NEUROPHARMACOLOGY
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2025
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IF 4.6
Wei Wang,Yingzhuo Ding,Chunxia Yu,Qingqing Chi,Xia Fu,Mengjiao Deng,Dongxia Duan,Jinbao Wei,Ronghua Ding,Yufei Xi,Qin Li,Le Ma
Neuro-inflammation contributes to neuropathic pain by sensitizing ionic channels. Kinsenoside, a traditional Chinese medicine, has recognized anti-inflammatory properties. However, it remains unclear whether kinsenoside can be used for pain therapy. Network pharmacology analysis revealed that 57 % of its targets are associated with pain, including inflammation and synaptic transmission. The analgesic effects of kinsenoside were confirmed in SNL and formalin rat models, with ED50 values of 47.99 μg and 36.80 μg, respectively. Transcriptome and WGCNA analyses indicated the involvement of cytokine release, anti-inflammatory activity, and synapse enrichment in the blue module. Furthermore, we confirmed that kinsenoside's efficacy was mainly mediated by IL-10 induction, phosphorylation of STAT3, and SOCS3 expression. Pretreatment with kinsenoside significantly inhibited the release of TNF-α, IL-1β, and IL-6. Kinsenoside also attenuated ER stress in both microglia and neural cells. Molecular docking analysis demonstrated significantly high binding energies of IL-10, STAT3, and SOCS3 with MHC. Additionally, whole-cell recordings revealed that bath application of kinsenoside reduced the frequency and amplitude of spinal glutamatergic transmission in a dose-dependent manner. In summary, pharmacological prediction and biological validation collectively indicate that kinsenoside significantly exerts significant analgesic effects by attenuating ER stress and inhibiting inflammatory responses via the IL-10/p-STAT3/SOCS3 axis, precisely regulating spinal glutamatergic transmission for pain relief.
研究领域:
药理学
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神经科学
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分子生物学
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DOI
PubMed
高影响因子
JOR Spine
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2024
·Vol. 7
·期 4
·e70004
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IF 3.4
Daqian Zhou,Tao Liu,Yongliang Mei,Jiale Lv,Kang Cheng,Weiye Cai,Silong Gao,Daru Guo,Xianping Xie,Zongchao Liu
Background Intervertebral disc degeneration (IVDD) is an age-related orthopedic degenerative disease characterized by recurrent episodes of lower back pain, the pathogenesis of which is not fully understood. This study aimed to identify key biomarkers of IVDD and its causes. Methods We acquired three gene expression profiles from the Gene Expression Omnibus (GEO) database, GSE56081, GSE124272, and GSE153761, and used limma fast differential analysis to identify differentially expressed genes (DEGs) between normal and IVDD samples after removing batch effects. We applied weighted gene co-expression network (WGCNA) to identify the key modular genes in GSE124272 and intersected these with DEGs. Next, A protein–protein interaction network (PPI) was constructed, and Cytoscape was used to identify the Top 10 hub genes. Functional enrichment analyses were performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Three key genes were validated using Western Blot (WB) and qRT-PCR. Additionally, we predicted miRNAs involved in hub gene co-regulation and analyzed miRNA microarray data from GSE116726 to identify four differentially expressed miRNAs. Results We identified 10 hub genes using bioinformatics analysis, gene function enrichment analysis revealed that they were primarily enriched in pathways, such as the TNF signaling pathway. We chose JUNB, SOCS3, and CEBPB as hub genes and used WB and qRT-PCR to confirm their expression. All three genes were overexpressed in the IVDD model group compared to the control group. Furthermore, we identified four miRNAs involved in the co-regulation of the hub genes using miRNet prediction: mir-191-5p, mir-20a-5p, mir-155-5p, and mir-124-3p. Using limma difference analysis, we discovered that mir-191-5p, mir-20a-5p, and mir-155-5p were all down-regulated and expressed in IVDD samples, but mir-124-3p showed no significant change. Conclusion JUNB, SOCS3, and CEBPB were identified as key genes in IVDD, regulated by specific miRNAs, providing potential biomarkers for early diagnosis and therapeutic targets.
