The relationship between prebiotic supplementation and anthropometric and biochemical parameters in patients with nafld—a systematic review and meta-analysis of randomized controlled trials

We aim to systematically review the efficacy of prebiotics in reducing anthropometric and biochemical parameters in individuals with non-alcoholic fatty liver disease (NAFLD). A systematic search using PubMed/MEDLINE, Embase, clinicaltrials.gov, Cinahl, and Web of Science of articles published up to 20 March 2020 was performed for randomized controlled trials enrolling >20 adult patients. Random-effect meta-analysis for metabolic outcomes in NAFLD patients was performed for anthropometric data in addition to liver enzyme, carbohydrate, and lipid parameters. We found six trials (comprising a total of 242 patients) with NAFLD, with subjects aged 38–52 years. The mean time of fiber administration varied between 10 and 12 weeks. The main fiber types were psyllium (seeds or powder), Ocimum basilicum (seeds), and high-performance inulin and oligofructose powder at doses of either 10 or 16 g per day. The control group received either maltodextrin (powder or capsules) or crushed wheat (powder). Patients on the diet with added fiber had improvements in body mass index (BMI) (standardized mean difference (SMD) = −0.494, 95% confidence interval (CI): −0.864 to −0.125, p = 0.009); alanine aminotransferase (ALT) (SMD = −0.667, 95% CI: −1.046 to −0.288, p = 0.001); aspartate aminotransferase (AST) (SMD = −0.466, 95% CI: −0.840 to −0.091, p = 0.015); fasting insulin (SMD = −0.705, 95% CI: −1.115 to −0.295, p = 0.001); and homeostasis model assessment for insulin resistance (HOMA-IR) (SMD = −0.619, 95% CI: −1.026 to −0.211, p = 0.003). Hence, the results show that fiber supplements result in favorable changes as reflected in the measurement of anthropometric, metabolic, and liver-related biomarkers, i.e., body mass index (BMI), homeostasis model assessment for insulin resistance (HOMA-IR), insulin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). These effects suggest the potential benefits of fiber consumption for NAFLD populations. More prospective, controlled studies should be conducted to reveal specific details regarding the fiber type, dosage, and duration for optimal intervention

Diet, the intestinal microbiota, and immune health in aging

Many countries are facing aging populations, with those over 65 years of age likely to represent the largest population over the next 10–20 years. Living longer often comes with poor health and, in particular, a decline in the immune function characterized by poor vaccine responses and increased risk of infection and certain cancers. Aging and diet represent major intrinsic and extrinsic factors that influence the makeup and activity of resident intestinal microbes, the microbiota, the efficient functioning of which is essential for sustaining overall health and the effectiveness of the immune system. The provision of elderly specific dietary recommendations appears to be lacking but is necessary since this population has an altered microbiota and immune response and may not respond in the same way as their healthy and younger counterparts. We have reviewed the evidence supporting the role of diet and, in particular, dietary carbohydrate, protein, and fat in influencing the microbiota and its generation of key metabolites that influence the efficient functioning of immune cells during aging, and how dietary intervention might be of benefit in improving the intestinal health and immune status in the elderly

Quercetin Suppresses Cyclooxygenase-2 Expression and Angiogenesis through Inactivation of P300 Signaling

