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.Risk factors of non-alcoholic fatty liver disease in children
Zuotao GENG ; Dan ZHANG ; Xiaotong ZHU ; Lanyi LI ; Xuehai LI ; Yongli YANG
Chinese Journal of Child Health Care 2024;32(4):412-418
Non-alcoholic fatty liver disease(NAFLD) has become the main cause of chronic liver disease in children worldwide, and the incidence of NAFLD shows an increasing trend year by year. The risk factors leading to the onset of NAFLD in children are diversified and different from those in adults. At present, most medical institutions still pay little attention to NAFLD in children. This paper summarizes the risk factors and mechanisms for NAFLD in children, including gene polymorphism, maternal and fetal conditions, diet and living habits, environmental exposure, metabolic syndrome, endocrine-related mechanisms and intestinal microecology, in order to provide reference for the prevention and management of childhood NAFLD.
3.Dual-task treadmill training improves the motor functioning of children with bilateral spastic cerebral palsy
Guangjin LUO ; Xuan ZHANG ; Hui LUO ; Xiaoping LI ; Yu CHEN ; Shuting WANG ; Dianrong SUN ; Lijiang WANG ; Mei HOU ; Aiyun YUAN
Chinese Journal of Physical Medicine and Rehabilitation 2023;45(4):330-334
Objective:To explore any effect of the single- and dual-task treadmill training on the functioning of children with bilateral spastic cerebral palsy.Methods:Fifty children with bilateral spastic cerebral palsy were randomly divided into a single-task treadmill training group (the control group, n=25) and a dual-task treadmill training group (the observation group, n=25). All of the children also received routine rehabilitation training, and the control and observation groups also conducted single- and dual-task treadmill training in addition to the routine rehabilitation training, respectively. Before and after 2 months of treatment, each child′s gross motor functioning was quantified using sections D (standing) and E (walking, running and jumping) of the Gross Motor Function Measurement-88 (GMFM-88) instrument. Balance was quantified using the Pediatric Balance Scale (PBS) and walking mobility was quantified using a 1 minute walking test (1MWT). Modified and dual task Timed Up and Go (mTUG) tests and dual-task effects (DTE) tests were also administered. Results:There were no significant differences in average test scores between the two groups before the treatment. After the treatment significant improvement was observed in both groups. There was no significant difference between the two groups in terms of average GMFM-88, PBS and 1MWT scores, but significantly greater improvement was observed in the average dual-task mTUG and DTE results of the observation group.Conclusion:Both single- and dual-task treadmill training are effective supplements to routine rehabilitation training for children with bilateral spastic cerebral palsy. Dual-task treadmill training is more effective than the single-task version.
4.Gene expression signature analysis of peripheral blood mononuclear cells from patients with for high altitude pulmonary hypertension and value for potential drug selection.
Xin Hua WU ; Zhang Rong CHEN ; Ze Yuan HE ; Yu DONG ; Ying YANG ; Qiu Yan ZHAO ; Wei YANG ; Li Ying WANG ; Cai Jun FU ; Xiao Dan YANG ; Hong LIU
Chinese Journal of Cardiology 2022;50(6):577-584
Objective: To investigate the gene expression characteristics of peripheral blood mononuclear cells from patients with high altitude pulmonary hypertension (HAPH) in Naxi residents living in Lijiang, Yunnan, and to explore the underlying pathogenesis and value for potential drug selection. Methods: This is a case-control study. Six patients with HPAH (HPAH group) and 4 normal subjects (control group) were selected from the Naxi residents who originally lived in Lijiang, Yunnan Province. The general clinical data of the two groups were collected, and the related indexes of pulmonary artery pressure were collected. Peripheral blood mononuclear cells of the subjects were collected for RNA sequencing. The differences on gene expression, regulatory network of transcription factors and drug similarity between the two groups were compared. The results were compared with the public data of idiopathic pulmonary arterial hypertension (IPAH). Biological processes and signal pathways were analyzed and compared between HPAH and IPAH patients. Results: The age of 6 patients with HAPH was (68.1±8.3) years old, and there were 2 males (2/6). The age of 4 subjects in the control group was (62.3±10.9) years old, and there were 2 males (2/4). Tricuspid regurgitation velocity, tricuspid pressure gradient and pulmonary systolic pressure in HAPH group were significantly higher than those in control group (all P<0.05). The results of RNA sequencing showed that compared with the control group, 174 genes were significantly upregulated and 169 genes were downregulated in peripheral blood mononuclear cells of HAPH group. These differentially expressed genes were associated with 220 biological processes, 52 molecular functions and 23 cell components. A total of 21 biological processes and 2 signal pathways differed between HPAH and IPAH groups, most of which were related to inflammation and immune response. ZNF384, SP1 and STAT3 were selected as highly correlated transcription factors by transcription factor prediction analysis. Trichostatin A and vorinostat were screened out as potential drugs for the treatment of HAPH by drug similarity analysis. Conclusions: There are significant differences in gene expression in peripheral blood monocytes between HAPH patients and normal population, and inflammation and immune dysfunction are the main pathogenic factors. Trichostatin A and Vorinostat are potential drugs for the treatment of HAPH.
