Shanghai University of Traditional Chinese Medicine

The uncontrollable dendritic growth and interfacial parasitic reactions severely hinder the large‐scale operation of aqueous zinc‐ion batteries (AZIBs), root in the fundamental kinetics imbalance between the excessively rapid electrochemical reduction rate and retarded bulk mass transfer. To resolve this dilemma, a rationally structure‐designed ketone additive, butane‐2,3‐dione (BD), was screened from a series of counterparts to achieve highly reversible Zn plating/stripping by moderating electroreduction kinetics. Specifically, the BD molecule preferentially adsorbs in the inner Helmholtz plane to repel solvated Zn‐ions via the steric‐hindrance effect. The modulated electroreduction kinetics alters zinc deposition behavior, guiding directional Zn (002) texture. Moreover, the constructed H2O‐poor electric double layer mitigates parasitic reactions. Notably, the rebalancing of interfacial consumption rate and ion diffusion rate endows Zn anode with superb reversibility (average 99.7% during 1825 cycles) and great cycling durability (2827 h at 1 mA cm⁻² and 1276 h at 5 mA cm⁻²). The outstanding electrochemical performance of Zn anode under harsh conditions (423 h, 50 mA cm⁻² and 50 mAh cm⁻², 76% depth of discharge) and assembled full cells coupled with multifarious cathodes (Zn//δ‐MnO2 and Zn//NaV3O8·1.5H2O) further highlights the versatility of the steric‐hindrance additive in AZIBs.

Astrocytic neuroinflammation contributes as a key player in neurodegenerative diseases. Capsazepine is a frequently used transient receptor potential vanilloid 1 (TRPV1) inhibitor; however, its effects, as well as the target, on inflammation remain controversial. This study examines the anti‐inflammatory actions of capsazepine and explores mechanisms beyond TRPV1 inhibition. By assessing astrocytic inflammation in vitro and in vivo experiments, capsazepine was found to inhibit astrocyte activation and attenuate neuroinflammation, with reduced levels of interleukin‐6 and complement 3. When utilizing TRPV1 deficient models, no significant decrease was observed in the anti‐inflammatory effects of capsazepine, suggesting there could be alternative targets in addition to TRPV1. Further investigations used drug affinity responsive target stability analysis, siRNA knockdown, cellular thermal shift assay, and molecular docking to hunt for new targets. Syntaxin 7, a modulator in cytokine trafficking and phagosome maturation, was identified as a crucial target to interact with capsazepine in the inhibition of astrocytic inflammation. This study verifies the anti‐inflammatory effects of capsazepine and identifies Syntaxin 7 as a potential novel therapeutic target for treating neuroinflammation.

Pancreatic cancer remains one of the most lethal malignancies in the digestive system, with limited available drugs and a need for improved efficacy. This unmet clinical need highlights the urgency to discover novel, highly efficient small‐molecule compounds. Herein, a novel cyano‐containing artemisinin dimer derivative, ZQJ29, is synthesized through structural modifications of artemisinin. Biological evaluation demonstrated that ZQJ29 effectively inhibits the proliferation of pancreatic cancer cells both in vitro and in vivo. ZQJ29 selectively targets PARP1 and has distinct structural features comparable to established PARP1 inhibitors such as Olaparib. Notably, ZQJ29 is the first reported artemisinin derivative to inhibit PARP1. Furthermore, the inhibition of PARP1 by ZQJ29 enhances the expression of TP53 and inhibits the SLC7A11/GPX4 pathway. The work first demonstrates that targeting PARP1 can induce ferroptosis in pancreatic cancer. These findings not only identify promising artemisinin derivatives for the development of therapies targeting pancreatic cancer but also provide scientific evidence supporting therapeutic strategies aimed at inducing ferroptosis in pancreatic cancer. This research lays a robust foundation for subsequent preclinical studies.

