摘要：
BACKGROUND: Astragaloside IV (AS-IV) is the main active component of "Astragalus membranaceus (Fisch.) Bunge, a synonym of Astragalus propinquus Schischkin (Fabaceae)", which demonstrated to be useful for the treatment of intracerebral hemorrhage (ICH). However, due to the low bioavailability and barrier permeability of AS-IV, the gut microbiota may be an important key regulator for AS-IV to work. OBJECTIVE: To explore the influences of gut microbiota on the effects of AS-IV on ICH. METHODS: Mice were randomly divided into five groups: sham, ICH, and AS-IV-treated groups (25mg/kg, 50mg/kg, and 100mg/kg). Behavioral tests, brain histopathology, and immunohistochemistry analysis were used to evaluate the degree of brain injury. Western blot was employed to verify peri‑hematoma inflammation. The plasma lipopolysaccharide (LPS) leakage, the fluorescein isothiocyanate-dextran permeability, the colonic histopathology, and immunohistochemistry were detected to evaluate the barrier function of intestinal mucosal. Moreover, 16S rDNA sequencing and metabolomic analysis was applied to screen differential bacteria and metabolites, respectively. The correlation analysis was adopted to determine the potential relationship between differential bacteria and critical metabolites or neurological deficits. RESULTS: AS-IV alleviated neurological deficits, neuronal injury and apoptosis, and blood-brain barrier disruption. This compound reduced tumor necrosis factor (TNF)-α expression, increased arginase (Arg)-1 and interleukin (IL)-33 levels around the hematoma. Next, 16S rRNA sequencing indicated that AS-IV altered the gut microbiota, and inhibited the production of conditional pathogenic bacteria. Metabolomic analysis demonstrated that AS-IV regulated the serum metabolic profiles, especially the aminoacid metabolism and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Additionally, AS-IV mitigated intestinal barrier damage and LPS leakage. CONCLUSION: This study provides a new perspective on the use of AS-IV for the treatment of ICH. Among them, gut microbiota and its metabolites may be the key regulator of AS-IV in treating ICH.
摘要：
Enhancing the clearance of proteins associated with Alzheimer's disease (AD) emerges as a promising approach for AD therapeutics. This study explores the potential of Radix Stellariae, a traditional Chinese medicine, in treating AD. Utilizing transgenic C. elegans models of AD, we demonstrated that a 75% ethanol extract of Radix Stellariae (RSE) (at 50µg/mL) effectively diminishes Aβ and Tau protein expression, and alleviates their induced impairments including paralysis, behavioral dysfunction, neurotoxicity, and ROS accumulation. Additionally, RSE enhances the stress resistance of C. elegans. Further investigations revealed that RSE promotes autophagy, a critical cellular process for protein degradation, in these models. We found that inhibiting autophagy-related genes negated the neuroprotective effects of RSE, suggesting a central role for autophagy in the actions of RSE. In PC-12 cells, we observed that RSE not only inhibited Aβ fibril formation but also promoted the degradation of AD-related proteins and reduced their cytotoxicity. Mechanistically, RSE was found to induce autophagy via modulating PI3K/AKT/mTOR and AMPK/mTOR signaling pathways. Importantly, inhibiting autophagy counteracted the beneficial effects of RSE on the clearance of AD-associated proteins. Moreover, we identified Dichotomine B, a β-carboline alkaloid, as a key active constituent of RSE in mitigating AD pathology in C. elegans at concentrations ranging from 50 to 1000µM. Collectively, our study presents novel discoveries that RSE alleviates AD pathology and toxicity primarily by inducing autophagy, both in vivo and in vitro. These findings open up new avenues for exploring the therapeutic potential of RSE and its active component, Dichotomine B, in treating neurodegenerative diseases like AD.
摘要：
Osteoarthritis (OA) is a chronic joint disease characterized by progressive cartilage degeneration, which imposes a heavy physical and financial burden on the middle-aged and elderly population. As the pathogenesis of OA has not been fully elucidated, it is of great importance to develop targeted therapeutic or preventive medications. Traditional therapeutic drugs, such as non-steroidal anti-inflammatory drugs, steroids and opioids, have significant side effects, making the exploration for safe and effective alternative therapeutic drugs urgent. In recent years, many studies have reported the role of plant-derived polysaccharides in anti-inflammation, anti-oxidation, regulation of chondrocyte metabolism and proliferation, and cartilage protection, and have demonstrated their great potential in the treatment of OA. Therefore, by focusing on studies related to the intervention of plant-derived polysaccharides in OA, including in vivo and in vitro experiments, this review aimed to classify and summarize the existing research findings according to different mechanisms of action. In addition, reports on plant-derived polysaccharides as nanoparticles were also explored. Then, candidate monomers and theoretical bases were provided for the further development and application of novel drugs in the treatment of OA.
