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.Stimulation mechanism of osteoblast proliferation and differentiation by Duzhong Decoction-containing serum through L-VGCCs.
Ze-Bin CHEN ; Lan-Lan LUO ; Xin-Yi SHI ; Rui-Tong ZHAO ; Cai-Xian HU ; Yun-Ying FU ; Su-Zhen CHAO ; Bo LIU
China Journal of Chinese Materia Medica 2025;50(12):3335-3345
This paper aimed to explore the effects of Duzhong Decoction(DZD)-containing serum on the proliferation and osteoblast differentiation of MC3T3-E1 cells through L-type voltage-gated calcium channels(L-VGCCs). L-VGCCs inhibitors, nifedipine and verapamil, were used to block L-VGCCs in osteoblasts. MC3T3-E1 cells were divided into a control group, a low-dose DZD-containing serum(L-DZD) group, a medium-dose DZD-containing serum(M-DZD) group, a high-dose DZD-containing serum(H-DZD) group, a nifedipine group, a H-DZD + nifedipine group, verapamil group, and a H-DZD + verapamil group. The CCK-8 method was used for cell proliferation analysis, alkaline phosphatase(ALP) assay kits for intracellular ALP activity measurement, Western blot for protein expression level in cells, real-time fluorescence quantitative PCR technology for intracellular mRNA expression level determination, fluorescence spectrophotometer for free Ca~(2+) concentration determination in osteoblasts, and alizarin red staining(ARS) for mineralized nodule formation in osteoblasts. The experimental results show that compared to the control group, DZD groups can promote MC3T3-E1 cell proliferation, ALP activity, and mineralized nodule formation, increase intracellular Ca~(2+) concentrations, and upregulate the protein expression of bone morphogenetic protein 2(BMP2), collagen Ⅰ(COL1), α2 subunit protein of L-VGCCs(L-VGCCα2), and the mRNA expression of Runt-related transcription factor 2(RUNX2), and BMP2. After blocking L-VGCCs with nifedipine and verapamil, the intervention effects of DZD-containing serum were inhibited to varying degrees. Both nifedipine and verapamil could inhibit ALP activity, reduce mineralized nodule areas, and downregulate the expression of bone formation-related proteins. Moreover, the effects of DZD-containing serum on increasing MC3T3-E1 cell proliferation, osteoblast differentiation, and Ca~(2+) concentrations, upregulating the mRNA expression of osteoprotegerin(OPG) and protein expression of phosphorylated protein kinase B(p-Akt) and phosphorylated forkhead box protein O1(p-FOXO1), and upregulating phosphatase and tensin homolog(PTEN) expression were reversed by nifedipine. The results indicate that DZD-containing serum can increase the Ca~(2+) concentration in MC3T3-E1 cells to promote bone formation, which may be mediated by L-VGCCs and the PTEN/Akt/FoxO1 signaling pathway, providing a new perspective on the mechanism of DZD in treating osteoporosis.
Animals
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Osteoblasts/metabolism*
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Cell Proliferation/drug effects*
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Cell Differentiation/drug effects*
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Mice
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Drugs, Chinese Herbal/pharmacology*
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Calcium Channels, L-Type/genetics*
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Alkaline Phosphatase/genetics*
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Serum/chemistry*
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Cell Line
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Osteogenesis/drug effects*
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Bone Morphogenetic Protein 2/genetics*
3.Association of Loneliness and Social Isolation with Ischemic Heart Disease: A Bidirectional and Network Mendelian Randomization Study.
Shu Yao SU ; Wan Yue WANG ; Chen Xi YUAN ; Zhen Nan LIN ; Xiang Feng LU ; Fang Chao LIU
Biomedical and Environmental Sciences 2025;38(3):351-364
OBJECTIVE:
Observational studies have shown inconsistent associations of loneliness or social isolation (SI) with ischemic heart disease (IHD), with unknown mediators.