Objectives To investigate the anti-fibrotic mechanisms of Shen Shuai II Recipe (SSR) in chronic kidney disease (CKD), focusing on its modulation of hypoxia-associated inflammatory pathways and the TLR4/MyD88/NF-κB/NLRP3 axis Methods A 5/6 nephrectomy-induced chronic renal failure (CRF) rat model and hypoxia-exposed human renal tubular epithelial (HK-2) cells were utilized. In vivo, renal function was assessed via serum creatinine, urea nitrogen, and creatinine clearance measurements, alongside histopathological evaluation of renal fibrosis and inflammation. In vitro, hypoxia-treated HK-2 cells were analyzed for fibrotic markers (fibronectin, collagen I, α-smooth muscle actin) and pro-inflammatory cytokines (IL-1β, IL-18). Molecular mechanisms were probed through protein expression analysis of HIF-1α and the TLR4/MyD88/NF-κB pathway, with NLRP3 inflammasome activity evaluated. Results SSR treatment significantly improved renal function in CRF rats, reducing serum creatinine (Scr) and urea nitrogen (BUN) while enhancing creatinine clearance. Histopathology revealed preserved renal architecture with attenuated fibrosis and inflammatory infiltration. In hypoxic HK-2 cells, SSR downregulated fibrotic markers and suppressed IL-1β and IL-18 levels. Mechanistically, SSR reduced HIF-1α expression, inhibited TLR4/MyD88/NF-κB signaling, and suppressed NLRP3 inflammasome activation in both models. Conclusions SSR alleviates renal fibrosis and CKD progression by mitigating hypoxia-driven inflammation and blocking the TLR4/MyD88/NF-κB/NLRP3 pathway.

Background Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a frequently encountered disorder characterized by voiding symptoms and pelvic or perineal pain. Proinflammatory T helper 17 (Th17) cells are essential for triggering the development of CP/CPPS. High-salt diet (HSD) consumption has been found to cause an accumulation of sodium chloride in peripheral organs, inducing autoimmune responses via the Th17 cell axis. It is currently unknown whether HSD affects the etiology and course of CP/CPPS. Methods Patients diagnosed with CP/CPPS were evaluated with the National Institutes of Health Chronic Prostatitis Symptom Index scoring system, and the correlation between the symptoms of CP/CPPS with HSD was analyzed. The experimental autoimmune prostatitis (EAP) mouse was established and the mice were fed either a normal-salt diet (NSD) or HSD for 6 weeks to investigate the impact of HSD on CP/CPPS. Then, 16S ribosomal RNA sequencing and untargeted metabolomics were introduced to detect the differences in the gut microflora composition and metabolite profiles between NSD-fed and HSD-fed mice, followed by fecal microbiota transplantation, 5-hydroxyindole acetic acid (5-HIAA) supplementation, aryl hydrocarbon receptor (AHR) inhibition, and in vitro Th17 differentiation experiments, which were performed to explore the mechanisms underlying HSD-aggravated CP/CPPS. Finally, chromatin immunoprecipitation assay and quantitative polymerase chain reaction were conducted to validate whether AHR can serve as a transcription factor by interacting with the serum and glucocorticoid-regulated kinase 1 ( Sgk1 ) promoter in CD4 ⁺ T cells. Results Increased salt consumption had a positive correlation with symptom scores of CP/CPPS patients, which was validated by feeding EAP mice with HSD, and HSD worsened the prostate inflammation and tactile allodynia in EAP mice through promoting the differentiation of CD4 ⁺ T cells to Th17 cells. HSD exacerbated EAP by significantly reducing the relative abundance of beneficial gut microflora, such as Lactobacillaceae, and gut microbiota metabolite 5-HIAA, which is related to tryptophan metabolism. The prostate inflammation, tactile allodynia, and proportion of Th17 cells in mice that received fecal suspensions from the EAP + HSD group were significantly more severe or higher than those in mice that received fecal suspensions from the EAP + NSD group. However, 5-HIAA supplementation ameliorated the symptoms of EAP caused by HSD through inhibiting the differentiation of CD4 ⁺ T cells to Th17 cells, while AHR inhibition abrogated the protective effects of 5-HIAA supplementation on EAP mice fed a HSD through promoting the differentiation of CD4 ⁺ T cells to Th17 cells. Mechanistically, it has been revealed that the SGK1/forkhead box protein O1 (FOXO1) pathway was significantly activated during cytokine-induced Th17 cell differentiation, and AHR has been shown to inhibit SGK1 transcription by interacting with the Sgk1 promoter in CD4 ⁺ T cells to inhibit FOXO1 phosphorylation, consequently restoring the equilibrium of Th17 cell differentiation. Conclusion Our findings indicated that high salt intake represented a risk factor for the development of CP/CPPS as it promoted the differentiation of CD4 ⁺ T cells to Th17 cells through the 5-HIAA/AHR/SGK1/FOXO1 axis, which might be a potential therapeutic target for CP/CPPS.

