Rationale: Chronic migraine is characterized by persistent trigeminal sensitization and neuroinflammation. however, the molecular mechanisms underlying its maintenance and mediate the therapeutic effects of acupuncture remian incompletely understood.
Method: A chronic migraine-like state was induced in mice by repeated dural inflammatory soup (IS), followed by electroacupuncture (EA). Behavioral hypersensitivity was assessed, and molecular changes in the spinal trigeminal nucleus caudalis (Sp5C) were analyzed using transcriptomic, biochemical, and functional approaches.
Result: Repeated inflammatory stimulation markedly increased CXCL13 and CXCR5 expression and ERK phosphorylation in the Sp5C, accompanied by mechanical allodynia, thermal hyperalgesia, glial activation, and elevated IL-6 and CCL2 levels. EA significantly attenuated pain hypersensitivity and reduced CXCL13/CXCR5 expression, ERK activation, glial reactivity, and inflammatory mediator release. EA also decreased migraine-related neuropeptides and synaptic plasticity markers, including substance P, PACAP, and NR2B. Functional manipulation experiments demonstrated bidirectional regulation of pain behaviors by CXCR5, establishing its causal role in chronic migraine-like sensitization. MicroRNA profiling identified a dysregulated miRNA signature converging on the transcription factor FOXO3, which indirectly regulated CXCR5 transcription, defining a miRNA-FOXO3-CXCR5 regulatory pathway.
Conclusion: Our study reveals the CXCL13/CXCR5/ERK axis as a previously unrecognized pathway in migraine neuroinflammation and demonstrates electroacupuncture's multimodal therapeutic mechanisms. These findings provide: (1) novel mechanistic insights into migraine pathophysiology through CXCR5-mediated signaling, and (2) translational implications for chronic migraine treatment by targeting the CXCL13/CXCR5/ERK axis. This work establishes a foundation for future development of targeted therapies and validates electroacupuncture as a viable intervention for migraine management.
Background: Psoralea corylifolia(PF) is widely utilized for the treatment of conditions such as kidney yang deficiency, frequent urination, and cold pain in the waist and knees. However, both basic research and clinical reports indicate that it induce hepatotoxicity. Our preliminary research has confirmed that PF has hepatotoxicity and in vitro research indicated that psoralidin is hepatotoxic. but it remains unclear whether psoralidin is the hepatotoxic component of PF and the mechanism of psoralidin induces hepatotoxicity. This study aimed to investigate the hepatotoxicity induced by psoralidin and its toxic mechanisms.
Methods: Kunming mice were used to conduct long-term toxicity experiments. Liver function indices, organ coefficients, and histopathological observations were employed to assess the hepatotoxicity of psoralidin. Non-targeted metabolomics and proteomics analyses were conducted to elucidate the potential pathways and targets associated with psoralidin-induced hepatotoxicity. Furthermore, immunofluorescence staining, molecular docking and Western blotting analyses were utilized to validate the mechanisms underlying psoralidin hepatotoxicity.
Results: The elevation of ALT and AST, accompanied by hepatic steatosis and lipid droplet aggregation were observed after psoralidin treatement. Psoralidin affected biosynthesis of unsaturated fatty acid, fatty acid metabolism, arachidonic acid metabolism, phospholipid metabolism, and oxidative phosphorylation. Further validation research found that psoralidin induced the expressions of Acot4 and Plin5, which in turn caused up-regulations of TGs and FFA in mice, and increased the HSD17B12 level, thereby promoting the synthesis of long-chain fatty acids and facilitating lipid synthesis. And psoralidin catalyzed the conversion of phosphatidylcholine into LPC by enhancing Pla2g6 and Pla2g12b levels, which promoted the synthesis and accumulation of TGs, ultimately inducing disorders in glycerophospholipid metabolism. Furthermore, psoralidin caused upregulation of ROS and mitochondrial damage, leading to a decrease in FA oxidation.
