摘要：
目的:利用网络药理学方法和实验验证分析脊痛消胶囊治疗腰椎间盘突出症(lumbar disc herniation,LDH)的作用机制.方法:从中药系统药理学(Traditional Chinese Medicine Systems Pharmacology,TCMSP)、中药分子机理的生物信息学分析工具(Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine,BATMAN-TCM)、中医药资料@Taiwan和Swiss数据库中检索并筛选脊痛消胶囊的有效成分及其作用靶点,并使用GeneCards、人类孟德尔遗传(Online Mendelian Inher-itance in Man,OMIM)和DisGeNET数据库预测LDH的疾病靶点,再将活性成分作用靶点与疾病靶点进行映射,得到脊痛消胶囊治疗LDH潜在靶点,继续在STRING数据库中进行蛋白互作分析(protein-protein interaction,PPI),将结果导入Cytoscape软件获取PPI网络图和"药物-活性成分-潜在靶点"网络图.利用clusterProfiler包对潜在靶点进行基因本体(Gene Ontology,GO)功能、京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析,用Autodock Vina和Discovery Studio软件对活性成分和关键靶点进行分子对接验证.最后以脊痛消胶囊为干预因素,在LDH模型大鼠进行实验验证.结果:网络药理学结果显示,共收集到脊痛消胶囊活性成分139 种、靶点479 个,获得LDH靶点590 个,映射得到84 个交集靶点,通过PPI网络筛选得到脊痛消胶囊治疗LDH的关键治疗靶点 10 个:信号转导和转录激活因子 3(signal transducer and activator of transcription 3,STAT3)、转录因子 JUN(transcription factor Jun-1,JUN)、白细胞介素(interleukin,IL)-6、IL-10、丝裂原活化蛋白激酶 1(mitogen-activated protein kinase 1,MAPK1)、FOS蛋白(protein c-fos,FOS)、连环素(catenin beta-1,CTNNB1)、丝裂原活化蛋白激酶14(MAPK14)、蛋白激酶B(protein kinase B,PKB/AKT1)和肿瘤坏死因子(tumor nec-rosis factor,TNF),GO功能富集分析显示交集靶点涉及2 163 种生物学过程、36 种细胞组分和102 种分子功能,KEGG通路富集分析显示,共涉及155 条信号通路,分子对接结果显示核心靶点与成分对接结合良好.实验验证结果显示,脊痛消胶囊可显著降低LDH模型大鼠血清IL-6 和TNF-α水平,提高血清IL-10 水平,降低髓核组织p-JUN/JUN、p-FOS/FOS、p-JNK/JNK和p-p38MAPK/p38MAPK水平.结论:脊痛消胶囊可以通过抑制炎症反应和JNK/MAPK信号通路的激活从而起到保护LDH模型大鼠的作用.
期刊：
CURRENT MOLECULAR MEDICINE,2024年 ISSN：1566-5240
作者机构：
[Xiong, Wu] Department of Burns and Plastic Surgery, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410007, China;[Zhang, Xi] Clinical Medical School of Hunan University of Chinese Medicine, Hunan Brain Hospital, Changsha, 410007, China;[Zou, Xiao-Ling] Department of Endocrinology, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410007, China;[Peng, Sai; Lei, Hua-Juan] Department of Anesthesiology, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410007, China;[Liu, Xiang-Nan] College of Acupuncture & Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, 410208, China
摘要：
BACKGROUND: Chronic hyperglycemia in diabetes induces oxidative stress, leading to damage to the vascular system. In this study, we aimed to evaluate the effects and mechanisms of AS-IV-Exos in alleviating endothelial oxidative stress and dysfunction caused by high glucose (HG). METHODS: Histopathological changes were observed using HE staining, and CD31 expression was assessed through immunohistochemistry (IHC). Cell proliferation was evaluated through CCK8 and EDU assays. The levels of ROS, SOD, and GSH-Px in the skin tissues of each group were measured using ELISA. Cell adhesion, migration, and tube formation abilities were assessed using adhesion, Transwell, and tube formation experiments. ROS levels in HUVEC cells were measured using flow cytometry. The levels of miR-210 and Nox2 were determined through quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of Nox2, SOD, GSH-Px, CD63, and CD81 was confirmed using WB. RESULTS: The level of miR-210 was reduced in diabetes-induced skin damage, while the levels of Nox2 and ROS increased. Treatment with AS-IV increased the level of miR-210 in EPC-Exos. Compared to Exos, AS-IV-Exos significantly reduced the proliferation rate, adhesion number, migration speed, and tube-forming ability of HGdamaged HUVEC cells. AS-IV-Exos also significantly decreased the levels of SOD and GSH-Px in HG-treated HUVEC cells and reduced the levels of Nox2 and GSH-Px. However, ROS levels and Nox2 could reverse this effect. CONCLUSION: AS-IV-Exos effectively alleviated endothelial oxidative stress and dysfunction induced by HG through the miR-210/Nox2/ROS pathway.
