Background:Yangxin Dawayimixike honey paste(YDHP)is a representative traditional Chinese medicine,and its main function is curing angina pectoris,palpitation and neurasthenia.However,it is unclear whether YDHP can sup...Background:Yangxin Dawayimixike honey paste(YDHP)is a representative traditional Chinese medicine,and its main function is curing angina pectoris,palpitation and neurasthenia.However,it is unclear whether YDHP can suppress the development of atherosclerosis.The aim of this study was to validate the potential application of YDHP in atherosclerosis therapy and search for its potential mechanisms.Methods:Seven-week-old ApoE^(-/-)mice were randomly divided into a normal group fed a normal diet,an atherosclerosis model group fed a high-fat diet,YDHP groups fed a high-fat diet mixed with different doses of YDHP and positive control groups fed a high-fat diet mixed with atorvastatin or rosuvastatin.After feeding for 10 weeks,body weight,blood lipids,liver and kidney function indexes,serum inflammatory cytokines and atherosclerotic plaque areas were measured.Serum metabolic profiles were detected by an automatic biochemical analyser.Serum inflammatory cytokines were quantified by enzyme-linked immunosorbent assay kits.Atherosclerotic plaque areas were analysed using Oil Red O staining.Results:The YDHP(200,400 and 800 mg/kg/d)treated groups showed reduced serum levels of low density lipoprotein-cholesterol(P<0.05,when 200 or 400 mg/kg/d of YDHP group compared with the atherosclerosis model group;P<0.01,when 800 mg/kg/d of YDHP group compared with the atherosclerosis model group),total cholesterol(P<0.05,when 200 mg/kg/d of YDHP group compared with the atherosclerosis model group;P<0.01,when 400 or 800 mg/kg/d of YDHP group compared with the atherosclerosis model group)and triglyceride(P<0.01),however,elevated serum levels of high-density lipoprotein cholesterol(P<0.01)compared to the atherosclerosis model group.YDHP inhibited the area of atherosclerotic lesions.In addition,YDHP suppressed the levels of serum inflammatory cytokines such as interleukin 6(P<0.05,when 200 mg/kg/d of YDHP group compared with the atherosclerosis model group;P<0.01,when 400 or 800 mg/kg/d of YDHP group compared with the atherosclerosis model group)and tumor necrosis factorα(P<0.05,when 200 mg/kg/d of YDHP group compared with the atherosclerosis model group;P<0.01,when 400 or 800 mg/kg/d of YDHP group compared with the atherosclerosis model group).Conclusion:Our study demonstrated that YDHP showed considerable activity in alleviating the formation of atherosclerotic plaques in ApoE^(-/-)mice by reducing blood lipids and exerting anti-inflammatory activity.展开更多
We search for nuclear recoil signals of dark matter(DM)models with a light mediator using data taken from a p-type point-contact germanium detector of the CDEX-10 experiment at the China Jinping Underground Laboratory...We search for nuclear recoil signals of dark matter(DM)models with a light mediator using data taken from a p-type point-contact germanium detector of the CDEX-10 experiment at the China Jinping Underground Laboratory.The 90%confidence level upper limits on the DM-nucleon interaction cross section from 205.4 kg-day exposure data are derived,excluding the new parameter space in 2−3 GeV DM mass when the mediator mass is comparable to or lower than the typical momentum transfer.We further interpret our results to constrain a specific self-interacting DM model with a light mediator coupling to the photon through kinetic mixing and set experimental limits on the model parameter region favored by astrophysical observations.展开更多
The autophagy adaptor protein SQSTM1/p62 is overexpressed in breast cancer and has been identified as a metastasis-related protein.However,the mechanism by which SQSTM1/p62 contributes to breast cancer progression and...The autophagy adaptor protein SQSTM1/p62 is overexpressed in breast cancer and has been identified as a metastasis-related protein.However,the mechanism by which SQSTM1/p62 contributes to breast cancer progression and tumor microenvironment remains unclear.This study revealed that silencing SQSTM1/p62 expression suppressed breast cancer progression via regulating cell proliferation and reshaping the tumor microenvironment(TME).Here,we found that SQSTM1/p62 was overexpressed in multiple human cancer tissue types and that was correlated with poor patient overall survival(OS)and disease-free survival(DFS).Moreover,we found that short-hairpin RNA(shRNA)-mediated knockdown of p62 expression significantly inhibited cell proliferation,migration,and invasion,and promoted cell death in vitro,as well as suppressed breast cancer growth and lung metastasis in vivo.In addition,flow cytometry analysis of splenocytes and tumor infiltrating lymphocytes(TILs)indicated that the numbers of CD8α+interferon(IFN)-γ+cells(CTLs)and CD4+IFN-γ+(Th1)cells were increased while those of CD4+IL-4+(Th2)cells,tumor-associated macrophages(TAMs)and myeloid-derived suppressor cells(MDSCs)were decreased.RT-PCR analyses showed that the gene expression of Th1/Th2 cytokines changed in the tumor microenvironment.Silencing SQSTM1/p62 suppressed tumor cell lung metastasis.Together,our results provide strong evidence that silencing tumor cell SQSTM1/p62 inhibited tumor growth and metastasis through cell cycle arrest and TME regulation.This finding provides a novel molecular therapeutic strategy for breast cancer progression and metastasis treatment.展开更多
基金the Wuhan Municipal Health Commission Foundation(No.wx21Q38).
