent biofeedback therapy in Sara Gastrointestinal clinic in Tehran, Iran during 2015-2018 were retrospectively reviewed and analyzed. All participants underwent a comprehensive evaluation of anorectal function that included anorectal manometry and a balloon expulsion test at the baseline and after biofeedback therapy. Maximum anal squeeze pressure and sustained anal squeeze pressure were improved up to 100% and 94.7% of normal values in the patients after biofeedback, respectively (P < 0.001). First rectal sensation, was significantly decreased (25 ± 18.5 vs. 15.5 ± 5.2) while the maximum tolerable volume was significantly increased (233.6 ± 89.7 vs. 182.4 ± 23.1) after biofeedback therapy (P < 0.001). Type I dyssynergia was the most common type, effecting 82 cases (71.9%) of our patients. Dyssynergia parameters were improved 50-80% in 34 (41.5%) and 10 (31.3%) type I and non-type I patients, respectively. Over 80% improvement of dyssynergia parameters occurred in 48 (58.5%) and 22 (68.8%) type I and non-type I patients, respectively. These differences were not statistically significant between the two groups (P = 0.3). In addition, the ability to reject the balloon was significantly better in post intervention measurements (P < 0.001). Biofeedback not only improves the symptoms in patients of FED but also reverses more than 80% the dyssynergic parameters of defecation. However, due to the general effectiveness of biofeedback treatment in different types of DD, there were no significant differences between their improvement scores.

Coenzyme Q10 supplementation and oxidative stress parameters: a systematic review and meta-analysis of clinical trials.

PURPOSE: Oxidative stress (OS) is associated with several chronic complications and diseases. The use of coenzyme Q10 (CoQ10) as an adjuvant treatment with routine clinical therapy against metabolic diseases has shown to be beneficial. However, the impact of CoQ10 as a preventive agent against OS has not been systematically investigated. METHODS: A systematic literature search was performed using the PubMed, SCOPUS, EMBASE, and Cochrane Library databases to identify randomized clinical trials evaluating the efficacy of CoQ10 supplementation on OS parameters. Standard mean differences and 95% confidence intervals were calculated for net changes in OS parameters using a random-effects model. RESULTS: Seventeen randomized clinical trials met the eligibility criteria to be included in the meta-analysis. Overall, CoQ10 supplementation was associated with a statistically significant decrease in malondialdehyde (MDA) (SMD - 0.94; 95% CI - 1.46, - 0.41; I2 = 87.7%) and a significant increase in total antioxidant capacity (TAC) (SMD 0.67; 95% CI 0.28, 1.07; I2 = 74.9%) and superoxide dismutase (SOD) activity (SMD 0.40; 95% CI 1.12, 0.67; I2 = 9.6%). The meta-analysis found no statistically significant impact of CoQ10 supplementation on nitric oxide (NO) (SMD - 1.40; 95% CI - 0.12, 1.93; I2 = 92.6%), glutathione (GSH) levels (SMD 0.41; 95% CI - 0.09, 0.91; I2 = 70.0%), catalase (CAT) activity (SMD 0.36; 95% CI - 0.46, 1.18; I2 = 90.0%), or glutathione peroxidase (GPx) activities (SMD - 1.40; 95% CI: - 0.12, 1.93; I2 = 92.6%). CONCLUSION: CoQ10 supplementation, in the tested range of doses, was shown to reduce MDA concentrations, and increase TAC and antioxidant defense system enzymes. However, there were no significant effects of CoQ10 on NO, GSH concentrations, or CAT activity.

Vitamin D3 Supplementation in Diarrhea-Predominant Irritable Bowel Syndrome Patients: The Effects on Symptoms Improvement, Serum Corticotropin-Releasing Hormone, and Interleukin-6 - A Randomized Clinical Trial.

OBJECTIVES: This study aimed to evaluate whether vitamin D deficiency is associated with the severity of symptoms of irritable bowel syndrome (IBS) patients. Stress and gut inflammation can increase the serum level of corticotropin-releasing hormone (CRH) and interleukin-6 (IL-6), leading to a change in bowel movements. The aim of this study was to evaluate the anti-inflammatory and psychological effects of vitamin D3 supplementation on the symptom improvement of patients with a diarrhea-predominant form of IBS (IBS-D). METHODS: Eighty-eight IBS-D patients (age: 18-65 years) based on Rome IV criteria who suffered from vitamin D deficiency and/or insufficiency were enrolled in this randomized, placebo-controlled trial from February 2017 to May 2018 at Rasoul-e-Akram Hospital, Tehran, Iran. Participants were randomly divided into two groups. The intervention group received 50,000 IU vitamin D3 weekly and the control group received a placebo for 9 weeks. All patients received Mebeverine 135 mg twice a day besides supplementation. The IBS Severity Score System (IBS-SSS), serum 25(OH) vitamin D3, CRH, and IL-6 were measured before and after interventions. RESULTS: Seventy-four patients completed the study. The severity of IBS symptoms (p < 0.01) and IL-6 (p = 0.02) decreased significantly in the intervention group as compared to the control group, but there was no significant difference in the serum level of CRH. Also, in the treatment group, IBS-SSS and IL-6 were significantly reduced at the end of the study from baseline (p < 0.01 and p < 0.03, respectively). CONCLUSION: Our findings indicate that vitamin D3 supplementation can modulate the serum level of CRH and IL-6 and can improve symptoms in IBS-D patients. Vitamin D3 supplementation should be considered in IBS-D patients who suffer from vitamin D deficiency and/or insufficiency.

