Diet greatly influences gut microbiota. Dietary methionine restriction (MR) prevents and ameliorates age-related or high-fat-induced diseases and prolongs life span. This study aimed to reveal the impact of MR on gut microbiota in middle-aged mice with low-, medium-, high-fat diets. C57BL/6J mice were randomly divided into six groups with different MR and fat-content diets. Multiple indicators of intestinal function, fat accumulation, energy consumption, and inflammation were measured. 16S rRNA gene sequencing was used to analyze cecal microbiota. Our results indicated that MR considerably reduced the concentrations of lipopolysaccharide (LPS) and increased short-chain fatty acids (SCFAs) by upregulating the abundance of Corynebacterium and SCFA-producing bacteria Bacteroides, Faecalibaculum, and Roseburia and downregulating the LPS-producing or proinflammatory bacteria Desulfovibrio and Escherichia–Shigella. The effect of MR on LPS and SCFAs further reduced fat accumulation and systemic inflammation, enhanced heat production, and mediated the LPS/LBP/CD14/ TLR4 pathway to strength the intestinal mucosal immunity barrier in middle-aged mice.
BackgroundKIF20A plays an indispensable role in cytokinesis regulation, which is important for tumor proliferation and growth. Recently, the oncogenic role of KIF20A has been well documented in several cancers. However, its clinical role in epithelial ovarian cancer (EOC) remains not reported yet. We investigated its expression and its role in promoting invasion and chemoresistance in EOC cells.Patients and methodsKIF20A transcription and translation levels were investigated in normal ovarian epithelial cell, ovarian cancer cells, and 10 pairs of fresh EOC tissues and adjacent normal ovarian tissues by real-time quantitative polymerase chain reaction and Western blots. Moreover, KIF20A protein level was also examined by immunohistochemistry in 150 EOC tissues. The correlation between KIF20A expression and clinical variables was analyzed by statistical methods. We also used wound healing assay, transwell assay MTT, and Annexin V/PI to explore KIF20A functions.ResultsKIF20A expression was obviously elevated at both mRNA and protein levels in EOC cell lines and clinical cancer tissues compared with normal ovarian epithelial cell and adjacent normal ovarian tissues. KIF20A protein expression was highly correlated with International Federation of Gynecology and Obstetrics stage (P=0.008), lymph node metastasis (P=0.002), intraperitoneal metastasis (P<0.001), vital status at last follow-up (P<0.001), intraperitoneal recurrence (P=0.030), tumor recurrence (P=0.005), drug resistance (P=0.013), and ascites with tumor cells (P<0.001). KIF20A overexpression was closely related to poorer overall survival and disease progression-free survival. Furthermore, Cox regression analysis revealed that KIF20A can act as an independent hazard indicator for predicting clinical outcomes in EOC patients. Interestingly, KIF20A overexpression promoted invasion and metastasis of EOC cells and also confers resistance to cisplatin.ConclusionOur findings indicated that KIF20A overexpression predicts unfavorable clinical outcome, revealing that KIF20A holds a promising potential to serve as a useful prognostic biomarker for EOC patients.
T he sex difference in blood pressure (BP) has long been recognized between premenopausal women and agedmatched men.1 Women are protected from most cardiovascular events compared with age-matched men before menopause, and postmenopausal women are at increased risk of cardiovascular complications compared with premenopausal women. 2 The pathophysiological mechanisms have been extensively explored, and increasing evidences have shown that the female hormone is one of the major mechanisms contributing to the above phenomena.3 Several studies have demonstrated the importance of the interaction between sex hormones and the renin-angiotensin system in regulating cardiovascular function and BP. 4,5 Angiotensin-II (Ang-II) is a key player in the development of hypertension. Ang-II type-1 (AT 1 R) and type-2 (AT 2 R) receptors play opposite roles in BP regulation, 6,7 with AT 2 R exerting a cardioprotective action in essential hypertension. 8 Early study demonstrates that AT 2 R provides a major clue for solving the mystery of sex differences in AT 2 R-mediated vasodilation 9 and hypertension. 10 However, the majority of researches on hypertension to date has been conducted in male animals and focused largely on the target organs, such as the heart, blood vessels, and kidney. The sex differences in neurocontrol of circulation at baroreflex level have almost been neglected although AT 1 R or AT 2 R has been identified in nodose ganglia (NG) or nucleus of tractus solitary (NTS). 11,12 Recent literatures have shown that adult female rats express Abstract-This study aims to understand the special expression patterns of angiotensin-II receptor (AT 1 R and AT 2 R) in nodose ganglia and nucleus of tractus solitary of baroreflex afferent pathway and their contribution in sex difference of neurocontrol of blood pressure regulation. In this regard, action potentials were recorded in baroreceptor neurons (BRNs) using whole-cell patch techniques; mRNA and protein expression of AT 1 R and AT 2 R in nodose ganglia and nucleus of tractus solitary were evaluated using real time-polymerase chain reaction, Western blot, and immunohistochemistry at both tissue and single-cell levels. The in vivo effects of 17β-estradiol on blood pressure and AT 2 R expression were also tested. The data showed that AT 2 R, rather than AT 1 R, expression was higher in female than age-matched male rats. Moreover, AT 2 R was downregulated in ovariectomized rats, which was restored by the administration of 17β-estradiol. Single-cell real time-polymerase chain reaction data indicated that AT 2 R was uniquely expressed in Ah-type BRNs. Functional study showed that long-term administration of 17β-estradiol significantly alleviated the blood pressure increase in ovariectomized rats. Electrophysiological recordings showed that angiotensin-II treatment increased the neuroexcitability more in Ah-than C-type BRNs, whereas no such effect was observed in A-types. In addition, angiotensin-II treatment prolonged action potential duration, which was not further changed...
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