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Background and purpose:Exogenous bone morphogenetic protein 9(BMP9)inhibits the malignant progression of human breast cancer,but its expression is often abnormally low in breast cancer.In this study,we intended to explore the expression and role of epigenetically-modified histone lysine-specific demethylase 4A(KDM4A)in breast cancer,and to investigate the relationship between KDM4A and BMP9 and its possible regulatory mechanism.Methods:The expression of KDM4A in breast cancer and its relationship with BMP9 were analyzed by bioinformatics and verified by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)and Western blot.Chromatin immunoprecipitation(ChIP)verified the regulatory role of KDM4A on BMP9,and RNA stability experiments and CHX protein stability experiments verified the effect of KDM4A in BMP9 expression.Exogenous recombinant MDA-MB-231 cells transfected with KDM4A small interfering RNA(siKDM4A)or infected with siBMP9 adenovirus(Ad-siBMP9)were constructed using RNA interference technology and adenoviruses knocking down BMP9,and the migratory and invasive abilities of the cells were detected by scratch healing assay and transwell assay,respectively.Results:Bioinformatics analysis showed that the expression of KDM4A was significantly higher in breast cancer than in normal tissues,and there was a negative correlation between the expression of KDM4A and that of BMP9 in breast cancer;RTFQ-PCR and Western blot showed that KDM4A was highly expressed in different breast cancer cell lines,and the knockdown of KDM4A significantly up-regulated BMP9.ChIP experiment confirmed that KDM4A could be significantly enriched in the promoter region of BMP9 gene,reducing its histone lysine 36 position instead of position 4 methyl status,thus silencing the expression of BMP9.RNA stability assay and CHX protein stability assay confirmed that KDM4A had no significant effect on the mRNA of BMP9,but could affect its protein degradation.After knocking down KDM4A,the migration and invasion abilities of breast cancer cells MDA-MB-231 were significantly inhibited,and this effect could be partially reversed by knocking down BMP9.Conclusion:KDM4A is highly expressed in breast cancer and breast cancer cell MDA-MB-231,and can silence its expression by down-regulating the level of histone methylation in the promoter region of the BMP9 gene,as well as affecting the stability of BMP9 at the protein level rather than at the level of mRNA,and promoting the migration and invasion of breast cancer.
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OBJECTIVE To analyze the current status， hotspots and development trends of research on the treatment of non-alcoholic fatty liver disease （NAFLD）， providing reference for subsequent research. METHODS Searching the Web of Science database， the literature related to the treatment of NAFLD from the establishment of the database to December 31， 2022 were collected. CiteSpace 6.1.R6 was used to construct a visual atlas， perform collaborative network analysis on authors， countries and institutions， and conduct keyword co-occurrence， clustering and emergence analysis to explore its research status and hotspots. RESULTS A total of 3 882 articles were included， and the number of publications had been increasing year by year. The top three countries in terms of publication volume were China， the United States， and Japan. The author with the highest volume of publications was Sanyal from the United States （37 articles）， while the institution with the highest volume of publications was the University of California， San Diego （75 articles）. A closely connected research team abroad mainly conducted large-scale randomized controlled trials （RCT） to evaluate the effectiveness and safety of various interventions， including medication and lifestyle， in treating NAFLD. However， domestic researches mainly focused on basic researches about the treatment of NAFLD with effective medicinal ingredients， and were characterized by traditional Chinese medicine. There were relatively few high-quality large-scale RCT studies related to it. Keyword analysis showed that researches in various countries mainly focused on regulating liver oxidative stress and inflammation， improving the overall balance of glucose and lipid metabolism. Except for hypoglycemic drugs， drugs that act on various comprehensive metabolic homeostasis targets in the body had entered clinical research， and had enormous therapeutic potential. CONCLUSIONS The research on NAFLD treatment continues to grow in popularity and tends to research targets and drugs for regulating systemic metabolic homeostasis. As the main force of research， China should strengthen communication with the international community， grasp the trends and directions of basic research， attach importance to clinical research， and continuously tap the therapeutic potential of traditional Chinese medicine.
