1.Targeting PPARα for The Treatment of Cardiovascular Diseases
Tong-Tong ZHANG ; Hao-Zhuo ZHANG ; Li HE ; Jia-Wei LIU ; Jia-Zhen WU ; Wen-Hua SU ; Ju-Hua DAN
Progress in Biochemistry and Biophysics 2025;52(9):2295-2313
Cardiovascular disease (CVD) remains one of the leading causes of mortality among adults globally, with continuously rising morbidity and mortality rates. Metabolic disorders are closely linked to various cardiovascular diseases and play a critical role in their pathogenesis and progression, involving multifaceted mechanisms such as altered substrate utilization, mitochondrial structural and functional dysfunction, and impaired ATP synthesis and transport. In recent years, the potential role of peroxisome proliferator-activated receptors (PPARs) in cardiovascular diseases has garnered significant attention, particularly peroxisome proliferator-activated receptor alpha (PPARα), which is recognized as a highly promising therapeutic target for CVD. PPARα regulates cardiovascular physiological and pathological processes through fatty acid metabolism. As a ligand-activated receptor within the nuclear hormone receptor family, PPARα is highly expressed in multiple organs, including skeletal muscle, liver, intestine, kidney, and heart, where it governs the metabolism of diverse substrates. Functioning as a key transcription factor in maintaining metabolic homeostasis and catalyzing or regulating biochemical reactions, PPARα exerts its cardioprotective effects through multiple pathways: modulating lipid metabolism, participating in cardiac energy metabolism, enhancing insulin sensitivity, suppressing inflammatory responses, improving vascular endothelial function, and inhibiting smooth muscle cell proliferation and migration. These mechanisms collectively reduce the risk of cardiovascular disease development. Thus, PPARα plays a pivotal role in various pathological processes via mechanisms such as lipid metabolism regulation, anti-inflammatory actions, and anti-apoptotic effects. PPARα is activated by binding to natural or synthetic lipophilic ligands, including endogenous fatty acids and their derivatives (e.g., linoleic acid, oleic acid, and arachidonic acid) as well as synthetic peroxisome proliferators. Upon ligand binding, PPARα activates the nuclear receptor retinoid X receptor (RXR), forming a PPARα-RXR heterodimer. This heterodimer, in conjunction with coactivators, undergoes further activation and subsequently binds to peroxisome proliferator response elements (PPREs), thereby regulating the transcription of target genes critical for lipid and glucose homeostasis. Key genes include fatty acid translocase (FAT/CD36), diacylglycerol acyltransferase (DGAT), carnitine palmitoyltransferase I (CPT1), and glucose transporter (GLUT), which are primarily involved in fatty acid uptake, storage, oxidation, and glucose utilization processes. Advancing research on PPARα as a therapeutic target for cardiovascular diseases has underscored its growing clinical significance. Currently, PPARα activators/agonists, such as fibrates (e.g., fenofibrate and bezafibrate) and thiazolidinediones, have been extensively studied in clinical trials for CVD prevention. Traditional PPARα agonists, including fenofibrate and bezafibrate, are widely used in clinical practice to treat hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) levels. These fibrates enhance fatty acid metabolism in the liver and skeletal muscle by activating PPARα, and their cardioprotective effects have been validated in numerous clinical studies. Recent research highlights that fibrates improve insulin resistance, regulate lipid metabolism, correct energy metabolism imbalances, and inhibit the proliferation and migration of vascular smooth muscle and endothelial cells, thereby ameliorating pathological remodeling of the cardiovascular system and reducing blood pressure. Given the substantial attention to PPARα-targeted interventions in both basic research and clinical applications, activating PPARα may serve as a key therapeutic strategy for managing cardiovascular conditions such as myocardial hypertrophy, atherosclerosis, ischemic cardiomyopathy, myocardial infarction, diabetic cardiomyopathy, and heart failure. This review comprehensively examines the regulatory roles of PPARα in cardiovascular diseases and evaluates its clinical application value, aiming to provide a theoretical foundation for further development and utilization of PPARα-related therapies in CVD treatment.