期刊：
Naunyn-Schmiedeberg's Archives of Pharmacology,2023年396(6):1187-1203 ISSN：0028-1298
通讯作者：
Dan Zhou<&wdkj&>Wei Zhang
作者机构：
[Li, Junxi; Ding, Huang; Zhou, Dan; Zhang, Wei; Liu, Jingze; Yan, Fanchen] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.;[Sun, Zhengji] Hunan Univ Chinese Med, Yueyang Tradit Chinese Med Hosp, Changsha 414021, Hunan, Peoples R China.
通讯机构：
[Dan Zhou; Wei Zhang] T;The Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine On Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China<&wdkj&>The Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine On Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China
摘要：
Buyang Huanwu decoction (BYHWD) is a classical traditional prescription. Glycosides are effective extracts of BYHWD, which have been proven to protect blood vessels and prevent atherosclerosis (AS). However, the mechanism of glycosides in inhibiting abnormal angiogenesis in atherosclerosis is still unclear. The specific amygdalin (AG), paeoniflorin (PF), and astragaloside IV (ASV) contents in the BYHWD-containing serum were detected using mass spectrometry. Network pharmacology and molecular docking are used to screen the targets of glycosides for treating atherosclerosis. The predicted targets were validated in an AS model of rat thoracic aortic endothelial cells (RTAEC) induced by oxidized low-density lipoprotein (ox-LDL). According to the mass spectrometry data, the specific contents of AG, PF, and ASV in the serum were 24.11ng/ml, 20.94ng/ml, and 69.87ng/ml, respectively. Results of bioinformatics analysis show that signal transducer and activator of transcription (STAT)-3, hypoxia-inducible factor (HIF)-1, and vascular endothelial-derived growth factor (VEGF) may be involved in the treatment of AS with glycosides. The results of cell experiments revealed that glycoside combinations could treat atherosclerosis by inhibiting STAT3, HIF-1, and VEGF. AG, PF, and ASV are the effective ingredients of BYHWD. Glycoside combinations significantly ameliorate atherosclerosis by inhibiting STAT3, HIF-1, and VEGF.
期刊：
Frontiers in Public Health,2023年11:1293134 ISSN：2296-2565
通讯作者：
Song, Zhenyan;Cheng, SW
作者机构：
[Song, Zhenyan; Guo, Minhua; Cheng, Shaowu; Song, ZY; He, Jiawei; Cheng, SW; Wang, Shiwei] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Peoples R China.;[Song, Zhenyan; Guo, Minhua; Cheng, Shaowu; Song, ZY; He, Jiawei; Cheng, SW; Wang, Shiwei] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410128, Peoples R China.;[Wang, Weijie] Hunan Univ Chinese Med, Sch Informat, Changsha, Peoples R China.
通讯机构：
[Song, ZY; Cheng, SW ] H;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Peoples R China.;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410128, Peoples R China.
关键词：
Barthel Index (BI);activities of daily living;machine learning algorithm;memory-related diseases;the China health and retirement longitudinal survey
摘要：
INTRODUCTION: Memory-related diseases (MDs) pose a significant healthcare challenge globally, and early detection is essential for effective intervention. This study investigates the potential of Activities of Daily Living (ADL) as a clinical diagnostic indicator for MDs. Utilizing data from the 2018 national baseline survey of the China Health and Retirement Longitudinal Study (CHARLS), encompassing 10,062 Chinese individuals aged 45 or older, we assessed ADL using the Barthel Index (BI) and correlated it with the presence of MDs. Statistical analysis, supplemented by machine learning algorithms (Support Vector Machine, Decision Tree, and Logistic Regression), was employed to elucidate the relationship between ADL and MDs. BACKGROUND: MDs represent a significant public health concern, necessitating early detection and intervention to mitigate their impact on individuals and society. Identifying reliable clinical diagnostic signs for MDs is imperative. ADL have garnered attention as a potential marker. This study aims to rigorously analyze clinical data and validate machine learning algorithms to ascertain if ADL can serve as an indicator of MDs. METHODS: Data from the 2018 national baseline survey of the China Health and Retirement Longitudinal Study (CHARLS) were employed, encompassing responses from 10,062 Chinese individuals aged 45 or older. ADL was assessed using the BI, while the presence of MDs was determined through health report questions. Statistical analysis was executed using SPSS 25.0, and machine learning algorithms, including Support Vector Machine (SVM), Decision Tree Learning (DT), and Logistic Regression (LR), were implemented using Python 3.10.2. RESULTS: Population characteristics analysis revealed that the average BI score for individuals with MDs was 70.88, significantly lower than the average score of 87.77 in the control group. Pearson's correlation analysis demonstrated a robust negative association (r = -0.188, p < 0.001) between ADL and MDs. After adjusting for covariates such as gender, age, smoking status, drinking status, hypertension, diabetes, and dyslipidemia, the negative relationship between ADL and MDs remained statistically significant (B = -0.002, β = -0.142, t = -14.393, 95% CI = -0.002, -0.001, p = 0.000). The application of machine learning models further confirmed the predictive accuracy of ADL for MDs, with area under the curve (AUC) values as follows: SVM-AUC = 0.69, DT-AUC = 0.715, LR-AUC = 0.7. Comparative analysis of machine learning outcomes with and without the BI underscored the BI's role in enhancing predictive abilities, with the DT model demonstrating superior performance. CONCLUSION: This study establishes a robust negative correlation between ADL and MDs through comprehensive statistical analysis and machine learning algorithms. The results validate ADL as a promising diagnostic indicator for MDs, with enhanced predictive accuracy when coupled with the Barthel Index. Lower levels of ADL are associated with an increased likelihood of developing memory-related diseases, underscoring the clinical relevance of ADL assessment in early disease detection.