Conclusion: Psoralidin is one of the hepatotoxic components of PF, which induced hepatotoxicity via promoting lipid synthesis and inhibiting lipid oxidative degradation.
Objective: Herbal prescriptions hold significant importance in Traditional Chinese Medicine (TCM) diagnosis and treatment, embodying millennia of clinical case summaries and wisdom. Despite numerous proposed methods for herbal prescription recommendation (HPR), significant challenges persist due to the lack of comprehensive clinical data, particularly regarding the relationships between symptoms and herbs. This scarcity poses considerable hurdles for effective HPR modeling.
Methods: In this study, we introduced a novel herbal prescription recommendation framework with cross-domain neural collaborative filtering (termed PresRecCDL). The cross-domain learning mechanism is introduced to learn the noise-reduced cross-domain features of herbs and symptoms in the unified space, which alleviated the sparsity of data, and the neural collaborative filtering is utilized to carry out prescription recommendations.
Results: Comprehensive experiments demonstrate the superiority of the proposed PresRecCDL model over the SOTA model. The effectiveness of each module in PresRecCDL and model robustness are validated by the ablation and hyper-parameter tuning experiments, respectively. The case study based on network pharmacology further validates the effectiveness of the proposed approach, particularly its scientific rigor and feasibility at the molecular mechanism level.
Conclusion: This study contributes to enhancing the performance of the HPR model, ultimately benefiting the efficiency and precision of clinical treatment.
Background: As an important component of external therapies in traditional Chinese medicine (TCM), the specific mechanism of acupuncture in improving UC has not been fully elucidated. This study investigates the regulatory effects of acupuncture on ferroptosis and the JAK2/STAT3 signaling pathway in colon epithelial cells of dextran sulfate sodium (DSS)-induced UC mice, thereby providing an in-depth exploration of the potential molecular mechanisms underlying acupuncture treatment for UC.
Methods: In the first phase, using a sham electroacupuncture (SEA) group as a control, the effects of electroacupuncture (EA) on ferroptosis, intestinal mucosal barrier function, oxidative stress levels, and the inflammatory response in DSS-induced colon epithelial cells were investigated. Furthermore, the expression levels of the JAK2/STAT3 signaling pathway in colon tissue were examined. In the second phase, the ferroptosis-specific activator erastin was co-administered to further validate the critical mechanistic role of ferroptosis inhibition in EA treatment. In the third phase, the JAK2-specific inhibitor AG490 was used to intervene in UC. A comparative analysis was conducted to assess the effect equivalence between JAK2/STAT3 pathway inhibition and EA treatment for UC, further clarifying the JAK2/STAT3 pathway as a key regulatory target of acupuncture in UC treatment.
Results: Compared to the control (Con) group, the DSS group showed significant upregulation of ferroptosis-related indicators, impaired intestinal mucosal barrier function, markedly increased levels of oxidative stress and inflammatory response, along with upregulated expression of the JAK2/STAT3 signaling pathway. Compared to the DSS group, the DSS + EA group exhibited significant improvement in colon histopathological damage, a substantial reduction in ferroptosis levels in colon epithelial cells, and corresponding downregulation of JAK2 and STAT3 expression levels. Notably, the therapeutic effects of the DSS + EA group were superior to those of the DSS + SEA group. The ferroptosis-specific activator erastin reversed the anti-ferroptosis effects of EA and its protective effects on the colon. In addition, the effect of EA treatment in ameliorating ferroptosis and colon injury was comparable to the intervention with the JAK2-specific inhibitor AG490.
Conclusions: EA may alleviate ferroptosis in colonic epithelial cells by inhibiting the JAK2/STAT3 pathway, significantly reducing oxidative stress injury, improving intestinal mucosal barrier integrity, and inhibiting the DSS-induced inflammatory cascade in UC mice. This study provides important modern scientific evidence for the application of acupuncture therapy in treating gastrointestinal diseases.
