Background:Polygonati Rhizoma (Huangjing) is a traditional Chinese medicinal herb long used to “tonify the kidney and replenish essence,” with documented benefits for reproductive function. Its effects against chemotherapy-induced male reproductive dysfunction remain unclear.Purpose:This study investigated the protective effects of CP-1, low-molecular-weight polysaccharides from black-bean-processed Polygonati Rhizoma, against cyclophosphamide (CTX)-induced asthenozoospermia(AZS) and explored underlying molecular mechanisms.Methods:A CTX-induced asthenozoospermia model was established in C57BL/6J mice through intraperitoneal injection of CTX for five consecutive days. CP-1 was subsequently administered orally for 30 days. Sperm parameters, testicular histology, and serum reproductive hormones were assessed. Single-cell RNA sequencing (scRNA-seq) was performed to construct the testicular cell atlas, identify differentially expressed genes, and analyze spermatogenic developmental trajectories. The proposed molecular mechanism was further validated by qPCR, ELISA, and Western blot analyses. Additionally, miR-27b mimic and inhibitor were designed to target the candidate gene, and the intervention effect of CP-1 was verified in the GC-2spd(ts) cells.Results:CP-1 improved sperm concentration and motility, mitigated testicular damage, and restored endocrine balance in CTX-treated mice. scRNA-seq revealed that CP-1 promoted the transition from spermatocytes to spermatids and reactivated transcriptional programs associated with spermatogenesis and sperm motility, including Crisp2, Smcp, and CatSper-related genes. Mechanistically, CP-1 suppressed the expression of miR-27b and consequently upregulated Crisp2, thereby enhancing sperm motility. Additionally, CP-1 alleviated oxidative stress and inflammatory responses in germ cells.Conclusion:CP-1 protects against CTX-induced AZS by restoring germ-cell differentiation and sperm motility via the miR-27b/CRISP2 axis, providing mechanistic evidence supporting the traditional use of Polygonati Rhizoma for male reproductive health.

BACKGROUND:Spatholobus suberectus Dunn (SSD), known in traditional Chinese medicine as Jixueteng, has historically been used to treat conditions characterized by blood stasis. Modern research has validated its anticancer potential. Recent studies reveal broad-spectrum antiviral activity. PURPOSE:This review synthesizes these two research frontiers. It proposes a unified host-directed therapy paradigm as the core mechanism underlying SSD's dual therapeutic capability. METHODS:A comprehensive analysis of peer-reviewed literature was conducted. This included phytochemical studies, in vitro and in vivo pharmacological investigations, and computational modeling related to SSD. Emphasis was placed on integrating the latest mechanistic findings on its antiviral action against SARS-CoV-2 with its established anticancer profile. RESULTS:SSD contains bioactive flavonoids, such as isoliquiritigenin and procyanidins. These compounds enable multi-target interactions with host proteins. In cancer, SSD acts as a host-directed anticancer agent by inhibiting lactate dehydrogenase A, activating AMP-activated protein kinase, inducing apoptosis and pyroptosis, and arresting the cell cycle at the G2/M checkpoint. Against SARS-CoV-2, SSD functions as a direct inhibitor of the host angiotensin-converting enzyme 2 receptor. It blocks viral entry with pan-variant efficacy validated in vivo. The anticancer evidence for SSD is extensive and derived from multiple independent laboratories. The antiviral data are currently more limited. Published studies have identified SSD as active against SARS-CoV-2 and demonstrated that isoliquiritigenin inhibits viral replication via NRF2 activation. Mechanistic ACE2-targeting data remain preliminary. A comparative synthesis reveals that SSD's efficacy in both oncology and virology converges on the modulation of host protein targets. SSD targets dysregulated host enzymes in cancer and a hijacked host receptor in viral infection. This strategy provides a high barrier to therapeutic resistance. CONCLUSION:SSD represents a promising natural host-directed therapeutic platform. Its dual ability to disrupt cancer cell physiology and inhibit SARS-CoV-2 entry via distinct host targets positions it as a potential template for developing resistance-evasive strategies against complex diseases. Future efforts must focus on isolating the precise ACE2-inhibiting compounds, optimizing disease-specific delivery, and advancing translational studies to realize its clinical potential.