摘要：
Objective Based on the theory of supramolecular"imprinting template",the fingerprint of Liuwei Dihuang Concentrated Pills(六味地黄丸浓缩丸,LDCP)was divided and integrated,and it was characterized as a material unit,and the spectralquality control and evaluation reaearch were conducted.Methods The matching frequency statistical moment method was used to divide,integrate and characterize the material units of 50 batches of LDCP fingerprints.According to Lambert-Beer's law,the total peak area of each material unit and the paste yield were subjected to multiple linear regression to establish a spectral equation for spectral research.Results The UPLC fingerprints of 50 batches of LDCP were divided into 35 material units(A1-A35).The spectral equations of the total peak area and the paste yield of the 35 material units(A1-A35)were obtained by multiple linear regression:PT=23.390+0.041 06 A1-9.100 × 10-3 A2+0.014 68 A3+0.027 98 A4-0.033 61 A5-0.042 25 A6-6.608 × 10-3 A7-0.025 90 A8-0.145 60 A9+0.165 00 A10-0.027 50 A11+3.408 × 10-3 A12-0.021 03 A13-1.070 × 10-3 A14+2.833 × 10-5 A15-8.774 × 10-3 A16+0.018 52 A17-1.882 9 × 10-3 A18+0.023 61 A19+8.566 × 10-3 A20+0.013 94 A21-5.894 × 10-3 A22-0.012 27 A23-0.014 91 A24+1.792 × 10-3 A25-1.571 × 10-4 A26-3.942 × 10-3A27-0.054 80 A28+0.083 15 A29+0.119 30 A30-0.060 71 A31-0.083 42 A32+0.014 96 A33-2.989 × 10-3 A34+0.063 17 A35(r=0.915).Conclusion This method can divide,integrate and characterize the LDCP fingerprint material units with high accuracy,and retain the total statistical moment characteristics of the original fingerprint.Its spectral equation can better predict the paste rate of LDCP and the average paste rate,which can provide new ideas and methods for the quality control of LDCP.
期刊：
Supportive Care in Cancer,2024年32(2):136 ISSN：0941-4355
通讯作者：
So, WKW
作者机构：
[Xu, Binbin] Hunan Univ Chinese Med, Sch Nursing, Changsha, Peoples R China.;[So, Winnie K. W.; Choi, Kai Chow; Xu, Binbin; So, WKW] Chinese Univ Hong Kong, Nethersole Sch Nursing, Hong Kong, Peoples R China.
通讯机构：
[So, WKW ] C;Chinese Univ Hong Kong, Nethersole Sch Nursing, Hong Kong, Peoples R China.
关键词：
COmprehensive Score for financial Toxicity;Cut-off score;Cost-related treatment nonadherence;Health-related quality of life;Cancer;Chinese
摘要：
PURPOSE: This study aimed to determine a cut-off for the simplified Chinese version of the COmprehensive Score for financial Toxicity (COST) that could identify cost-related treatment nonadherence among Chinese patients with cancer. The study also sought to validate this cut-off score by using it to assess impaired health-related quality of life (HRQoL) in the same population. METHODS: A secondary analysis was conducted using data from a cross-sectional survey of 1208 Chinese patients with cancer who were recruited from 12 hospitals in six cities across three provinces of the Chinese mainland. Sociodemographic information and data on financial toxicity (FT), cost-related treatment nonadherence, and HRQoL were used in the analysis. Receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off for the simplified Chinese version of the COST. RESULTS: The ROC analysis identified a COST cut-off of 18.5 for identifying cost-related treatment nonadherence, yielding a sensitivity of 76.5% and specificity of 71.4%. In the validation study, this cut-off score yielded a sensitivity of 64.2% and a specificity of 67.1% for identifying impaired HRQoL. CONCLUSION: Early and dynamic assessment of cancer-related FT in routine clinical practice may play a crucial role in the early identification and management of FT. Accordingly, a COST cut-off of 18.5 was identified to indicate cost-related treatment nonadherence and impaired HRQoL in a population of patients with cancer from the Chinese mainland. This finding may facilitate the implementation of universal FT screening among patients with cancer in specific settings such as the Chinese mainland.