摘要：
Respiratory diseases are an emerging public health concern, that pose a risk to the global community. There, it is essential to establish effective treatments to reduce the global burden of respiratory diseases. Astragaloside IV (AS-IV) is a natural saponin isolated from Radix astragali (Huangqi in Chinese) used for thousands of years in Chinese medicine. This compound has become increasingly popular due to its potential anti-inflammatory, antioxidant, and anticancer properties. In the last decade, accumulated evidence has indicated the AS-IV protective effect against respiratory diseases. This article presents a current understanding of AS-IV roles and mechanisms in combatting respiratory diseases. The ability of the agent to suppress oxidative stress, cell proliferation, and epithelial-mesenchymal transition (EMT), to attenuate inflammatory responses, and modulate programmed cell death (PCD) will be discussed. This review highlights the current challenges in respiratory diseases and recommendations to improve disease management.
作者机构：
[Wu, Zixuan; Song, Zhenyan; Cheng, Shaowu; Feng, Xiang; Zhu, Xu; Cheng, SW; Yang, Miao; Yu, Wenjing; Deng, Sisi] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410128, Peoples R China.
通讯机构：
[Cheng, SW ] H;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410128, Peoples R China.
摘要：
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that usually manifests in childhood and is thought to be caused by a complex interaction of genetic, environmental, and immune factors. The majority of current ASD diagnostic methods rely on subjective behavioral observation and scale assessment, making early detection difficult. In this study, we confirmed that lysosomal-associated membrane protein 1 (LAMP1), a functional marker of immune cell activation and cytotoxic degranulation, was upregulated in ASD blood, brain cortex, and various genetic animal models or cells using bioinformatics approaches. The prognostic value of LAMP1 was investigated by correlating its expression with clinical ASD rating scales, and the receiver operating characteristic (ROC) curve analysis in ASD also revealed that it has a favorable diagnostic ability in distinguishing ASD from control cohort. According to gene set enrichment analysis (GSEA) results, LAMP1 correlated with genes that were enriched in natural kill and T cell immune function. Taking all of the evidence into account, we discovered that abnormal elevations of LAMP1 mRNA and protein in the blood of ASD children, may influence the development of ASD through its involvement in immune cell activity regulation. This report highlights a novel marker for ASD early detection as well as potential therapeutic targets.
期刊：
European Journal of Medical Research,2023年28(1):1-15 ISSN：2047-783X
通讯作者：
Changqing Deng
作者机构：
[Yahong Cai] Chronic Disease Management Department, The First Hospital of Hunan University of Chinese Medicine, Changsha, China;[Changqing Deng] The Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China;[Linquan Liu] Chronic Disease Management Department, The First Hospital of Hunan University of Chinese Medicine, Changsha, China<&wdkj&>The Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China
通讯机构：
[Changqing Deng] T;The Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China
摘要：
Pyroptosis plays an important role in the pathological process of ischemic stroke (IS). However, the exact mechanism of pyroptosis remains unclear. This paper aims to reveal the key molecular markers associated with pyroptosis in IS. We used random forest learning, gene set variation analysis, and Pearson correlation analysis to screen for biomarkers associated with pyroptosis in IS. Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen and glucose deprivation/reoxygenation (OGD/R) models were constructed in vitro and in vivo. Cells were transfected with an Annexin A3 silencing (si-ANXA3) plasmid to observe the effects of ANXA3 on OGD/R + lipopolysaccharides (LPS)-induced pyroptosis. qRT‒PCR and western blotting were used to detect the expression of potential biomarkers and pyroptotic pathways. Samples from a total of 170 IS patients and 109 healthy individuals were obtained from 5 gene expression omnibus databases. Thirty important genes were analyzed by random forest learning from the differentially expressed genes. Then, we investigated the relationship between the above genes and the pyroptosis score, obtaining three potential biomarkers (ANXA3, ANKRD22, ADM). ANXA3 and ADM were upregulated in the MCAO/R model, and the fold difference in ANXA3 expression was greater. Pyroptosis-related factors (NLRP3, NLRC4, AIM2, GSDMD-N, caspase-8, pro-caspase-1, cleaved caspase-1, IL-1β, and IL-18) were upregulated in the MCAO/R model. Silencing ANXA3 alleviated the expression of pyroptosis-related factors (NLRC4, AIM2, GSDMD-N, caspase-8, pro-caspase-1, cleaved caspase-1, and IL-18) induced by OGD/R + LPS or MCAO/R. This study identified ANXA3 as a possible pyroptosis-related gene marker in IS through bioinformatics and experiments. ANXA3 could inhibit pyroptosis through the NLRC4/AIM2 axis.