2.Based on the interaction between supramolecules of traditional Chinese medicine and enterobacteria to explore the material basis of combination of Rhei Radix et Rhizoma - Coptidis Rhizoma
Xiao-yu LIN ; Ji-hui LU ; Yao-zhi ZHANG ; Wen-min PI ; Zhi-jia WANG ; Lin-ying WU ; Xue-mei HUANG ; Peng-long WANG
Acta Pharmaceutica Sinica 2024;59(2):464-475
Based on the interaction between supramolecule of traditional Chinese medicine and enterobacteria, the material basis of
3.Downregulation of MUC1 Inhibits Proliferation and Promotes Apoptosis by Inactivating NF-κB Signaling Pathway in Human Nasopharyngeal Carcinoma
Shou-Wu WU ; Shao-Kun LIN ; Zhong-Zhu NIAN ; Xin-Wen WANG ; Wei-Nian LIN ; Li-Ming ZHUANG ; Zhi-Sheng WU ; Zhi-Wei HUANG ; A-Min WANG ; Ni-Li GAO ; Jia-Wen CHEN ; Wen-Ting YUAN ; Kai-Xian LU ; Jun LIAO
Progress in Biochemistry and Biophysics 2024;51(9):2182-2193
ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.
4.Antipyretic and anti-inflammatory effects and quality evaluation of a new type of Lonicera Japonicae Flos granule raw decoction piece
Zhi-jun GUO ; Meng-meng HOU ; Dan GAO ; Yu-han WU ; Ze-min YANG ; Jia-lu WANG ; Bo GAO ; Xi-wen LI
Acta Pharmaceutica Sinica 2024;59(7):2087-2097
Traditional decoction pieces have low efficiency, poor batch-to-batch consistency, and irregular physical form, making it difficult to meet the demands of modern automated production and precise and rapid clinical blending. Therefore, this study aims to develop a new type of granular drinking tablet to meet the demand for high-quality development in the traditional Chinese medicine industry. In the current study, the differences and similarities between the new Lonicerae Japonicae Flos (LJF) granular drinking tablets and the traditional ones were evaluated based on the flowability, the paste rate of the standard soup, the characterization fingerprint, the degree of pasting, the content of active ingredients, the transfer rate, and its traditional antipyretic and anti-inflammatory efficacy, using the traditional
5.Spatiotemporal distribution of newly diagnosed echinococcosis patients in Qinghai Province from 2016 to 2022
Xinlu CUI ; Xiao MA ; Na LIU ; Jia LIU ; Wen LEI ; Shusheng WU ; Xianglan QIN ; Chunhua GONG ; Xiaojin MO ; Shijie YANG ; Ting ZHANG ; Li CAO
Chinese Journal of Schistosomiasis Control 2024;36(5):474-480
Objective To investigate the spatiotemporal distribution characteristics and potential influencing factors of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022, so as to provide insights into the formulation of the echinococcosis control strategy in Qinghai Province. Methods The number of individuals screened for echinococcosis, number of newly diagnosed echinococcosis cases, number of registered dogs and number of stray dogs were captured from the annual reports of echinococcosis control program in Qinghai Province from 2016 to 2022, and the detection of newly diagnosed echinococcosis cases was calculated. The number of populations, precipitation, temperature, wind speed, sunshine hours, average altitude, number of year-end cattle stock, number of year-end sheep stock, gross domestic product (GDP) per capita, and number of village health centers in each county (district) of Qinghai Province were captured from the Qinghai Provincial Statistical Yearbook, and county-level electronic maps in Qinghai Province were downloaded from the National Platform for Common Geospatial Information Services. The software ArcGIS 10.8 was used to map the distribution of newly diagnosed echinococcosis cases in Qinghai Province, and the spatial autocorrelation analysis of newly diagnosed echinococcosis cases was performed. In addition, the spacetime scan analyses of number of individuals screened for echinococcosis, number of newly diagnosed echinococcosis cases and geographical coordinates in Qinghai Province were performed with the software SaTScan 10.1.2, and the spatial stratified heterogeneity of the detection of newly diagnosed echinococcosis cases was investigated with the software GeoDetector. Results A total of 6 569 426 residents were screened for echinococcosis in Qinghai Province from 2016 to 2022, and 5 924 newly diagnosed echinococcosis cases were found. The detection of newly diagnosed echinococcosis cases appeared a tendency towards a decline over years from 2016 to 2022 (χ2 = 11.107, P < 0.01), with the highest detection in Guoluo Tibetan Autonomous Prefecture in 2017 (82.12/105). There were spatial clusters in