Aplastic anemia (AA) is a life-threatening blood disorder characterized by bone marrow failure and pancytopenia. Treatments such as immunosuppressive therapy (IST) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) have limitations, including poor long-term remission and donor shortages. Exosomes, nanosized extracellular vesicles, are promising drug delivery systems (DDS) due to their biocompatibility, targeted delivery, and capacity to penetrate biological barriers. Traditional Chinese medicine (TCM) regulates hematopoiesis and immunity but faces challenges with delivery. This review discusses exosomes loaded with TCM constituents (Exo-TCM) for AA, summarizing AA pathogenesis, exosome features, TCM potential, Exo-TCM preparation, and preclinical efficacy, and translational challenges, highlighting Exo-TCM as a novel therapeutic approach for AA.
Traditional Chinese Medicine (TCM) is a valuable medical treasure trove that not only demonstrated unique advantages in treating complex and refractory diseases but also left behind a rich legacy of ancient texts and valuable evidence-based medical data based on its human experience for future generations. Nevertheless, the extensive data within TCM has been plagued by challenges, including inadequate data standardization, inconsistent data quality, limited data structuring, and obstacles in interdisciplinary integration. Recent advancements in artificial intelligence (AI) techniques have markedly improved the efficiency and effectiveness with which multimodal data in TCM, including machine learning (ML), deep learning (DL), knowledge graphs (KG), and natural language processing (NLP), particularly large language models (LLMs). These advancements have facilitated more precise data analysis, enhanced clinical decision-making, and improved research outcomes in TCM, such as target discovery, virtual screening of natural products (NPs), symptom differentiation and auxiliary prescription. This article presents a comprehensive review of the progress in applying AI across four dimensions: multiscale data in TCM, TCM research and development, TCM diagnosis and treatment, and LLMs. In summary, the application of AI technology in the modernization of TCM is expected to motivate researchers to achieve a deeper understanding of state-of-the-art applications in data-driven TCM complex systems, fundamental scientific research, and precision medicine, thereby bringing more opportunities and innovations for the modernization of TCM.
Background: Ulcerative colitis (UC) is a chronic inflammatory disorder marked by epithelial barrier disruption and persistent intestinal inflammation. Despite extensive research, its complex etiology continues to pose therapeutic challenges. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has recently been implicated in UC pathogenesis. Additionally, the gut microbiota and its metabolites play a pivotal role in maintaining intestinal homeostasis and barrier integrity.
Purpose: This study aimed to investigate the therapeutic potential of a phytotherapeutic agent QCHS to alleviate UC by modulating ferroptosis and the microbiota-metabolome axis, with a particular focus on the role of Lactobacillus gasseri (L. gasseri).
Methods: A DSS-induced UC mouse model was used to evaluate QCHS efficacy. Gut microbial composition and metabolomic alterations were analyzed via 16S rDNA sequencing and UHPLC-MS/MS. L. gasseri was cultured in vitro to assess the impact of QCHS on its growth. RSL3-induced cell death was modeled in NCM-460 cells and ferroptosis-related changes were examined using transmission electron microscopy, immunohistochemistry, quantitative PCR, and Western blotting.
Results: QCHS significantly mitigated DSS-induced ferroptosis in colonic tissues, with L. gasseri identified as a key mediator. Notably, L. gasseri was found to act as a novel ferroptosis inhibitor. In vitro studies confirmed that L. gasseri suppressed RSL3-induced ferroptosis in NCM-460 cells via activation of the GSH/GPX4 pathway.
Conclusion: This study provides compelling evidence for the regulatory role of QCHS on the microbiota-metabolome axis and ferroptosis in UC. It also uncovers a novel function of L. gasseri as a ferroptosis inhibitor, offering promising insights into microbiota-targeted and ferroptosis-modulating therapeutic strategies for UC.
