期刊：
Journal of Applied Toxicology,2025年 ISSN：0260-437X
通讯作者：
He, X
作者机构：
[Guo, Bing] Hunan Univ Chinese Med, Grad Sch, Changsha, Hunan, Peoples R China.;[He, Xuan; He, X] Changsha Med Univ, Coll Tradit Chinese Med, Changsha, Hunan, Peoples R China.
通讯机构：
[He, X ] C;Changsha Med Univ, Coll Tradit Chinese Med, Changsha, Hunan, Peoples R China.
摘要：
The increasing prevalence of environmental pollutants has raised public concern about their potential role in diseases such as atherosclerosis (AS). Existing studies suggest that chemicals, including bisphenol S (BPS), may adversely affect cardiovascular health, but the specific mechanisms remain unclear. This study aims to elucidate the effects of BPS on AS and the underlying mechanisms. Through an extensive search of databases such as ChEMBL, STITCH, SwissTargetPrediction, SuperPred, SEA, and GEO, we identified 34 potential targets related to BPS-induced AS. A target network was constructed using the STRING platform and Cytoscape software. GO and KEGG functional enrichment analysis using the DAVID database revealed that BPS may promote the occurrence of AS by interfering with critical biological processes such as glutathione metabolism, nitrogen metabolism, and tyrosine metabolism. This was followed by the selection of 4 core targets-aminopeptidase n (ANPEP), alcohol dehydrogenase 5 (ADH5), lysosomal pro-x carboxypeptidase (PRCP), and microsomal glutathione s-transferase 1 (MGST1)-using five machine learning methods. These core targets play a pivotal role in BPS-induced AS. Furthermore, molecular docking confirmed the tight binding between BPS and these core targets. In conclusion, this study provides a theoretical framework for understanding the molecular mechanisms of BPS-induced AS and contributes scientific evidence for the development of prevention and treatment strategies for cardiovascular diseases triggered by BPS exposure.
期刊：
Frontiers in Pharmacology,2025年16:1417603 ISSN：1663-9812
通讯作者：
Fu, W;Zhou, Q
作者机构：
[You, Xujun] Hunan Univ Chinese Med, Grad Sch, Changsha, Peoples R China.;[Li, Qixin; Fu, Wei; You, Xujun] Guangzhou Univ Chinese Med, Shenzhen Baoan Tradit Chinese Med Hosp, Dept Androl, Shenzhen, Peoples R China.;[Wu, Yongrong] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;[Sheng, Wen] Hunan Univ Chinese Med, Androl Lab, Changsha, Peoples R China.;[Zhou, Qing; Zhou, Q] Hunan Univ Chinese Med, Dept Androl, Affiliated Hosp 1, Changsha, Peoples R China.
通讯机构：
[Fu, W ] G;[Zhou, Q ] H;Guangzhou Univ Chinese Med, Shenzhen Baoan Tradit Chinese Med Hosp, Dept Androl, Shenzhen, Peoples R China.;Hunan Univ Chinese Med, Dept Androl, Affiliated Hosp 1, Changsha, Peoples R China.
关键词：
prostate cancer;autophagy;PI3K/AKT;Astragalus–Scorpio;Astragaloside IV;polypeptide extract from scorpion venom
摘要：
Fluticasone propionate nasal spray is widely regarded as a first-line therapy for allergic rhinitis. To establish bioequivalence between the test and reference products of fluticasone propionate nasal spray, an open-label, randomized, single-dose, and 2-sequence crossover study was conducted on 84 healthy Chinese subjects under fasting conditions to determine the pharmacokinetic bioequivalence of the 2 products. Following a single-dose administration (200µg) of fluticasone propionate nasal spray, pharmacokinetic parameters, including maximum plasma concentration, area under the concentration-time curve from administration to the last measurable concentration, and area under the concentration-time curve from administration to infinity, exhibited similarity between the 2 products, with 90% confidence intervals for the test/reference ratios falling within the bioequivalence range of 80%-125%.