METHODS:
Using data from genome-wide association studies of predominantly European ancestry, we performed a bidirectional two-sample Mendelian Randomization (MR) study to estimate causal effects of loneliness ( N = 487,647) and SI traits on IHD ( N = 184,305). SI traits included whether individuals lived alone, participated in various types of social activities, and how often they had contact with friends or family ( N = 459,830 to 461,369). A network MR study was conducted to evaluate the mediating roles of 20 candidate mediators, including metabolic, behavioral and psychological factors.
RESULTS:
Loneliness increased IHD risk ( OR= 2.129; 95% confidence interval [ CI]: 1.380 to 3.285), mediated by body fat percentage, waist-hip ratio, total cholesterol, and low-density lipoprotein cholesterol. For SI traits, only fewer social activities increased IHD risk ( OR= 1.815; 95% CI: 1.189 to 2.772), mediated by hypertension, high-density lipoprotein cholesterol, triglycerides, fasting insulin, and smoking cessation. No reverse causality of IHD with loneliness and SI was found.
CONCLUSION
These findings suggested more attention should be paid to individuals who feel lonely and have fewer social activities to prevent IHD, with several mediators as prioritized targets for intervention.
Loneliness/psychology*
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Humans
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Mendelian Randomization Analysis
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Social Isolation
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Myocardial Ischemia/etiology*
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Male
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Female
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Middle Aged
;
Genome-Wide Association Study
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Risk Factors
;
Aged
4.Two sample Mendelian randomization study on causal relationship between insulin-like growth factor-1 and colorectal cancer
Huaxia MU ; Weixiao BU ; Shuting DING ; Mengyao GAO ; Weiqiang SU ; Zhen ZHANG ; Qifu BO ; Feng LIU ; Fuyan SHI ; Qinghua WANG ; Yujia KONG ; Suzhen WANG
Journal of Jilin University(Medicine Edition) 2025;51(2):479-485
Objective:To explore the causal association between insulin-like growth factor-1(IGF-1)and colorectal cancer(CRC)based on two sample Mendelian randomization(MR)analysis.Methods:A bidirectional two sample MR analysis was conducted based on publicly aggregated data from the IEU OpenGWAS project.The inverse variance weighted(IVW)method was used as the main analysis model to assess the causal relationship between IGF-1 and CRC.Additional analyses were performed using weighted median(WM),MR-Egger regression,weighted mode estimator(WME),and simple mode(SM)methods.Sensitivity analysis was performed to assess the robustness of the results.Results:A total of 386 single nucleotide polymorphisms(SNPs)were selected as instrumental variables(IVs)with IGF-1 as the exposure factor.The MR analysis results revealed a positive causal association between IGF-1 and the risk of CRC[odds ratio(OR)=1.178,95%confidence interval(CI):1.092-1.272)](P<0.001),and the association remained significant after adjusting for height[OR(95%CI)=1.214(1.111,1.327)](P<0.001).Cochran's Q-test showed heterogeneity among the IVs(P<0.05),while the horizontal pleiotropy of IV was not detected by the MR-Egger regression(P>0.05).The leave-one-out analysis showed that the MR results were robust.Reverse MR analysis indicated no reverse causal relationship between IGF-1 and CRC[OR(95%CI):1.017(0.997,1.037)](P=0.103).Conclusion:There is a causal relationship between IGF-1 level and CRC,and elevated IGF-1 level could be a risk factor for CRC.
5.Topical adhesive spatio-temporal nanosystem co-delivering chlorin e6 and HMGB1 inhibitor glycyrrhizic acid for in situ psoriasis chemo-phototherapy.