Numerous medical and food dual-purpose herbs have been used for thousands of years and are still gaining influence in our daily lives. However, there are still two major questions, including chemical standardization and efficacy of these herbs, remaining to be addressed. In this special issue, we received the latest studies on the chemical composition and health efficacy of medical and food dual-purpose herbs. These findings enrich our understanding of the chemical composition and health efficacy of medical and food dual-purpose herbs, which can be helpful to develop functional foods and drugs for the prevention and control of various diseases.

ETHNOPHARMACOLOGICAL RELEVANCE:Traditional Chinese medicine (TCM) has long employed herbal formulas for conditions manifesting as menstrual irregularities, galactorrhea, and infertility-symptom constellations overlapping with hyperprolactinemia (HPRL). Classical formulas such as Peony-Glycyrrhiza Decoction, documented for "liver constraint" patterns associated with amenorrhea, provide an ethnopharmacological rationale for investigating their relevance to antipsychotic-induced HPRL through modern mechanistic studies and network pharmacology. AIM OF THE STUDY:This review critically evaluates the scientific evidence supporting TCM interventions for antipsychotic-induced HPRL, elucidating multi-target mechanisms via network pharmacology and experimental data, thereby linking traditional uses with pharmacological validation. METHODS:This narrative review synthesizes literature from PubMed, CNKI, TCMSP, and HERB databases (January 2000-December 2024) on TCM interventions for antipsychotic-induced HPRL. Network pharmacology analyses, molecular docking studies, experimental validations, and clinical studies of individual herbs and complex formulas were critically evaluated. RESULTS:TCM ameliorates HPRL through multi-dimensional mechanisms: dopaminergic modulation via DRD2 upregulation and MAO inhibition; epigenetic regulation through DNMT inhibition and DRD2 promoter demethylation; restoration of the gut-brain-pituitary axis via microbiota modulation and anti-inflammatory effects; and regulation of key signaling pathways (JAK2/STAT5, NF-κB, PI3K/Akt). Network pharmacology reveals convergent pathway enrichment across formulas, including dopaminergic synapse, TGF-β signaling, and neuroactive ligand-receptor interactions. Clinically, Peony-Glycyrrhiza Decoction reduces prolactin by -32.69 ng/mL (p < 0.00001) with favorable safety. CONCLUSION:TCM represents a promising multi-target approach for antipsychotic-induced HPRL, addressing complex neuroendocrine dysregulation through component synergy. Network pharmacology effectively bridges TCM theory with mechanistic research, supporting evidence-based integration into psychiatric care.

