2.Cytoplasmic and nuclear NFATc3 cooperatively contributes to vascular smooth muscle cell dysfunction and drives aortic aneurysm and dissection.
Xiu LIU ; Li ZHAO ; Deshen LIU ; Lingna ZHAO ; Yonghua TUO ; Qinbao PENG ; Fangze HUANG ; Zhengkun SONG ; Chuanjie NIU ; Xiaoxia HE ; Yu XU ; Jun WAN ; Peng ZHU ; Zhengyang JIAN ; Jiawei GUO ; Yingying LIU ; Jun LU ; Sijia LIANG ; Shaoyi ZHENG
Acta Pharmaceutica Sinica B 2025;15(7):3663-3684
This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.
3.Shenlian Extract Protects against Ultrafine Particulate Matter-Aggravated Myocardial Ischemic Injury by Inhibiting Inflammation and Cell Apoptosis.
Shui Qing QU ; Yan LIANG ; Shuo Qiu DENG ; Yu LI ; Yue DAI ; Cheng Cheng LIU ; Tuo LIU ; Lu Qi WANG ; Li Na CHEN ; Yu Jie LI
Biomedical and Environmental Sciences 2025;38(2):206-218
OBJECTIVE:
Emerging evidence suggests that exposure to ultrafine particulate matter (UPM, aerodynamic diameter < 0.1 µm) is associated with adverse cardiovascular events. Previous studies have found that Shenlian (SL) extract possesses anti-inflammatory and antiapoptotic properties and has a promising protective effect at all stages of the atherosclerotic disease process. In this study, we aimed to investigated whether SL improves UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis.
METHODS:
We established a mouse model of MI+UPM. Echocardiographic measurement, measurement of myocardialinfarct size, biochemical analysis, enzyme-linked immunosorbent assay (ELISA), histopathological analysis, Transferase dUTP Nick End Labeling (TUNEL), Western blotting (WB), Polymerase Chain Reaction (PCR) and so on were used to explore the anti-inflammatory and anti-apoptotic effects of SL in vivo and in vitro.
RESULTS:
SL treatment can attenuate UPM-induced cardiac dysfunction by improving left ventricular ejection fraction, fractional shortening, and decreasing cardiac infarction area. SL significantly reduced the levels of myocardial enzymes and attenuated UPM-induced morphological alterations. Moreover, SL significantly reduced expression levels of the inflammatory cytokines IL-6, TNF-α, and MCP-1. UPM further increased the infiltration of macrophages in myocardial tissue, whereas SL intervention reversed this phenomenon. UPM also triggered myocardial apoptosis, which was markedly attenuated by SL treatment. The results of in vitro experiments revealed that SL prevented cell damage caused by exposure to UPM combined with hypoxia by reducing the expression of the inflammatory factor NF-κB and inhibiting apoptosis in H9c2 cells.
CONCLUSION
Overall, both in vivo and in vitro experiments demonstrated that SL attenuated UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. The mechanisms were related to the downregulation of macrophages infiltrating heart tissues.