Lijun SU ; Yixi ZHU ; Xuebo LI ; Di WANG ; Xiangyu CHEN ; Zhen LIU ; Jingjing LI ; Chen ZHANG ; Jinming ZHANG
Acta Pharmaceutica Sinica B 2025;15(2):1126-1142
Recently, photodynamic therapy (PDT) has gained considerable attention as a promising therapeutic approach for the treatment of psoriasis. Unfortunately, the activation of high mobility group box 1 protein (HMGB1) by PDT triggers innate and adaptive immune responses, which exacerbate skin inflammation. Herein, we combined glycyrrhizic acid (GA), a natural anti-inflammatory compound and immunomodulator derived from the herb Glycyrrhiza uralensis Fisch., with PDT actuated by the photosensitizer chlorin e6 (Ce6) by co-loading them in GA-based lipid nanoparticles coated with a catechol-modified quaternary chitosan salt (GC NPs/QCS-C). GC NPs/QCS-C exhibited high drug loading efficacy, uniform size distribution, an ideal topical adhesive property, enhanced skin retention and penetration in psoriasis-like lesions, and high intracellular uptake in epidermal cells compared with the counterparts. Subsequently, the transdermal administration of GC NPs/QCS-C followed by near-infrared laser radiation in an imiquimod-induced psoriasis-like mouse model significantly ameliorated psoriasis symptoms, promoted the apoptosis of hyperproliferative epidermal cells, and alleviated the inflammatory cascade. The significant therapeutic outcomes of GC NPs/QCS-C were attributed to the synergistic effects of GA and PDT on modulating immune cell recruitment and inhibiting dendritic cell maturation. Our results demonstrated that the topical bio-adhesive nanosystem that combines GA and Ce6 offers a synergistic chemo-phototherapeutic strategy for psoriasis treatment.
6.Key technology and equipment development status of first-aid robotics
Zhen-bao WANG ; Zi-jian WANG ; Xin-xi XU ; Xin LIU ; Tao CHENG ; Pei-peng LIU ; Xiu-guo ZHAO ; Chen SU
Chinese Medical Equipment Journal 2025;46(3):96-114
The development status of the key technologies of first-aid robotics was introduced in autonomous system,embo-died intelligence,digital twins,large artificial intelligence model and autonomous unmanned medical treatment.The present situation in first-aid robotics equipment was reviewed for first-aid diagnosis,treatment,assistance and transportation.The development trends of the key technology and equipment of first-aid robotics were analyzed.It was pointed out the involve-ment of big model-based embodied intelligence technology and digital twins technology in first aid might provide new pers-pectives for the application and advancement of specialized first-aid robotics.[Chinese Medical Equipment Journal,2025,46(3):96-114]
7.Application and research progress of artificial intelligence in the assessment of subsolid nodules
Fei LI ; Zhen BAI ; Jin-Long LIU ; Dan-Yang SU ; Shen-Yu YANG ; Yuan-Bo MA ; Ya-Man LI ; Yu-Fang DU ; Xiao-Peng YANG
Medical Journal of Chinese People's Liberation Army 2025;50(10):1243-1249
Lung cancer has the highest incidence and mortality among malignant tumors in China.Persistent subsolid nodules(SSNs)are closely associated with early-stage lung adenocarcinoma.Artificial intelligence(AI),as an emerging technology,is capable of performing in-depth analysis of large-scale imaging data through autonomous learning and possesses the ability to predict outcomes from new data,demonstrating great potential and application prospects in the assessment of SSNs.AI can not only effectively assist radiologists in diagnosis and treatment,but also improve work efficiency while reducing misdiagnosis and missed diagnosis rates.This review summarizes the recent applications and research progress of AI in the assessment of SSNs,to provide new insights for the diagnosis and treatment of SSNs.
8.Gallstones, cholecystectomy, and cancer risk: an observational and Mendelian randomization study.