摘要：
BACKGROUND: Intervertebral disc degeneration (IDD) significantly contributes to low back pain (LBP), yet effective treatment options are scarce. BSHXF, a classical traditional Chinese medicine formula, demonstrates dual pharmacological actions: tonifying kidneys, strengthening bones, activating blood circulation, and resolving stasis. It has been widely used in IDD management. Given its potential, combining BSHXF with miRNA regulation and stem cell therapy may enhance therapeutic outcomes by targeting molecular and cellular pathways underlying IDD pathogenesis. AIM OF THE STUDY: IDD is recognized as one of the primary causes of low back pain, yet effective therapeutic interventions for this condition remain limited. This study explores the role of BSHXF drug-containing serum combined with adipose-derived stem cells (ADSCs) in slowing IDD progression via the miR-199a-3p/TGF-β/Smad signaling pathway. By comprehensively investigating the synergistic effects of this combination therapy, we aim to propose a novel multi-target strategy that addresses the complex pathogenesis of IDD. MATERIALS AND METHODS: This study employed a combination of in vivo and in vitro models. An IDD model was induced in rat caudal intervertebral discs through needle puncture, while an oxidative stress-induced ADSCs injury model was created in vitro using tert-butyl hydroperoxide (T-BHP). Cell viability was measured with the CCK-8 assay. Cell cycle distribution and mitochondrial reactive oxygen species (ROS) levels were assessed using flow cytometry. Cellular senescence was assessed using SA-β-galactosidase staining. Lactate dehydrogenase (LDH) activity was quantified to evaluate cellular damage. Differentiation into nucleus pulposus-like cells was assessed using immunofluorescence double staining for CD73 and COL2A1. ELISA was used to measure inflammatory cytokines (TNF-α, IL-1β, IL-4, IL-10) in cell supernatants. miR-199a-3p expression was determined using RT-qPCR. Western blotting was employed to quantify COL2A1, SOX9, and ACAN protein levels, reflecting nucleus pulposus-like differentiation and extracellular matrix (ECM) synthesis capacity. Western blotting was employed to assess pathway activity by analyzing the protein expressions of TGF-β1, Smad2, Smad3, and their phosphorylated forms, P-Smad2 and P-Smad3. In vivo experiments assessed histopathological degeneration through hematoxylin-eosin (HE) and Safranin O-Fast Green staining. Immunohistochemistry (IHC) analyzed COL1A1 and COL2A1 expression levels. RT-qPCR quantified miR-199a-3p expression. Western blotting was employed to assess the expression levels of TGF-β1, Smad2, Smad3, P-Smad2, and P-Smad3 for pathway regulation evaluation. RESULTS: Our experimental results demonstrated that serum containing BSHXF significantly alleviated T-BHP-induced oxidative stress, improved the cellular microenvironment, promoted ADSCs proliferation, and decelerated cellular senescence. Further mechanistic analysis revealed that BSHXF significantly activated the TGF-β/Smad signaling pathway, driving the differentiation of ADSCs into nucleus pulposus-like cells and restoring normal cell cycle progression. Overexpression of miR-199a-3p inhibited the TGF-β/Smad pathway, leading to ECM degradation and elevated expression of inflammatory factors (TNF-α, IL-1β). In contrast, BSHXF restored TGF-β/Smad pathway activity by downregulating miR-199a-3p expression. In vivo experiments demonstrated that miR-199a-3p overexpression exacerbated IDD, characterized by reduced COL2A1 expression, elevated COL1A1 levels, and increased disc fibrosis. BSHXF intervention markedly attenuated IDD progression by downregulating miR-199a-3p expression, reducing disc fibrosis, and effectively restoring collagen expression. CONCLUSION: BSHXF activated the TGF-β/Smad pathway to promote the differentiation of ADSCs into nucleus pulposus-like cells. It exerted protective effects by alleviating oxidative stress damage, improving the microenvironment, delaying senescence, and enhancing cellular functions. This study is the first to reveal that miR-199a-3p overexpression exacerbates intervertebral disc fibrosis and degeneration. BSHXF restored TGF-β/Smad pathway activity by downregulating miR-199a-3p expression, thereby improving disc structure and function. This integrated approach offers a novel multi-target intervention strategy for IDD, demonstrating significant therapeutic potential.
期刊：
BMC Complementary Medicine and Therapies,2025年25(1):1-13 ISSN：2662-7671
通讯作者：
Li, XP
作者机构：
[Cai, Jialuo; Li, Xiaoping] Hunan Univ Chinese Med, Hosp 1, Prevent Treatment Dis Ctr, Changsha 410007, Peoples R China.;[Zhu, Yilin] Hunan Univ Tradit Chinese Med, Grad Sch, Changsha 410208, Peoples R China.;[Deng, Guiming] Hunan Univ Chinese Med, Hosp 1, Dept Sci Res, Changsha 410208, Peoples R China.;[Ouyang, Linqi; Xiao, Wangzhong] Hunan Univ Chinese Med, Hosp 1, Dept Pharm, Changsha 410007, Peoples R China.;[Zhou, Fang] Hunan Univ Chinese Med, Hosp 1, Dept Hlth Management, Changsha 410007, Peoples R China.
通讯机构：
[Li, XP ] H;Hunan Univ Chinese Med, Hosp 1, Prevent Treatment Dis Ctr, Changsha 410007, Peoples R China.
关键词：
Pre-diabetes;Traditional Chinese medicine;Inflammation;Oxidative stress;Gene regulation
摘要：
Insulin secretion deficiency and increased insulin resistance are key pathological pathways that lead to pre-diabetes. Without intervention, pre-diabetes can easily develop into type 2 diabetes mellitus. However, no specific medicine is available for treating pre-diabetes except for intervention through lifestyle changes. Huangjing Qianshi decoction (HJQST) is a qi-replenishing and yin-nourishing Chinese medicinal compound. However, the mode and mechanism of action of HJQST in improving pre-diabetes remain unclear. Here, we studied the effect of HJQST on pre-diabetes. BKS-db mice were induced to develop pre-diabetes and treated with HJQST and metformin (MET). After treatment for 51 days, hematoxylin-eosin and oil red O staining were used to analyze the pathological damage and lipid droplet formation in the pancreatic, liver and skeletal muscle of pre-diabetic mice. Serum levels of free fat acid (FFA), glycated hemoglobin A1c (HbA1c), fasting insulin (INS), reactive oxygen species (ROS), and tumor necrosis factor-α (TNF-α) were analyzed. Levels of glucose transporter 4 (GLUT-4), INS, nuclear receptor subfamily 3 group c member 2 (NR3C2), phosphorylated-signal transducer and activator of transcription 1 (p-STAT1), peroxisome proliferator activated receptor co-activator 1 α (PGC-1α), and protein inhibitor of activated STAT1 (PIAS1) protein were analyzed by immunohistochemistry and western blot. The body weight, fasting blood glucose (FBS) levels, and serum levels of HbA1c, FFA, ROS, and TNF-α were significantly decreased, whereas the insulin level was significantly increased in pre-diabetic BKS-db mice after HJQST treatment. Additionally, HJQST treatment improved pancreatic and liver damage and the lipid droplet formation in liver and skeletal muscle. Furthermore, the increased NR3C2 and p-STAT1 protein levels and decreased GLUT-4, INS, PIAS1, and PGC-1a protein levels in pre-diabetic mice were reversed by HJQST treatment. HJQST treatment could reverse high FBS level and aberrant lipid metabolism, oxidative stress, and inflammation in pre-diabetes, all of which are related to the NR3C2/PIAS1/STAT1/PGC-1α signal axis.