Combination of laser and human adipose-derived stem cells in repair of rabbit anal sphincter injury: a new therapeutic approach.

BACKGROUND: Anal sphincter injury leads to fecal incontinence. Based on the regenerative capability of laser and human adipose-derived stem cells (hADSCs), this study was designed to assess the effects of co-application of these therapies on anal sphincter recovery after injury. DESIGN: Male rabbits were assigned to equal groups (n = 7) including control, sphincterotomy, sphincterotomy treated with laser (660 nm, 90 s, immediately after sphincterotomy, daily, 14 days), hADSCs (2 × 106 hADSCs injected into injured area of the sphincter immediately after sphincterotomy), and laser + hADSCs. Ninety days after sphincterotomy, manometry and electromyography were performed, sphincter collagen content was evaluated, and Ki67, myosin heavy chain (MHC), skeletal muscle alpha-actin (ACTA1), vascular endothelial growth factor A (VEGFA), and vimentin mRNA gene expression were assessed. RESULTS: The laser + hADSCs group had a higher resting pressure compared with the sphincterotomy (p < 0.0001), laser (p < 0.0001), and hADSCs (p = 0.04) groups. Maximum squeeze pressure was improved in all treated animals compared with the sphincterotomized animals (p < 0.0001), without a significant difference between treatments (p > 0.05). In the laser + hADSCs group, motor unit numbers were higher than those in the laser group (p < 0.0001) but did not differ from the hADSCs group (p = 0.075). Sphincterotomy increased collagen content, but the muscle content (p = 0.36) and collagen content (p = 0.37) were not significantly different between the laser + hADSCs and control groups. Laser + hADSCs increased ACTA1 (p = 0.001) and MHC (p < 0.0001) gene expression compared with laser or hADSCs alone and was associated with increased VEGFA (p = 0.009) and Ki67 mRNA expression (p = 0.01) and decreased vimentin mRNA expression (p < 0.0001) compared with laser. CONCLUSION: The combination of laser and hADSCs appears more effective than either treatment alone for promoting myogenesis, angiogenesis, and functional recovery after anal sphincterotomy.

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.

Effect of soy milk consumption on glycemic status, blood pressure, fibrinogen and malondialdehyde in patients with non-alcoholic fatty liver disease: a randomized controlled trial.

OBJECTIVE: Diet plays a critical role in the management of non-alcoholic fatty liver disease (NAFLD). Studies on the NAFLD's experimental models have reported that soy had positive effects on the improvement of metabolic parameters. However, there is a lack of clinical trials regarding the efficacy of whole soy foods. Therefore, this study was conducted to determine the effect of soy milk on some of the metabolic characteristics in patients with NAFLD. METHODS: Sixty-sex patients diagnosed with NAFLD were included in this randomized, parallel, controlled trial and were randomly assigned to either the soy milk or control group. Both groups received a 500-deficit calorie diet plan. Also, patients in the soy milk group consumed 240 ml/day soy milk for 8 weeks. Fasting blood sugar (FBS), serum insulin, HOMA-IR, HOMA-ß%, and QUICKI as well as serum malondialdehyde (MDA), plasma fibrinogen, and blood pressure (BP) were measured at the beginning and end of the study. RESULTS: After 8-weeks of intervention, soy milk group had a greater significant reduction in serum insulin(-3.44 ± 5.02 vs. -1.09 ± 3.77 µIU/ml, P = 0.04), HOMA-IR (-0.45±0.64 vs -0.14 ± 0.47, P = 0.03), systolic (-3.81±4.15 vs -1.48±2.93 mmHg, P = 0.01) and diastolic (-2.39±2.80 vs. -0.94±2.76 mmHg, P = 0.04) BP, and also, a significant increase in QUICKI (0.02± 0.032 vs. 0.008±0.018, P = 0.04) compared to the control group. While, changes in the FBS, HOMA-ß%, fibrinogen, and MDA were not significantly different between the study groups. CONCLUSION: A low-calorie diet containing soy milk had beneficial effects on serum insulin, HOMA-IR, QUICKI, and BP in patients with NAFLD.