Effect of vitamin D on inflammatory and clinical outcomes in patients with rheumatoid arthritis: a systematic review and dose-response meta-analysis of randomized controlled trials.

CONTEXT: Rheumatoid arthritis is a chronic inflammatory disease that causes synovitis. Vitamin D deficiency is common in rheumatoid arthritis. OBJECTIVE: This systematic review and meta-analysis investigated whether vitamin D supplementation affects the inflammatory and clinical outcomes in patients with rheumatoid arthritis on the basis of randomized clinical trials. DATA SOURCES: A literature search was performed in the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, MEDLINE, Embase, and Google Scholar for articles published until May 2022. DATA EXTRACTION: The studies were selected according to PRISMA guidelines, and the risk of bias was assessed for randomized controlled trials. DATA ANALYSIS: A random effects model was used to conduct a meta-analysis, and heterogeneity was assessed using the I2 statistic. Of 464 records, 11 studies were included from 3049 patients. Conclusion: Vitamin D supplementation did not significantly reduce C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), disease activity score in 28 joints (DAS28), or the health assessment questionnaire score; however, the response to supplementation was highly heterogeneous. The pooled analysis showed that vitamin D significantly reduced the pain-visual analogue scale (VAS) weighted mean difference (WMD = -1.30, 95% confidence interval [CI] [-2.34, -27], P = .01), DAS28-CRP (WMD = -.58, 95% CI [-.86, -.31], P < .0001), and DAS28-ESR (WMD = -.58, 95% CI [-.86, -.31], P = .0001). Subgroup analysis for vitamin D doses (>100 µg per day versus <100 µg per day) showed that the higher doses had a more significant effect on CRP than the lower doses (P < .05). CONCLUSIONS: There was no significant difference between the effect of 2 vitamin D doses on ESR and DAS28. To minimize the high heterogeneity among studies in this meta-analysis, other confounding factors such as baseline vitamin D, age, dietary vitamin D, time of year, sun exposure, drug interaction, effect dosage, and power of study should be examined.

Conjugated linoleic acid and L-carnitine combination effects on obesity-related miRNAs in diet-induced obese rats.

OBJECTIVES: Obesity is a major global health issue, resulting in significant costs and increased mortality rates. Finding effective treatments for obesity is therefore essential. This study investigated the combined effects of L-Carnitine (LC) and Conjugated Linoleic Acid (CLA) on weight loss and adipose tissue microRNA levels. SUBJECTS /METHODS: Forty male Wistar rats weighing 150-200 g and about 8 weeks old were fed either a normal fat diet (NFD) or a high-fat diet (HFD) for 8 weeks. Afterwards, the HFD group was randomly divided into four subgroups: control, LC (200 mg kg-1), CLA (500 mg kg-1), and both (n = 8 in each group). The study lasted for an additional 4 weeks. The animals' weights were recorded regularly, and after 12 weeks, miRNAs were extracted from epididymal adipose tissue and analysed using real-time PCR. The miRNA expression levels of miR-27a and miR-143 were compared between groups using Kolmogorov-Smirnov and one-way ANOVA tests in SPSS software. RESULTS: At the end of the first 8 weeks, the HFD group weighed significantly more than the NFD group. LC significantly decreased weight gain (4.2%) compared to the control group, whereas CLA alone (3.5%) or in combination with LC (3.1%) did not significantly slow weight gain. Real-time PCR results showed that the HFD group had higher miR-143 levels and lower miR-27a levels compared to the NFD group. LC and CLA increased miR-27a expression after 4 weeks, but their combination decreased miR-27a expression. CLA alone reduced miR-143 expression, whereas LC had almost no effect. Their combination also reduced miR-143 expression. CONCLUSION: CLA and LC, which are considered weight loss supplements, can potentially regulate metabolism and cellular pathways. However, their combination did not show a synergistic effect on weight loss, possibly due to the reduction in miR-27a expression. Further studies are needed to evaluate the effects of combined fat burners on obesity treatment.

In vitro Eradication of Pseudomonas aeruginosa Persister Cell Producers by Peganum harmala.

BACKGROUND: Because of increasing antibiotic failure and recurrence of infections in patients with P. aeruginosa, the present study was designed to determine the antibiotic resistance status, presence of persister cells and investigate the antipersister effect of Peganum harmala in P. aeruginosa clinical isolates in vitro in Ilam, Iran. METHODS: Thirty P. aeruginosa urinary clinical isolates were collected from hospitals in Ilam, Iran and identified by common microbiological and biochemical tests. Afterward, antibiotic susceptibility assay, persister cell assay, P. harmala extraction, cell culture, and cell viability assays were performed. RESULTS: A high rate of antibiotic resistance was observed. All isolates were resistant to co-amoxiclav. Also, 83.3% (n = 25), 90% (n = 27), and 36.6% (n = 11) of isolates showed resistance to ceftazidime, kanamycin, and tobramycin, respectively. The MIC and MBC values for imipenem were ≤ 2 and 2 µg/mL for susceptible isolates, respectively. In addition, 6.66% (n = 2) of isolates were persister cells and were also sensitive to imipenem by MIC but did not show any MBC. IC50 for P. harmala was 35 µg/mL. Eventually, MIC value of P. harmala against two P. aeruginosa persister cell producer isolates was 3 µg/mL and 1 µg/mL, and the value of MBC was 10 µg/mL and 30 µl/mL. CONCLUSIONS: Our findings demonstrated that P. harmala may be a suitable antipersister herbal medicine against P. aeruginosa clinical isolates. In this regard, comprehensive research is needed in the future to gain more information in this area.