研究领域:
分子生物学
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生物信息学
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骨科医学
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产品关联
DOI
PubMed
高影响因子
American Journal of Translational Research
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2019
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IF 3.266
Hua Liu,Xiao-De Feng,Beng Yang,Rong-Liang Tong,Yue-Jie Lu,Di-Yu Chen,Lin Zhou,Hai-Yang Xie,Shu-Sen Zheng,Jian Wu
Dimethyl fumarate (DMF) is generally used to treat psoriasis and multiple sclerosis. In the present study, we aimed to investigate the effects of DMF on hepatocellular carcinoma progression and its mechanism of action. In vitro , cell viability was examined using CCK-8 assay; cell cycle was analyzed by flow cytometry; angiogenesis was detected using tube formation assay; and autophagic flux assay results were examined using fluorescence microscopy. We also used western blotting to explore the potential mechanisms. In vivo , tumor xenograft experiment was performed with nude mice, and liver function, renal function, and routine blood counts were assessed using biochemical tests. Dimethyl fumarate inhibited tumor growth and angiogenesis in hepatocellular carcinoma, both in vitro and in vivo . Dimethyl fumarate decreased autophagy in hepatocellular carcinoma cells. Treatment with DMF activated SOCS3, which led to repression of JAK1 and STAT3 phosphorylation. DMF inhibited cell proliferation, angiogenesis, and autophagy via activation of the SOCS3/JAK1/STAT3 signaling pathway. This finding may provide a novel approach for the treatment of hepatocellular carcinoma.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Chinese Herbal Medicines
·
2026
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IF 11.2
Aifen Liu,Jingyan Hu,Weili Yu,Chuanyu Cang,Chuanjing Shi,Xi Wang,Rui Wang,Xuanwei Cai,Fengbo Zhao,Lei Zhang
Objective Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder characterized by ovulatory dysfunction. Formononetin (FMN), a bioactive compound derived from leguminous plants, including Glycyrrhiza uralensis , Trifolium pratense , and Astragalus membranaceus , exhibits anti-inflammatory and anti-fibrotic properties. This study aimed to evaluate the therapeutic effects of FMN in a PCOS rat model and elucidate its underlying molecular mechanisms. Methods A PCOS-like model was established in 3-week-old female Sprague-Dawley rats by daily dehydroepiandrosterone (DHEA) injections. The efficacy of FMN was assessed by monitoring estrous cycles, hormone levels, glucose tolerance, and ovarian tissue morphology. Network pharmacology and transcriptome sequencing were used to predict the molecular targets and signaling pathways of FMN. The binding and stabilizing effects of FMN on suppressor of cytokine signaling 3 (SOCS3) were confirmed using molecular docking, molecular dynamics (MD) simulations, and cellular thermal shift assay (CETSA)-Western blotting (WB) (CETSA-WB). The expression of SOCS3, inflammation- and fibrosis-related markers, and the components of the transforming growth factor beta1 (TGF- β 1)/Smad pathway were quantified by quantitative polymerase chain reaction (qPCR), Western blotting, and immunohistochemistry. Functional validation was performed using SOCS3 small interfering RNA (siRNA). Results DHEA successfully induced a PCOS-like phenotype, including disrupted estrous cycle, hyperandrogenism, an elevated luteinizing hormone to follicular stimulating hormone (LH/FSH) ratio, insulin resistance, and abnormal ovarian morphology. FMN treatment significantly reversed these abnormalities and reduced ovarian collagen deposition. Network pharmacology and transcriptome analyses indicated that the therapeutic efficacy of FMN was primarily attributable to its anti-fibrotic and anti-inflammatory properties, with SOCS3 identified as a potential key molecule. Molecular docking and MD simulations, along with CETSA-WB, further revealed that FMN directly binds to SOCS3, enhancing its stability and thereby inhibiting ovarian fibrosis in PCOS. Moreover, qPCR, Western blotting, and immunohistochemistry confirmed that FMN regulates the TGF- β 1/Smad signaling pathway. Importantly, SOCS3siRNA abolished fibrotic-related collagen levels and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) expression, supporting the notion that FMN ameliorates PCOS-induced ovarian fibrosis via SOCS3. Conclusion FMN alleviated ovarian dysfunction and hyperandrogenism in DHEA-induced PCOS rats by stabilizing SOCS3 and inhibiting TGF- β 1/Smad signaling, thereby attenuating ovarian fibrosis and inflammation. This reveals a novel SOCS3-centered mechanism for FMN and underscores its therapeutic potential for PCOS.