摘要：
INTRODUCTION: Innate and acquired chemoresistance in colorectal cancer (CRC) often results in 5-fluorouracil (5-FU) treatment failure. This study aimed to investigate the potential of Jianpi Jiedu (JPJD) decoction to reverse 5-FU resistance in CRC and clarify its potential mechanism of action. METHODS: The CCK-8 assay was employed to assess cell activity. Flow cytometry was employed to assess various parameters including cell apoptosis, cell cycle distribution, P-glycoprotein (P-gp) activity, reactive oxygen species levels, and lipid peroxidation. Metabolomics analysis was conducted to identify differentially expressed metabolites. Western blotting was utilized for protein expression analysis. RESULTS: In this study, we demonstrated that the combined JPJD and 5-FU treatment reversed 5-FU resistance in HCT8/5-FU cells, inducing cell apoptosis, causing G2/M-phase cell cycle arrest, and reducing P-gp protein expression and activity. Metabolomics analysis revealed ferroptosis as a key pathway in the development of 5-FU resistance. Furthermore, the combination treatment reversed drug resistance primarily by impacting ferroptosis and triggering critical ferroptosis events through the suppression of the cystine/glutamate transporter (xCT)/glutathione (GSH)/glutathione peroxidase (GPX4) axis. CONCLUSION: JPJD decoction primarily suppressed the xCT/GSH/GPX4 axis to trigger ferroptosis, thereby effectively reversing 5-FU resistance in colorectal cancer (CRC).
通讯机构：
[Peng, QH ; Yao, XL] H;Hunan Univ Tradit Chinese Med, Changsha, Hunan, Peoples R China.;Hunan Univ Tradit Chinese Med, Affiliated Hosp 1, Dept Ophthalmol, Changsha, Hunan, Peoples R China.
关键词：
nonspecific orbital inflammation (NSOI);purine metabolism genes (PMGs);LASSO regression;SVM-RFE;bioinformatics
摘要：
Background Nonspecific orbital inflammation (NSOI) represents a perplexing and persistent proliferative inflammatory disorder of idiopathic nature, characterized by a heterogeneous lymphoid infiltration within the orbital region. This condition, marked by the aberrant metabolic activities of its cellular constituents, starkly contrasts with the metabolic equilibrium found in healthy cells. Among the myriad pathways integral to cellular metabolism, purine metabolism emerges as a critical player, providing the building blocks for nucleic acid synthesis, such as DNA and RNA. Despite its significance, the contribution of Purine Metabolism Genes (PMGs) to the pathophysiological landscape of NSOI remains a mystery, highlighting a critical gap in our understanding of the disease's molecular underpinnings.Methods To bridge this knowledge gap, our study embarked on an exploratory journey to identify and validate PMGs implicated in NSOI, employing a comprehensive bioinformatics strategy. By intersecting differential gene expression analyses with a curated list of 92 known PMGs, we aimed to pinpoint those with potential roles in NSOI. Advanced methodologies, including Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA), facilitated a deep dive into the biological functions and pathways associated with these PMGs. Further refinement through Lasso regression and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) enabled the identification of key hub genes and the evaluation of their diagnostic prowess for NSOI. Additionally, the relationship between these hub PMGs and relevant clinical parameters was thoroughly investigated. To corroborate our findings, we analyzed expression data from datasets GSE58331 and GSE105149, focusing on the seven PMGs identified as potentially crucial to NSOI pathology.Results Our investigation unveiled seven PMGs (ENTPD1, POLR2K, NPR2, PDE6D, PDE6H, PDE4B, and ALLC) as intimately connected to NSOI. Functional analyses shed light on their involvement in processes such as peroxisome targeting sequence binding, seminiferous tubule development, and ciliary transition zone organization. Importantly, the diagnostic capabilities of these PMGs demonstrated promising efficacy in distinguishing NSOI from non-affected states.Conclusions Through rigorous bioinformatics analyses, this study unveils seven PMGs as novel biomarker candidates for NSOI, elucidating their potential roles in the disease's pathogenesis. These discoveries not only enhance our understanding of NSOI at the molecular level but also pave the way for innovative approaches to monitor and study its progression, offering a beacon of hope for individuals afflicted by this enigmatic condition.
