Investigation of the effect of oligo-xylulose on the intestinal flora under pressure overload in mice based on 16S rRNA gene sequencing.

The relationship between gut microbiota dysbiosis and heart failure has been drawing increasing attention. This study aimed to investigate the effects of oligo-xylulose (XOS) on the gut microbiota of mice with heart failure induced by pressure overload. A chronic heart failure mouse model was constructed by pressure overload, and XOS were administered in their diet. The gut microbiota was analyzed using 16S rRNA gene sequencing, and the effects of XOS on the microbiota composition were evaluated. . XOS supplementation improved the balance of intestinal microbiota in mice under pressure overload, increasing the abundance of beneficial bacteria, such as Bifidobacterium and Lactobacillus, while decreasing the abundance of harmful bacteria, such as Desulfovibrio and Enterococcus. XOS has potential as a dietary supplement to improve the balance of intestinal microbiota and benefit individuals with heart failure. The findings of this study suggest that modulating the gut microbiota could be a novel strategy for treating heart failure.

Autophagy and senescence of rat retinal precursor cells under high glucose.

Backgrounds: Diabetic retinopathy (DR) is a common diabetic ocular disease characterized by retinal ganglion cell (RGC) changes. An abnormal environment, hyperglycemia, may progressively alter the structure and function of RGCs, which is a primary pathological feature of retinal neurodegeneration in DR. Accumulated studies confirmed autophagy and senescence play a vital role in DR; however, the underlying mechanisms need to be clarified. Methods: This study included the microarray expression profiling dataset GSE60436 from Gene Expression Omnibus (GEO) to conduct the bioinformatics analysis. The R software was used to identify autophagy-related genes (ARGs) that were differentially expressed in fibrovascular membranes (FVMs) and normal retinas. Co-expression and tissue-specific expression were elicited for the filtered genes. The genes were then analyzed by ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Set Enrichment Analysis (GSEA). R28 cells were cultured with high glucose, detected by reverse transcription-quantitative (RT-qPCR) and stained by apoptosis kit. Results: In the retina, 31 differentially expressed ARGs (24 up-regulated genes) were discovered and enriched. The enrichment results revealed that differentially expressed ARGs were significantly enriched in autophagy, apoptosis, aging, and neural function. Four hub genes (i.e., TP53, CASP1, CCL2, and CASP1) were significantly up-regulated. Upregulation of cellular autophagy and apoptosis level was detected in the hyperglycemia model in vitro. Conclusions: Our results provide evidence for the autophagy and cellular senescence mechanisms involved in retinal hyperglycemia injury, and the protective function of autophagy is limited. Further study may favour understanding the disease progression and neuroprotection of DR.

Ellagic Acid and Its Microbial Metabolite Urolithin A Alleviate Diet-Induced Insulin Resistance in Mice.

SCOPE: This work aims at evaluating the effect of dietary ellagic acid (EA) and its microbial metabolite urolithin A (UA) on glucose metabolism and insulin resistance (IR) in mice with diet-induced IR. METHODS AND RESULTS: DBA2J mice are fed a high fat/high sucrose diet (HF/HS) for 8 weeks to induce IR and then 0.1% EA, UA, or EA and UA (EA+UA) are added to the HF/HS-diet for another 8 weeks. UA significantly decreases fasting glucose and increases adiponectin compared with HF/HS-controls. During intraperitoneal insulin tolerance test, EA+UA significantly improve insulin-mediated glucose lowering effects at 15 and 120 min and reduce blood triglycerides compared with HF/HS-controls. Serum free fatty acids are significantly decreased by EA, UA, and EA+UA. Differential expression of genes related to mitochondrial function by EA, UA, and EA+UA in liver and skeletal muscle is observed. Primary hepatocytes from IR-mice have higher proton leak, basal and ATP-linked oxygen consumption rates compared with healthy controls. EA and EA+UA but not UA reduce the proton leak in hepatocytes from IR-mice. CONCLUSION: EA and UA induce different metabolic benefits in IR mice. The effects of EA and UA on mitochondrial function suggest a potentially novel mechanism modulating metabolism.

Pomegranate Juice and Extract Consumption Increases the Resistance to UVB-induced Erythema and Changes the Skin Microbiome in Healthy Women: a Randomized Controlled Trial.

In vitro and animal studies have demonstrated that topical application and oral consumption of pomegranate reduces UVB-induced skin damage. We therefore investigated if oral pomegranate consumption will reduce photodamage from UVB irradiation and alter the composition of the skin microbiota in a randomized controlled, parallel, three-arm, open label study. Seventy-four female participants (30-45 years) with Fitzpatrick skin type II-IV were randomly assigned (1:1:1) to 1000 mg of pomegranate extract (PomX), 8 oz of pomegranate juice (PomJ) or placebo for 12 weeks. Minimal erythema dose (MED) and melanin index were determined using a cutometer (mexameter probe). Skin microbiota was determined using 16S rRNA sequencing. The MED was significantly increased in the PomX and PomJ group compared to placebo. There was no significant difference on phylum, but on family and genus level bacterial composition of skin samples collected at baseline and after 12 week intervention showed significant differences between PomJ, PomX and placebo. Members of the Methylobacteriaceae family contain pigments absorbing UV irradiation and might contribute to UVB skin protection. However, we were not able to establish a direct correlation between increased MED and bacterial abundance. In summary daily oral pomegranate consumption may lead to enhanced protection from UV photodamage.