Aged
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Altitude
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Altitude Sickness/genetics*
;
Case-Control Studies
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China
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Familial Primary Pulmonary Hypertension/genetics*
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Humans
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Hydroxamic Acids/therapeutic use*
;
Hypertension, Pulmonary/genetics*
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Inflammation
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Leukocytes, Mononuclear/pathology*
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Male
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Middle Aged
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Transcription Factors
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Transcriptome/genetics*
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Vorinostat/therapeutic use*
5.DNA barcoding of Gentiana crassicaulis in Lijiang and evaluation of root processing methods
Wen-jing JI ; Yu-xuan ZHANG ; Zhi-li ZHAO ; Liang-hong NI ; Wei-tao LI ; Chen-xin ZHU ; Xiang CHEN ; Shao-hua YANG
Acta Pharmaceutica Sinica 2022;57(2):507-513
The key factors for producing the best quality Chinese herbal medicines are high-quality germplasm, suitable cultivation area and the proper processing methods for herbal raw materials.
6.The healing effect of paeoniflorin on the wound and regulation of NGF/Akt/GSK3β pathway on rats with diabetic foot
Hongyu ZHOU ; Jixian WANG ; Ai Asila LIJIANG ; Li LI
International Journal of Traditional Chinese Medicine 2022;44(6):650-656
Objective:To analyze the healing effect of paeoniflorin on the wound of rats and regulation of NGF/Akt/GSK3β pathway on rats with diabetic foot.Methods:60 rats were randomly divided into normal control group, model group, low, medium and high dose paeoniflorin groups, 12 rats in each group. Diabetic foot model was established by intraperitoneal injection of streptozotocin (STZ) and electrothermal scald. Paeoniflorin groups were injected intraperitoneally with 20 mg/kg, 40 mg/kg and 80 mg/kg paeoniflorin, once a day for 21 days. The wound healing rate of the rats was measured. The fasting blood glucose was measured by blood glucose meter, HbAlc, TC, LDL-C and TG were measured by automatic biochemical analyzer. Serum CRP, IL-6, IL-1β and TNF-α were measured by ELISA. The histopathological changes of the wound were examined by HE staining, the levels of NGF, Akt and GSK3 β mRNA in skin tissue were measured by real-time quantitative polymerase chain reaction (RTq-PCR), the protein and phosphorylation levels of NGF, Akt and GSK3 β were determined by Western blot.Results:Compared with the model group, the healing rate the rats' wounded surface in the low, medium and high dose groups of paeoniflorin was increased ( P<0.05). The levels of fasting blood glucose, HbAlc, TC, LDL-C, TG levels and serum CRP, IL-6, IL-1β, TNF-α was decreased ( P<0.05). The expression of rat skin tissue NGF mRNA (0.83±0.12, 3.17±0.11, 4.54±0.25 vs. 0.31±0.06), Akt mRNA (1.71±0.14, 2.96±0.27, 4.10±0.34 vs. 0.97±0.20) increased ( P<0.05), expression of GSK3β mRNA (4.28±0.35, 2.82±0.14, 1.22±0.33 vs. 7.62±0.43) decreased ( P<0.05), expression of NGF (0.46±0.02, 0.70±0.04, 0.87±0.04 vs. 0.30±0.06), Akt (0.51±0.09, 0.63±0.03, 0.79±0.06 vs.0.41±0.05),p-NGF/NGF (0.47±0.06, 0.61±0.04, 0.83±0.07 vs. 0.25±0.03), p-Akt/Akt(0.54±0.08, 0.83±0.11,0.96±0.07 vs. 0.13±0.05) was increased( P<0.05), the expression of GSK3β (0.67±0.05, 0.54±0.04,0.45±0.03 vs. 0.86±0.05), and the ratio of p-GSK3β/GSK3β (0.78±0.09, 0.64±0.07, 0.42±0.07 vs. 0.97±0.05) was decreased ( P<0.05), and the changes of each index were dependent on the dose of paeoniflorin. Conclusion:Paeoniflorin can regulate the level of blood glucose and blood lipid, inhibit the level of serum inflammatory factors and promote the healing of the wound in diabetic foot rats, and its mechanism may be related to the regulation of NGF/Akt/GSK3β pathway.