摘要：
This study explores the diagnostic and therapeutic potential of SCN5A, an immunogenic cell death (ICD)-related gene, in hepatocellular carcinoma (HCC). Integrated analysis of four databases identified 62 ICD-associated genes (ICDGs), with SCN5A emerging as a key player linked to HCC prognosis and immune microenvironment modulation. Single-cell RNA sequencing revealed correlations between ICD activity and tumor immune dynamics. Bulk RNA sequencing categorized HCC into distinct molecular subtypes with varied immunological features. Machine learning-based prognostic models highlighted SCN5A's clinical relevance, supported by phenome-wide association studies connecting SCN5A to liver malignancies. Experimental validation showed elevated SCN5A expression in HepG2 cells, where siRNA-mediated knockdown significantly impaired proliferation (CCK8 and colony formation assays), invasion (Transwell), migration (wound healing), and apoptotic index (TUNEL assays and Bax, Bcl-2 expression). Molecular docking identified propafenone as a high-affinity SCN5A binder, which suppressed SCN5A expression and mirrored knockdown effects by inhibiting HCC cell growth and metastasis while promoting apoptosis. These findings position SCN5A as a novel ICD-linked biomarker and therapeutic target in HCC, with propafenone repurposing showing promising anti-tumor efficacy through SCN5A modulation. This work bridges computational biology with experimental oncology to advance ICD-targeted HCC treatment strategies.
摘要：
Headspace-gas chromatography-ion migration spectrometry (HS-GC-IMS) combined with chemometrics was used to analyze the changes in volatile aroma compounds (VOCs) at different production stages of steaming Polygonatum cyrtonema Hua. Fifty-seven representative compounds in the process of steaming were identified, including 17 aldehydes, 15 alcohols, 15 ketones, 5 esters, 3 furans, and 2 acids. After steaming, the content of 21 compounds decreased. Among them, 3 compounds gradually decreased along with an increase in steaming times; they were 1-hexanol dimer, 1-hexanol monomer, and 3-methylbutan-1-ol dimer. The content of 14 compounds increased than before, and that of three, 1-(2-furanyl)ethanone monomer, 2-furaldehyde, and 3-methyl butanal, increased significantly in the steaming times. The VOCs of the different samples can be classified by GC-IMS data combined with principal component analysis (PCA) and heatmap cluster analysis. A reliable prediction set was established by orthogonal partial least squares discriminant analysis (OPLS-DA), and 18 different VOCs with projected variable importance (VIP) greater than 1.0 were screened out, which could be used as differentiating markers. Therefore, HS-GC-IMS and PCA were used to rapidly identify and classify the VOCs in different production stages of steaming P. cyrtonema Hua.
摘要：
Homoharringtonine is a natural alkaloid with significant pharmacological potential that has demonstrated promising efficacy in the treatment of hematological malignancies in recent years. This article systematically reviews the pharmacological mechanisms of Homoharringtonine, focusing on its key roles in inducing apoptosis, inhibiting cell cycle progression, and reducing cell migration and invasion. Additionally, HHT exhibits multiple biological activities, including immunomodulation, antiviral effects, and anti-fibrotic properties, with recent studies also revealing its potential neuroprotective functions. In clinical trials, Homoharringtonine has demonstrated promising efficacy in the treatment of hematological malignancies, particularly in various types such as acute myeloid leukemia and chronic myeloid leukemia. Despite the significant antitumor effects observed in clinical applications, its low bioavailability and potential side effects remain major challenges that limit its widespread use. This article details the latest research advancements aimed at enhancing the bioavailability of Homoharringtonine, including various drug delivery systems such as nanoparticles and liposomes, as well as chemical modification strategies. These approaches not only improve HHT’s bioavailability in vivo but also enhance its targeting ability while reducing toxicity to normal cells. Furthermore, the combination of HHT with other drugs presents broader prospects for clinical treatment. By exploring the diverse pharmacological activities of Homoharringtonine in depth, this article aims to provide a foundation for developing novel therapeutic approaches based on natural products, thereby advancing HHT’s application research in cancer treatment and other fields.
期刊：
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY,2025年84(3):210-222 ISSN：0022-3069
通讯作者：
Liu, F
作者机构：
[Zhou, Shengqiang; Liu, Fang] Hunan Acad Tradit Chinese Med, Hunan Prov Hosp Integrated Tradit Chinese & Wester, Affiliated Hosp, Natl TCM Master Liu Zuyi Inheritance Studio, 58 Lushan Rd, Changsha 410006, Hunan, Peoples R China.;[Li, Bo] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Pediat, Changsha, Hunan, Peoples R China.;[Wu, Dahua] Hunan Acad Tradit Chinese Med, Hunan Prov Hosp Integrated Tradit Chinese & Wester, Affiliated Hosp, Dept Neurol, Changsha, Hunan, Peoples R China.;[Chen, Yanjun; Tan, Lingjuan; Zeng, Wen; Huang, Jia] Hunan Univ Chinese Med, Grad Sch, Changsha, Hunan, Peoples R China.;[Mao, Guo] Hunan Acad Tradit Chinese Med, Hunan Prov Hosp Integrated Tradit Chinese & Wester, Affiliated Hosp, Key Project Off, Changsha, Hunan, Peoples R China.