文摘Background:Yangxin Dawayimixike honey paste(YDHP)is a representative traditional Chinese medicine,and its main function is curing angina pectoris,palpitation and neurasthenia.However,it is unclear whether YDHP can suppress the development of atherosclerosis.The aim of this study was to validate the potential application of YDHP in atherosclerosis therapy and search for its potential mechanisms.Methods:Seven-week-old ApoE^(-/-)mice were randomly divided into a normal group fed a normal diet,an atherosclerosis model group fed a high-fat diet,YDHP groups fed a high-fat diet mixed with different doses of YDHP and positive control groups fed a high-fat diet mixed with atorvastatin or rosuvastatin.After feeding for 10 weeks,body weight,blood lipids,liver and kidney function indexes,serum inflammatory cytokines and atherosclerotic plaque areas were measured.Serum metabolic profiles were detected by an automatic biochemical analyser.Serum inflammatory cytokines were quantified by enzyme-linked immunosorbent assay kits.Atherosclerotic plaque areas were analysed using Oil Red O staining.Results:The YDHP(200,400 and 800 mg/kg/d)treated groups showed reduced serum levels of low density lipoprotein-cholesterol(P<0.05,when 200 or 400 mg/kg/d of YDHP group compared with the atherosclerosis model group;P<0.01,when 800 mg/kg/d of YDHP group compared with the atherosclerosis model group),total cholesterol(P<0.05,when 200 mg/kg/d of YDHP group compared with the atherosclerosis model group;P<0.01,when 400 or 800 mg/kg/d of YDHP group compared with the atherosclerosis model group)and triglyceride(P<0.01),however,elevated serum levels of high-density lipoprotein cholesterol(P<0.01)compared to the atherosclerosis model group.YDHP inhibited the area of atherosclerotic lesions.In addition,YDHP suppressed the levels of serum inflammatory cytokines such as interleukin 6(P<0.05,when 200 mg/kg/d of YDHP group compared with the atherosclerosis model group;P<0.01,when 400 or 800 mg/kg/d of YDHP group compared with the atherosclerosis model group)and tumor necrosis factorα(P<0.05,when 200 mg/kg/d of YDHP group compared with the atherosclerosis model group;P<0.01,when 400 or 800 mg/kg/d of YDHP group compared with the atherosclerosis model group).Conclusion:Our study demonstrated that YDHP showed considerable activity in alleviating the formation of atherosclerotic plaques in ApoE^(-/-)mice by reducing blood lipids and exerting anti-inflammatory activity.
基金Supported by the National Key Research and Development Program of China(2023YFA1607101)the National Natural Science Foundation of China(12425507,12322511,12175112)。
文摘We search for nuclear recoil signals of dark matter(DM)models with a light mediator using data taken from a p-type point-contact germanium detector of the CDEX-10 experiment at the China Jinping Underground Laboratory.The 90%confidence level upper limits on the DM-nucleon interaction cross section from 205.4 kg-day exposure data are derived,excluding the new parameter space in 2−3 GeV DM mass when the mediator mass is comparable to or lower than the typical momentum transfer.We further interpret our results to constrain a specific self-interacting DM model with a light mediator coupling to the photon through kinetic mixing and set experimental limits on the model parameter region favored by astrophysical observations.
基金supported by the CAMS Initiative for Innovative Medicine(No.2016-I2M-1-019)2017-I2M-3-022,the Fundamental Research Funds for the Central Universities of China(No.3332019162)+1 种基金the funds for IMBCAMS PhD Innovation(No.2018018001)the Foundation for Studying Abroad from the China Scholarship Council(No.201808110121,201906210477).
文摘The autophagy adaptor protein SQSTM1/p62 is overexpressed in breast cancer and has been identified as a metastasis-related protein.However,the mechanism by which SQSTM1/p62 contributes to breast cancer progression and tumor microenvironment remains unclear.This study revealed that silencing SQSTM1/p62 expression suppressed breast cancer progression via regulating cell proliferation and reshaping the tumor microenvironment(TME).Here,we found that SQSTM1/p62 was overexpressed in multiple human cancer tissue types and that was correlated with poor patient overall survival(OS)and disease-free survival(DFS).Moreover,we found that short-hairpin RNA(shRNA)-mediated knockdown of p62 expression significantly inhibited cell proliferation,migration,and invasion,and promoted cell death in vitro,as well as suppressed breast cancer growth and lung metastasis in vivo.In addition,flow cytometry analysis of splenocytes and tumor infiltrating lymphocytes(TILs)indicated that the numbers of CD8α+interferon(IFN)-γ+cells(CTLs)and CD4+IFN-γ+(Th1)cells were increased while those of CD4+IL-4+(Th2)cells,tumor-associated macrophages(TAMs)and myeloid-derived suppressor cells(MDSCs)were decreased.RT-PCR analyses showed that the gene expression of Th1/Th2 cytokines changed in the tumor microenvironment.Silencing SQSTM1/p62 suppressed tumor cell lung metastasis.Together,our results provide strong evidence that silencing tumor cell SQSTM1/p62 inhibited tumor growth and metastasis through cell cycle arrest and TME regulation.This finding provides a novel molecular therapeutic strategy for breast cancer progression and metastasis treatment.