Animals
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Apoptosis/drug effects*
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Particulate Matter/adverse effects*
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Mice
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Male
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Inflammation/drug therapy*
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Drugs, Chinese Herbal/therapeutic use*
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Mice, Inbred C57BL
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Myocardial Ischemia/drug therapy*
;
Cell Line
4.Preparation of heparinized acellular vascular scaffold and hemocompatibility evaluation
Xiafei LI ; Lingling ZHAO ; Feng LIANG ; Xuewei ZHANG ; Jinjin ZHANG ; Fei LIN ; Tuo YANG ; Liang ZHAO
Chinese Journal of Tissue Engineering Research 2024;28(17):2631-2636
BACKGROUND:Acellular vascular scaffolds can mimic the microstructure and function of native blood vessels,but some extracellular matrix loss occurs during their preparation,which affects their hemocompatibility.Therefore,it is necessary to modify them to improve their hemocompatibility. OBJECTIVE:To assess the hemocompatibility of acellular vascular scaffold prepared by Triton-x100/heparin sodium treatment. METHODS:The abdominal aorta was taken from SD rats and randomly divided into control and experimental groups.The control group was treated with Triton-x100 for 48 hours.The experimental group was treated with Triton-x100 for 48 hours and then treated with heparin sodium.The morphology and hydrophilicity of the two groups of acellular vascular scaffolds were detected.The hemocompatibility of the two groups of acellular vascular scaffold was evaluated by recalcification coagulation time test,platelet adhesion test,dynamic coagulation time test,hemolysis test,and complement activation test. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the surface of the two groups of vascular scaffolds was relatively intact,and a large number of fiber filaments appeared on the surface of the scaffolds after decellularity treatment,and the surface microstructure changed significantly.The water contact angle of the two groups of vascular scaffolds was smaller than that of natural vessels(P<0.000 1).There was no significant difference in water contact angle between the two groups(P>0.05).(2)The coagulation time of vascular scaffold was longer in the experimental group than in the control group(P<0.05).The number of platelets attached to the scaffold membrane was less in the experimental group than that in the control group(P<0.000 1).The coagulation index was greater in the experimental group than that in the control group(P<0.01),and the complement level was lower in the experimental group than that in the control group(P<0.001).The hemolysis rate of the two groups was lower than 5%of the national standard.(3)To conclude,acellular scaffold treated with Triton-x100/heparin sodium has excellent hemocompatibility.
5.Study on the risk factors of cefoperazone/sulbactam-induced coagulation dysfunction in adult patients:a systematic review
Mingfu TUO ; Cai’e TANG ; Kun YANG ; Yabing SHEN ; Shixin LEI ; Liang YANG
China Pharmacy 2024;35(4):488-493
OBJECTIVE To systematically evaluate the risk factors for cefoperazone/sulbactam-induced coagulation dysfunction in adult patients. METHODS Retrieved from CNKI, VIP, CBM, Wanfang data, PubMed, Embase and Cochrane Library, randomized controlled trial (RCT), case-control study or cohort study about cefoperazone/sulbactam-induced coagulation dysfunction in adult patients were collected from the inception to Apr. 30th, 2023. After literature screening, data extraction and quality evaluation, meta-analysis was carried out by using RevMan 5.3 software. RESULTS A total of 13 studies were included, among which 11 studies were case-control studies, and 2 studies were cohort studies, involving 18 387 patients in total. Meta- analysis showed that the proportion of advanced age [OR=2.04, 95%CI (1.14, 3.64), P=0.02], liver insufficiency [OR=5.95, 95%CI (4.21, 8.40), P<0.000 01], renal insufficiency [OR=3.51, 95%CI (3.04, 4.05), P<0.001], hypoproteinemia [OR= 1.90, 95%CI(1.37, 2.62), P<0.001], poor diet [OR=7.25, 95%CI (5.13, 10.24), P<0.000 01], daily dose of cefoperazone/ sulbactam ≥9 g [OR=3.95, 95%CI (2.45,6.37), P<0.001], medication duration of cefoperazone/sulbactam ≥10 d [OR=2.43, 95%CI (1.81, 3.28), P<0.001], combined use of anticoagulant drugs [OR=2.84, 95%CI (2.03, 3.97), P<0.001], combined with malignant tumor [OR=1.60, 95%CI (1.20, 2.15),P<0.001] in patients with abnormal coagulation function were significantly higher than those with normal coagulation function. CONCLUSIONS Advanced age, liver insufficiency, renal insufficiency, complicated with malignant tumors and hypoalbuminemia, combined use of anticoagulant drugs, poor diet, daily dose ≥9 g, and medication duration≥10 days are risk factors for coagulation dysfunction caused by cefoperazone/sulbactam.