Understanding the molecular underpinnings of CAD is essential for developing effective therapeutic strategies. This study aims to identify and analyze differentially expressed hub biomarkers in the peripheral blood of CAD patients. Based on RNA-seq datasets from the Gene Expression Omnibus database, machine learning algorithms including LASSO, RF, and SVM-RFE were applied. Furthermore, the hub biomarkers were enriched to ascertain their roles in immune cell expression and signaling pathways through GO, KEGG, GSVE, and GSVA. An in vivo experiment was conducted to verify the hub biomarkers. Eleven hub biomarkers (ITM2B, GNA15, PLAU, GNG11, HIST1H2BH, SLC11A1, RPS7, DDIT4, CD83, GNLY, and S100A12) were identified and associated with CD8 + T cells and NK cells. They were mainly involved in immune responses, cardiac muscle contraction, oxidative phosphorylation, and apoptotic signaling pathways. Moreover, ITM2B had the most importance and significance to be the biomarker of CAD patients. In conclusion, these findings point to the possibility of ITM2B as a biomarker on the inflammatory pathogenesis of CAD and suggest new options for therapeutic intervention.

Introduction This study investigates the role of STXBP1 in glioma, particularly its involvement in regulating ferroptosis and epithelial-mesenchymal transition (EMT), and examines its impact on glioma cell behavior. Material and methods Differential gene expression analysis was performed on a glioma dataset, and protein-protein interaction (PPI) network analysis identified genes with significant prognostic value. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis further narrowed the scope. Key genes were obtained through nomogram analysis and expression verification was performed. In in vitro cell experiments, knockdown of STXBP1 was performed in glioma cell lines and the effects on cell proliferation, migration, invasion, cell cycle distribution, apoptosis, and markers of ferroptosis and EMT were assessed. Results After bioinformatics analysis, STXBP1 was identified as a hub gene, and in vitro cell experiments were performed. STXBP1 knockdown in glioma cells increased proliferation, migration, and invasion, altered cell cycle distribution (reducing S phase and increasing G1 phase), and decreased apoptosis. Ferroptosis markers showed elevated GPX4 expression and reduced 12-HETE and 15-HETE levels. Ferroptosis inducers (Sorafenib, erastin) heightened LDH release and reduced viability, while inhibitors (ferrostatin-1, U0126) had opposing effects. STXBP1 knockdown also reduced lipid peroxidation and mitigated the cytotoxic effects of Sorafenib, indicating a role in ferroptosis regulation. Additionally, STXBP1 knockdown impacted EMT markers, decreasing N-cadherin and Vimentin and increasing E-cadherin. Conclusions STXBP1 functions as a tumor suppressor in glioma, regulating ferroptosis and EMT. It presents potential as a therapeutic target in glioma management.