Hyperleptinemia and mitochondrial dysfunction in obesity form a vicious cycle, underscoring the need for targeted interventions. This study suggests that berberine reduces leptin synthesis and improves leptin resistance by upregulating adipose tissue pseudokinase TRIB1 expression, promoting COP1-mediated C/EBPα ubiquitination and degradation, enhancing STAT3 phosphorylation, and suppressing SOCS3 expression. Meanwhile, TRIB1 appears to mediate the remodeling of mitochondrial dynamics by increasing the expression of fusion proteins MFN1 and L-OPA1, inhibiting the activity of the fission protein DRP1, reversing mitochondrial fragmentation, improving respiratory metabolic capacity, and thereby enhancing brown adipose tissue (BAT) thermogenesis. In TRIB1 knockout mice, the dual effects of berberine-central reduction of high-fat diet intake and peripheral promotion of lipolysis and thermogenesis-were largely abolished. Collectively, these findings support a model in which TRIB1 serves as a critical mediator through which berberine coordinates leptin signaling and mitochondrial function, providing mechanistic insight that may inform future strategies for obesity intervention.
Background: Non-alcoholic fatty liver disease (NAFLD), often accompanied by insulin resistance, obesity, and hyperlipidemia, is a challenging metabolic disorder to treat. Ge-Lian Qi-Shen Decoction, a traditional Chinese herbal formula, has been clinically used to alleviate symptoms associated with NAFLD, but its underlying mechanisms remain unclear.
Methods: A NAFLD model was established in C57BL/6J mice using a high-fat diet (HFD). The effects of 4-week GQD intervention at different doses on NAFLD-related symptoms were assessed using biochemical analyses, pathological sections, and oral glucose tolerance tests. ELISA and qPCR were employed to investigate the impact of GQD on serum GLP-1 levels and intestinal Gcg gene expression in NAFLD mice. The direct stimulatory effects of GQD on GLP-1 secretion were examined in NCI-H716 cells and HFD-fed mice. UPLC-MS/MS was used to analyze the composition of ileal contents in GQD-treated mice, and the regulatory effects of 24 identified compounds on GLP-1 secretion were evaluated. Additionally, 16S rDNA sequencing, metabolomics and fecal microbiota transplantation were utilized to explore the role of gut microbiota in GQD's anti-NAFLD effect.
Results: GQD improved HFD-induced hepatic steatosis, impaired glucose tolerance, and elevated blood lipid levels in a dose-dependent manner. It increased serum GLP-1 levels, reduced energy intake, and enhanced glucose tolerance in mice. A single dose of GQD directly elevated serum GLP-1 levels in HFD-fed mice and improved glucose tolerance in a GLP-1-dependent manner. In NCI-H716 cells, GQD promoted intracellular calcium influx and GLP-1 release by activating two G-protein-coupled receptors (GPCRs): bitter taste receptors and TGR5. Compounds such as berberine, coptisine, nuciferine, liensinine, higenamine, aurantio-obtusin, and obtusifolin in GQD activated bitter taste receptors, while maslinic acid and cycloastragenol activated TGR5, facilitating GLP-1 secretion. Furthermore, GQD gavage increased the levels of Muribaculaceae and Akkermansia in mouse feces, leading to elevated concentrations of short-chain fatty acids (SCFAs) such as acetate, propionate, butyrate, and valerate. These SCFAs potentially activated fatty acid-related GPCRs, such as GPR41, in the colon, thereby enhancing colonic Gcg expression. FMT experiment showed that gut microbiota can partially mediate the effect of GQD in increasing GLP-1 levels thus alleviating NAFLD.
Conclusion: Some alkaloids, anthraquinones, and triterpenoids in GQD can activate GPCRs, including bitter taste receptors and TGR5, in intestinal endocrine cells, promoting GLP-1 secretion. Simultaneously, GQD regulates gut microbiota composition and metabolism, increasing SCFA levels and Gcg gene expression, leading to sustained elevation of GLP-1 levels. These combined effects contribute to the alleviation of NAFLD symptoms.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：