通讯机构：
[Liu, F ] H;Hunan Acad Tradit Chinese Med, Hunan Prov Hosp Integrated Tradit Chinese & Wester, Affiliated Hosp, Natl TCM Master Liu Zuyi Inheritance Studio, 58 Lushan Rd, Changsha 410006, Hunan, Peoples R China.
关键词：
EGFR/Ca2+ signaling;axonal regeneration;fibrinogen;middle cerebral artery occlusion;neuronal energy crisis
摘要：
Ischemic stroke results in inhibition of axonal regeneration but the roles of fibrinogen (Fg) in neuronal signaling and energy crises in experimental stroke are under-investigated. We explored the mechanism of Fg modulation of axonal regeneration and neuronal energy crisis after cerebral ischemia using a permanent middle cerebral artery occlusion (MCAO) rat model and primary cortical neurons under low glucose-low oxygen. Behavioral tests assessed neurological deficits; immunofluorescence, immunohistochemistry, and Western-blot analyzed Fg and protein levels. Fluo-3/AM fluorescence measured free Ca2+ and ATP levels were gauged via specific assays and F560nm/F510nm ratio calculations. Mito-Tracker Green labeled mitochondria and immunoprecipitation studied protein interactions. Our comprehensive study revealed that Fg inhibited axonal regeneration post-MCAO as indicated by reduced GAP43 expression along with elevated free Ca2+, both suggesting an energy crisis. Fg impeded mitochondrial function and mediated impairment through the EGFR/Ca2+ axis by trans-activating EGFR via integrin alpha v beta 3 interaction. These results indicate that the binding of Fg with integrin alpha v beta 3 leads to the trans-activation of the EGFR/Ca2+ signaling axis thereby disrupting mitochondrial energy transport and axonal regeneration and exacerbating the detrimental effects of ischemic neuronal injury.
摘要：
Patients with autism spectrum disorder (ASD) are often accompanied by inflammatory bowel disease (IBD) in observational research; however, the potential causal link between the two conditions remains unknown. In this study, we used a two-sample bidirectional Mendelian randomization (MR) approach to assess the causal relationship between ASD and IBD and its main subtypes, Crohn's disease (CD), and ulcerative colitis (UC). Independent genetic instruments from a genome-wide association study (GWAS) for IBD (25,042 cases and 34,915 controls) were used to investigate the association of IBD with ASD data obtained from the PGC and the iPSYCH consortia (N = 46,351). The primary analysis employed the random effects inverse variance weighting (IVW) method. Horizontal pleiotropy was detected using the MR Egger regression and the MR-pleiotropy residual sum and outlier (MR-PRESSO) analysis while heterogeneity was detected using Cochran's Q. The IVW method indicated a positive causal relationship of IBD with ASD (odds ratio (OR) = 1.028, 95% confidence interval (CI) = 1.001-1.056, p = 0.042). In subtype analyses, CD was positively related to ASD (OR = 1.036; 95% CI = 1.004-1.069; p = 0.02); however, UC showed no relationship (OR = 1.021; 95% CI = 0.999-1.044; p = 0.065). In contrast, no evidence of a causal relationship between ASD and IBD or its subtypes (p > 0.05) was found. Our findings provided evidence in support of potential causal associations between IBD/CD and ASD.
期刊：
European Archives of Psychiatry and Clinical Neuroscience,2025年:1-13 ISSN：0940-1334
通讯作者：
Li, Fang;Li, CQ
作者机构：
[Li, Chang-Qi; Li, CQ; Lu, Xiao-Yu; Li, Fang; Cui, Yan-Hui; Yao, Jia-Yu; Li, F; Chen, Zhao-Rong] Cent South Univ, Xiangya Sch Basic Med Sci, Dept Anat & Neurobiol, Changsha 410013, Hunan, Peoples R China.;[Chen, Zhao-Rong] Hunan Univ Chinese Med, Grad Sch, Changsha 410208, Hunan, Peoples R China.;[Zhang, Nian-Nian] Cent South Univ, Xiangya Hosp, Dept Neurol, Changsha 410008, Hunan, Peoples R China.;[Cao, Wen-Yu] Univ South China, Clin Anat & Reprod Med Applicat Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Liu, Qian] Lituo Drug Rehabil Inst Hunan Prov, Changsha 410000, Hunan, Peoples R China.
通讯机构：
[Li, CQ ; Li, F] C;Cent South Univ, Xiangya Sch Basic Med Sci, Dept Anat & Neurobiol, Changsha 410013, Hunan, Peoples R China.
关键词：
Substance use disorder;Affected family members;Mental health;Social avoidance;Quality of life;BDNF;Cortisol
摘要：
This cross-sectional study assessed the well-being of family members affected (AFMs) by substance use disorder (SUD) of other family members. Mental symptoms, social avoidance, and quality of life (QoL) were measured for 775 Chinese AFMs and 206 controls. Saliva from 65 AFMs and 31 controls was analyzed for cortisol, BDNF, proBDNF, and mRNA levels of BDNF and its receptors (TrkB, P75(NTR), Sortilin). AFMs had significantly higher SCL-90 scores (t = 3.45, p < 0.01) and lower SF-36 scores (t = -4.70, p < 0.01). Of AFMs, 22.1% exhibited mental symptoms. Social support partially mediated the relationship between exposure to SUD patients and mental symptoms (effect = 0.31, SE = 0.16; 95% CI [0.02, 0.67]). Positive coping (effect = 0.03, SE = 0.01; 95% CI [0.01, 0.05]) and social support (effect = 0.02, SE = 0.01; 95% CI [0.01, 0.04]) mediated the effect of exposure to family SUD on social avoidance; positive coping mediated the effect on QoL (effect = -3.03, SE = 0.72; 95% CI [-4.58, -1.75]). AFMs exhibited higher cortisol (t = 2.10, p < 0.05) and proBDNF (t = 2.39, p < 0.05) levels and increased mRNA expression of BDNF (t = 0.66, p < 0.05) and TrkB (t = 1.12, p < 0.05). Cortisol positively predicted mental symptoms, and proBDNF negatively predicted QoL. In China, AFMs of SUD have increased risk of mental health issues and reduced QoL, likely due to elevated cortisol and proBDNF levels. Positive coping and social support are critical to mitigate these negative effects.