the detection of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2018 (Moran’s I = 0.34 to 0.65, all Z values > 1.96, all P values < 0.05), and the distribution of newly diagnosed echinococcosis cases appeared random distribution from 2019 to 2022 (Moran’s I = −0.09 to 0.04, all Z values < 1.96, all P values > 0.05). Local spatial autocorrelation analysis showed high-high clusters and low-low clusters in the detection of new diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022, and space-time scan analysis showed that the first most likely cluster areas of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022 were mainly distributed in Yushu Tibetan Autonomous Prefecture and Guoluo Tibetan Autonomous Prefecture. GeoDetector-based analysis of the driving factors for the spatial stratified heterogeneity of detection of newly diagnosed echinococcosis cases in Qinghai Province showed that average altitude, number of village health centers, number of cattle and sheep stock, GDP per capita, annual average sunshine hours, and annual average temperature had a strong explanatory power for the spatial distribution of newly diagnosed echinococcosis cases, with q values of 0.630, 0.610, 0.600, 0.590, 0.588, 0.537 and 0.526, respectively. Conclusions The detection of newly diagnosed echinococcosis cases appeared a tendency towards a decline in Qinghai Province over years from 2016 to 2022, showing spatial clustering. Targeted control measures are required in cluster areas of newly diagnosed echinococcosis cases for further control of the disease.
6.Exploration on the Medication Rules of HUANG Li in Treating Recurrent Angina Pectoris After Percutaneous Coronary Intervention for Coronary Heart Disease
Shi-Yi TAO ; Xian-Wen TANG ; Lin-Tong YU ; De-Shuang YANG ; Rui-Qi YAO ; Lan-Xin ZHANG ; Jia-Yun WU ; Li HUANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(6):1598-1606
Objective To explore the medication rules of Professor HUANG Li for the treatment of recurrent angina pectoris after percutaneous coronary intervention(PCI)for coronary heart disease by data mining method.Methods The prescriptions for effective cases of recurrent angina pectoris after PCI for coronary heart disease treated by Professor HUANG Li in the outpatient department of China-Japan Friendship Hospital were collected.SPSS Statistics 26.0 software and SPSS Modeler 18.0 software were used for frequency statistics,analysis of the therapeutic actions,properties,flavors and meridian tropism of the prescribed herbs as well as association rule analysis,cluster analysis and factor analysis of the herbs.Results A total of 344 Chinese medicine prescriptions were obtained,involving 209 herbs,with a cumulative frequency of 5 874 times.The top 30 Chinese medicinals were named as the high-frequency Chinese medicines,and the herbs with the frequency over 100 times in descending order were Astragali Radix,Chuanxiong Rhizoma,Puerariae Lobatae Radix,Rhodiolae Crenulatae Radix et Rhizoma,Notoginseng Radix et Rhizoma,Poria,Dalbergiae Odoriferae Lignum,Atractylodis Macrocephalae Rhizoma,Curcumae Rhizoma,Sparganii Rhizoma,Dioscoreae Rhizoma,Citri Reticulatae Pericarpium,Pinelliae Rhizoma Praeparatum,Codonopsis Radix,and Glycyrrhizae Radix et Rhizoma.The high-frequency Chinese medicinals were mostly classified as blood-activating and stasis-resolving drugs and qi-replenishing drugs.The medicinal properties of the drugs were characterized by being warm,mild,or cold,the flavors were predominated by being sweet,pungent or bitter,and the medicinals usually had the meridian tropism of the spleen,lung and liver meridians.A total of 30 association rules were mined out,cluster analysis yielded 5 herbal groups,and factor analysis yielded 11 groups of common factors.Conclusion For the treatment of cardiovascular diseases,Professor HUANG Li follows the theory of qi,blood and water,and especially pays more attention to the ascending and descending of qi movement.For qi deficiency and blood stasis contribute to the basic pathogenesis of recurrent angina pectoris after PCI,the therapy of benefiting qi,activating blood and removing stasis is recommended.Moreover,the simultaneous regulation of five zang-organs and simultaneous use of the cold and warm herbs are performed,and the herbs of benefiting qi and invigorating spleen,resolving phlegm and inducing diuresis,tranquilizing mind,promoting qi and dissipating masses,and activating blood to eliminate stasis are used for adjuvant therapy.