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Objective@#To investigate the inhibition of tanshinoneⅡA (TanⅡA) on the proliferation of lung cancer cells.@*Methods@#Human lung cancer cell lines A549, SK-MES-1, H446 and H460 were cultured in vitro and treated with TanⅡA at concentrations of 0.3, 0.6, 1.3, 2.5, 5.0, 10.0 mg/mL, while untreated cells served as controls. Cell proliferation was measured by using CCK-8 assay, and apoptosis was measured using flow cytometry, while the expression of apoptosis-related proteins was determined using Western blotting. The apoptotic rate of lung cancer cells was compared between Tan ⅡA-treated cells and untreated cells.@*Results@# Tan ⅡA inhibited lung cancer cell proliferation in a time-dependent and concentration-dependent manner, and the survival rates of A549, SK-MS-1, H446 and H460 cells reduced with the concentration of TanⅡA (t=4.503, 2.114, 2.103 and 3.567; all P<0.05) and the duration of TanⅡA treatment (t=5.189, 3.079, 3.023 and 3.845; all P<0.05). The 48 h half maximal inhibitory concentrations (IC50 values) of TanⅡA were (1.18±0.12), (0.78±0.08), (1.55±0.16) and (1.27±0.14) mg/mL against A549, SK-MES-1, H446 and H460 cells, respectively. Following 48 h treatment with Tan ⅡA at a concentration of 2.5 mg/mL, the apoptotic rates of A549, SK-MS-1, H446 and H460 cells were (34.97±3.78)%, (37.62±2.48)%, (18.27±2.98)% and (19.17±2.30)%, which were significantly significantly higher than those of untreated cells [(4.86±0.36) %, (3.21±0.48) %, (3.25±0.26)% and (2.66±0.19)%, all P<0.05]. Reduced Akt1 protein expression, elevated Bax/Bcl-2 expression ratio, and elevated caspase-9 and caspase-3 protein expression were detected in lung cancer cells treated with 2.5 mg/mL TanⅡA for 48 h relative to untreated cells@*Conclusion@#TanⅡA may inhibit lung cancer cell proliferation in a time- and concentration-dependent manner via the Bax/Bcl-2/caspase-9/caspase-3 pathway.
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Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high mortality in clinical practice. With the development of imaging and interventional techniques, transcatheter arterial chemoembolization and local ablation are more and more widely used for treatment and can even achieve a similar effect as surgery in the treatment of some types of early-stage HCC. In addition, precision medicine and biomedicine have also developed vigorously; radiochemotherapy is more accurate and effective in the treatment of HCC, and molecular targeted therapy, immunotherapy, and gene therapy have become the directions for breakthrough in the future. This article reviews the latest advances in the non-surgical treatment of HCC.
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Objective:To study the effect of insulin intraperitoneal injection on abnormal blood lipid intype 2 diabetic KKAy mice.Methods:Type 2 diabetic mice model was established by feeding high fat and high sugar diet. KKAy model mice were randomly divided into intraperitoneal injection group ( n=6), subcutaneous injection group ( n=6) and no-treatment group ( n=3). At the same time, healthy C57BL/6J mice were selected as normal group ( n=6), and healthy KKAy mice as disease-free group ( n=6). The treatment process was divided into two stages. The first stage consists of 6 weeks, in which the mice in the intraperitoneal and subcutaneous groups were treated with insulin intraperitoneally and subcutaneously respectively. The second stage consists of 4 weeks, in which the mice in intraperitoneal and subcutaneous groups were subcutaneously injected with insulin. The mice in the remaining 3 groups were not treated. The changes of related indicators were detected every two weeks, including body weight, fasting blood sugar, 2 hours after meal blood sugar, triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). Results:Changing the injection solution in the medium term of the treatment had no effect on the body mass and blood sugar of KKAy mice with type 2 diabetes. Under this condition, the effect of intraperitoneal injection of insulin on HDL-C and LDL-C is significantly better than that of subcutaneous injection. Besides, both injection solutions are effective in regulating TG, but the effect of reducing total cholesterol is not obvious.Conclusions:The intraperitoneal injection of insulin has a certain effect on the blood lipid abnormality of type 2 diabetic KKAy mice. It can promote the increase of HDL-C, the decrease of LDL-C, and the decrease of TG.
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The innovative healthcare plus elderly care model is a major move for China to combat population aging. Given its initial success, there still exist challenges in the systems and economic conditions, for which family doctors can play a key role as population health " gatekeepers" . From the perspective of supply-side reform, this paper analyzed the current progress and challenges in this regard, and proposed a win-win mode. This mode combined the advantages of the family doctor system to optimize the community-based healthcare and elderly care as well as aging care resources.Family doctors are centered to build a community elderly care supply mode, to promote mutual development of primary medical institutions and the elderly-healthcare sector in China.