作者机构：
[Luo, Min] Cent South Univ, Xiangya Hosp 2, Dept Nephrol, 139 Middle Renmin Rd, Changsha 410011, Hunan, Peoples R China.;[Luo, Min; Hu, Zongren; He, Qinghu] Hunan Univ Med, Dept Rehabil Med & Hlth Care, Huaihua 418000, Hunan, Peoples R China.;[Luo, Min; Hu, Zongren; He, Qinghu] Hunan Univ Chinese Med, Coll Tradit Chinese Med, Changsha, Hunan, Peoples R China.;[Liu, Ziyu] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Hunan, Peoples R China.
通讯机构：
[Min Luo; Qinghu He] D;Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China<&wdkj&>Department of Rehabilitation Medicine and Health Care, Hunan University of Medicine, Huaihua, Hunan Province, China<&wdkj&>College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan Province, China<&wdkj&>Department of Rehabilitation Medicine and Health Care, Hunan University of Medicine, Huaihua, Hunan Province, China<&wdkj&>College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan Province, China
关键词：
CI-AKI cell model;HuangKui;cell injury and apoptosis;NEAT1
作者机构：
[Tang, Qianli; Liao, Xianjiu] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[Li, Qingli; Tang, Qianli; Liao, Xianjiu] Youjiang Med Univ Nationalities, West Guangxi Key Lab Prevent & Treatment High Inc, Baise 533000, Guangxi, Peoples R China.;[Liu, Zhao; Qiu, Shang; Wu, Shengyue; Gao, Fenglei; Cai, Zhiheng; Ge, Kezhen] Xuzhou Med Univ, Sch Pharm, Jiangsu Key Lab New Drug Res & Clin Pharm, Xuzhou 221004, Jiangsu, Peoples R China.
通讯机构：
[Tang, Qianli] H;[Gao, Fenglei] X;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;Xuzhou Med Univ, Sch Pharm, Jiangsu Key Lab New Drug Res & Clin Pharm, Xuzhou 221004, Jiangsu, Peoples R China.
摘要：
Amyloid beta-peptide oligomer (A beta O) has received extensive attention from researchers because of its clinical therapeutic intervention targets and the value of reliable biological macromolecules markers for early diagnosis of Alzheimer's disease. We have developed a novel label-free electrochemical detection sensor for A beta O based on hybridization chain reaction (HCR)-triggered poly adenine to absorb silver nanoparticles (AgNPs). In this method, we first use the "capture probe" to immobilize the aptamer 1 on the surface of the gold electrode (GE) via poly adenine-Au. Next, aptamer 2 and A beta O were deposited on the electrode surface. The HCR process was initiated by the aptamer 2 fragment as a primer, producing a large number of long DNA sequences, which contained many adenines. Thereafter, the HCR product with long-repeated adenines could absorb many AgNPs on the surface of the electrode, which were used for subsequent electrochemical stripping of the AgNPs. The concentration range of the electrochemical signal of A beta O was 1 pMe10 nM, and the detection limit was 430 fM, which indicated that that the detection system has high selectivity for the target protein. (C) 2021 Elsevier B.V. All rights reserved.
期刊：
Clinical and Experimental Pharmacology and Physiology,2022年49(10):1042-1049 ISSN：0305-1870
通讯作者：
Qinghu He<&wdkj&>Shijin Xia
作者机构：
[Liu, Lumei; He, Qinghu] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;[Xia, Shijin; Wei, Yaqin] Fudan Univ, Shanghai Inst Geriatr, Huadong Hosp, Shanghai, Peoples R China.;[Giunta, Sergio] Casa Cura Prof Nobili GHC Garofalo Hlth Care, Bologna, Italy.;[He, Qinghu] Hunan Univ Med, Huaihua, Peoples R China.