期刊：
Current Eye Research,2025年50(2):190-202 ISSN：0271-3683
通讯作者：
Qin, YH
作者机构：
[Deng, Jie; Qin, YuHui] Hunan Univ Chinese Med, Clin Coll Tradit Chinese Med 1, Changsha, Hunan, Peoples R China.;[Deng, Jie; Qin, YuHui] Hunan Univ Chinese Med, Grad Sch, Changsha, Peoples R China.
通讯机构：
[Qin, YH ] H;Hunan Univ Chinese Med, Clin Coll Tradit Chinese Med 1, Changsha, Hunan, Peoples R China.
关键词：
Depression;neuroticism;subjective well-being;sensitivity to environmental stress and adversity;age-related macular degeneration
摘要：
PURPOSE: While some studies have started to focus on the link between psychological well-being and age-related macular degeneration (AMD), the relationship remains uncertain. Our research aims to provide new insights into this association, laying a foundation for future interventions and addressing existing knowledge gaps. METHODS: We utilized the "TwoSampleMR" package in R for a bidirectional Mendelian randomization analysis of psychological well-being (subjective well-being, depression, neuroticism, and Sensitivity to Environmental Stress and Adversity) and early-stage AMD. Causal effects were estimated using the inverse-variance weighted method, and additional methods included weighted median and MR-Egger regression. Sensitivity analyses included Cochran's Q test, MR-Egger intercept analysis, MR-PRESSO, and leave-one-out analysis. RESULTS: The study found that the population with genetic predisposition to neuroticism had a 39.7% lower risk of early-stage AMD (OR = 0.603, 95% CI = 0.385-0.945, p = 0.027). Conversely, the population with genetic predisposition to subjective well-being had a 3.2% increased risk of early-stage AMD (OR = 1.032, 95% CI = 1.003-1.063, p = 0.029). No significant causal relationships were found from depression or Sensitivity to Environmental Stress and Adversity to early-stage AMD, nor from early-stage AMD to psychological well-being. CONCLUSION: This study provides preliminary evidence that the relationship between psychological well-being and early-stage AMD may be complex and multifaceted. It suggests that moderate neuroticism levels might reduce early-stage AMD risk through health behaviors, pathophysiological mechanisms, and other factors, while high subjective well-being levels might increase this risk similarly. However, these findings are insufficient for preventive strategies due to a lack of substantial evidence and still require extensive experimental research for further validation.
期刊：
CURRENT COMPUTER-AIDED DRUG DESIGN,2025年21(4):534-548 ISSN：1573-4099
通讯作者：
Zeng, Jingqi;Wang, F
作者机构：
[Ma, Huaiyu; Xu, Haoran; Wu, Jie; Wu, Ruizhe; Wang, F; Zeng, Jingqi; Zeng, JQ; Chen, Weixing; Wang, Fan; Jin, Hui] Hunan Univ Chinese Med, Affiliated Hosp 2, Dept Orthoped, Changsha 410005, Peoples R China.;[Wu, Jie; Wu, Ruizhe] Hunan Univ Chinese Med, Grad Sch, Changsha 410208, Peoples R China.;[Li, Linghui] China Acad Chinese Med Sci, Wangjing Hosp, Dept Sports Med, Beijing 100102, Peoples R China.
通讯机构：
[Wang, F ; Zeng, JQ] H;Hunan Univ Chinese Med, Affiliated Hosp 2, Dept Orthoped, Changsha 410005, Peoples R China.
关键词：
Intervertebral disc degeneration;Qing’e Pill;in vivo experiments;molecular mechanisms;molecular docking;network pharmacology.
摘要：
Objective The Qing’e Pill (QEP) is widely used to alleviate low back pain and sciatica caused by Intervertebral Disc Degeneration (IDD). However, its active components, key targets, and molecular mechanisms are not fully understood. The aim of this study is to elucidate the molecular mechanisms through which the QEP improves IDD using database mining techniques.
The Qing’e Pill (QEP) is widely used to alleviate low back pain and sciatica caused by Intervertebral Disc Degeneration (IDD). However, its active components, key targets, and molecular mechanisms are not fully understood. The aim of this study is to elucidate the molecular mechanisms through which the QEP improves IDD using database mining techniques.
Methods Active components and candidate targets of the QEP were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine. IDD-related targets were obtained from the GeneCards database, and liver- and kidney-specific genes were retrieved from the BioGPS database. The intersection of these candidate targets was analyzed to identify potential targets for the QEP in IDD. A protein-protein interaction network analysis was performed using STRING and Cytoscape 3.7.2 software. Core targets were further analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking was used to assess the binding affinity of active components to candidate targets, and animal experiments were conducted for validation.