Quercetin, a polyphenolic bioflavonoid, possesses multiple pharmacological actions including anti-inflammatory and antitumor properties. However, the precise action mechanisms of quercetin remain unclear. Here, we reported the regulatory actions of quercetin on cyclooxygenase-2 (COX-2), an important mediator in inflammation and tumor promotion, and revealed the underlying mechanisms. Quercetin significantly suppressed COX-2 mRNA and protein expression and prostaglandin (PG) E(2) production, as well as COX-2 promoter activation in breast cancer cells. Quercetin also significantly inhibited COX-2-mediated angiogenesis in human endothelial cells in a dose-dependent manner. The in vitro streptavidin-agarose pulldown assay and in vivo chromatin immunoprecipitation assay showed that quercetin considerably inhibited the binding of the transactivators CREB2, C-Jun, C/EBPβ and NF-κB and blocked the recruitment of the coactivator p300 to COX-2 promoter. Moreover, quercetin effectively inhibited p300 histone acetyltransferase (HAT) activity, thereby attenuating the p300-mediated acetylation of NF-κB. Treatment of cells with p300 HAT inhibitor roscovitine was as effective as quercetin at inhibiting p300 HAT activity. Addition of quercetin to roscovitine-treated cells did not change the roscovitine-induced inhibition of p300 HAT activity. Conversely, gene delivery of constitutively active p300 significantly reversed the quercetin-mediated inhibition of endogenous HAT activity. These results indicate that quercetin suppresses COX-2 expression by inhibiting the p300 signaling and blocking the binding of multiple transactivators to COX-2 promoter. Our findings therefore reveal a novel mechanism of action of quercetin and suggest a potential use for quercetin in the treatment of COX-2-mediated diseases such as breast cancers

Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009

Insulin resistance is a hallmark of type 2 diabetes mellitus and is associated with a metabolic and cardiovascular cluster of disorders (dyslipidaemia, hypertension, obesity [especially visceral], glucose intolerance, endothelial dysfunction), each of which is an independent risk factor for cardiovascular disease (CVD). Multiple prospective studies have documented an association between insulin resistance and accelerated CVD in patients with type 2 diabetes, as well as in non-diabetic individuals. The molecular causes of insulin resistance, i.e. impaired insulin signalling through the phosphoinositol-3 kinase pathway with intact signalling through the mitogen-activated protein kinase pathway, are responsible for the impairment in insulin-stimulated glucose metabolism and contribute to the accelerated rate of CVD in type 2 diabetes patients. The current epidemic of diabetes is being driven by the obesity epidemic, which represents a state of tissue fat overload. Accumulation of toxic lipid metabolites (fatty acyl CoA, diacylglycerol, ceramide) in muscle, liver, adipocytes, beta cells and arterial tissues contributes to insulin resistance, beta cell dysfunction and accelerated atherosclerosis, respectively, in type 2 diabetes. Treatment with thiazolidinediones mobilises fat out of tissues, leading to enhanced insulin sensitivity, improved beta cell function and decreased atherogenesis. Insulin resistance and lipotoxicity represent the missing links (beyond the classical cardiovascular risk factors) that help explain the accelerated rate of CVD in type 2 diabetic patients

Preoperative medical treatment in Cushing's syndrome : frequency of use and its impact on postoperative assessment : data from ERCUSYN

Background: Surgery is the definitive treatment of Cushing's syndrome (CS) but medications may also be used as a first-line therapy. Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial. Objective: (1) Evaluate how frequently PMT is given to CS patients across Europe; (2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery and (3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS). Patients and methods: 1143 CS patients entered into the ERCUSYN database from 57 centers in 26 countries. Sixty-nine percent had PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS) and 1% were classified as having CS from other causes (OTH-CS). Results: Twenty per cent of patients took PMT. ECT-CS and PIT-CS were more likely to receive PMT compared to ADR-CS (P < 0.001). Most commonly used drugs were ketoconazole (62%), metyrapone (16%) and a combination of both (12%). Median (interquartile range) duration of PMT was 109 (98) days. PIT-CS patients treated with PMT had more severe clinical features at diagnosis and poorer quality of life compared to those undergoing primary surgery (SX) (P < 0.05). Within 7 days of surgery, PIT-CS patients treated with PMT were more likely to have normal cortisol (P < 0.01) and a lower remission rate (P < 0.01). Within 6 months of surgery, no differences in morbidity or remission rates were observed between SX and PMT groups. Conclusions: PMT may confound the interpretation of immediate postoperative outcome. Follow-up is recommended to definitely evaluate surgical results