SOAT1 regulates cholesterol metabolism to induce EMT in hepatocellular carcinoma.

Cholesterol metabolism reprogramming is one of the significant characteristics of hepatocellular carcinoma (HCC). Cholesterol increases the risk of epithelial-mesenchymal transition (EMT) in cancer. Sterol O-acyltransferases 1 (SOAT1) maintains the cholesterol homeostasis. However, the exact mechanistic contribution of SOAT1 to EMT in HCC remains unclear. Here we demonstrated that SOAT1 positively related to poor prognosis of HCC, EMT markers and promoted cell migration and invasion in vitro, which was mediated by the increased cholesterol in plasmalemma and cholesterol esters accumulation. Furthermore, we reported that SOAT1 disrupted cholesterol metabolism homeostasis to accelerate tumorigenesis and development in HCC xenograft and NAFLD-HCC. Also, we detected that nootkatone, a sesquiterpene ketone, inhibited EMT by targeting SOAT1 in vitro and in vivo. Collectively, our finding indicated that SOAT1 promotes EMT and contributes to hepatocarcinogenesis by increasing cholesterol esterification, which is suppressed efficiently by nootkatone. This study demonstrated that SOAT1 is a potential biomarker and therapeutic target in NAFLD-HCC and SOAT1-targeting inhibitors are expected to be the potential new therapeutic treatment for HCC.

pH Sensitive Quercetin Nanoparticles Ameliorate DSS-Induced Colitis in Mice by Colon-Specific Delivery.

SCOPE: Ulcerative colitis (UC) is a classic inflammatory bowel disease (IBD) that represents a serious threat to human health. As a natural flavonoid with multiple biological activities, quercetin (QCT) suffers from low bioavailability through limitations in chemical stability. Here, the study investigates the regulatory effects of quercetin nanoparticles (QCT NPs) on dextran sulfate sodium (DSS) induced colitis mice. METHODS AND RESULTS: Chitosan is modified to obtain N-succinyl chitosan (NSC) with superior water solubility. Nanoparticles composed of sodium alginate (SA) and NSC can encapsulate QCT after cross-linking, forming QCT NPs. In vitro drug release assays demonstrate the pH sensitivity of QCT NPs. Compared with free quercetin, QCT NPs have better therapeutic efficacy in modulating gut microbiota and its metabolites short chain fatty acid (SCFAs) to relieve DSS-induced colitis in mice, thereby alleviating colon inflammatory infiltration, increasing goblet cells density and mucus protein, ameliorating TNF-α, IL-1ß, IL-6, IL-10, and Myeloperoxidase (MPO) levels, and recovering intestinal barrier integrity. CONCLUSION: pH sensitive QCT nanoparticles can reduce inflammatory reaction, improve gut microbiota, and repair intestinal barrier by targeting colon, thus improving DSS induced colitis in mice, providing reference for the treatment of colitis.

Sea Cucumber Peptide Alleviates Ulcerative Colitis Induced by Dextran Sulfate Sodium by Alleviating Gut Microbiota Imbalance and Regulating miR-155/SOCS1 Axis in Mice.

Sea cucumber peptides have been proven to exhibit a variety of biological activities. Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the mucosa of the rectum and colon with increasing incidence and long duration, and is difficult to cure. The effect of sea cucumber peptide on UC is currently unknown. In this study, 1.5% dextran sulfate sodium (DSS) was added to the drinking water of mice to induce a UC model, and the daily doses of sea cucumber peptide (SP) solution of 200 mg/kg·BW, 500 mg/kg·BW, and 1000 mg/kg·BW were given to UC mice to detect the relieving effect of SP. The results showed that SP can reduce the disease activity index (DAI) of UC mice induced by DSS and can alleviate colon shortening, intestinal tissue damage, and the loss of intestinal tight junction proteins (Claudin-1, Occludin). SP decreased the spleen index, pro-inflammatory factors (IL-1ß, IL-6, TNF-α), and myeloperoxidase (MPO) levels in UC mice. SP can alleviate the imbalance of gut microbiota in UC mice, increase the abundance of the Lachnospiraceae NK4A136 group, Prevotellaceae UCG-001, and Ligilactobacillus, and reduce the abundance of Bacteroides and the Eubacterium rum group, as well as alleviating the decrease in short-chain fatty acid (SCFA) content in the feces of UC mice. Notably, SP inhibited miR-155 expression in the colon tissue of UC mice and increased its target protein, suppressor of cytokine signaling 1 (SOCS1), which acts as an inflammatory inhibitor. In summary, the ameliorative effect of SP on UC may be achieved by improving the imbalance of gut microbiota and regulating the miR-155/SOCS1 axis. This study provides a new idea for developing SP as a nutritional supplement to maintain intestinal health.