Introduction Previous observational studies have suggested a potential association between gut microbiota (GM) and venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT). However, the causal nature of this association remains uncertain due to potential confounding factors. Material and methods The summary statistics for VTE, PE, and DVT were obtained from the GWAS conducted by the FinnGen consortium R9. The genetic data for relevant GM SNPs were extracted from the meta-analysis of GWAS performed by the global MiBioGen consortium. Using SNPs as instrumental variables, the IVW method was primarily employed to assess the bidirectional causal relationship between GM and VTE, PE, and DVT. Results For the risk of VTE onset, Candidatus Solea ferrea, Ruminococcaceae UCG002, and Ruminococcaceae UCG004 were negatively correlated, while Eubacterium hallii group, Butyricimonas, and Dorea were positively correlated. For PE, Intestinimonas, Unknown genus, and Firmicutes were negatively correlated, while Veillonella, Erysipelatoclostridium, and Lentisphaerae were positively correlated. For DVT, Mollicutes, Actinobacteria, and Bifidobacteriaceae were negatively correlated, while Adlercreutzia, Collinsella, and Desulfovibrio were positively correlated. After multiple corrections using the Bonferroni method, a significant causal relationship was identified between Ruminococcaceae and VTE. Cochran’s Q test was performed to evaluate instrumental variable heterogeneity (P > 0.05), MR-Egger regression analyses were performed to examine pleiotropy (P > 0.05), and Leave-one-out analysis was conducted to assess the impact of each SNP on the outcome. Conclusions Specific GM may have causal effects on VTE, PE, and DVT, potentially contributing to the development of microbiota-centered therapeutic approaches and the identification of novel biomarkers for targeted preventive strategies.

Purpose Differentiating between pyogenic (PS) and brucellar (BS) spondylitis is clinically challenging due to their similar clinical symptoms, with delayed diagnosis or misdiagnosis common, causing trouble for surgeons in selecting appropriate treatment strategies. Currently, radiology-based diagnostic models for PS and BS are lacking. This study aimed to combine magnetic resonance (MR) and radiographic imaging to elucidate the differences between PS and BS and develop a novel diagnostic model for differential diagnosis. Methods We collected and analyzed the differences between MR and radiological images of patients with PS and BS from two medical institutions. A nomogram was constructed using least absolute shrinkage and selection operator (LASSO) regression, alongside univariate and multivariate analyses to select the best features of the predictive model. Model discrimination, calibration, and clinical utility were assessed using receiver operating characteristic, calibration, and decision curve analyses. Results Among the enrolled 342 patients with PS (n = 167) or BS (n = 175), we found significant differences in MR and radiological characteristics between the two groups. LASSO regression analysis revealed that thoracic involvement, involved vertebrae number, parrot beak osteophyte presence, endplate destruction, and intervertebral disc signal strength on T1-weighted sequences were independent predictive factors for differentiating between PS and BS. The imaging-based clinical prediction model showed high accuracy in the training and validation sets, with the area under the curve achieving 0.861 and 0.908, respectively, and a significant net benefit in the threshold probability, indicating high clinical potential of the model. Conclusion This imaging-based model offers a useful tool for efficiently differentiating PS and BS, facilitating prompt diagnosis and treatment and mitigating incorrect or delayed diagnosis.