Ethnopharmacological relevance: As a frequent complication of type 2 diabetes, diabetic nephropathy (DN) is the leading cause of mortality among affected individuals. DN is categorized under “thirsting,” “edema,” and “turbid urine” in traditional Chinese medicine (TCM). Zishen Yuzhen Pill (ZYP), a traditional Chinese medicine preparation containing 14 distinct herbs, has been clinically prescribed to DN. Nevertheless, the underlying mechanisms of ZYP ameliorates DN still unclear.Purpose: To investigate the protective effects of ZYP on DN in vivo and in vitro, and to unveil its underlying mechanism.Methods: Network analysis was carried out to identify the primary target of ZYP in treating DN. Subsequently, the therapeutic efficacy of ZYP (2.34, 4.68 g/kg) was evaluated in db/db mice. Following drug administration for 6 weeks, blood and kidney tissue were collected for analysis. Biochemical markers and metabolic parameters were detected using commercial kits. Histopathological staining was performed to monitor morphological changes of kidneys in mice. High glucose (50 mM) induced-HK-2 cells were used to evaluate the kidney protective effects of Ginsenoside Re (an active compound of ZYP). The action mechanism of ZYP was verified by western blotting and immunofluorescence. Furthermore, the target binding interaction was rigorously validated through molecular docking, molecular dynamics simulation (MD) and the cellular thermal shift assay (CETSA).Results: Through network pharmacology, ZYP exerted therapeutic effects against DN through multiple pathways, including PI3K/AKT, MAPK and TNF signaling pathway. In vivo experimental data revealed that ZYP exerted the ability to regulate the disorder in glucose/lipid metabolism, inflammatory response, oxidative stress and apoptosis, and improve kidney dysfunction. Additionally, ZYP alleviated the histopathological damage and significantly upregulated the phosphorylation of PI3K and AKT, and down regulated P38 phosphorylation in kidney tissues. According to molecular docking results, Ginsenoside Re exhibited a high binding affinity towards the targets ALB, TNF, AKT and PI3K. In vitro experimental studies demonstrated that Ginsenoside Re markedly elevated intracellular levels of glutathione (GSH) and catalase (CAT), while reducing reactive oxygen species (ROS) and malondialdehyde (MDA). It also enhanced interleukin-10 (IL-10) while suppressing interleukin-6 (IL-6) and tumor necrosis factor (TNF-a). Mechanistic study indicated that Ginsenoside Re promoted the phosphorylation of PI3K and AKT proteins and decreased the level of p-P38 protein. MD and CETSA further demonstrated a robust binding affinity between the Ginsenoside Re and the core target. Moreover, its restorative effect was abolished by a PI3K inhibitor.Conclusion: This study provides evidence that ZYP improves DN by inhibiting the inflammatory response, oxidative stress and apoptosis via the PI3K/AKT/p38 MAPK signaling pathway.

Traditional pile fermentation of Liupao tea relies primarily on endogenous tea constituents as nutrient sources for microbial activity. This study investigated the application of a saccharified Polygonatum solution as an additional fermentable matrix during pile fermentation in order to examine its association with microbial succession and with the formation of colour-, taste- and flavour-related metabolites. Microbiome profiling revealed that Polygonatum fortification was associated with earlier microbial reorganisation, accompanied by earlier shifts in notable genera such as Staphylococcus and Thermomyces. Under the same piling conditions, the fortified piles showed earlier moderation of bitterness, an earlier transition to a characteristic bright-red infusion, and distinct treatment-related trajectories in volatile compounds. Non-volatile profiling further showed earlier increases in theabrownins and a higher final level in the fortified piles, together with shifts in catechin-derived pigment transformation. Taken together, these results indicate that the introduction of saccharified Polygonatum was associated with coordinated microbial and chemical changes during Liupao tea pile fermentation, providing a useful basis for further investigation of Polygonatum-associated dark-tea fermentation under practical piling conditions.

Background Ulcerative colitis (UC) is a type of inflammatory bowel disease. Macrophage polarization is crucial in the development of UC. Oxypalmatine (OPAL) is an isoquinoline alkaloid that can be isolated from various plant, including Phellodendron amurense and Sinomenium acutum. It is also an oxidative metabolite derived from the hepatic biotransformation of palmatine (PAL), which is one of the active constituents of Coptis chinensis that demonstrates anti-inflammatory and antioxidant properties. Purpose This study aimed to explore the anti-inflammatory properties of OPAL and the mechanisms involved. Methods Efficacy of OPAL and its impact on macrophage polarization were assessed in a dextran sodium sulfate (DSS)-induced mouse model of colitis. Necessity of macrophage in the alleviation by OPAL was confirmed with a macrophage-depletion model. Transcriptomics analysis was performed on the colon to identify the corresponding signaling pathways. In an in vitro model of THP-1-derived macrophage, the effect of OPAL was assessed in terms of cell energy metabolism, cytokines production, and epithelium damage. Target of OPAL was explored by limited proteolysis-mass spectrometry (LiP-MS) analysis and siRNA-mediated knockdown. Results OPAL significantly ameliorated DSS-induced colitis by reducing colon shortening, weight loss and intestinal barrier damage, which relied on the inhibition on M1 polarization as confirmed by flowcytometry and macrophage-depletion. In vitro, OPAL suppressed the inflammatory response in THP-1-derived macrophages, and reprogrammed the energy metabolism profile by reducing the glycolysis and enhancing basal respiration and maximal respiration. Mechanistically, OPAL inhibited M1 polarization via suppressing the JAK-STAT signaling pathway, which mainly relied on binding to RAB8A protein to suppress STAT1 phosphorylation and the consequent HK2 expression. Conclusion OPAL ameliorated UC by suppressing M1 macrophage polarization via the RAB8A/STAT1 axis, highlighting a promising treatment strategy for UC management.