Nutritional management of diabetes mellitus during the pandemic of COVID-19: a comprehensive narrative review.

Objectives: According to the recent epidemiological studies, patients with diabetes mellitus (DM) may be at higher risk of hospitalization due to COVID-19. Regarding the important role of nutrition on the immunity, the present review article aimed to outline nutritional support of DM during the outbreak of COVID-19 with a mechanistic insight. Methods: Searches were performed in PubMed/MEDLINE, ScienceDirect, Scopus, and Google Scholar databases from 2000 until December 2020 using the following keywords. All relevant clinical and experimental studies published in English were included. Results: Evidences revealed that hyperglycemia is a significant predictor of some viral infections including COVID-19 which can exacerbate the complications of DM. According to the literature review, adequate intake of dietary protein, fiber, essential fatty acids and some micronutrients especially vitamins D, C, B12, folate, zinc and selenium has beneficial effects on the prevention and treatment of COVID-19 in diabetic patients through modulation of innate and adaptive immune responses or direct effects on virus enzymes or the rate of cell entrance. Conclusions: It is well understood that malnutrition may increase susceptibility to viral infections and disease progression. Therefore, considering nutritional status of diabetic patients and reasonable supplementation of the above mentioned nutrients can ameliorate the symptoms of COVID-19 in DM. However, further well-designed clinical trials are needed to determine their therapeutic dose.

Dietary ω-3 fatty acids and their influence on inflammation via Toll-like receptor pathways.

Dietary intake of long-chain, highly unsaturated ω-3 fatty acids (FAs) is considered indispensable for humans. The ω-3 FAs have been known to be anti-inflammatory and immunomodulatory dietary factors; however, the modes of action on pathogen recognition receptors (PRRs) and downstream signaling pathways have not been fully elucidated. Dietary sources contain various amounts of ω-3 long-chain fatty acids (LCFAs) of different lengths and the association between intake of these polyunsaturated fatty acids (PUFAs) with underlying mechanisms of various immune-related disorders can be of great interest. The potential anti-inflammatory role for ω-3 LCFAs can be explained by modification of lipid rafts, modulation of inflammatory mediators such as cytokines and PRRs. Toll-like receptors (TLRs) are a group of PRRs that play an important role in the recognition of bacterial infections and ω-3 FAs have been implicated in the modulation of downstream signaling of TLR-4, an important receptor for recognition of gram-negative bacteria. The ω-3 FAs docosahexaenoic acid and eicosapentaenoic acid have been investigated in vivo and in vitro for their effects on the nuclear factor-κB activation pathway. Identification of the effects of ω-3 FAs on other key molecular factors like prostaglandins and leukotrienes and their signals may help the recognition and development of medicines to suppress the main mediators and turn on the expression of anti-inflammatory cytokines and nuclear receptors.

Differential Effects of Dietary Supplementation of Krill Meal, Soybean Meal, Butyrate, and Bactocell® on the Gene Expression of Atlantic Salmon Head Kidney.

The head kidney is a key organ that plays a fundamental role in the regulation of the fish immune response and in the maintenance of endocrine homeostasis. Previous studies indicate that the supplementation of exogenous dietary components, such as krill meal (KM), soybean meal (SM), Bactocell® (BA), and butyrate (BU), can have a significant effect on the immune function of the head kidney. The aim of this study was to investigate the differential effect of these four dietary ingredients on the transcriptional profiles of the head kidney of the Atlantic salmon. This study revealed that just a small number of genes were responsive to the feeding regime after a long-term (12 weeks) treatment, and evidenced that the most significant alterations, both in terms of the number of affected genes and magnitude of changes in gene expression, were detectable in the BU- and KM-fed groups compared with controls, while the SM diet had a nearly negligible effect, and BA had no significant effects at all. Most of the differentially expressed genes were involved in the immune response and, in line with data previously obtained from pyloric caeca, major components of the complement system were significantly affected. These alterations were accompanied by an increase in the density of melanomacrophage centers in the KM- and SM-fed group and their reduction in the BU-fed group. While three types of dietary supplements (BU, KM, and SM) were able to produce a significant modulation of some molecular players of the immune system, the butyrate-rich diet was revealed as the one with the most relevant immune-stimulating properties in the head kidney. These preliminary results suggest that further investigations should be aimed towards the elucidation of the potential beneficial effects of butyrate and krill meal supplementation on farmed salmon health and growth performance.