Background Ovarian cancer (OC) is a formidable gynecological tumor marked with the highest mortality rate. The lack of effective biomarkers and treatment drugs places a substantial proportion of patients with OC at significant risk of mortality, primarily due to metastasis. Glycolysis metabolism, lipid metabolism, choline metabolism, and sphingolipid metabolism are closely intertwined with the occurrence and progression of OC. Thus, it is of utmost significance to identify potent prognostic biomarkers and delve into the exploration of novel therapeutic drugs and targets, in pursuit of advancing the treatment of OC. Methods Single-cell RNA sequencing (scRNA-seq) data related to OC were analyzed using AUCell scores to identify subpopulations at the single-cell level. The “AddModuleScore” function of the “Seurat” package was adopted to score and select marker genes from four gene sets: glycolysis metabolism, lipid metabolism, choline metabolism, and sphingolipid metabolism. A prognostic model for metabolism-related genes (MRGs) was constructed and validated using OC-related marker genes selected from bulk RNAseq data. The MRG-based prognostic model was further utilized for functional analysis of the model gene set, pan-cancer analysis of genomic variations, spatial transcriptomics analysis, as well as GO and KEGG enrichment analysis. CIBERSORT and ESTIMATE algorithms were utilized for assessing the immune microenvironment of TCGA-ovarian serous cystadenocarcinoma (OV) samples. Furthermore, the Tracking Tumor Immunophenotype (TIP) database was employed to examine the anti-cancer immune response in patients with OC. To gain a more in-depth understanding of the process, the frequency of somatic mutations and different types of mutated genes were visualized through the somatic mutation profile of the TCGA database. Moreover, the benefits of immune checkpoint inhibitor (ICI) therapy in individuals with OC were predicted in the TIDE database. In addition, the CMap database was used to predict small-molecule drugs for the treatment of OC. Furthermore, immunohistochemistry, RT-qPCR, CCK-8, Transwell assay, and in vivo tumor xenograft experiments were conducted to validate the prognostic ability of the MRG Triggering Receptor Expressed on Myeloid Cells-1 (TREM1) in OC. Results Monocytes were selected using AUCell scoring, and two subpopulations of monocytes, marked by the expression of C1QC⁺ tumor-associated macrophages (TAMs) and FCN1⁺ resident tissue macrophages (RTMs), were identified as marker genes for OC. Subsequently, a prognostic model consisting of 12 MRGs was constructed and validated. Genomic exploration of the prognostic model unveiled an array of biological functions linked with metabolism. Furthermore, copy number variation (CNV), mRNA expression, single nucleotide variation (SNV), and methylation were significantly different across diverse tumors. Analysis of the TIP database demonstrated that the low-risk group, as determined by the MRG-based prognostic model, exhibited significantly higher anti-cancer immune activity relative to the high-risk group. Furthermore, predictions from the TIDE database revealed that individuals in the high-risk group were more prone to immune evasion when treated with ICIs. The resulting data identified candesartan and PD-123319 as potential therapeutic drugs for OC, possibly acting on the target ATGR2. In vitro and in vivo experiments elucidated that the targeted downregulation of TREM1 effectively inhibited the proliferation and migration of OC cells. Conclusion The MRG-based prognostic model constructed through the combined analysis of glycolysis metabolism, lipid metabolism, choline metabolism, and sphingolipid metabolism is potentially effective as a prognostic biomarker. Furthermore, candesartan and PD-123319 may be potential therapeutic drugs for OC, possibly acting on the target ATGR2. Graphical Abstract

Environmental factors, including poor dietary habits and unhealthy drinking patterns, contribute to ulcerative colitis (UC). While the relationship between diet‐related malnutrition and UC has been extensively explored, the impact of drinking water temperature remains largely overlooked, prompting us to investigate its influence on UC pathogenesis and explore the underlying mechanisms. In the present study, we observed that, unlike external thermal and cold therapy, varying drinking water temperatures transiently altered the internal body temperature of the digestive tract. Specifically, chronic drinking of 0°C water had significant anti‐inflammatory effects and preserved the integrity of the mucosal barrier in a colitis mouse model. Mechanistically, this temperature spectrum changed the composition of the gut microbiota from inflammation‐prone (25°C drinking water) to a resting pattern similar to that of the negative control. Specifically, the abundances of Blautia and Parasutterella, two beneficial genera, were strongly increased in response to 0°C water, accompanied by elevated levels of short‐chain fatty acids. In contrast, drinking 40°C water had opposite effects on all the examined parameters and generally aggravated the development of colitis. This study is the first to demonstrate how modifying the temperature of habitual drinking water can modulate colitis progression, providing a novel and noninvasive approach to UC management. Specifically, chronic consumption of 0°C water alleviated the severity of colitis, whereas 40°C water aggravated the disease. Therefore, by focusing on commonly consumed drinking water temperatures, our findings suggest that this simple intervention could be a safe, convenient, and effective therapeutic strategy.

Cancer metastasis is a primary contributor to cancer-related mortality, and mitigating the risk of metastasis has emerged as a central concern in oncology research. In recent years, exercise therapy, as a non-pharmacological intervention, has received considerable attention for its ability to enhance patients' quality of life and prognosis. Exercise significantly inhibits cancer spread, diminishes cancer risk, and improves therapy outcomes. Nonetheless, the exact mechanisms via which exercise inhibits the dissemination and metastasis of cancer cells are not fully elucidated. This review seeks to examine the mechanisms and prospective research avenues of exercise treatment in mitigating the risk of cancer metastasis. Moreover, it methodically examines pertinent clinical and scientific data, along with the efficacy of exercise therapies in real-world applications. The evaluation moreover suggests future research avenues, including a more profound exploration of mechanisms, the augmentation of clinical trials, the advancement of personalized and precision exercise therapy, and enhanced multidisciplinary collaboration. Exercise therapy shows significant potential in mitigating the risk of cancer metastasis, and its incorporation into holistic cancer treatment frameworks is advised to improve patients' general health and prognostic results. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-025-03846-7.