Bioavailability and bioactivity of free ellagic acid compared to pomegranate juice.

Pomegranates are an excellent source of ellagic acid (EA), ellagitannins (ETs), anthocyanins and other phytochemicals. The health benefits of pomegranate (Pom) have been mainly related to its EA and ET content. The objective of the present study was to determine EA bioavailability and bioactivity from different sources such as pure/free or natural form (PomJ). This was a cross-over study with healthy volunteers consuming one dose of EA dietary supplement (500 mg free EA) vs. one serving of PomJ (237 mL, ∼120 mg of EA) in a random order. Our data showed that there was no difference in plasma EA concentration between PomJ and EA intake; however, urinary dimethylellagic acid glucuronide (DMEAG), normalized to creatinine, was significantly higher after the consumption of PomJ compared to EA. Plasma insulin at 1 h increased after PomJ consumption compared to the baseline while decreased after EA consumption compared to the baseline. Plasma glucose decreased below the baseline 2 h after the consumption of PomJ but not EA. Plasma leptin was significantly decreased at 1 and 2 h after PomJ and EA consumption. Plasma MCP1 decreased only after PomJ but not after pure EA consumption. To conclude, one serving of PomJ provided the same level of EA in blood, while the increase in phase II metabolism of EA and an acute suppression of plasma MCP1 were only observed after PomJ consumption, suggesting that other constituents present in PomJ, in addition to EA, are bioactive and likely play a role in regulating EA phase II metabolism.

Effects of Prebiotic Fiber Xylooligosaccharide in Adenine-Induced Nephropathy in Mice.

SCOPE: This study evaluates the effect of the prebiotic fiber xylooligosaccharide (XOS) on kidney function and gut microbiome in mice with adenine-induced chronic kidney disease (CKD). METHOD AND RESULTS: Mice are fed the control diet containing adenine for 3 weeks to induce CKD and are switched to XOS supplemented (2 or 7%) or control diets for another 3 weeks. Mice with CKD exhibit increased blood urea nitrogen (BUN), creatinine, and kidney histopathology. XOS significantly reverses kidney injuries in CKD mice. Analysis of cecum microbiota reveales that adenine-induced CKD does not change alpha diversity, and XOS induces a decrease of alpha diversity in control mice and mice with CKD. Beta diversity analysis shows significant clustering according to experimental groups. Six out of the nine bacterial genera enriched in CKD are significantly reduced with XOS intervention. Furthermore, XOS increases cecal short-chain fatty acid (SCFA) production in both control and CKD mice. Cecal SCFAs and blood propionate are negatively correlated with BUN. XOS also decreases blood p-cresol sulfate in CKD mice, likely resulting from altered microbial tyrosine metabolism. CONCLUSION: These results show that XOS intervention improves kidney function in mice with CKD, and is associated with profound changes in microbial composition and metabolism.

[Expression of integrin alphavbeta3, tissue factor, and vascular endothelial growth factor in experimental choroidal neovascularization].

OBJECTIVE: To study the expression of vascular endothelial growth factor (VEGF), integrin alphavbeta3, and tissue factor (TF) in choroidal neovascularization (CNV). METHODS: CNV was induced in 25 Brown Norway (BN) rats by diode laser with 532 nm wave length. In every BN rat, one eye was induced to produce CNV, and the other eye served as the normal control eye. Fundus photography and fundus fluorescein angiography (FFA) were performed just before euthanasia on 3, 7, 14, 21, and 28 d after laser photocoagulation. The retina was processed for histopathology and immunohistochemical analysis to detect the expressions of VEGF, integrin alphavbeta3, and TF. RESULTS: There was no CNV, no expression of intergrin alphavbeta3 and TF in the normal control eyes. Only a few VEGFs were expressed in the ganglion cell layer of the retina, inner nuclear layer, retinal pigment epithelium, and vascular endothelial cell of the retina and choroid in normal eyes. FFA revealed disc-like leakage of fluorescein 7 days after the photo-coagulation, meaning there was CNV. VEGF, intergrin alphavbeta3, and TF were all expressed in the ganglion cell layer of the retina, inner nuclear layer, retinal pigment epithelium, and vascular endothelial cell of the retina and choroids 3 days after the photo-coagulation. With the development of CNV, expressions of integrin alphavbeta3, VEGF, and TF were gradually increasing (P<0.01). The expression of integrin alphavbeta3 in the retina was at peak on 7th day, VEGF on 14th day, and TF on 21st day. CONCLUSION: Expressions of VEGF, integrin alphavbeta3, and TF in CNV were found at the early, middle and late stage of CNV formation. It is important to determine the time of anti-neovascularization.