6.Innovation of Methods for Efficacy Evaluation of Traditional Chinese Medicine Compound Prescriptions: Establishment of Characterization System for Simultaneous Treatment/Regulation Based on Correlation Patterns of Five Zang-organs
Yujie LI ; Tuo LIU ; Luqi WANG ; Lina CHEN ; Yan LIANG ; Chengcheng LIU ; Yu LI ; Xiaoxin ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):19-26
The clinical efficacy advantages of traditional Chinese medicine (TCM) compound prescriptions have always been inadequately characterized in experimental research,which has become a bottleneck restricting the development of TCM pharmacology and even the progress of TCM. The concept of simultaneous treatment/regulation,guided by the theory of mutual generation and restriction of five zang-organs,has guiding significance in the clinical practice of TCM throughout history and is still widely used in the current clinical practice. However,this unique and clinically valuable diagnostic and therapeutic medication system based on the syndrome differentiation has been completely ignored in the modern research of TCM pharmacology,which might be one of the key factors restricting the pharmacological characterization of the therapeutic advantages of TCM compound prescriptions. On the basis of systematically summarizing the phased progress and achievements of the efficacy evaluation of TCM compound prescriptions,this article explores the path of exploring the pharmacological advantages of TCM compound prescriptions on simultaneous treatment/regulation on the basis of the correlation patterns of five zang-organs,from the theory of Zangxiang,the core concept of five zang-organs,and the TCM disease recognition based on the theory of mutual generation and restriction of five zang-organs. With the heart-lung correlation as a breakthrough point,this study explored a new characterization method for the pharmacological advantages of TCM,aiming to provide new ideas for evaluating the efficacy of TCM compound prescriptions.
7.Effect of Artemisinin and Its Derivatives in Treatment of Nervous System Diseases: A Review
Yan LIANG ; Shuiqing QU ; Yu LI ; Yue DAI ; Chengcheng LIU ; Luqi WANG ; Lina CHEN ; Tuo LIU ; Yujie LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):292-299
With the rapid development of social economy, the number of patients with nervous system diseases has increased, and the incidence of the population has a trend of younger, which has a serious impact on life health and social economy. Artemisinin is an active antimalarial component extracted and isolated from Artemisia annua, a Chinese medicinal material. Artemisinin and its derivatives, in addition to the antimalarial effect, also have anti-parasitic, anti-fungal, anti-viral, hypoglycemic, hypolipidemic, anti-tumor, and anti-inflammatory effects, showing a wide range of pharmacological activities. In the past five years, research on the new pharmacological effects of artemisinin and its derivatives has been deepening, and the efficacy of artemisinin and its derivatives in nervous system diseases has attracted much attention, including anti-neuroinflammation, anti-oxidative stress, maintaining the stability of the blood-brain barrier, regulating the release of neurotransmitters, repairing neuronal damage, and promoting neuronal regeneration. These pharmacological effects indicate that artemisinin and its derivatives are potentially capable of neuroprotection. By sorting out literature on the pharmacological activity of artemisinin and its derivatives in nervous system during 2019-2024, this paper systematically summarized the protective effects of artemisinin and its derivatives against nervous system diseases such as stroke, neurodegenerative diseases, neuroimmunological diseases, neuralgia, and nervous system tumors. This review is expected to provide clues and evidence for new indication expansion of artemisinin drugs, innovative drug development, and clinical treatment of nervous system diseases.
8.Mechanisms of Outdoor Air Pollution Affecting Cardiovascular Diseases: A Review
Chengcheng LIU ; Yu LI ; Yan LIANG ; Shuiqing QU ; Yue DAI ; Tuo LIU ; Lina CHEN ; Luqi WANG ; Yujie LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):318-326
The impact of air pollution on human health has always been a research hotspot in the global health field. Outdoor air pollutants composed of multiple components can enter the human body through various pathways. Cardiovascular diseases are a group of diseases caused by outdoor air pollutants. Studies have shown that the incidence of cardiovascular diseases, including hypertension, arrhythmia, and heart failure, is significantly increased among people exposed to air pollution environments. Air pollutants such as fine particulate matter, nitrogen dioxide, ozone, carbon monoxide, and sulfur dioxide are closely related to the occurrence of cardiovascular diseases, and short-term and long-term exposure causes different cardiovascular risks. By reviewing the relevant research reports from 2019 to 2024, this article summarizes the epidemiological evidence of cardiovascular diseases caused by different air pollutants. It generalizes the pathways through which air pollutants accelerate the progression of cardiovascular diseases. These pathways include oxidative stress, inflammatory response, thrombosis, extracellular vesicle release, endoplasmic reticulum stress, apoptosis, endothelial dysfunction, autonomic nervous system imbalance, and their interactions. Based on the different mechanisms of air pollution on cardiovascular diseases, the article analyzes the main progress in drug intervention and summarizes the roles of various active ingredients and compound prescriptions of traditional Chinese medicine in treating air pollution-related cardiovascular diseases, providing reference for the research on the mechanisms and drug interventions of air pollution-related cardiovascular diseases.