Carbon tetrachloride (CCl4), a potent hepatotoxin, is known to induce liver injury, but its effects on neuropsychiatric behavior through the liver-brain axis remain poorly understood. This study investigates how subacute versus chronic CCl4 exposure drives distinct behavioral phenotypes via monoamine oxidase A (MAOA)-mediated serotonin dysregulation. Male C57BL/6 mice were subjected to subacute (23 days) or chronic (49 days) CCl4 exposure (n = 10/group). Liver injury was assessed through serum ALT/AST, histopathology, and fibrotic markers. Neurobehavioral changes were evaluated using open field, tail suspension, and sucrose preference tests. MAOA, serotonin (5HT), and its metabolite 5-hydroxyindoleacetic acid (5HIAA) were quantified in liver and brain tissues. In vitro, conditioned medium from CCl4-exposed hepatocytes (AML12/MIHA) was applied to C17.2 neural cells to assess neuroinflammatory responses. Subacute CCl4 exposure induced hepatotoxicity alongside depressive-like behaviors, correlating with elevated hepatic MAOA protein expression, 5HT depletion, and elevated 5HIAA. In contrast, chronic exposure resulted in sustained liver damage but a behavioral shift toward hyperactivity and aggression, linked to brain reduced MAOA protein levels and partial 5HT recovery. Conditioned medium from CCl4-treated hepatocytes triggered neuroinflammation and synaptic dysfunction in neural cells. Hippocampal reduced MAOA protein levels, particularly in the dentate gyrus, was associated with hyperlocomotion. CCl4 drives distinct neuropsychiatric changes at subacute and chronic timepoints through time-dependent altered MAOA protein expression: early elevated hepatic MAOA protein levels deplete serotonin (depressive phase), while late brain reduced MAOA protein levels and COMT upregulation suggest potential dysregulation of catecholamine metabolism (hyperactive/aggressive phase). These findings uncover a novel liver-brain axis mechanism in which hepatocyte-derived factors alter monoaminergic homeostasis, providing new insights into hepatic encephalopathy-related behavioral disorders.

The stems and leaves of Polygonatum sibiricum Red. are underused food byproducts whose polysaccharides and bioactivities remain poorly characterized. In this study, a novel homogeneous polysaccharide, PSLP-1 (4.287 kDa), was isolated and identified as a fructan-rich fraction with a →1)-β-d-Fruf-(2→ backbone and C6 side-chain substitution. In a chronic restraint stress mouse model, PSLP-1 showed clear antidepressant-like activity by reducing immobility time in both the forced swim and tail suspension tests. PSLP-1 was also associated with restoration of tryptophan metabolism, characterized by suppression of the indoleamine 2,3-dioxygenase 1-mediated kynurenine pathway and promotion of tryptophan hydroxylase-related 5-hydroxytryptamine synthesis. These effects were accompanied by gut microbiota remodeling, including increased Akkermansia and decreased Lactobacillus and Alistipes. These findings support P. sibiricum stems and leaves as a promising source of bioactive polysaccharides.