通讯机构：
[Qinghu He] C;[Shijin Xia] S;Shanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai, People's Republic of China<&wdkj&>College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, People's Republic of China<&wdkj&>Hunan University of Medicine, Huaihua, People's Republic of China
摘要：
Pulmonary arterial hypertension (PAH) is a rare and chronic lung vasculature disease characterised by pulmonary vasculature remodelling, including abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) and dysfunctional endothelial cells (ECs). Remodelling of the pulmonary vasculature occurs from maturity to senescence, and it has become apparent that cellular senescence plays a central role in the pathogenesis of various degenerative vascular diseases and pulmonary pathologies. Cellular senescence represents a state of stable proliferative arrest accompanied by the senescence-associated secretory phenotype (SASP), which entails the copious secretion of proinflammatory signals in the tissue microenvironment. Evidence shows that in PAH patients, higher levels of cytokines, chemokines and inflammatory mediators can be detected and correlate with clinical outcome. Moreover, senescent cells accrue with age in epithelial, endothelial, fibroblastic and immunological compartments within human lungs, and evidence has shown that ECs and PASMCs in lungs from patients with chronic obstructive pulmonary disease were characterised by a higher number of senescent cells. However, there is little evidence uncovering the molecular pulmonary vasculature senescence in PAH. Herein, we review the cellular senescence in pulmonary vascular remodelling, and emphasise its importance in PAH. We further introduce some signalling pathways which might be involved in vasculature senescence and PAH, with the intent to discuss the possibility of the PAH therapy via targeting cellular senescence and reduce PAH progression and mortality.
作者机构：
[Tian, Xue-fei; Zhang, Zhen] Hunan Univ Chinese Med, Coll Integrated Chinese & Western Med, Dept Internal Med, Changsha 410208, Peoples R China.;[Tian, Xue-fei; Zhang, Zhen; Gao, Wen-hui] Hunan Univ Chinese Med, Hunan Key Lab TCM Prescript & Syndromes Translat, Changsha 410208, Peoples R China.;[Li, Jun-wei] Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Pharm, Shenzhen 518020, Guangdong, Peoples R China.;[Li, Jun-wei] Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China.;[Zeng, Pu-hua] Hunan Acad Tradit Chinese Med, Affiliated Hosp, Dept Oncol, Changsha 410006, Peoples R China.
通讯机构：
[Xue-fei Tian] D;Department of Internal Medicine, College of Integrated Chinese and Western Medicine of Hunan University of Chinese Medicine, Changsha, China<&wdkj&>Hunan Key Laboratory of TCM Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha, China
关键词：
Chinese medicine;primary liver cancer;system pharmacology;bioinformatics;tumor microenvironment
作者机构：
[Zhu, Xu] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Dept Epidemiol & Hlth Stat, Changsha, Hunan, Peoples R China.;[Xue, Jing] Cent South Univ, Xiangya Hosp, Dept Sci Res, Changsha, Hunan, Peoples R China.;[Liu, Zheng] Shandong First Med Univ, Hosp Affiliated 1, Dept Anesthesiol, Shandong Prov Qianfoshan Hosp, Jinan, Shandong, Peoples R China.;[Xiang, Jingsha; Dai, Wenjie] Cent South Univ, Xiangya Sch Publ Hlth, Changsha, Hunan, Peoples R China.;[Zhou, Qiaoling; Xu, Hui; Chen, Wenhang] Cent South Univ, Xiangya Hosp, Dept Nephrol, Changsha, Hunan, Peoples R China.
摘要：
OBJECTIVE: The effect of the serum chloride (Cl) level on mortality in critically ill patients with acute kidney injury (AKI) remains unknown. We sought an association between mortality and serum Cl. METHODS: We identified AKI patients in the eICU Collaborative Research Database from 2014 to 2015 at 208 US hospitals. The outcomes included in-hospital and intensive care unit (ICU) mortality. Time-varying covariates Cox regression models and the Kaplan-Meier (K-M) curves were used to assess the association between serum Cl levels and mortality. Multivariable adjusted restricted cubic spline models were used to analyze the potential nonlinear relationship between mortality and serum Cl. RESULTS: In total, 4,234 AKI patients were included in the study. Compared with normochloremia (98≤chloride<108mEq/L), hypochloremia (Cl<98mEq/L) was associated with mortality (adjusted hazard ratio [HR] for in-hospital mortality 1.46, 95% confidence interval [CI] 1.20-1.80, P = 0.0003; adjusted HR for ICU mortality 1.37, 95% CI 1.05-1.80, P = 0.0187). Hyperchloremia showed no significant difference in mortality compared to normochloremia (adjusted HR for in-hospital mortality 0.89, 95% CI 0.76-1.04, P = 0.1438; adjusted HR for ICU mortality 0.87, 95% CI 0.72-1.06, P = 0.1712). Smoothing curves revealed continuous non-linear associations between serum Cl levels and mortality. The K-M curve showed that patients with hypochloremia presented with a lower survival rate. CONCLUSIONS: Lower serum Cl levels after ICU admission was associated with increased in-hospital and ICU mortality in critically ill patients with AKI. The results should be verified in well-designed prospective studies.
