The switch of cellular metabolism from mitochondrial respiration to glycolysis is the hallmark of cancer cells and associated with tumor malignancy. However, the mechanism of this metabolic switch remains largely unknown. Herein, we reported that hypoxia-inducible factor-1 (HIF-1) induced pyruvate dehydrogenase kinase-3 (PDK3) expression leading to inhibition of mitochondrial respiration. Promoter activity assay, small interference RNA knockdown assay, and chromatin immunoprecipitation assay demonstrated that hypoxia-induced PDK3 gene activity was regulated by HIF-1 at the transcriptional level. Forced expression of PDK3 in cancer cells resulted in increased lactic acid accumulation and drugs resistance, whereas knocking down PDK3 inhibited hypoxia-induced cytoplasmic glycolysis and cell survival. These data demonstrated that increased PDK3 expression due to elevated HIF-1␣ in cancer cells may play critical roles in metabolic switch during cancer progression and chemoresistance in cancer therapy.
Non-alcoholic fatty liver disease (NAFLD) is an emerging chronic liver disease that may lead to liver cirrhosis and hepatocellular carcinoma. We aimed to determine the association between the prevalence of metabolic syndrome (MetS) and NAFLD severity using semi-quantitative ultrasonography (US). A total of 614 participants were recruited from the community. NAFLD was evaluated according to the ultrasonographic Fatty Liver Indicator (US-FLI), which is a semi-quantitative liver ultrasound score. Insulin resistance was estimated with the homeostasis model assessment index for insulin resistance (HOMA-IR). NAFLD and MetS were found in 53.7 and 17.3% of the participants, respectively. Linear relationships were found between the severity of NAFLD and waist circumference, fasting glucose, HOMA-IR, triglycerides, HDL-C and blood pressure. After adjusting for confounding factors, i.e., body mass index and HOMA-IR, the odds ratios for MetS were 3.64 (95% confidence interval (CI): 1.5–8.83) for those with mild NAFLD and 9.4 (95% CI: 3.54–24.98) for those with moderate-to-severe NAFLD compared to those without NAFLD. The combination of the HOMA-IR and US-FLI scores better differentiated MetS than the HOMA-IR alone. In addition to obesity, the severity of NAFLD and the HOMA-IR both play important roles in MetS. Whether NAFLD is a component of MetS warrants further research.
Endometriosis is the primary cause of infertility in women, with a prevalence rate ranging from 5% to 10%. Women with endometriosis suffer from symptoms such as chronic pelvic pain, dysmenorrhea and dyspareunia, which significantly reduce the quality of life. Endometriosis is a polygenic disease with a complex, multifactorial etiology. The mechanism responsible for the initiation and development of this disease remains largely unknown. Prostaglandin E(2) (PGE(2)), a versatile eicosanoid that exerts numerous physiological and pathological functions, has been implicated to play critical roles in the development of endometriosis. A growing body of evidence demonstrates that PGE(2) regulates many pathophysiological processes including cell proliferation, antiapoptosis, immune suppression and angiogenesis during the development of endometriosis. This review focuses on recent advances in cellular and molecular mechanisms triggered by PGE(2) that contribute to the pathological processes of endometriosis.
The switch of cellular metabolism from mitochondrial respiration to glycolysis is the hallmark of cancer cells and is associated with tumor malignancy. Pyruvate dehydrogenase kinase-1 (PDK1) and PDK3 participate in the metabolic switch of cancer cells; however, the medical significance of PDK1 and PDK3 in cancer progression is not known. Here, we assessed the expression profiles of PDK1 and PDK3 in colorectal cancer. Western blot analysis (n = 74) demonstrated that PDK3 was markedly increased in colon cancer compared to that in adjacent normal tissues, whereas PDK1 was decreased in cancer cells. In addition, PDK3 expression was positively correlated with that of hypoxia inducible factor-1α (HIF-1α) in cancer cells. Further analysis using immunohistochemical staining revealed that PDK3 levels were positively associated with severity of cancer and negatively associated with disease-free survival. In vitro studies using several colon cancer cell lines showed that PDK3 expression was controlled by HIF-1α and contributed to hypoxia-induced increased drug resistance, perhaps explaining why patients with PDK3 overexpression have a greater incidence of treatment failure. Taken together, our findings suggest that PDK3 plays an important role in the metabolic switch and drug resistance of colon cancer and is potentially a novel target for cancer therapy.