Longgu (fossilized bone), a mineral medicine in traditional Chinese medicine, has been used for centuries to treat symptoms resembling modern anxiety and insomnia. This review evaluates the hypothesis that Longgu's therapeutic effects arise from a synergistic network of its constituent metal ions. We synthesized evidence from chemical analyses, pharmacological studies of Ca, Mg, Zn, Fe, Cu, and Mn, and clinical trials of Longgu-containing formulations. The metal ions form an integrated network exhibiting three emergent properties. First, ionostatic balance is achieved through Ca/Mg-mediated regulation of neuronal excitability. Second, cross-pathway synergy occurs where zinc concurrently modulates neurotransmission and promotes neuroplasticity via BDNF. Third, systemic integration involves zinc and manganese co-regulating the gut-brain axis. Clinical studies demonstrate that Longgu-containing formulations improve outcomes in depression, anxiety, and insomnia, particularly for comorbid conditions, and show synergistic effects when combined with conventional antidepressants. This network pharmacology framework repositions Longgu as a model for developing multi-target therapeutics, offering a strategy to overcome limitations of single-target psychiatric drugs.

ETHNOPHARMACOLOGICAL RELEVANCE:Long Gu (Os Draconis), a mineral medicine with over 2000 years of use in traditional Chinese medicine, is facing a critical juncture. Its identity has been clarified scientifically-from a mythologized "dragon bone" to a fossilized mammalian bioapatite-yet its sustainable clinical application is threatened by resource depletion, widespread domestic and international adulteration, and the lack of modern quality standards. AIM OF THE STUDY:This review aims to systematically analyze the evolution of Long Gu through historical materia medica, define its authentic characteristics using modern science, diagnose the root causes of its current market and regulatory crisis, and propose a robust, multi-dimensional framework for quality evaluation and sustainable sourcing. MATERIALS AND METHODS:A systematic review of Chinese materia medica literature from the Pre-Qin to Qing Dynasties was conducted. Historical textual research was integrated with evidence from modern mineralogy, paleontology, geochemistry, and pharmacology to validate traditional knowledge and establish scientific identification criteria. RESULTS:The understanding of Long Gu evolved from mythological origins to a scientific conclusion in the Ming Dynasty, with Li Shizhen correctly identifying it as fossilized ancient mammalian bones. Modern research confirms authentic "Wuhua Long Gu" from the Shanxi-Shaanxi region is primarily carbonated hydroxyapatite, characterized by high porosity (>35%), significant hygroscopicity, and a unique trace element profile (Zn, Sr). These properties underpin its advertised therapeutic effects. However, the market is now saturated with dangerous adulterants, including fluoride-rich dinosaur fossils and processed modern bones, due to resource exhaustion and inadequate pharmacopoeial standards focused solely on calcium content. CONCLUSION:The future of Long Gu depends on transcending outdated quality controls. Ensuring its efficacy and safety necessitates a paradigm shift to a comprehensive standard system that combines paleontological and geochronological origin verification, quantitative microstructural analysis, chemical fingerprinting of key components, and strict safety monitoring. Complementary research into biomimetic synthesis and accelerated mineralization is urgently needed to develop sustainable alternatives for this invaluable yet endangered medicinal resource.

Emerging evidence establishes hepatic dysfunction as a critical modulator of breast cancer (BC) progression through metabolic, endocrine, and inflammatory crosstalk, yet the molecular mediators remain incompletely characterized. This review systematically examines the liver-BC axis to identify mechanistic drivers and therapeutic opportunities for patients with comorbid conditions. We conducted an integrated analysis combining a comprehensive literature review with computational biology approaches, including protein-protein interaction network analysis, functional pathway enrichment (KEGG/GO), and multi-omics data mining from GEO, TCGA, and CPTAC databases, supplemented by experimental validations from preclinical models. Our analysis revealed hepatic dysfunction promotes BC progression through five interconnected pathways: insulin resistance-driven IGF1-PI3K/AKT activation, estrogen metabolism imbalance via CYP19A1/ESR1, IL6-STAT3/NLRP3-mediated inflammation, HMOX1/APOE-dependent metabolic rewiring, and FAK-Src/MMP9-regulated ECM remodeling. Key molecular mediators include nuclear receptors (ESR1), cytokines (IL-1β), growth factors (HGF), and receptor tyrosine kinases, with SPP1 and PTPN2 emerging as potential circulating biomarkers linking hepatic dysfunction to aggressive BC phenotypes. The crosstalk between hepatic dysfunction and BC is mediated by a network of proteins and pathways, offering potential targets for therapeutic intervention. Future research should focus on translational validation and personalized strategies for BC patients with comorbid liver conditions. This mechanistic insight may advance early diagnosis and precision treatment paradigms.