7.Chemical constituents of steroidal saponins in rhizome of Paris polyphylla var. yunnanensis cultured in vitro.
Ying-Ying ZHANG ; Lin JIN ; Yu-Ying WU ; Rui LI ; Kai-Ling WANG ; Hai-Feng LI
China Journal of Chinese Materia Medica 2021;46(19):4936-4944
In this study, liquid chromatography-mass spectrometry(LC-MS) and high performance liquid chromatography(HPLC) were employed for qualitative and quantitative analysis of the steroidal saponins in rhizomes of Paris polyphylla var. yunnanensis from three different habitats cultured in vitro, in an attempt to explore whether the rhizomes of the medicinal herb cultured in vitro can synthesize the steroidal saponins, including polyphyllinsⅠ, Ⅱ, and Ⅶ, the quality markers specified in Chinese Pharmacopoeia(2020 edition). A total of 20 steroidal saponins were identified in the rhizomes from Changxin, Yunlong(S1), Fengyi, Dali(S2), and Niujie, Eryuan(S3): parisyunnanoside A and parisyunnanoside D or E, proto-polyphyllin Ⅱ, polyphyllins G and H, polyphyllinsⅠ, Ⅱ, Ⅴ, Ⅵ, and Ⅶ, dioscin, gracillin, prosapogenin A, Tg, isomer of Th, saponin Th, reclinatoside, proto-pairs D, pseudoproto-dioscin, and 23-O-glc-(23S,25R)-spirost-5-en-3β,23α,27-triol-3-O-rha-(1→2)-[ara(1→4)]-glc or 27-O-glc-(23S,25R)-spirost-5-en-3β,27α-diol-3-O-rha-(1→2)-[ara(1→4)]-glc. Among them, polyphyllinsⅠ, Ⅱ, and Ⅶ were detected in the rhizomes from S1, with the mass fraction of 0.109 1%, 0.165 2%, and 0.051 03%, respectively(total 0.325 3%). Polyphyllins Ⅱ and Ⅶ were identified in the rhizomes from S2 with the respective mass fraction of 0.192 2% and 0.074 23% and total content of 0.266 5%. Moreover, polyphyllins Ⅱ and Ⅶ were also found in the rhizomes from S3, which had the mass fraction of 0.207 7% and 0.186 9%, separately, with the total content of 0.394 6%. Thus, steroidal saponins, including the quality makers polyphyllins Ⅰ, Ⅱ, and Ⅶ recorded in Chinese Pharmacopoeia(2020 edition) can be synthesized in rhizomes of Paris polyphylla var. yunnanensis cultured in vitro, but their total content fails to meet the standard(0.60% in Chinese Pharmacopoeia). Therefore, in vitro culture of the Paris polyphylla var. yunnanensis is feasible, but the culture conditions need to be further improved.
Chromatography, High Pressure Liquid
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Liliaceae
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Melanthiaceae
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Rhizome
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Saponins
8.Usage of ethnomedicine on COVID-19 in China.