Sarcopenia, highly linked with fall, frailty, and disease burden, is an emerging problem in aging society. Higher protein intake has been suggested to maintain nitrogen balance. Our objective was to investigate whether pre-sarcopenia status was associated with lower protein intake. A total of 327 community-dwelling elderly people were recruited for a cross-sectional study. We adopted the multivariate nutrient density model to identify associations between low muscle mass and dietary protein intake. The general linear regression models were applied to estimate skeletal muscle mass index across the quartiles of total protein and vegetable protein density. Participants with diets in the lowest quartile of total protein density (<13.2%) were at a higher risk for low muscle mass (odds ratio (OR) 3.03, 95% confidence interval (CI) 1.37–6.72) than those with diets in the highest quartile (≥17.2%). Similarly, participants with diets in the lowest quartile of vegetable protein density (<5.8%) were at a higher risk for low muscle mass (OR 2.34, 95% CI 1.14–4.83) than those with diets in the highest quartile (≥9.4%). Furthermore, the estimated skeletal muscle mass index increased significantly across the quartiles of total protein density (p = 0.023) and vegetable protein density (p = 0.025). Increasing daily intakes of total protein and vegetable protein densities appears to confer protection against pre-sarcopenia status.
The prognosis of advanced non-small cell lung cancer (NSCLC) patients is poor. One of the reasons for this hampered progress has been a lack of in vitro models that would faithfully recapitulate the heterogeneity of tumors and response to treatment. In this study, surgically resected tumors were obtained from patients with stage I/II NSCLC during curative-intent surgery. Using a 3D patient-derived tumor spheroids culture system, our results demonstrate successful long-term expansion of primary NSCLC cells in vitro (> 120 days). Patient-derived tumor spheroid (PDS) cultures could be established with a success rate of 100% (3 out of 3 samples). Consistent with their growth in culture and their cancer type, many cells within the tumor spheroids were stained positive for Ki67 and thyroid transcription factor-1. The result of this study supports the establishment of an expandable 3D in vitro NSCLC model for drug screening, and enables the potential long term studies such as the establishment of drug resistant models.
Objective: Investigate the nature of the relationship between chronic hepatitis B virus (HBV) infection and metabolic syndrome among nondiabetic adults. Methods: This was a cross-sectional analysis of 17,030 nondiabetic adults (7437 males and 9593 females; mean age, 36.0 6 3.9 years) in northern Taiwan from 2008 to 2009. The associations of hepatitis B surface antigen (HBsAg) seropositivity with metabolic syndrome and cardio-metabolic parameters were assessed. A structural equation model was constructed to elucidate the pathways between chronic HBV infection and individual cardiometabolic risk factors. Results: A total of 2982 (17.5%) participants were HBsAg-seropositive. Of the seropositive and seronegative subjects, 15.5 and 16.9% had metabolic syndrome, respectively. The HBsAg-seropositive subjects had a lower odds of having metabolic syndrome compared with the seronegative subjects irrespective of gender and age (OR: 0.76, 95% CI: 0.68-0.85). The inverse associations remained significant after adjusting for body mass index and serum alanine aminotransferase levels. HBsAg seropositivity was inversely associated with hypertriglyceridemia (OR: 0.59, 95% CI: 0.52-0.66), and low serum levels of high-density lipoprotein cholesterol (OR: 0.86, 95% CI: 0.79-0.93) after adjustments. The structural equation model revealed chronic HBV infection had a significant negative effect on dyslipidemia both in males (B 5 20.054) and females (B 5 20.064). Conclusions: The inverse relationship between chronic HBV infection and metabolic syndrome may be attributable to the net beneficial effects on lipid profiles.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
334 Leonard St
Brooklyn, NY 11211
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.