Summary What is already known about this topic?Previous studies have predominantly examined the micro-level aspects of women aging inflection points,while macro-level research using big data on the inflection points o...Summary What is already known about this topic?Previous studies have predominantly examined the micro-level aspects of women aging inflection points,while macro-level research using big data on the inflection points of aging among middle-aged and elderly women in China is currently limited.展开更多
Background and Aims:Osteopontin(OPN)is reported to be associated with the pathogenesis of nonalcoholic fatty liver disease(NAFLD).However,the function of OPN in NAFLD is still inconclusive.Therefore,our aim in this st...Background and Aims:Osteopontin(OPN)is reported to be associated with the pathogenesis of nonalcoholic fatty liver disease(NAFLD).However,the function of OPN in NAFLD is still inconclusive.Therefore,our aim in this study was to evaluate the role of OPN in NAFLD and clarify the involved mechanisms.Methods:We analyzed the expression change of OPN in NAFLD by bioinformatic analysis,qRT-PCR,western blotting and immunofluorescence staining.To clarify the role of OPN in NAFLD,the effect of OPN from HepG2 cells on macrophage polarization and the involved mechanisms were examined by FACS and western blotting.Results:OPN was significantly upregulated in NAFLD patients compared with normal volunteers by microarray data,and the high expression of OPN was related with disease stage and progression.OPN level was also significantly increased in liver tissue samples of NAFLD from human and mouse,and in HepG2 cells treated with oleic acid(OA).Furthermore,the supernatants of OPN-treated HepG2 cells promoted the macrophage M1 polarization.Mechanistically,OPN activated the janus kinase 1(JAK1)/signal transducers and activators of transcription 1(STAT1)signaling pathway in HepG2 cells,and consequently HepG2 cells secreted more high-mobility group box 1(HMGB1),thereby promoting macrophage M1 polarization.Conclusions:OPN promoted macrophage M1 polarization by increasing JAK1/STAT1-induced HMGB1 secretion in hepatocytes.展开更多
Gain-of-function (GOF), the most malicious oncogenic activity of a cancer-promoting protein, is well illustrated to three hotspot p53 mutations at R248, R175, and R273 with distinct molecular mechanisms. Yet, less is ...Gain-of-function (GOF), the most malicious oncogenic activity of a cancer-promoting protein, is well illustrated to three hotspot p53 mutations at R248, R175, and R273 with distinct molecular mechanisms. Yet, less is known about another hotspot p53 mutant, R249S (p53-R249S). p53-R249S is the sole hotspot mutation in hepatocellular carcinoma (HCC) that is highly associated with chronic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin B1 (AFB1). Its GOF is suggested by the facts that this mutant is associated with earlier onset of HCC and poorer prognosis of cancer patients and that its overexpression drives HCC proliferation and tumorigenesis. By contrast, simply knocking in this mutant in normal mice did not show apparent GOF activity. Hence, the GOF activity for p53-R249S and its underlying mechanisms have been elusive until recent findings offered some new insights. This review will discuss these findings as well as their clinical significance and implications for the development of a strategy to target multiple molecules as a therapy for p53-R249S-harboring HCC.展开更多
基金Supported by the National Key R&D Program of China(2018YFC2002000,2018YFC2002002,2020YFC2002901)National Natural Science Foundation of China(82071581,81960620 and 81360446 to HH,81960611,81560550 to LW)+2 种基金Shanghai Municipal Health Commission(2021WB04,201940415,JKKPYL-2022-15)Key Discipline Projects of Huadong Hospital(LCZX2202)Excellent Talent Projects of Huadong Hospital(HDGG2017018).
文摘Summary What is already known about this topic?Previous studies have predominantly examined the micro-level aspects of women aging inflection points,while macro-level research using big data on the inflection points of aging among middle-aged and elderly women in China is currently limited.
基金supported by National Natural Science Foundation of China grants (81760089,82160094 to MJ,82060112 to LD)Jiangxi Provincial Department of Science and Technology,China (20202BAB206087 to MJ).
文摘Background and Aims:Osteopontin(OPN)is reported to be associated with the pathogenesis of nonalcoholic fatty liver disease(NAFLD).However,the function of OPN in NAFLD is still inconclusive.Therefore,our aim in this study was to evaluate the role of OPN in NAFLD and clarify the involved mechanisms.Methods:We analyzed the expression change of OPN in NAFLD by bioinformatic analysis,qRT-PCR,western blotting and immunofluorescence staining.To clarify the role of OPN in NAFLD,the effect of OPN from HepG2 cells on macrophage polarization and the involved mechanisms were examined by FACS and western blotting.Results:OPN was significantly upregulated in NAFLD patients compared with normal volunteers by microarray data,and the high expression of OPN was related with disease stage and progression.OPN level was also significantly increased in liver tissue samples of NAFLD from human and mouse,and in HepG2 cells treated with oleic acid(OA).Furthermore,the supernatants of OPN-treated HepG2 cells promoted the macrophage M1 polarization.Mechanistically,OPN activated the janus kinase 1(JAK1)/signal transducers and activators of transcription 1(STAT1)signaling pathway in HepG2 cells,and consequently HepG2 cells secreted more high-mobility group box 1(HMGB1),thereby promoting macrophage M1 polarization.Conclusions:OPN promoted macrophage M1 polarization by increasing JAK1/STAT1-induced HMGB1 secretion in hepatocytes.
文摘Gain-of-function (GOF), the most malicious oncogenic activity of a cancer-promoting protein, is well illustrated to three hotspot p53 mutations at R248, R175, and R273 with distinct molecular mechanisms. Yet, less is known about another hotspot p53 mutant, R249S (p53-R249S). p53-R249S is the sole hotspot mutation in hepatocellular carcinoma (HCC) that is highly associated with chronic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin B1 (AFB1). Its GOF is suggested by the facts that this mutant is associated with earlier onset of HCC and poorer prognosis of cancer patients and that its overexpression drives HCC proliferation and tumorigenesis. By contrast, simply knocking in this mutant in normal mice did not show apparent GOF activity. Hence, the GOF activity for p53-R249S and its underlying mechanisms have been elusive until recent findings offered some new insights. This review will discuss these findings as well as their clinical significance and implications for the development of a strategy to target multiple molecules as a therapy for p53-R249S-harboring HCC.