作者机构：
[Ding, Huang; Tan, Wei; Zhang, Wei; Long, Qingyin; Fu, Xinying; Liu, Xiaodan] Hunan Univ Chinese Med, Coll Integrated Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.;[Sun, Zhengji] Hunan Univ Chinese Med, Yueyang Tradit Chinese Med Hosp, Changsha 414021, Hunan, Peoples R China.;[Wu, Lu] Hunan Univ Chinese Med, Liuyang Tradit Chinese Med Hosp, Changsha 410399, Hunan, Peoples R China.;[Wang, Yang] Cent South Univ, Xiangya Hosp, Inst Integrat Med, Key Lab Hunan Prov Liver Manifestat Tradit Chinese, Changsha 410008, Hunan, Peoples R China.
通讯机构：
[Wei Zhang] C;College of Integrated Chinese and Western Medicine, Key Laboratory of Hunan Provincial for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Hunan 410208, China
摘要：
BACKGROUND: Buyang Huanwu Decoction (BYHWD) has been used to treat or prevent cardiovascular disease. The prescription and its glycosides have the effects of protecting blood vessels, and resisting atherosclerosis. However, their protective mechanism of anti-atherosclerosis remains unclear. PURPOSE: This study aims to explore whether glycosides are the main effective components of BYHWD in anti-atherosclerotic inflammation and whether their mechanism is related to the classical JAK/STAT inflammatory signaling pathway. METHODS: UPLC-MSMS method was used to determine the main components of BYHWD and its glycosides. Network pharmacological analysis and molecular docking were used to predict the potential therapeutic targets of glycosides. Atherosclerosis model was prepared by feeding HFD in ApoE(-/-) mice. The effects of glycosides on atherosclerosis were detected by blood lipids measurement, Masson staining, immunohistochemistry, immunofluorescence, western-blot and droplet digital PCR. RAW264.7 cells were used to establish foam cells model. The mechanism of glycosides anti-atherosclerotic inflammation was detected by measuring intracellular lipids, Oil Red O staining, ELISA, western-blot and droplet digital PCR. RESULTS: 1. Glycosides were absorbed into the blood through oral administrations and existed in the blood in the form of glycosides structures. 2. Glycosides attenuated hyperlipidemia, alleviated atherosclerotic lesions and inhibited inflammatory reaction. They could regulate blood lipids by decreasing TC, TG, LDL-c, increasing HDL-c level in ApoE(-/-) mice, alleviating intimal area and thickness, and inhibiting atherosclerotic plaque formation, which were similar to BYHWD. 3. Glycosides anti-atherosclerotic inflammation was related to JAK/STAT signaling pathway by network pharmacology analysis. Interactions between glycosides (astragaloside IV, paeoniflorin and amygdalin) and JAK/STAT pathway-related proteins by molecular docking. 4. Glycosides alleviated atherosclerotic inflammation by decreasing the release of pro-inflammatory factors and adhesions molecules, inhibiting the activation of JAK/STAT pathway in vivo. 5. Glycosides reduced the number of foam cells and intracellular lipid content. It also prevented the inflammation of macrophages by decreasing the levels of pro-inflammatory factors, reducing the phosphorylation of JAK2, STAT1 and STAT3 in vitro. CONCLUSION: This study demonstrated that glycosides were the main active components of BYHWD, and they could inhibit atherosclerosis by alleviating atherosclerotic inflammation. the mechanism is inhibiting the activation of JAK/STAT signaling pathway.
作者机构：
[Wang, Yang; Yang, Zhao-yu; Hu, Ming -rui; Li, Xue-xuan; Wu, Yao; Feng, Dan -dan; Tang, Tao] Cent South Univ, Xiangya Hosp, Inst Integrat Med, Dept Integrated Tradit Chinese & Western Med, Changsha 410008, Peoples R China.;[Li, Peng-fei] Zhengzhou Univ, Dept Resp & Crit Care Med, Affiliated Hosp 1, Zhengzhou 450052, Peoples R China.;[Dai, Feng] Cent South Univ, Xiangya Hosp, Emergency Med, Changsha 410008, Peoples R China.;[Zhang, Wei; Zheng, Fei] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Peoples R China.;[Wang, Yang; Yang, Zhao-yu; Hu, Ming -rui; Li, Xue-xuan; Wu, Yao; Feng, Dan -dan; Tang, Tao; Dai, Feng] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Peoples R China.