Active components and candidate targets of the QEP were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine. IDD-related targets were obtained from the GeneCards database, and liver- and kidney-specific genes were retrieved from the BioGPS database. The intersection of these candidate targets was analyzed to identify potential targets for the QEP in IDD. A protein-protein interaction network analysis was performed using STRING and Cytoscape 3.7.2 software. Core targets were further analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking was used to assess the binding affinity of active components to candidate targets, and animal experiments were conducted for validation.
Results We identified 65 potentially active components of the QEP that corresponded to 1,093 candidate targets, 2,108 IDD-related targets, and 1,113 liver- and kidney-specific genes. Key components included quercetin, berberine, isorhamnetin, and emodin. The primary candidate targets were Wnt5A, CTNNB1, IL-1β, MAPK14, MMP9, and MMP3. The GO and KEGG analyses revealed the involvement of these targets in Wnt signaling, TNF signaling, Wnt receptor activation, Frizzled binding, and Wnt-protein interactions. Molecular docking showed strong binding between these components and their targets. Animal experiments demonstrated that the QEP treatment significantly reduced the expression of Wnt5A, CTNNB1, IL-1β, MAPK14, MMP9, and MMP3 at high, medium, and low doses compared with the model group.
We identified 65 potentially active components of the QEP that corresponded to 1,093 candidate targets, 2,108 IDD-related targets, and 1,113 liver- and kidney-specific genes. Key components included quercetin, berberine, isorhamnetin, and emodin. The primary candidate targets were Wnt5A, CTNNB1, IL-1β, MAPK14, MMP9, and MMP3. The GO and KEGG analyses revealed the involvement of these targets in Wnt signaling, TNF signaling, Wnt receptor activation, Frizzled binding, and Wnt-protein interactions. Molecular docking showed strong binding between these components and their targets. Animal experiments demonstrated that the QEP treatment significantly reduced the expression of Wnt5A, CTNNB1, IL-1β, MAPK14, MMP9, and MMP3 at high, medium, and low doses compared with the model group.
Conclusion The QEP alleviated IDD by modulating the Wnt/MAPK/MMP signaling pathways and reducing the release and activation of key factors.
The QEP alleviated IDD by modulating the Wnt/MAPK/MMP signaling pathways and reducing the release and activation of key factors.
摘要：
Liver hepatocellular carcinoma (LIHC) is a prevalent and lethal malignancy with a complex molecular landscape. Fibrosis and ferroptosis are implicated in LIHC progression, yet their roles remain to be elucidated. The present study investigated the expression and prognostic significance of calcitonin receptor (CALCR), a gene that intersects the pathways of fibrosis and ferroptosis, across LIHC and other types of cancer. Data were obtained from The Cancer Genome Atlas and the Molecular Signatures Database. LIHC patients were classified into two clusters based on fibrosis‑related gene expression using ConsensusClusterPlus. Single‑sample gene set enrichment analysis was employed to quantify fibrosis and ferroptosis levels. Correlation, survival and nomogram analyses were performed to assess the prognostic value of CALCR. Additionally, single‑cell RNA sequencing data from the Tumor Immune Single Cell Hub 2 (TISCH2) and pan‑cancer analyses of genomic heterogeneity features were incorporated. The present study also identified a putative regulatory role for CALCR in LIHC cell migration, proliferation and apoptosis. CALCR was identified as a significant prognostic marker for LIHC. Patients with high CALCR expression exhibited shortened overall survival (OS) and disease‑specific survival (DSS). Specifically, the hazard ratios (HRs) for OS and DSS were 1.76 [95% confidence interval (CI): 1.23=2.49) and 1.77 (95% CI: 1.13=2.78], respectively, with corresponding P‑values of 0.002 for OS and 0.013 for DSS. Analyses of immune cell infiltration revealed a more complex immune environment in patients with low CALCR expression, suggesting differential responses to immunotherapy. Furthermore, in HepG‑2 and HuH‑7 cells, small interfering (si)‑CALCR increased apoptosis while reducing proliferation and migration compared with si‑negative control. CALCR serves as a significant prognostic biomarker for LIHC, influencing both molecular pathways and the immune landscape. Its expression is associated with improved survival outcomes and distinct genomic features, positioning it as a potential therapeutic target and predictor of immunotherapy efficacy.
摘要：
BACKGROUND: The pathological features of Parkinson's disease (PD) include the formation of Lewy bodies composed mainly of aggregated alpha-synuclein (α-Syn) and extensive neurodegeneration. Synaptic dysfunction is a key factor contributing to disease progression among the various cellular and molecular mechanisms of PD. This study aims to analyze the research hotspots, frontier trends, and future directions of PD and synapses. METHOD: Relevant publications were obtained using the Web of Science database. Software CiteSpace, VOSviewer, and bibliometrix were used for visualization and quantitative analysis. RESULTS: A total of 3,823 publications were included for analysis, and the number of publications related to the research topic showed an increasing trend from 2001 to 2024. North America, Asia, and Europe were the main research forces with high activity. The United States was the main leader in this field, followed by China and Italy. Emory University was the institution with the largest number of publications. Journal of Neuroscience was the core journal with a large number of publications. Dr. Calabresi, Paolo was a leader in the field of research. High-frequency keywords included PD, α-Syn, synaptic plasticity, basal ganglia, dopamine, substantia-nigra. In recent years, neuroinflammation has been the subject of active research. CONCLUSION: Communication and collaboration between different countries, institutions, and authors have promoted the development of this field. The research content mainly focused on α-Syn, synaptic plasticity, and mouse model. Neuroinflammation may be the direction of future research.