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DOI
高影响因子
Cell Reports
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2025
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IF 6.9
Kangtai Xu,Xuefei Liu,Qian Zeng,Yaqi Liu,Leyan Shan,Luyao Ji,Yifei Wu,Jiawei Wu,Yiming Chen,Yitong Li,Songqiang Huang,Changyu Jiang,Xin Hong,Chaoran Wu,Zilong Wang
Chronic itch is a devastating clinical condition, and its central mechanisms remain poorly understood. We reported that spinal cannabinoid receptor type 2 (CB 2 R) activation exerts antipruritic effects and that itch escalates in mice lacking Cnr2 in mouse models of dermatitis and psoriasis. In the spinal cord, CB 2 R is mainly expressed in microglia, and microglial ablation or inhibition attenuated chronic itch, suggesting that microglial activation contributes to chronic itch. Particularly, conditional Cnr2 deletion in microglia also exacerbated chronic itch in mice. Single-cell RNA sequencing and molecular mechanistic studies suggest that CB 2 R activation reprogrammed microglia by inducing anti-inflammatory suppressor of cytokine signaling 3 (SOCS3) and reducing itch-related p38 and signal transducer and activator of transcription 1 (STAT1) phosphorylation. Finally, CB 2 R activation suppressed neuronal excitability and synaptic transmission in gastrin-releasing peptide (GRP)/GRP receptor (GRPR) interneurons and ascending projection neurons by inhibiting microglia-derived cytokines. These findings demonstrate that microglial activation contributes to chronic itch, while CB 2 R activation in microglia alleviates chronic itch via neuro-immune interactions.
研究领域:
神经科学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
HISTOCHEMISTRY AND CELL BIOLOGY
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2023
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IF 2.3
Jin Xin,Xu Hainan,Hu Qing,Yin Yitong,Qin Meiying,Xia Zhijun
Pelvic organ prolapse (POP) is a common disorder among women that negatively affects women’s quality of life. Early growth response 2 (EGR2) is a transcription factor that regulates cell growth. The present study aimed to explore the role of EGR2 in POP progression and provided a new target for the treatment and prevention of POP. Firstly, we extracted primary vaginal anterior wall fibroblasts from POP tissues and non-POP tissues and then constructed an EGR2-silencing lentivirus for further study. Immunoblotting, qPCR, TUNEL assay, CCK-8 assay, dual luciferase assay, and ELISA assay were carried out. EGR2 expression was much higher in POP tissues than in control tissues, and EGR2 expression positively correlated with cytokine signaling 3 (SOCS3) expression. Knockdown of EGR2 increased cell proliferation, upregulated PCNA expression, and reduced apoptosis in POP fibroblasts. Moreover, we found that the knockdown of EGR2 increased COL1A1 , COL3A1 , and Elastin expression and decreased MMP2 and MMP9 activities, and knockdown of EGR2 increased TGF-β/Smad pathway activity in POP fibroblasts. Interestingly, the results of dual luciferase assay demonstrated that EGR2 was able to increase SOCS3 transcriptional activity. EGR2 knockdown alleviated the apoptosis of POP fibroblasts by reducing SOCS3 expression and improving the proliferation and collagen synthesis of POP fibroblasts. Overall, our study illustrated that EGR2 was highly expressed in POP tissues, and knockdown of EGR2 alleviated apoptosis and reduced matrix degradation in POP fibroblasts. This study might provide a new insight into the pathogenesis of POP.
研究领域:
妇科学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
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