Yuanyue ZHU ; Linhui SHEN ; Yanan HUO ; Qin WAN ; Yingfen QIN ; Ruying HU ; Lixin SHI ; Qing SU ; Xuefeng YU ; Li YAN ; Guijun QIN ; Xulei TANG ; Gang CHEN ; Yu XU ; Tiange WANG ; Zhiyun ZHAO ; Zhengnan GAO ; Guixia WANG ; Feixia SHEN ; Xuejiang GU ; Zuojie LUO ; Li CHEN ; Qiang LI ; Zhen YE ; Yinfei ZHANG ; Chao LIU ; Youmin WANG ; Shengli WU ; Tao YANG ; Huacong DENG ; Lulu CHEN ; Tianshu ZENG ; Jiajun ZHAO ; Yiming MU ; Weiqing WANG ; Guang NING ; Jieli LU ; Min XU ; Yufang BI ; Weiguo HU
Frontiers of Medicine 2025;19(1):79-89
This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans
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Mendelian Randomization Analysis
;
Gallstones/complications*
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Female
;
Male
;
Cholecystectomy/statistics & numerical data*
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Middle Aged
;
Risk Factors
;
Aged
;
Adult
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Neoplasms/etiology*
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Stomach Neoplasms/epidemiology*
9.Application of dual-energy computed tomography imaging for evaluation of bone repair
Danyang SU ; Yuanbo MA ; Jinlong LIU ; Haoran ZHANG ; Shenyu YANG ; Qiuju MIAO ; Zhen BAI ; Xiaopeng YANG
Chinese Journal of Comparative Medicine 2025;35(1):155-162
Bone defect repair is an urgent problem in the field of orthopedics,and numerous researchers are working to develop more effective treatment plans.The accurate evaluation of bone repair after surgery is a crucial step.In line with the development of computed tomography(CT)imaging,dual-energy CT imaging has shown significant advantages in analyzing bone composition and reducing metal artifacts.This article reviews the application of dual-energy CT imaging for the evaluation of bone repair in animals.
10.Effect of the thicknesses of different reconstruction layer and the ROI thicknesses on the measurement of BMD value of QCT
Jinlong LIU ; Danyang SU ; Haoran ZHANG ; Yuanbo MA ; Qiuju MIAO ; Zhen BAI ; Xiaopeng YANG
China Medical Equipment 2025;22(1):19-23
Objective:To assess the effect of using different thicknesses of reconstruction layer and different thicknesses of region of interest (ROI) on the results of vertebral bone mineral density (BMD) values that were measured by quantitative computed tomography (QCT). Methods:A total of 100 patients who underwent QCT screening for opportunistic osteoporosis between May and September 2021 at the First Affiliated Hospital of Zhengzhou University were retrospectively collected. Images that the thicknesses of QCT reconstruction layer were respectively 1 and 5 mm were transferred to the QCT Pro workstation,and ROI thicknesses were adjusted to 5,7,and 9 mm,respectively. The average BMD values of QCT measurements were recorded under different thicknesses of reconstruction layer and different ROI thicknesses. Then,the effects of the choose of different thicknesses of reconstruction layer and the different ROI thicknesses on BMD values that were measured by QCT were analyzed. Results:The average BMD values of 1 mm and 5 mm thicknesses of reconstruction layer were respectively (117.41±45.97) mg/cm3 and (118.77±44.84) mg/cm3 when ROI thickness was 5 mm,with a statistically significant difference (t=-2.283,P<0.05). The average BMD values of 1 mm and 5 mm thicknesses of reconstruction layer were respectively (116.38±46.06) mg/cm3 and (119.06±44.55) mg/cm3 when the ROI thickness was 7mm,and the difference was statistically significant (t=-3.280,P<0.05). The average BMD values of 1 mm and 5 mm thicknesses of reconstruction layer were respectively (116.25±45.36) mg/cm3 and (120.12±44.10) mg/cm3 when the ROI thickness was 9 mm,and the difference was statistically significant (t=-5.841,P<0.001). The differences in BMD measurement values among 5,7 and 9 mm ROI thicknesses were not statistically significant when the thicknesses of reconstruction layer were respectively 1 and 5 mm. Conclusion:There is an effect of the thickness of QCT reconstruction layer on average BMD measurement values,and 1 mm thickness of reconstruction layer is more suitable to clinical application,while there is not significant effect in ROI thickness on average BMD measurement value of QCT. In clinical application,it is feasible to adjust ROI thickness according to actual situation so as to avoid the effect caused by some factors such as fracture or vertebral implants.

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