期刊：
Pharmacology Research & Perspectives,2025年13(2):e70077 ISSN：2052-1707
通讯作者：
Chen, XD
作者机构：
[Liu, Zhimin; Hu, Zhuoyu; Chen, Xiangdong] Hunan Univ Chinese Med, Hosp 1, Changsha, Hunan, Peoples R China.;[Hu, Qi; Zou, Menglong] Hunan Univ Chinese Med, Grad Sch, Changsha, Hunan, Peoples R China.
通讯机构：
[Chen, XD ] H;Hunan Univ Chinese Med, Hosp 1, Changsha, Hunan, Peoples R China.
关键词：
apoptosis;Chinese medicine monomer;dry eye disease;inflammation;vicious cycle
摘要：
Dry eye disease (DED) is a chronically inflammatory ocular surface disorder of unknown pathogenesis. Anti-inflammatory medications, artificial tears, autologous serum, and LipiFlow have been shown to be highly beneficial in alleviating symptoms. Nevertheless, these interventions often provide only short-term results and do not address the underlying problems of the disease. There is growing evidence that the risk of DED is associated with a vicious cycle of inflammation. This vicious cycle of inflammation is produced by the interaction of several factors, including tear film hyperosmolarity, tear film instability, inflammation, and apoptosis. Chinese medicine monomers, distinguished by their multicomponent and multitarget advantages, have been shown to help treat DED by modulating tear film status, and inhibiting inflammatory responses, and apoptosis, providing a new way of thinking of the management of DED in Chinese medicine.
摘要：
BACKGROUND: Evidence of changes in the composition and function of the gut microbiota (GM) in post-stroke depression (PSD) patients is gradually accumulating. This study aimed to systematically evaluate the relationship between PSD and GM. METHODS: We searched in PubMed, Web of Science, Embase, Cochrane databases, Wangfang, VIP, CBM, and CNKI from the establishment of the database to April 17, 2024, and systematic review and meta-analysis were performed to investigate the differences of GM between patients with PSD spectrum and healthy controls (HC) or stroke spectrum. RESULT: There were 14 studies consisting a total of 1,556 individuals included in the meta-analysis. The pooled results showed that PSD spectrum demonstrated significantly increased α diversity as indexed by Chao1 index, ACE indexes, Shannon index, and Simpson index as compared to HC. Additionally, stroke spectrum significantly increased α diversity as indexed by Simpson index compared to PSD. Furthermore, the pooled estimation of relative abundance showed that Bacteroidota, Fusobacteriota, and Pseudomonadota in PSD patients were significantly higher than those in the HC group, while the abundance of Bacillota was higher in the HC group. Moreover, significant differences in GM were observed between PSD patients and HC at the family and genus levels. CONCLUSION: This study found that the α diversity of PSD patients was higher than that of HC. Moreover, there were also differences in the distribution of GM at the phylum, family, and genus levels, respectively. At the same time, the level of Lachnospira in PSD patients was lower than that in the stroke group. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024582708.
摘要：
BACKGROUND: Parkinson's disease (PD) is characterized pathologically by the degeneration of dopaminergic neurons and the formation of Lewy bodies. Among the various cellular and molecular mechanisms of PD, astrocyte dysfunction is one of the causes of disease development. This study aims to explore the research hotspots, frontiers, and prospective directions regarding PD and astrocytes. METHOD: Relevant academic publications were searched through the Web of Science database. CiteSpace, VOSviewer, and bibliometrix were used for visualization and quantitative evaluation. RESULTS: A total of 2,408 publications related to the study topic were included in the analysis. From 2001 to 2024, annual publications gradually increased. Activated countries were concentrated in North America, Asia, and Europe. The United States and China were the main research leaders. Nanjing Medical University was the active institution with the largest number of publications, and the University of Cambridge had the highest influence on publications. International Journal of Molecular Sciences was the core journal with the most publications. Dr. Hu, Gang was the most productive author, and Dr. Saarma, Mart was the most influential author. Research hotspots included astrocytes, PD, neuroinflammation, alpha-synuclein (α-Syn), microglia, oxidative stress, and neurodegeneration. In recent years, NLRP3 inflammasome, extracellular vesicles (EVs), and signaling pathway were the research topics with strong burst power. CONCLUSION: Collaboration among different countries, organizations, and authors has effectively promoted the rapid development of this field, and the research achievements have gradually increased. The research hotspots mainly focused on neuroinflammation, α-Syn, microglia, oxidative stress, and neurodegeneration. NLRP3 inflammasome, EVs, and signaling pathway are research directions in the future.
摘要：
This study outlines the sustainable synthesis of hybrid biopolymer hydrogels supported with octahedral Cu 2 O nanoparticles (NPs), alongside their biological assessments and characterizations. A composite hydrogel made of chitosan and guar gum (CS-GG) was employed as a template for the environmentally friendly synthesis of nanoparticles. Leveraging their electron-rich functional groups, the biopolymers acted as stabilizing agents for the Cu 2 O NPs and as green reductants, facilitating the reduction of copper ions. The material's physicochemical properties were thoroughly examined using advanced techniques, such as X-ray diffraction (XRD), Field-Emission Scanning Electron Microscopes (FE-SEM), Eneregy Dispersive X-ray Electron Spectroscopy (EDX), Fourier Transformed Infrared Spectroscopy (FT-IR), Transmission Electron Microscopy (TEM) and ICP-OES. The resulting CS-GG/Cu 2 O NPs nanocomposite was investigated as a reusable heterogeneous nanocatalyst, demonstrating its efficiency in the phosphine-free, palladium-free, and ligand-free synthesis of various stilbene derivatives with high yields through the Sonogashira coupling reaction. The catalyst showed no significant reduction in activity after being reused seven times consecutively. The cytotoxic effects of the CS-GG/Cu 2 O NPs nanocomposite on NCI-H661 lung cancer cells and normal cells (HUVEC) were assessed over 48 h using MTT assay. The cancer cell's viability decreased after exposure to the CS-GG/Cu 2 O NPs, with an IC 50 value of 82 μg/mL. The CS-GG/Cu 2 O NPs nanocomposite controls the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) system, which in turn impacts apoptosis and cell proliferation in NCI-H661 cells, according to a detailed examination of the mTOR pathway. The pathway could act a role in the cell cycle inhibition and apoptosis induced by the CS-GG/Cu 2 O NPs nanocomposite. The CS-GG/Cu 2 O NPs nanocomposite could be a useful natural anti-cancer agent for the treatment of lung cancer.