7.Exploring the Medication Rules and Mechanism of Traditional Chinese Medicine Master XUAN Guo-Wei in the Treatment of Vitiligo Based on Data Mining and Network Pharmacology
Qin LIU ; Ting-Jing ZHONG ; Yue PEI ; Jin-Dian DONG ; Wen-Feng WU ; Jia-Fen LIANG ; Hong-Yi LI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(11):3025-3034
Objective To deeply explore the principles of drug combinations in the treatment of vitiligo by traditional Chinese medicine master XUAN Guo-Wei by data mining technology,and to analyze the potential mechanism of action of the core drug pairs by network pharmacology.Methods The original case records of Professor XUAN Guo-Wei in treating vitiligo were compiled,and then TCM inheritance Computing Platform was used to analyze the frequency of drugs in the prescriptions,the association rules between drugs,and the core combinations of drugs by the association rule method,and the core drug pairs of Professor XUAN Guo-Wei's treatment of vitiligo were obtained based on the results of the data mining,additionally,the mechanism of the core pairs of drugs was analyzed by using the method of network pharmacology.Results A total of 243 prescriptions were collected,among which the high-frequency drugs were Glycyrrhizae Radix et Rhizoma,Tribuli Fructus,Ecliptae Herba,Cuscutae Semen,Scrophulariae Radix,Angelicae Dahuricae Radix,etc.,and the core pair was Tribuli Fructus-Ecliptae Herba.The main components of Tribuli Fructus-Ecliptae Herba for the treatment of vitiligo were quercetin,kaempferol,etc.,there were 47 targets for the intersection of the active ingredients with the disease,among which TP53,TNF,IL-1β,CASP3,VEGFA,PTGS2,IL10,IL2,IFNG,and IL4 may be the core targets for the treatment of vitiligo by Tribuli Fructus-Ecliptae Herba.The main pathways of Tribuli Fructus-Ecliptae Herba drug pairs against the disease were PI3K-Akt signaling pathway,NF-κB signaling pathway,JAK-STAT signaling pathway and MAPK signaling pathway.Conclusion The core drug pair of Professor XUAN Guo-Wei in the treatment of vitiligo is Tribuli Fructus-Ecliptae Herba,which involves targets such as TP53,TNF,IL-1β,CASP3,VEGFA,PTGS2,IL10,IL2,IFNG,IL4,etc.,Tribuli Fructus-Ecliptae Herba drug pair maybe exert an effect in the treatment of vitiligo through PI3K-Akt signaling pathway,NF-κB signaling pathway,JAK-STAT signaling pathway and MAPK signaling pathway.