Background: Chronic psychological stress drives metastasis in triple-negative breast cancer (TNBC), yet the underlying mechanisms remain poorly understood and effective interventions are lacking. Stress-induced expansion of myeloid-derived suppressor cells (MDSCs) and subsequent immune remodeling play critical roles, with aberrant myeloid differentiation of hematopoietic stem and progenitor cells (HSPCs) serving as a major source of MDSCs. This study investigates whether epicatechin gallate (ECG) suppresses stress-driven TNBC growth and lung metastasis by regulating HSPC myeloid differentiation. Methods: A mouse model of chronic unpredictable mild stress (CUMS) followed by 4T1 tumor implantation was used to evaluate the anti-tumor effects of ECG. CETSA-WB, molecular docking, HSPC differentiation assays, and MDSC functional validation assays, along with immunohistochemistry, immunofluorescence, and flow cytometry, were performed to elucidate how ECG modulates glucocorticoid (GC)/glucocorticoid receptor (GR) signaling and HSPC differentiation. Results: ECG dose-dependently alleviated depressive-like behaviors, reduced serum corticosterone (Cort), and inhibited tumor growth and lung metastasis. Notably, ECG decreased lung metastatic foci by 76.9% relative to the CUMS group. Mechanistically, chronic stress activated GR and induced its nuclear translocation in HSPCs, promoting aberrant HSPC-to-MDSC differentiation. ECG directly bound GR, blocked its nuclear translocation, and suppressed the myeloid differentiation of HSPCs into MDSCs, which was accompanied by downregulation of S100A8/A9, fibronectin, and MMP-2, as well as increased CD8+ T cell infiltration. Supernatants from ECG-pretreated and differentiated HSPCs reversed Cort-induced epithelial-mesenchymal transition (EMT) in 4T1 cells. Conclusions: ECG acts as a natural GR signaling blocker that directly targets GR to block chronic stress-driven abnormal myeloid differentiation of HSPCs, thereby remodeling the pulmonary immune microenvironment, suppressing EMT, and reducing breast cancer lung metastasis. These findings identify ECG as a promising GR signaling blocker and a potential adjuvant therapy for cancer patients under high-stress conditions.

Zishen Yuzhen Pill (ZYP) is a Chinese herbal product developed by Shenzhen TCM Hospital, which have been frequently used to treat osteoporosis (OP). This study aimed to determine the major chemical components of ZYP and its prototype compounds and metabolites in rat biological samples, as well as explore the potential effect of ZYP-containing serum in MC3T3-E1 cells. UPLC-Q/TOF-MS was used to identify the chemical components. Then, ZYP was orally administered to rat, and samples of plasma, urine, feces, bile, and tissue were collected to identify prototype compounds and metabolites. The viability of MC3T3-E1 cells was evaluated using the CCK-8 method after treatment with various concentrations (2%, 4%, and 8%) of ZYP-containing serum. Following treatment of MC3T3-E1 cells with ZYP-containing serum, the activity of alkaline phosphatase (ALP) and Alizarin red S (ARS) were measured, and the levels of Runx2, Opn, Opg and Osterix were quantified using the qPCR and Western blot analysis. And cells were collected for RNA-seq analysis. Results indicated that a total 152 compounds were identified in ZYP, including flavonoids, iridoid, lignans, triterpene saponins, etc. Furthermore, we detected a total of 70 prototype components and 99 metabolites distributed in different tissues. In addition, ZYP-containing serum observably promoted osteogenesis by increasing ALP and ARS activities, as well as up-regulating the expression of Runx2, Opn, Opg and Osterix in MC3T3-E1 cells. RNA-seq results indicated that the beneficial effects may be related to the upregulation of mitochondrial oxidative phosphorylation. This work provided further support for the traditional application of ZYP in the treatment of OP. And this study can promote the further pharmacokinetic and pharmacological evaluation of ZYP.