Zhi-Yong LI ; Ya TU ; Hai-Tao LI ; Jiang HE ; QUESHENG ; Guang-Ping DONG ; Ming-Shuo ZHANG ; Jian-Qin LIU ; Xiu-Lan HUANG ; Xiao-Rong WANG ; Makabel BOLAT ; Xin FENG ; Fang-Bo ZHANG ; Feng JIANG
China Journal of Chinese Materia Medica 2020;45(10):2265-2274
In December 2019, an outbreak of viral pneumonia began in Wuhan, Hubei Province, which caused the spread of infectious pneumonia to a certain extent in China and neighboring countries and regions, and triggered the epidemic crisis. The coronavirus disease 2019(COVID-19) is an acute respiratory infectious disease listed as a B infectious disease, which is managed according to standards for A infectious disease. Traditional Chinese medicine and integrated traditional Chinese and Western medicine have played an active role in the prevention and control of this epidemic. China's ethnomedicine has recognized infectious diseases since ancient times, and formed a medical system including theory, therapies, formula and herbal medicines for such diseases. Since the outbreak of the COVID-19 epidemic, Tibet Autonomous Region, Qinghai Province, Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region and Chuxiong Autonomous Prefecture of Yunnan, Qiandongnan Autonomous Prefecture of Guizhou have issued the prevention and control programs for COVID-19 using Tibetan, Mongolian, Uygur, Yi and Miao medicines. These programs reflect the wisdom of ethnomedicine in preventing and treating diseases, which have successfully extracted prescriptions and preventive measures for the outbreak of the epidemic from their own medical theories and traditional experiences. In this paper, we summarized and explained the prescriptions and medicinal materials of ethnomedicine in these programs, and the origin of Tibetan medicine prescriptions and Mongolian medicine prescriptions in ancient books were studied. These become the common characteristics of medical prevention and treatment programs for ethnomedicine to formulate therapeutic programs under the guidance of traditional medicine theories, recommend prescriptions and prevention and treatment methods with characteristics of ethnomedicine, and focus on the conve-nience and standardization. However, strengthening the support of science and technology and the popularization to the public, and improving the participation of ethnomedicine in national public health services and the capacity-building to deal with sudden and critical diseases are key contents in the development of ethnomedicine in the future.
Betacoronavirus
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China
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Coronavirus Infections
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drug therapy
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Humans
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Medicine, Traditional
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Pandemics
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Pneumonia, Viral
;
drug therapy
;
Tibet
9. A systematic review of the effects of auricular acupressure therapy on relieving acute and chronic nonmalignant pain and its operating methods
Miaomiao LIU ; Yingge TONG ; Ling CHAI ; Xiaoyan LI ; Jiajia CHEN
Chinese Journal of Practical Nursing 2019;35(26):2072-2081
Objective:
To evaluate the effect and implementation of auricular acupressure therapy (AAT) in the treatment of acute and chronic non-cancerous pain.
Methods:
Computer search China Knowledge Network, China Biomedical Literature Disc (CBM), Wanfang Database, Weip Chinese Science and Technology Journal Database, PubMed, Web of Science, EMbase, Ebsco, Cochrane databases, a randomized controlled trial of AAT in the treatment of acute and chronic non-cancerous pain was included. The main outcome of AAT treatment for pain was pain intensity and analgesic drug use.
Results:
Of the 29 studies included, 93.1% (27/29) indicated that AAT was effective in relieving pain and/or reducing the amount of analgesic drugs; 15 and 12 of them were for acute and chronic non
10.Research progress on Akkermansia muciniphila in human intestine
Longfei JIA ; Li WU ; Yuqiu HAN ; Hanying LYU ; Lijiang ZHANG ; Baohong WANG
Chinese Journal of Clinical Infectious Diseases 2019;12(5):385-392
Recent studies heve demonstrated that Akkermansia muciniphila (A.muciniphila) plays an important role in human health and disease , including regulating the development of the immune system and the metabolic phenotype of the host.This article reviews the research progress on A.muciniphila in recent years, focusing on the basic characteristics , the influencing factors of colonization , and the underlying mechanism of maintaining intestinal homeostasis of A.muciniphila.Additionally, the article summarizes the potential association between A.muciniphila and the chronic metabolic diseases such as obesity , atherosclerosis,diabetes mellitus and infectious diseases.The perspect of A.muciniphila as a new generation of probiotics in clinical medicine and the challenge for its industrialization are also discussed in the article .

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