8.The prognostic significance and biological effects of CYP27A1 in hepatocellular carcinoma
Xin-Tong ZHANG ; Hao WU ; Yan-Fen HU ; Wen-Tao ZHANG ; Jing-Jia CHANG ; Jian-Jun ZHU ; Li LI ; Ming LIU
Medical Journal of Chinese People's Liberation Army 2024;49(4):387-395
Objective To analyze the prognostic significance and biological effects of cytochrome P450 family 27 subfamily A member 1(CYP27A1)in hepatocellular carcinoma(HCC),and to preliminarily explore its molecular mechanism of regulating the malignant growth of HCC.Methods The Cance Genome Atlas(TCGA)database was used to analyze the expression level of CYP27A1 and its prognostic effect on HCC patients.The samples were divided into CYP27A1 high-expression group(n=170)and low-expression group(n=170)based on the median expression of CYP27A1 in HCC,gene set enrichment analysis(GSEA)was performed to investigate gene sets associated with CYP27A1 expression.The subcellular localization of CYP27A1 was detected by immunofluorescence staining and search database.The over-expression plasmid of CYP27A1 was constructed and then transfected into the HCC cells MHCC-97H and HCCLM3 cell lines,including two groups,namely control group(transfecting empty vector)and CYP27A1 over-expression group(transfecting CYP27A1 over-expressed vector).CCK-8,flow cytometer,and reactive oxygen species(ROS)fluorescence probe were applied to detect the effects of CYP27A1 over-expression on cell viability,apoptosis and ROS levels in HCC cells.Combining bioinformatics to analyze the correlation between CYP27A1 and the expression of ROS generation-related genes and HCC proliferation-related genes.Results Compared with the normal liver tissue,the expression level of CYP27A1 mRNA in HCC tissue was significantly reduced(P<0.01).The expression of CYP27A1 was significantly correlated with sex,T stage,tumor grade and tumor stage of HCC patients(P<0.05).Compared to the CYP27A1 high-expression group,patients in CYP27A1 low-expression group had lower survival rate(P<0.01).GSEA enrichment analysis revealed that the levels of HCC stem cell-related gene clusters and HCC proliferation gene clusters were remarkably increased in CYP27A1 low-expression group.The immunofluorescence showed that CYP27A1 was mainly located in nucleus in MHCC-97H and HCCLM3,whereas CYP27A1 was mainly located in mitochondria in HepG2.CYP27A1 over-expression attenuated cell viability(P<0.01),and reduced the ROS levels(P<0.05),whereas it had no effects on the apoptosis in HCC cells(P>0.05).The expression of CYP27A1 and the expression of inhibiting ROS generation-related genes were positively correlated(P<0.05),while the expression of inhibiting ROS generation-related genes and the expression of HCC proliferation-related genes were negatively correlated(P<0.05).Conclusions The expression of CYP27A1 was decreased in HCC,and down-regulated CYP27A1 promoted cell growth by enhancing ROS generation,although the precise mechanism requires future educidation.
9.Research progress on the impact of lipid metabolism on endometrial receptivity and embryo implantation
Li-Na MA ; Ying QIN ; Ke-Hua WANG ; Cong-Hui PANG ; Li-Ge LU ; Wen-Xian YUAN ; Duo-Jia ZHANG ; Xiao-Ke WU
Medical Journal of Chinese People's Liberation Army 2024;49(9):1088-1093
Lipids,including fats(triglycerides)and lipoids(phospholipids and sterols),not only serve as an energy source for the body but also play a pivotal role throughout the reproductive process,particularly in the establishment and maintenance of early pregnancy.This encompasses the regulate of early embryonic development and uterine tolerance,and the facilitation of embryo implantation.Given the diversity of lipids,this review focuses on extensively studied lipid mediators such as polyunsaturated fatty acids,endocannabinoids,prostaglandins,lysophosphatidic acid,sphingolipids and steroid hormones.It systematically elaborates on the regulatory effects of fatty acid,phospholipid,and cholesterol metabolism on the formation of endometrial receptivity and embryo implantation,as well as the potential underlying mechanisms.The review aims to provide new insights and feasible intervention approaches for predicting and improving the outcomes of natural pregnancy and/or assisted reproductive technology.
10.Evaluation of the efficacy and safety of intravenous infusion of ferric derisomaltose in the treatment of iron deficiency anemia: a single-center retrospective analysis
Shaoxue DING ; Yihui ZHAO ; Ting WANG ; Jing GUAN ; Limin XING ; Hong LIU ; Guojin WANG ; Xiaoming WANG ; Yuhong WU ; Wen QU ; Jia SONG ; Huaquan WANG ; Lijuan LI ; Zonghong SHAO ; Rong FU
Chinese Journal of Hematology 2024;45(2):178-183
Objective:To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) .Methods:A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period.Results:Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site.Conclusion:The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.

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