Introduction Non-alcoholic fatty liver disease (NAFLD) represents the most widespread liver disease globally, ranging from non-alcoholic fatty liver (NAFL) and steatohepatitis (NASH) to fibrosis/cirrhosis, with potential progression to hepatocellular carcinoma (HCC). Genome-wide association studies (GWASs) have identified several single nucleotide polymorphisms (SNPs) associated with NAFLD. However, numerous GWAS signals associated with NAFLD locate in non-coding regions, posing a challenge for interpreting their functional annotation. Results In this study, we utilized the Activity-by-Contact (ABC) model to construct the enhancer-gene maps of liver by integrating epigenomic data from 15 liver tissues and cell lines. We constructed the most comprehensive genome-wide regulatory maps of the liver, identifying 543,486 enhancer-gene connections, including 267,857 enhancers and 16,872 target genes. Enrichment analyses revealed that the ABC SNPs are significantly enriched in active chromatin regions and active chromatin state. By combining the ABC regulatory maps and NAFLD GWAS data, we systematically identified ABC SNPs associated with NAFLD risk. Through the functional annotations, such as pathway enrichment and drug-gene interaction analyses, we identified 6 genes (GGT1, ACTG1, SPP1, EPHA2, PROZ and SHMT1) as candidate NAFLD genes, with SHMT1 previously reported. Among the SNPs connected to the candidate genes, the ABC SNP rs2017869 (odds ratio [OR] for the C allele = 1.10, 95% CI = 1.04–1.16, P = 5.97 × 10− 4) had the highest ABC score. According to the ABC maps, rs2017869 links to GGT1, and several drugs targeting this gene, such as liothyronine, showed potential benefits to patients with NAFLD. Furthermore, we identified that another novel gene, EPHA2, may play a crucial role in NAFLD by regulating the GGT levels. Conclusions Our study provides the most comprehensive ABC regulatory maps of the liver to date. This resource offers a valuable reference for identifying regulatory variants and prioritizing susceptibility genes of liver diseases, such as NAFLD.

Introduction Dormant cancer cells, capable of reactivating from the G0 phase, drive tumor recurrence and therapy resistance. Current clinical strategies targeting dormancy remain limited. This study evaluates Punica granatum peel (PGP) and Dioscorea Nipponica (DN) for their ability to sustain dormancy in lung cancer cells and inhibit reactivation. Methods Dormancy was induced in A549 and H460 lung cancer cells via contact inhibition or serum deprivation. Subcutaneous and orthotopic xenograft mouse models were employed. Cells and mice were treated with PGP, DN, or their combination. SYBR Green assays, flow cytometry, and immunoblotting assessed DNA synthesis, cell cycle phases, and protein expression (p27, SKP2, cMYC, AURORA A, SUPT16H, SSRP1). Results Both PGP and DN significantly inhibited DNA synthesis and cell cycle re-entry (G0-to-G1 transition) in vitro. In vivo, tumor volume and weight decreased by 26–50% (p < 0.05) in treated mice. Treatments upregulated p27 while downregulating SKP2, cMYC, AURORA A, SUPT16H, and SSRP1. No synergistic effect was observed, but additive efficacy (Combination Index ≈1) was noted at a 10:1 PGP:DN ratio. Discussion PGP and DN sustain dormancy by modulating key cell cycle regulators, highlighting their potential to reduce recurrence and combat drug resistance. These findings underscore the therapeutic promise of traditional Chinese medicines in managing dormant cancer cells. Future studies should identify active compounds and validate mechanisms in advanced models.

Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, posing a significant threat to human health. Recently, gambogic acid (GA) has garnered attention for its anticancer properties in GC. However, it remains unclear whether GA can regulate other forms of cell death beyond apoptosis. In this study, we found that GA inhibited proliferation and induced ferroptosis in GC cells. Western blot analysis was employed to assess ferroptosis and endoplasmic reticulum (ER) stress-related proteins, as well as forkhead box A2 (FOXA2) expression. Additionally, malondialdehyde (MDA) and glutathione (GSH) levels were measured following GA treatment, and quantitative real-time polymerase chain reaction (RT-qPCR) was used to evaluate miR-1291 expression. Our findings revealed that GA treatment elevated reactive oxygen species (ROS) levels and promoted intracellular Fe[Formula: see text], MDA, and GSH accumulation. Furthermore, GA upregulated SLC7A11 and ferritin expression while suppressing glutathione peroxidase 4 (GPX4) in AGS and HGC27 cells, suggesting its role in ferroptosis induction. Notably, GA increased miR-1291 levels and downregulated FOXA2 expression. Subsequent analyses showed FOXA2 as a direct target of miR-1291. Functional experiments involving miR-1291 and FOXA2 knockdown or overexpression further suggested that the miR-1291/FOXA2 axis mediates ferroptosis. Finally, tumor xenograft models showed that GA effectively inhibited tumor growth by inducing ferroptosis. In conclusion, our study provides compelling evidence that GA induces ferroptosis in GC through the miR-1291/FOXA2 axis, highlighting its potential as a novel therapeutic strategy and preventive target for gastric cancer treatment.

The aim of this study was to evaluate the therapeutic effect of puerarin (PUE) on alcoholic liver disease (ALD) and elucidate the potential mechanism from the perspective of lipolysis and hepatic steatosis. Assessment of PUE efficacy against ALD was performed using serum biochemical parameters and the histological examination of liver and adipose tissue via Hematoxylin and eosin (H&E) staining. The potential mechanisms underlying the amelioration of ALD by PUE were investigated using Western blotting (WB) analysis and immunofluorescence (IHC) staining. We demonstrated that PUE attenuated steatosis in ALD by alleviating ethanol-induced liver damage and lipid accumulation, suppressing the expression of lipid synthesis genes, upregulating the expression of lipid metabolism genes, and reducing lipolysis by inhibiting adipose triglyceride lipase (ATGL) activation and the phosphorylation of hormone-sensitive lipase (HSL). In conclusion, PUE ameliorates ALD by inhibiting the sympathetic outflow-mediated activation of key lipolysis enzymes ATGL and HSL. These findings provide a solid theoretical foundation for the potential application of PUE in the clinical treatment of ALD.

It is crucial to prevent and treat liver fibrosis in patients with chronic liver disease. Dihydromyricetin (DMY) is a natural flavonoid compound from traditional Chinese medicine, known to alleviate chronic liver injury. However, its role in regulating inflammatory responses through gut microbiota and metabolic changes remains unclear. In this study, a mouse model of liver fibrosis was induced with carbon tetrachloride (CCl 4 ), and DMY was administered via gavage. Histopathology, immunohistochemistry, Reverse Transcription Polymerase Chain Reaction (RT-PCR), 16S rRNA sequencing, and untargeted metabolomics were employed to evaluate DMY’s pharmacological effects on CCl 4 -induced liver fibrosis and explore its underlying mechanisms. Our results show that DMY reduced the aspartate transaminase (AST) and alanine transaminase (ALT) serum levels in liver fibrosis model mice, and lowered the mRNA expression of pro-inflammatory cytokines and fibrosis markers. Additionally, DMY restored the richness and diversity of the gut microbiota, with several microbiota taxa significantly correlating with inflammatory markers. Metabolomic analysis of serum and liver tissue revealed that DMY significantly altered the liver metabolite disturbances induced by CCl 4 . Pearson correlation analysis demonstrated a strong relationship between microbial composition and liver metabolites. These results suggest that DMY alleviates liver fibrosis in mice by reshaping the gut microbiota and host metabolism, thereby improving the inflammatory response.