BACKGROUND:Tourette syndrome (TS) is a neuropsychiatric disorder that typically manifests in childhood. Currently, anti-psychotic drugs that aim to reduce dopaminergic hyperinnervation in the brain are recommended for TS. These drugs have been proven to increase the risk of extrapyramidal symptoms, which hinder their use. Gut microbiota has been shown to modulate dopamine (Da) metabolism along gut-brain axis and be relevant to the development of TS, and which may be a novel strategy for TS therapy. Xiao-Er-An-Shen Granule (XEASG) is a clinically prescribed herbal mixture that has demonstrated clinical efficacy in treating TS. The detailed mechanism of XEASG in alleviating TS symptoms through the gut-brain axis however remains incompletely understood. PURPOSE:This study aimed to investigate the effect of XEASG on TS through regulating Da synthesis both in the brain and gut microbiota. METHODS:XEASG at doses of 2 and 4 g/kg/d was administered orally to 3,3'-iminodipropionitrile (IDPN)-induced TS model mice. Behavioral assessments, targeted metabolomics analysis, 16S rRNA sequencing and enzyme-linkedimmunosorbent assay (ELISA) were employed to elucidate the therapeutic effects and mechanisms of XEASG for TS treatment. RESULTS:Data showed that XEASG treatment significantly alleviated IDPN-induced tic-like behavior in mice. XEASG significantly reduced Da level in the brain tissues of TS mice, resulting from down-regulated Da synthesis but up-regulated Da degradation. Aberrant Da metabolism was also found in serum and colon contents of TS mice, which was restored by XEASG treatment. Furthermore,16S rRNA sequence revealed that XEASG altered the microbial community composition. Finally, experimental validation confirmed that XEASG suppressed Da synthesis pathway by reducing tyrosine hydroxylase level in the gut microbiota. CONCLUSION:Our findings reveal that XEASG alleviates TS via inhibiting Da synthesis in the brain and gut, which suggests that the regulation of Da through gut microbiota by XEASG could be a therapeutic strategy for TS treatment.

The treatment of pancreatic cancer remains a formidable challenge. Despite recent advances in diagnostic techniques and therapeutic approaches, the overall five-year survival rate for patients with pancreatic cancer remains below 9%, reflecting a dismal prognosis. Currently, surgical resection is the only potentially curative option; however, only about 10% of patients are eligible for surgery at the time of diagnosis. For those with unresectable locally advanced or metastatic pancreatic cancer, chemotherapy remains the mainstay of treatment. In this context, gemcitabine (GEM), a conventional chemotherapeutic agent, holds significant clinical value due to its potent anti-pancreatic cancer activity. Nevertheless, its clinical application has long been hampered by limitations such as a short half-life, rapid metabolic degradation, poor tumor tissue penetration, and dose-dependent toxicity. Although conventional GEM-based nanoformulations have partially improved its pharmacokinetic properties, their therapeutic efficacy and safety still require further enhancement. In recent years, researchers have focused on developing novel nanodelivery systems aimed at overcoming the clinical limitations of GEM through innovative carrier designs and advanced delivery strategies. This review briefly introduces the mechanisms underlying gemcitabine resistance and systematically highlights recent advances in emerging nanoparticles loaded with GEM. Particular attention is given to functional nanocarriers for GEM monotherapy, self-assembled GEM prodrug nanostructures, and GEM-based combinational nanotherapies. Finally, this review discusses the current challenges and future opportunities for the clinical translation of these emerging nanoplatforms.