通讯机构：
[Tao Tang] D;Department of Integrated Traditional Chinese and Western Medicine, Institute of Integrative Medicine, Xiangya Hospital, Central South University, Changsha 410008, China<&wdkj&>National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
关键词：
Traumatic brain injury;Xuefu Zhuyu Decoctions;tRNA-derived small RNAs;Transcriptome;Biomarker
摘要：
BACKGROUND: Xuefu Zhuyu Decoction (XFZYD), a well-known traditional Chinese medicine prescription, has been widely used to treat traumatic brain injury (TBI). However, the underlying mechanisms involved in XFZYD therapy remain unclear. AIM OF THE STUDY: We explored new therapeutic targets of XFZYD in TBI by the tsRNA-sequencing (tsRNA-seq) method. MATERIAL AND METHODS: High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to assess the quality of XFZYD. Male Sprague-Dawley rats were randomly categorized into three groups: sham, TBI, and XFZYD. The protective effects of XFZYD were investigated in vivo by using the Morris water maze (MWM), modified neurological severity score (mNSS) tests, hematoxylin-eosin (H&E) staining, and Nissl staining. tsRNA-seq was applied to analyze the expression of tsRNAs in the rat cortex. Four tsRNAs were validated by qRT-PCR. The biological function of putative tsRNAs was investigated using bioinformatics techniques. The functions of tsRNAs targeting mRNAs were verified in vitro. RESULTS: The mNSS and MWM indicated that XFZYD notably improved neurological deficits and cognitive function after TBI (p<0.05). H&E staining and Nissl staining demonstrated that XFZYD suppressed damage and neuronal loss in the TBI rat cortex. We evaluated the dysregulated expression of 732 tsRNAs (128 tsRNAs were significantly altered in the TBI/sham group (fold change>2 and p<0.05), and 97 tsRNAs were dysregulated in the XFZYD/TBI group (fold change>2 and p<0.05)) in the TBI rat cortex. Interestingly, 41 tsRNAs were distinctly regulated by XFZYD. The qRT-PCR results of the four randomly chosen tsRNAs (tRF-54-75-Glu-TTC-2, tRF-55-75-Gln-CTG-2-M2, tRF-55-76-Val-TAC-1, tRF-64-85-Leu-AAG-1-M4) exhibited trends similar to those of the tsRNA-seq data. We certified the possible targets of tsRNAs and suggested the crosscurrent in the expression trend of the target genes. Bioinformatics analysis showed that XFZYD-related tsRNAs could contribute to regulating insulin resistance, the calcium signaling pathway, autophagy, and axon guidance. CONCLUSIONS: The current research implies that tsRNAs are putative therapeutic targets of XFYZD for TBI treatment. This research provides new insight into the therapeutic targets of XFZYD in treating TBI.
作者机构：
[罗起胜; 唐乾利] College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China;[罗琨祥; 黄海能; 郑传华; 蓝川琉; 罗起胜; 黄华东; 李传玉; 符黄德] Department of Neurosurgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China;[胡仁统; 罗宏成] Department of Laboratory Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China;[唐乾利] Department of Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China
作者机构：
[Yan, Miao; Zhang, Min] Cent S Univ, Xiangya Hosp 2, Dept Pharm, Changsha 410011, Hunan, Peoples R China.;[Fan, Xin-Rong; Chen, Yan; Yang, Mei-ju; Zhang, Min] China Acad Chinese Med Sci, Inst Basic Theory Chinese Med, Beijing 100700, Peoples R China.;[Zhang, Min] Shaanxi Univ Chinese Med, Clin Med Coll 1, Xianyang, Peoples R China.;[Nie, Yu-Song; Fan, Xin-Rong; Zhang, Ling; Xie, Hui] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Hunan, Peoples R China.
通讯机构：
[Yan, Miao; Fan, Xin-Rong] C;Cent S Univ, Xiangya Hosp 2, Dept Pharm, Changsha 410011, Hunan, Peoples R China.;China Acad Chinese Med Sci, Inst Basic Theory Chinese Med, Beijing 100700, Peoples R China.
摘要：
The purpose of this study was to investigate the renal protective effect of celastrol on diabetic rats. Furthermore, the mechanism of its action was discussed whether it was related to MAPK/NF-kappaB signaling pathway. There were a total of 36 rats. Six rats were randomly chosen as the control group. The remaining 30 rats were given 1% streptozotocin intraperitoneal injection (50 mg/kg) and were randomly divided into five groups: the model control group, the low-dose celastrol group, the high-dose celastrol group, the Tripterygium wilfordii polyglycosides group, and the MAPK/NF-kappaB inhibitor group. After 4 weeks of continuous administration, 24-hr urine volume, urinary protein, blood urea nitrogen, and serum creatinine content were observed, and hematoxylin-eosin (HE) staining of the kidney and liver were evaluated. p38MAPK was designated by immunohistochemical method, and NF-kappaB p65 in renal tissue was detected by western blotting. Our results showed that celastrol could not only reduce contents of creatinine and urea nitrogen in blood but also reduce excretion of urinary protein in diabetic rats, improve renal pathological injury, and down-regulate the expression of p38MAPK and NF-kappaB p65. In conclusion, celastrol could protect kidney of diabetic rats by regulating the signal pathway of MAPK/NF-kappaB, inhibiting inflammation and delaying renal injury.