9.Treatment of Cardiovascular Diseases in Diabetes Mellitus with Traditional Chinese Medicine: A Review
Yu ZHANG ; Yu LI ; Zhongyuan ZHENG ; Yan LIANG ; Chengcheng LIU ; Yue DAI ; Luqi WANG ; Tuo LIU ; Lina CHEN ; Yujie LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):327-337
The complex pathophysiological mechanisms between diabetes mellitus and cardiovascular diseases have not yet been fully elucidated, becoming one of the challenges in clinical care. Glucagon-like peptide-1 receptor agonist (GLP1-RA) and sodium glucose cotransporter-2 inhibitors (SGLT2) are clinically used to reduce the cardiovascular risk of patients with diabetes mellitus. Traditional Chinese medicine has diverse biological activities and unique advantages in the treatment of chronic complex diseases due to its multi-component and multi-target effects. Based on recent reports, this paper reviewed the common risk factors of diabetes mellitus and cardiovascular diseases (e.g., hyperglycemia, insulin resistance, and inflammation), related targets such as apolipoprotein C-Ⅲ (APOC3), S100 calcium-binding protein A8/A9 (S100A8/A9), growth/differentiation factor-15 (GDF-15), and NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), advanced glycation end products, insulin resistance, endothelial dysfunction, endoplasmic reticulum stress, mitochondrial dysfunction, and intestinal flora disorder. In addition, this paper summarized the research progress in the treatment of cardiovascular diseases in diabetes mellitus with the active ingredients (e.g., baicalein, puerarin, curcumin, notoginsenoside, and tanshinone ⅡA), single herbal medicines (e.g., Astragali Radix, Ginseng Radix et Rhizoma, Sophorae Flavescentis Radix, Cinnamomi Cortex, and Corni Fructus), and compound formulas (e.g., Buzang Tongluo Fang, Yiqi Yangyin Huoxue Fang, Shenqi Fang, Huangqisan, Danggui Buxue Tang, and Liuwei Dihuang Wan) of traditional Chinese medicine. Traditional Chinese medicine mainly treats cardiovascular diseases in diabetes mellitus by reducing inflammation and oxidative stress, ameliorating dyslipidemia and insulin resistance, protecting islet β cell function, repairing endothelial damage, inhibiting smooth muscle cell proliferation, foam cell formation, macrophage polarization, and cardiac hypertrophy and fibrosis, and regulating intestinal flora disorder. These processes involve insulin receptor substrate/ phosphatidylinositol 3-kinase/protein kinase B (IRS/PI3K/Akt), peroxisome proliferator-activated receptor α/γ (PPAR α/γ), nuclear factor-kappa B (NF-κB), adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK), hypoxia-inducible factor-1-BCH domain-containing protein (HIF-1-BNIP), vascular endothelial growth factor/hypoxia-inducible factor-1α (VEGF/HIF-1α) and other signaling pathways. This review is expected to provide a theoretical basis and reference for the treatment of cardiovascular diseases in diabetes mellitus with traditional Chinese medicine.
10.One case of coronary interventional treatment of severe stenosis caused by huge calcified plaque at the right coronary artery ostium
Li ZHOU ; Bing HUA ; Long-Hui MA ; Tuo LIANG ; Hui CHEN
Chinese Journal of Interventional Cardiology 2024;32(6):349-352
Coronary artery heavy calcification is always challenging scenarios for interventional cardiologists.Although the treatment strategy guided by intravascular imaging and guaranteed by rotational atherectomy(RA)is recommended by consensus,the application rate of RA in my country is still relatively low.Our center has accumulated a lot of experience in the use of rotational atherectomy to treat severe calcified lesions,especially in complex scenarios such as left main trunk lesions,ostial lesions,and severe vessel tortuosity.Here is a case of interventional treatment of severe eccentric stenosis caused by a huge calcified plaque at the right coronary artery ostium.The method and strategy of plaque modification and partial ablation by intravascular ultrasound-guided RA are discussed.

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