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.
3.Effect of Bushen Huoxue Granule on Clearance of Pathological α-Synuclein in MPP+-Induced PC12 Cells.
Zhen-Xian LUAN ; Xiang-Lin TANG ; Fei-Ran HAO ; Min LI ; Shao-Dan LI ; Ming-Hui YANG
Chinese journal of integrative medicine 2025;31(9):830-836
OBJECTIVE:
To investigate the effects of Bushen Huoxue Granule on the ubiquitin-proteasome system (UPS) in an in vitro model of Parkinson's disease.
METHODS:
After treated with 1-methyl-4-phenylpyridinium (MPP+, 1 mmol/L) for 24 h, the cells were incubated with drug-free serum, Madopar-containing serum or Bushen Huoxue Granule-containing serum (BCS, 5%, 10%, and 20%) for another 24 h. The levels of α-synuclein (α-syn), tyrosine hydroxylase (TH) and UPS-related proteins were detected by Western blot. The expression levels of α-syn in PC12 cells were also analyzed by Western blot after treated with proteasome inhibitor MG132 and WT-α-syn plasmid transfection, respectively, as well as the alterations induced by subsequent BCS intervention. Immunocytochemistry was performed to determine the changes in α-syn phosphorylation at serine 129 (pSer129-α-syn) expression. The 20S proteasome levels were measured by enzyme-linked immunosorbnent assay.
RESULTS:
BCS (volume fraction ⩽20%) intervention could alleviate the MMP+-induced cell viability decrease (P<0.05). In the MPP+ treated cells, α-syn was up-regulated, while TH and proteins of UPS such as ubiquitin (Ub), Ub binding with Ub-activating enzyme (UBE1), Parkin and Ub C-terminal hydrolase-1 (UCHL-1) were down-regulated (P<0.05). BCS intervention could attenuate the above changes (P<0.05). The activity of BCS on blocking α-syn accumulation was weakened by MG132 (P<0.05). While α-syn level was significantly increased in cells transfected with plasmid, and reduced by BCS intervention (P<0.05). pSer129-α-syn was increased in MPP+-induced PC12 cells, whereas decreased by later BCS intervention (P<0.05). The 20S proteasome activity of MPP+-induced PC12 cells was decreased, but increased after BCS intervention (P<0.05).
CONCLUSION
BCS intervention protected UPS function, increased 20S proteasome activity, promoted pathological α-syn clearance, restored cell viability, and reversed the damage caused by MPP+ in the in vitro model of Parkinson's disease.
PC12 Cells
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alpha-Synuclein/metabolism*
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Rats
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Animals
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1-Methyl-4-phenylpyridinium/toxicity*
;
Proteasome Endopeptidase Complex/metabolism*
;
Drugs, Chinese Herbal/pharmacology*
;
Ubiquitin/metabolism*
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Cell Survival/drug effects*
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Phosphorylation/drug effects*
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Tyrosine 3-Monooxygenase/metabolism*
4.Corrigendum to "Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52" J. Pharm. Anal. 14 (2024) 86-99.
Shengyou LI ; Xue GAO ; Yi ZHENG ; Yujie YANG ; Jianbo GAO ; Dan GENG ; Lingli GUO ; Teng MA ; Yiming HAO ; Bin WEI ; Liangliang HUANG ; Yitao WEI ; Bing XIA ; Zhuojing LUO ; Jinghui HUANG
Journal of Pharmaceutical Analysis 2025;15(4):101324-101324
[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].
5.Altered serum metabolic profile in patients with autoimmune gastritis compared to other chronic gastritis.
Jihua SHI ; Yang ZHANG ; Yiran WANG ; Yuxi HUANG ; Zhe CHEN ; Xue XU ; Wenbin LI ; Dan CHEN ; Hao LUO ; Qingfeng LUO ; Ruiyue YANG ; Xue QIAO
Journal of Pharmaceutical Analysis 2025;15(5):101104-101104
Image 1.
6.Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation.