期刊：
Prostaglandins & Other Lipid Mediators,2019年140:1-8 ISSN：1098-8823
通讯作者：
Zou, Guohui;Deng, Changqing
作者机构：
[Chen, Hongtao; Zou, Guohui; Liu, Zhongyong; Xu, Ri; Deng, Peng] Jiangxi Univ Tradit Chinese Med, Affiliated Hosp, Nanchang 330006, Jiangxi, Peoples R China.;[Zhu, Jinhua] Jiangxi Univ Tradit Chinese Med, Nanchang 330004, Jiangxi, Peoples R China.;[Wu, Lu] Hunan Univ Tradit Chinese Med, Affiliated Tradit & Western Med Hosp 2, Liuyang 410300, Peoples R China.;[Deng, Changqing] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Zou, Guohui] J;[Deng, Changqing] H;Jiangxi Univ Tradit Chinese Med, Affiliated Hosp, Nanchang 330006, Jiangxi, Peoples R China.;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.
关键词：
*Detoxification and activating blood circulation decoction;*Inflammatory reaction;*PCI operation;*Restenosis;*TLR4/NF-kappaB;*VSMCs proliferation
摘要：
Restenosis is a major problem after percutaneous coronary intervention (PCI) treatment. Inflammation is one of the major core mechanisms involved in the occurrence of restenosis, and plays an important role in intimal hyperplasia. Detoxification and activating blood circulation decoction (DABCD) is a traditional Chinese medicine that is used in the treatment and prevention of atherosclerotic and inflammatory diseases. Our previous studies demonstrated that DABCD-mediated cardioprotection involves anti-inflammatory mechanisms and could be developed as a novel drug for the treatment of vascular smooth muscle cell (VSMC) proliferation and aortic restenosis. A rat model of postoperative restenosis after PCI was generated by balloon injury to determine the protective effects and potential mechanisms of DABCD. The injured segments of aortae were collected on days 14 and 28 after the operation to observe the morphological changes in the vascular structure and measure the proportion of inflammatory factors in plasma and vascular tissues, as well as test the proliferative activity of VSMCs. The expression of related proteins, namely, Toll-like receptor (TLR) 4 and nuclear factor (NF)-kappaB, in the mechanistic study was clarified by western blot analysis. We tested the hypothesis that the cardioprotective effects of DABCD on aortic restenosis are associated with the inhibition of aortic intimal hyperplasia in this model. Our results showed that DABCD has protective effect on rat aortic restenosis and the anti-inflammatory mechanism of DABCD on balloon-induced restenosis in rat may be due to its ability to inhibit TLR4-mediated NF-kappaB signaling pathways. DABCD may be a potential therapeutic agent against restenosis.
摘要：
Purpose: There is no effective treatment for liver fibrosis, which is a common phase during the progression of many chronic liver diseases to cirrhosis. Previous studies found that Semen Brassicae therapy can effectively improve the clinical symptoms of patients with asthma, allergic rhinitis, and chronic lung diseases; however, its effects on liver fibrosis in rats and its possible mechanisms of action remain unclear. Methods: Rats were injected intraperitoneally with 4% thioacetamide aqueous solution (5 mL.kg(-1)) at a dose of 200 mg.kg(-1) twice a week for 8 consecutive weeks to establish the liver fibrosis model and were then treated with different concentrations of Semen Brassicae extract. A tier Semen Brassicae treatment, the morphology of the liver tissue was analyzed using hematoxylin and eosin and Masson's trichrome staining, and liver index and liver fibrosis grade were calculated. Thereafter, the levels of collagen-I, collagen-III, alpha-SM A, transforming growth factor (TGF)-beta 1, p-Smad 2/3, Smad 2/3, Smad4, NF-kappa B-p65, p-NF-kappa B-p65, IL-1 beta, IL-6, AKT, and p-AKT were determined using Western blotting. Results: Compared with the untreated model group, the Semen Brassicae-treated group showed significantly decreased liver function indices; expression levels of collagen-I, collagen-III, and alpha-SMA; and hepatic fibrosis. Further studies also showed that the expression of TGF-beta 1, Smad4, p-Smad 2/3, Smad 2/3,, p-NF-kappa B-p65/NF-KB-p65, IL-1 beta, IL-6, and p-AKT/AKT significantly decreased after the treatment. Conclusion: These results indicate that Semen Brassicae exhibits an anti-hepatic fibrosis effect, and the underlying mechanism of action may be related to the regulation of TGF-beta 1/Smad, NF-kappa B, and AKT signaling pathways and the reduction of extracellular matrix deposition.
