Interleukin-17A exacerbates high-fat diet-induced hepatic steatosis by inhibiting fatty acid ß-oxidation.

There is a growing body of evidence that the interleukin-17A (IL-17A) signaling pathway contributes to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the mechanism by which IL-17A signaling induces hepatocyte injury is unclear. The aim of the present study was to investigate the significance of the IL-17A axis in NAFLD and to explore the role of IL-17A in high-fat diet (HFD)-induced NAFLD in C57BL/6 mice and oleic acid (OA)-induced lipid accumulation in hepatocytes. Firstly, Consistent upregulation of IL-17A was observed in the HFD-induced steatosis mice but not the normal chow-fed control mice. Administration of IL-17A impaired liver function, aggravated hepatic lipid accumulation by inhibiting fatty acid oxidation in the HFD mice. Conversely, inhibition of IL-17A using an anti-IL-17A monoclonal antibody (mAb) significantly attenuated HFD-induced liver injury. Furthermore, IL-17A accelerated hepatic steatosis through activation of the JNK-PPARα pathway in the HFD mice and OA-preloaded hepatocytes. CONCLUSION: The present study demonstrated that a high fat diet induces IL-17A expression, which exacerbates the progression of NAFLD by inhibiting fatty acid ß-oxidation and promoting the accumulation of triglycerides (TG).

Active assimilators of soluble microbial products produced by wastewater anammox bacteria and their roles revealed by DNA-SIP coupled to metagenomics.

Heterotrophic bacteria grow on influent organics or soluble microbial products (SMP) in wastewater anammox processes, playing key roles in facilitating microbial aggregation and reducing excess nitrate. The overgrowth of heterotrophs represents one of the major causes of anammox process failure, while the metabolic functions of coexisting heterotrophs and their roles in anammox process remain vague. This study aimed at revealing metabolic interactions between AnAOB and active SMP assimilators by integrating 13C DNA-stable isotope probing, metabolomic and metagenomic approaches. Glycine, aspartate, and glutamate with low biosynthetic energy cost were the major SMP components produced by AnAOB (net yield: 44.8, 10.4, 8.1 mg·g NH4+-N-1). Glycine was likely synthesized by AnAOB via the reductive glycine pathway which is oxygen-tolerant, supporting heterotrophic growth. Fermentative Chloroflexi bacterium OLB13, denitrifying Gemmatimonadaceae and Burkholderiaceae bacterium JOSHI-001 were active SMP assimilators, which were prevalent in globally distributed wastewater anammox reactors as core taxa. They likely formed a mutualistic relationship with auxotrophic Ca. Kuenenia by providing necessities such as methionine, folate, 4'-phosphopantetheine, and molybdopterin cofactor, and receiving vitamin B12 for methionine synthesis. For the first time, the identify and metabolic features of SMP assimilators in wastewater anammox communities were revealed. Supplying necessities secreted by heterotrophs could be helpful to the endeavor of AnAOB enrichment. Practically, maintaining active but not overgrown SMP assimilators is critical to efficient and stable operation of wastewater anammox processes.

Dairy consumption and risk of esophagus cancer in the prostate, lung, colorectal, and ovarian cohort.

Background: Epidemiological studies provide limited information on the relationship between dairy consumption and the incidence of esophagus cancer (EC). We examined whether eating dairy foods is associated with a lower risk of EC in an American population. Methods: In our study, we analyzed data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial, which included 101,723 subjects. Dairy product consumption was assessed using a dietary history questionnaire. We used Cox regression and restricted cubic splines to assess whether dairy consumption is associated with EC incidence. Results: A total of 154 EC cases were identified after a median follow-up of 12.2 years. After adjusting for confounders, we discovered no statistically significant correlation between total dairy product consumption and EC risk (HR with 95% CI for ≥1.79 servings/day vs. ≤0.6 servings/day: 0.83, 0.50-1.38; p for trend = 0.465). Additionally, no associations were found between EC risk and other dairy foods such as milk, yogurt, and cheese. Conclusion: We concluded that the findings of the PLCO cohort do not suggest dairy consumption reduces the risk of EC.

Cholesterol efflux capacity is an independent predictor of all-cause and cardiovascular mortality in patients with coronary artery disease: A prospective cohort study.

BACKGROUND: Although diminished cholesterol efflux capacity is positively related with prevalent coronary artery disease, its prognostic value for incident cardiovascular events remains a topic of debate. This work aims to investigate the association between cholesterol efflux capacity and all-cause and cardiovascular mortality in patients with coronary artery disease. METHODS AND RESULTS: We measured cholesterol efflux capacity at baseline in 1737 patients with coronary artery disease from the Guangdong Coronary Artery Disease Cohort. During 6645 person-years of follow-up, 166 deaths were registered, 122 of which were caused by cardiovascular diseases. After multivariate adjustment for factors related to cardiovascular diseases, the hazard ratios of cholesterol efflux capacity in the fourth quartile compared with those in the bottom quartile were 0.24 (95% confidence intervals 0.13-0.44) for all-cause mortality (P < 0.001), and 0.17 (95% confidence intervals 0.08-0.39) for cardiovascular mortality (P < 0.001). Adding cholesterol efflux capacity to a model containing traditional cardiovascular risk factors significantly increases its discriminatory power and predictive ability for all-cause (area under receiver operating characteristic curve 0.79 versus 0.76, P = 0.001; net reclassification improvement 14.5%, P = 0.001; integrated discrimination improvement 0.016, P < 0.001) and cardiovascular (area under receiver operating characteristic curve 0.81 versus 0.78, P = 0.001; net reclassification improvement 18.4%, P < 0.001; integrated discrimination improvement 0.015, P < 0.001) death, respectively. CONCLUSIONS: Cholesterol efflux capacity may serve as an independent measure for predicting all-cause and cardiovascular mortality in patients with coronary artery disease.