Hang ZHAO ; Xin MA ; Hao WANG ; Xiao-Jie DING ; Le KUAI ; Jian-Kun SONG ; Zhan ZHANG ; Dan YANG ; Chun-Jie GAO ; Bin LI ; Mi ZHOU
Journal of Integrative Medicine 2025;23(3):309-319
OBJECTIVE:
To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD).
METHODS:
The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4+ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis.
RESULTS:
POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA.
CONCLUSION
Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy*
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Animals
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Humans
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Cell Differentiation/drug effects*
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Phosphorylation/drug effects*
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Mice
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Th2 Cells/drug effects*
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Keratinocytes/drug effects*
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Disease Models, Animal
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Mice, Inbred BALB C
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Calcitriol/analogs & derivatives*
7.The Sequential Mediating Roles of Body Pain and Self-Reported Health Status in the Relationship between Sleep Duration and Life Satisfaction.
Jia Feng LI ; Xue Wei FU ; Dan YANG ; Ye WANG ; Ting CHEN ; Yang PENG ; Feng Hao YANG ; Yu Chen ZHAN ; Yu WANG ; Xiang Dong TANG
Biomedical and Environmental Sciences 2025;38(1):47-55
OBJECTIVE:
This study examines the sequential mediating roles of body pain and self-reported health in the association between sleep duration and self-reported life satisfaction among elderly Chinese adults.
METHODS:
Data from the fifth wave of the China Health and Retirement Longitudinal Survey (CHARLS) were used to analyse the relationships between sleep duration and body pain, self-reported health, and life satisfaction through logistic regression and Restricted Cubic Spline (RCS) analyses. The sequential mediation effects of body pain and self-reported health status were examined via chain mediation analysis.
RESULTS:
Logistic regression analysis showed that sleeping fewer than 6 hours or 6-7 hours was linked to higher risks of body pain, poor health, and dissatisfaction with life compared to sleeping 7-8 hours (all P < 0.05). Additionally, those sleeping more than 9 hours also had increased risks of poor health and dissatisfaction with life compared to those sleeping 7-8 hours (all P < 0.05). Chain mediation analysis showed that body pain and self-reported health status sequentially mediated 46.15% of the association between sleep duration and life satisfaction.
CONCLUSION
Body pain and self-reported health may shape the relationship between sleep duration and life satisfaction in elderly Chinese adults.
Humans
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Male
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Female
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Aged
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Personal Satisfaction
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Sleep
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Health Status
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Self Report
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China
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Middle Aged
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Longitudinal Studies
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Pain/psychology*
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Sleep Duration
8.Associations of Genetic Risk and Physical Activity with Incident Chronic Obstructive Pulmonary Disease: A Large Prospective Cohort Study.
Jin YANG ; Xiao Lin WANG ; Wen Fang ZHONG ; Jian GAO ; Huan CHEN ; Pei Liang CHEN ; Qing Mei HUANG ; Yi Xin ZHANG ; Fang Fei YOU ; Chuan LI ; Wei Qi SONG ; Dong SHEN ; Jiao Jiao REN ; Dan LIU ; Zhi Hao LI ; Chen MAO
Biomedical and Environmental Sciences 2025;38(10):1194-1204
OBJECTIVE:
To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease.
METHODS:
This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used.
RESULTS:
During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity.