Apigenin remodels the gut microbiota to ameliorate ulcerative colitis.

Introduction: Ulcerative colitis (UC), a chronic non-specific colorectal inflammatory disease with unclear etiology, has long plagued human health. Gut microbiota dysbiosis destroy homeostasis of the colon, which is closely related to ulcerative colitis progress. Apigenin, a flavonoid widely present in celery, has been found to improve ulcerative colitis. However, the potential molecular mechanism of apigenin ameliorating ulcerative colitis through protecting intestinal barrier and regulating gut microbiota remains undefined. Methods: Dextran sodium sulfate (DSS)-induced colitis mouse model was conducted to evaluate the effect of apigenin on UC. Disease activity index score of mice, colon tissue pathological, cytokines analysis, intestinal tight junction proteins expression, and colonic content short-chain fatty acids (SCFAs) and 16S rRNA gene sequencing were conducted to reflect the protection of apigenin on UC. Results: The results indicated that apigenin significantly relieved the intestinal pathological injury, increased goblet cells quantity and mucin secretion, promoted anti-inflammatory cytokines IL-10 expression, and inhibited the expression of proinflammatory cytokines, TNF-α, IL-1ß, IL-6 and MPO activity of colon tissue. Apigenin increased ZO-1, claudin-1 and occludin expressions to restore the integrity of the intestinal barrier. Moreover, apigenin remodeled the disordered gut microbiota by regulating the abundance of Akkermansia, Turicibacter, Klebsiella, Romboutsia, etc., and its metabolites (SCFAs), attenuating DSS-induced colon injury. We also investigated the effect of apigenin supplementation on potential metabolic pathways of gut microbiota. Conclusion: Apigenin effectively ameliorated DSS-induced UC via balancing gut microbiome to inhibit inflammation and protect gut barrier. With low toxicity and high efficiency, apigenin might serve as a potential therapeutic strategy for the treatment of UC via regulating the interaction and mechanism between host and microorganism.

Clinical characteristics and improvement of the guideline-based management of acute myocardial infarction in China: a national retrospective analysis.

OBJECTIVE: This study is to document the clinical characteristics and improvement in management of acute myocardial infarction (AMI) in Chinese population. RESULTS: This study included 64,654 patients (23,805 patients in 2011, 40,849 patients in 2013), of which STEMI and NSTEMI account for 85.09% and 14.91%, respectively. From 2011 to 2013, significant improvement has been achieved in the recanalization rate of PCI (96.01% vs. 98.63%, P < 0.001) and in-hospital deaths (4.52% vs. 3.55%, P = 0.038). Although the time of door-to-balloon and the duration of PCI were satisfactorily controlled within 90min and 60min, respectively, the onset-to-FMC time (≈3.5h) and door-to-thrombolysis time (≈1.1h) limited the efficiency of management. The total cost of medical care showed no increase from 2011 to 2013, but the patient's paid Portion decreased from 20.33% to 13.96%. MATERIALS AND METHODS: The AMI patients admitted in the general hospitals in 2011 and 2013 were retrospectively analyzed according to the data reported to the Single Disease Quality Control Information Systemissued by Chinese Hospital Association. CONCLUSION: Compared to the Western countries, STEMI accounted for a larger portion of AMI, and the AMI management in China basically meets the standards of the quality control of guidelines. With improvement of management, there was no increase in the total medical cost, while the patient's paid portion was actually reduced. In future, improvement of transportation strategy and the public medical education are recommended to shorten the onset-to-FMC time to further improve the outcome of AMI patients.