Breast cancer (BC), characterized by its heterogeneity and diverse subtypes, necessitates personalized treatment strategies. This study presents MF3Ec-TBPP nanoparticles (NPs) as a promising approach, integrating an aggregation-induced emission (AIE)-based photosensitizer, TBPP, with the MF3Ec aptamer to enhance targeted photodynamic therapy (PDT) for Luminal A subtype BC cells. The nanoparticles also feature a 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) shell and dipalmitoyl phosphatidylcholine (DPPC), which stabilize the structure and inhibit singlet oxygen generation, effectively reducing off-target effects and protecting healthy tissues. Comprehensive in vitro and in vivo studies validate the NPs' specificity and effectiveness in targeting MCF-7 BC cells, achieving significant tumor growth inhibition with minimal damage to surrounding tissues. This study highlights the dual functionality of MF3Ec-TBPP NPs for both diagnosis and treatment, showcasing their potential to improve patient outcomes through precise diagnostic and therapeutic interventions.

Breast cancer, a complex disease influenced by metabolic and lipid profiles, requires a deeper understanding of causal relationships between dietary preferences, plasma metabolites, and cancer risk. This study employed Mendelian randomization (MR) to explore causal links between dietary preferences, plasma metabolites, and ER-negative/ER-positive breast cancer risk, alongside underlying mechanisms. The genome-wide association study (GWAS) data regarding dietary preferences, plasma metabolites, and plasma lipids were obtained from the GWAS database, with sample sizes of 161,625, 8,299, and 7,174 respectively. Meanwhile, the GWAS data related to breast cancer and its subtypes (ER + breast cancer and ER- breast cancer) were sourced from the IEU Open GWAS project, with sample sizes of 228,951, 175,475, and 127,442 respectively. Reverse MR and mediation analyses were conducted to assess bidirectional relationships and mediating roles of plasma biomarkers. The analysis revealed significant causal effects of dietary preferences and plasma metabolites on breast cancer risk. Mediation analysis identified key pathways: curry preference (β = -0.015, 95

BACKGROUND AND OBJECTIVE:Myocardial ischemia-reperfusion injury (MIRI) presents a prevalent global clinical challenge without an optimal treatment strategy. Shenxiong Yixin Decoction exhibits promising cardioprotective effects in clinical scenarios. Polysaccharides, particularly pivotal in cardioprotection, act systemically through the intestine. Exosomes, particularly miRNA-rich ones, are crucial in MIRI pathophysiology. However, the specific role of gut-derived exosomal miRNAs in cardiovascular disease remains unclear. This study aimed to evaluate the cardioprotective effects of Shenxiong Yixin Decoction polysaccharides (SXYXP) on MIRI and elucidate its mechanisms. METHODS:In vitro and in vivo models of MIRI were set up with H9c2 cells, C57BL/6 mice, and Sprague-Dawley rats. Exosomes from IEC-6 cells and plasma were detected. Various techniques like MTT, TTC, H&E staining, echocardiography, flow cytometry, immunofluorescence, RT-qPCR, and Western blot were employed for pharmacodynamic and mechanistic analyses. RESULTS:SXYXP treatment could reduce myocardial infarction area, improve cardiac function, and increase myocardial cell survival rate under MIRI. The SXYXP treatment significantly enhanced the release of enterocyte-derived exosomes and elevated the levels of miR-21 within these exosomes. These SXYXP-modulated exosomes demonstrated a significant protective effect against H/R injury in H9c2 cells. However, the application of miR-21 inhibitors in the SXYXP group negated the protective effects of exosomes, leading to diminished cardiomyocyte proliferation, exacerbated oxidative stress, and elevated apoptosis. CONCLUSION:SXYXP may protect against MIRI by targeting miR-21 in intestinal cell-derived exosomes, which are transported to the heart through the blood to restore the level of miR-21 in the damaged myocardium, thereby inhibiting oxidative stress and the expression of PDCD4.