CONCLUSION
Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans
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Pulmonary Disease, Chronic Obstructive/epidemiology*
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Exercise
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Male
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Female
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Middle Aged
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Prospective Studies
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Aged
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Genetic Predisposition to Disease
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Risk Factors
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United Kingdom/epidemiology*
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Incidence
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Adult
9.Screening and characterization of anti-SARS-CoV-2 receptor binding domain antibodies with broad-spectrum neutralizing activity
NI Wanqi ; REN Li ; JIN Changzhong ; YANG Furong ; SHEN Yumin ; WANG Shuo ; HU Caiqin ; HAO Yanling ; LIU Ying ; ZHU Biao ; SHAO Yiming ; LI Dan ; WANG Zheng
China Tropical Medicine 2024;24(3):258-
convalescents, and to screen for broad-spectrum neutralizing antibodies against the SARS-CoV-2 RBD. Methods Using biotinylated RBD as a molecular probe, flow cytometry was employed to perform single-cell sorting of B cells from peripheral blood mononuclear cells (PBMCs) of convalescents. The obtained B cells were lysed and subjected to reverse transcription, followed by nested PCR amplification of the heavy and light chains of antibodies was conducted using random primers. The amplified products were cloned into corresponding expression vectors, and the respective matched heavy-light chain plasmids were co-transfected into 293F cells for expression. Monoclonal antibodies were then purified using Protein A column chromatography. Neutralization experiments were conducted with the wild-type (WT) pseudovirus, and antibodies with IC50<0.1 μg/mL were selected for further testing of neutralizing breadth and potency against the wild-type (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and currently prevalent pseudovirus strains (XBB, BA.5, BF.7). Results A total of 21 RBD-specific monoclonal B cells were obtained from two recovered patients, resulting in the isolation of 13 pairs of antibody light/heavy chains. Nine antibodies were successfully expressed, with P1-A1, P1-B6, and P1-B9 exhibiting IC50 values below 0.1 μg/mL against the pseudovirus of the wild-type strain (WT). Specifically, P1-B6 effectively neutralized the wild-type strain (WT), Beta variant (B.1.351), and Delta variant (B.1.617.2), with IC50 values reaching 0.01 μg/mL. P1-B9 demonstrated effective neutralization against the wild-type strain (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and Gamma variant (P.1) pseudoviruses, with IC50 values of 0.42 μg/mL, 0.63 μg/mL, 0.28 μg/mL, and 2.50 μg/mL, respectively. Additionally, P1-B6 exhibited good neutralization against BA.5 and BF.7 pseudoviruses, with IC50 values of 0.06 μg/mL and 0.09 μg/mL, respectively. Conclusions Infection with the SARS-CoV-2 WT strain can induce the generation of neutralizing antibodies with broad-spectrum activity. Generating these broadly neutralizing antibodies does not require an excessively high somatic hypermutation. The obtained antibodies can be used as candidates for SARS-CoV-2 diagnosis and prevention.
10.Mechanism of treating hyperlipidemia with Ningzhi capsule based on network pharmacology and molecular docking technology
Hao XIE ; Yaoyang LI ; Bin ZHAO ; Dan YANG ; Qunli WU
Basic & Clinical Medicine 2024;44(3):346-351
Objective To screen the potential pharmacological targets of Ningzhi capsule,a lipid-lowering tradi-tional Chinese medicine,and explore its mechanism of effect.Methods The components and predicted targets of Ningzhi capsule′s constituent drugs were obtained from BATMAN-TCM database.Hyperlipidemia-related targets were obtained from DisGeNET and GeneCards databases.The Venny2.1.0 tool was used to map drug targets and disease targets to obtain common targets as potential pharmacological targets.Protein-protein interaction analysis(STRING),gene ontology and pathway enrichment analysis(DAVID)were performed for the common targets.Finally,Swiss dock was used for molecular docking verification.Results A total of 1 432 predicted targets of Ning-zhi capsule and 87 targets related to hyperlipidemia were found and 32 common targets were screened which covered 64 potential pharmacological ingredients of Ningzhi capsule.Potential pharmacological targets were most abundant for turmeric root-tuber,turmeric and cattail pollen,and potential pharmacological ingredients were most abundant for sickle senna seed,turmeric and turmeric root-tuber.Apolipoprotein E(APOE),nitric oxide synthase 3(NOS3)and peroxisome proliferator activated receptor alpha(PPARA)had the highest hyperlipidemia correlation scores and more protein interactions,which were potential core targets.The biological processes related to DNA transcription were significantly enriched.Cholesterol metabolism,cGMP-PKG and PPAR signaling pathways were involved with APOE,NOS3 and PPARA,respectively.Molecular docking showed good binding activity.Conclusions There are many potential pharmacological ingredients of Ningzhi capsule and the key components for lowering lipids include turmeric root-tuber,turmeric,cattail pollen and sickle senna seed.APOE,NOS3 and PPARA are believed to be the key targets for lowering lipids with potential mechanism related to cholesterol metabo-lism,cGMP-PKG and PPAR signaling pathways.

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