This study outlines the sustainable synthesis of hybrid biopolymer hydrogels supported with octahedral Cu 2 O nanoparticles (NPs), alongside their biological assessments and characterizations. A composite hydrogel made of chitosan and guar gum (CS-GG) was employed as a template for the environmentally friendly synthesis of nanoparticles. Leveraging their electron-rich functional groups, the biopolymers acted as stabilizing agents for the Cu 2 O NPs and as green reductants, facilitating the reduction of copper ions. The material's physicochemical properties were thoroughly examined using advanced techniques, such as X-ray diffraction (XRD), Field-Emission Scanning Electron Microscopes (FE-SEM), Eneregy Dispersive X-ray Electron Spectroscopy (EDX), Fourier Transformed Infrared Spectroscopy (FT-IR), Transmission Electron Microscopy (TEM) and ICP-OES. The resulting CS-GG/Cu 2 O NPs nanocomposite was investigated as a reusable heterogeneous nanocatalyst, demonstrating its efficiency in the phosphine-free, palladium-free, and ligand-free synthesis of various stilbene derivatives with high yields through the Sonogashira coupling reaction. The catalyst showed no significant reduction in activity after being reused seven times consecutively. The cytotoxic effects of the CS-GG/Cu 2 O NPs nanocomposite on NCI-H661 lung cancer cells and normal cells (HUVEC) were assessed over 48 h using MTT assay. The cancer cell's viability decreased after exposure to the CS-GG/Cu 2 O NPs, with an IC 50 value of 82 μg/mL. The CS-GG/Cu 2 O NPs nanocomposite controls the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) system, which in turn impacts apoptosis and cell proliferation in NCI-H661 cells, according to a detailed examination of the mTOR pathway. The pathway could act a role in the cell cycle inhibition and apoptosis induced by the CS-GG/Cu 2 O NPs nanocomposite. The CS-GG/Cu 2 O NPs nanocomposite could be a useful natural anti-cancer agent for the treatment of lung cancer.
期刊：
Frontiers in Medicine,2025年11:1492383 ISSN：2296-858X
通讯作者：
Xu, F
作者机构：
[He, Fang-Hui; Li, Zhi-Hang; Wu, Rong-Rong] Hunan Univ Chinese Med, Sch Pharm, Changsha, Hunan, Peoples R China.;[Nie, Duo-Rui] Hunan Univ Chinese Med, Grad Sch, Changsha, Peoples R China.;[Xu, Fei] Hunan Univ Chinese Med, Coll Pharm, Changsha, Peoples R China.;[Xu, Fei] Hunan Engn Technol Res Ctr Bioact Subst Discovery, Changsha, Peoples R China.;[Xu, Fei] Hunan Prov Sino US Int Joint Res Ctr Therapeut Dru, Changsha, Peoples R China.
通讯机构：
[Xu, F ] H;Hunan Univ Chinese Med, Coll Pharm, Changsha, Peoples R China.;Hunan Engn Technol Res Ctr Bioact Subst Discovery, Changsha, Peoples R China.;Hunan Prov Sino US Int Joint Res Ctr Therapeut Dru, Changsha, Peoples R China.
摘要：
OBJECTIVES: To explore the mechanism underlying the effect of Fructus Akebiae (FAE) against hepatic fibrosis in mice through combined network pharmacology, liver metabolomics, and 16S rDNA analyses of the gut microbiota. METHODS: In this study, we randomly divided mice into the control, model, FAE high-dose, FAE medium-dose, and FAE low-dose groups to analyze the pathological changes in the hepatic fibrosis and levels of the α-SMA, collagen 1, Nuclear Factor Kappa B (NF-κ B), Toll Like Receptor 4 (TLR4). The gut microbiota was analyzed through 16S rDNA sequencing analysis of liver metabolites using liquid chromatography-mass spectrometry. Furthermore, network pharmacology was used to determine the specific molecular regulation mechanism of FAE in hepatic fibrosis treatment. RESULTS: FAE treatment markedly improved the pathological changes in the hepatic fibrosis. Analysis revealed that FAE administration reversed the carbon tetrachloride (CCl(4))-induced dysbiosis by increasing the abundance of Akkermansia and reducing that of Cyanobacteria. Additionally, metabolomic analysis showed that FAE treatment reversed the CCl(4)-induced metabolic disorders by regulating amino and nucleotide sugar metabolism. Furthermore, correlation analysis showed that Akkermansia and Verrucomicobiota were closely related to D-tolasaccharide and maltotetraose saccharide. Moreover, network pharmacology indicated that FAE might regulate the signaling pathway through the JUN/CASP3/NOS3/PTGS2/HSP90AA1 during treatment. CONCLUSION: FAE may be a promising treatment for hepatic fibrosis, and its protective effects are associated with improvements in the microbiome and metabolic disorders.