Soy isoflavones and cholecalciferol reduce inflammation, and gut permeability, without any effect on antioxidant capacity in irritable bowel syndrome: A randomized clinical trial.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is more prevalent in women. Vitamin D deficiency and hormonal disorders are also prevalent in Iranian women, and may influence the severity of clinical outcomes mediated by microinflammation, oxidative stress and intestinal permeability pathways. Our objective was to investigate the effects of co-administration of soy and vitamin D on some inflammatory, antioxidant and gut permeability markers in women with IBS. METHODS: In a randomized clinical trial, women (18-75 years of age) were randomly allocated into four groups to receive soy isoflavones (40 mg/day), cholecalciferol (50,000 IU/15 days), both soy isoflavones and cholecalciferol, or placebo for six weeks. The outcomes were plasma inflammatory markers, antioxidant status and fecal protease activity at week 0 and week 6. RESULTS: After the intervention, plasma inflammatory markers and fecal protease activity were reduced significantly in all treatment groups compared to the placebo group; however, there was no significant effect on antioxidant status. CONCLUSION: This study suggests combined supplementation of soy isoflavones and active vitamin D can improve some biochemical parameters regarding inflammation and intestinal permeability of IBS in women. TRIAL REGISTRATION: Clinical.Trials.govNCT02026518.

Effects of Vitamin D Supplementation in Patients with Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVE: There are some evidence that Vitamin D supplementation may be beneficial for patients with irritable bowel syndrome (IBS). The aim of this study was to evaluate the effects of Vitamin D supplementation on symptoms and quality of life (QOL) in patients with IBS. METHODS: In a randomized, double-blind, placebo-controlled clinical trial, 116 patients with IBS were supplemented weekly with either a pearl of 50,000 IU Vitamin D or an identical pearl of placebo containing medium chain triglyceride for 6 weeks. RESULTS: Mean age of patients was 42.24 ± 12.26, and 40.06 ± 13.37 in Vitamin D and placebo groups, respectively. Dietary intakes were similar between and within groups. Serum concentration of 25-hydroxy Vitamin D increased significantly from 21.10 ± 5.23 to 36.43 ± 12.34 in the Vitamin D group (P < 0.001), while it was not significantly different before and after the trial in placebo group. The IBS symptoms severity scores (SSSs), disease-specific QOL, and total score were evaluated at weeks 0 and 6. IBS-SSS, IBS-QOL, and the total score were improved significantly more in Vitamin D group in comparison to the placebo group (P < 0.05). CONCLUSIONS: This study indicates that Vitamin D therapy can improve the severity of symptoms and QOL in patients with IBS; however, the long-term effects remained to be elucidated. Trial registration at IRCT: IRCT201402234010N11 IRB Number: 116/3976.

A novel treatment for weight reduction by the recombinant "Pichia pastoris" yeast expressing the hybrid protein of "irisin-furin-transferrin".

Obesity is a major health problem across the world, but there are few ways to effectively treat or manage it in the long term. Researchers are searching for more convenient, cost-effective and noninvasive therapies for overweight and obese people. Recent studies have illustrated that the microbiome of the body's different organs can be used as a vehicle for in-situ gene therapy. We suggest that the recombinant form of "Pichia pastoris" yeast expressing the hybrid protein of "irisin-furin-transferrin" under the control of the enolase 1 promoter is a new nutraceutical strategy to absorb fewer calories from intestinal nutrients, and induce a higher metabolic rate to expend more calories, similar to that from engaging in physical activity. By comparison, this method can be a long-term, noninvasive treatment and can be used for obese patients who have movement limitations.

Beneficial role of antioxidants on clinical outcomes and erythrocyte antioxidant parameters in rheumatoid arthritis patients.

BACKGROUND: This study aims to investigate the effect of antioxidants supplement on clinical outcomes and antioxidant parameters in rheumatoid arthritis (RA). METHODS: The pre-post study was conducted on 40 female patients with RA in 12 weeks that taken daily one Selenplus capsule contained 50 µg selenium, 8 mg zinc, 400 µg vitamin A, 125 mg vitamin C, and 40 mg vitamin E. About 5 mL venous blood sample was taken from all participants and disease activity score (DAS) was determined by DAS-28 formula and high-sensitive C-reactive protein (hs-CRP). Glutathione peroxidase (GPX) and superoxide dismutase (SOD) were measured by spectrophotometric kit and catalase (CAT) was measured by Abei method. Total antioxidant capacity (TAC) was determined by spectrophotometric kit. Distribution of the variables was assessed using histogram with normal curve as well as Kolmogorov-Smirnov test and data were analyzed with paired t-test for differences between pre-post data using SPSS software version 13.5. CONCLUSIONS: Our findings showed that antioxidants may improve disease activity significantly, but it did not affect the number of painful and swollen joints and increased erythrocyte antioxidant levels. Antioxidants may be useful for controlling of clinical outcomes and oxidative stress in RA.