Rheumatoid arthritis (RA), a form of autoimmune inflammation, is marked by enduring synovial inflammation and the subsequent impairment of joint function. Despite the availability of conventional treatments, they are often marred by significant side effects and the associated high costs. Plant-derived extracellular vesicles (PEVs) offer a compelling alternative, owing to their abundant availability, affordability, low immunogenicity, high biocompatibility, and feasibility for large-scale production. These vesicles enhance intercellular communication by transferring intrinsic bioactive molecules. In our research, we delve into the capacity of PEVs to treat RA, highlighting the role of ginger-derived extracellular vesicles (GDEVs). By conjugating GDEVs with folic acid (FA), we have developed FA-GDEVs that maintain their inherent immunomodulatory properties. FA-GDEVs are designed to selectively target M1 macrophages in inflamed joints via the folate receptors (FRs). Our in vitro findings indicate that FA-GDEVs promote the polarization towards a reparative M2 macrophage phenotype by modulating the PI3K-AKT pathway. Further corroboration comes from in vivo studies, which demonstrate that FA-GDEVs not only concentrate efficiently in the affected joints but also markedly reduce the manifestations of RA. Synthesizing these findings, it is evident that FA-GDEVs emerge as a hopeful candidate for RA treatment, offering benefits such as safety, affordability, and therapeutic efficacy.

Aims: There is growing evidence that the gut microbiota plays a significant part in the pathophysiology of chronic stress. The dysbiosis of the gut microbiota closely relates to dysregulation of microbiota–host cometabolism. Composition changes in the gut microbiota related to perturbations in metabolic profiles are vital risk factors for disease development. Hyperbaric oxygen therapy is commonly applied as an alternative or primary therapy for various diseases. Therefore, a metabolic and gut bacteria perspective is essential to uncover possible mechanisms of chronic stress and the therapeutic effect of hyperbaric oxygenation. We determined that there were significantly disturbed metabolites and disordered gut microbiota between control and chronic stress group. The study aims to offer further information on the interactions between host metabolism, gut microbiota, and chronic stress.Methods: At present, chronic unpredictable mild stress is considered the most widespread method of modeling chronic stress in animals, so we used a chronic unpredictable mild stress mouse model to characterize changes in the metabolome and microbiome of depressed mice by combining 16S rRNA gene sequencing and UHPLC–MS/MS‐based metabolomics. Pearson's correlation‐based clustering analysis was performed with above metabolomics and fecal microbiome data to determine gut microbiota‐associated metabolites.Results: We found that 18 metabolites showed a significant correlation with campylobacterota. Campylobacterota associated metabolites were significantly enriched mainly in the d‐glutamate and d‐glutamine metabolism. Hyperoxia treatment may improve depression‐like behaviors in chronic stress model mice through regulating the disrupted metabolites.Conclusions: Hyperbaric oxygen improves depression‐like behaviors in chronic stress model mice by remodeling Campylobacterota associated metabolites.

Post-stroke depression (PSD) is a debilitating condition affecting more than one-third of stroke survivors, leading to significant impairments in mood, cognitive function, and overall quality of life. While conventional treatments like selective serotonin reuptake inhibitors (SSRIs) are commonly used, their efficacy is often limited, and they are associated with adverse side effects. Emerging research underscores the critical roles of neuroinflammation, neurotransmitter imbalances, and disruptions in the gut-brain axis in the development and progression of PSD, suggesting that targeting these pathways could lead to more effective therapeutic outcomes. Traditional Chinese Medicine (TCM) presents a promising multi-faceted approach, addressing these complex biological mechanisms by regulating neurotransmitter systems, modulating immune responses, and restoring gut microbiota balance. Key herbs such as Salvia miltiorrhiza Bunge (Lamiaceae; Dan Shen) and Bupleurum chinense DC. (Apiaceae; Chai Hu) have shown significant potential in modulating neurotransmitter levels, reducing neuroinflammation, and providing neuroprotection. Additionally, TCM formulations like Chaihu Shugan Powder (CSP) and Shugan Jieyu Capsules (SG) further enhance these effects by promoting gut microbiota homeostasis and restoring metabolic balance. This review delves into the biological mechanisms underlying PSD, with a particular focus on neuroinflammation, neurotransmitter dysregulation, and gut-brain axis dysfunction. It also explores the potential of integrating TCM with advanced multi-omics technologies—such as metabolomics, metagenomics, and transcriptomics—to develop personalized treatment strategies for PSD. By combining the holistic principles of TCM with modern Western medicine and cutting-edge omics technologies, this integrative approach offers a comprehensive framework for managing PSD, with the potential to significantly improve recovery outcomes and enhance the quality of life for stroke survivors.

Background: Radix Salvia miltiorrhiza (Danshen) has been used as a principal herb in treating cardiovascular diseases in Chinese medicine. Salvianolic acid B (SA-B), a water-soluble active component of Danshen, was found to have anti-myocardial ischemia (anti-MI) effect. This study aims to investigate mechanisms of SA-B on MI. Methods: Five conventional Western medicines (isosorbide dinitrate, verapamil, propranolol, captopril and trimethazine) with different mechanisms for treating cardiovascular diseases were selected as positive references to compare with SA-B in changing of the metabolomic profiles in MI rats under treatment. Potential mechanisms of SA-B were further investigated in H9C2 cell line. Results: The metabolomic profiles between SA-B- and propranolol-treated MI rats were similar, since there was a big overlap between the two groups in the PLS-DA score plot. Finally, it was demonstrated that SA-B exhibited a protective effect on MI mainly by decreasing the concentration of cyclic adenosine monophosphate (cAMP) and Ca²⁺ and inhibiting protein kinase A (PKA). Conclusion: SA-B and propanolol exhibited similar metabolomic profiles, indicating that the two drugs might have a similar mechanism.

Renal fibrosis is the pathological repair reaction of the kidney to chronic injury, which is an important process of chronic kidney disease (CKD) progressing to end-stage renal failure. Nephrolithiasis is one of the most common renal diseases, with waist and abdomen pain, hematuria, urinary tract infection, and other clinical symptoms, which can increase the risk of renal fibrosis. Oxalate crystal-induced kidney injury is an early stage of nephrolithiasis; it is of great significance to explore the mechanism for the prevention and treatment of nephrolithiasis. A rodent model of calcium oxalate (CaOx) crystal-induced kidney injury was used in the present study, and a network analysis method combining proteomics and metabolomics was conducted to reveal the mechanism of crystal kidney injury and to provide potential targets for the intervention of nephrolithiasis. Using the metabolomics method based on the UHPLC-Q/TOF-MS platform and the iTRAQ quantitative proteomics method, we screened a total of 244 metabolites and 886 proteins from the kidney tissues that had significant changes in the Crystal group compared with that in the Control group. Then, the ingenuity pathway analysis (IPA) was applied to construct a protein-to-metabolic regulatory network by correlating and integrating differential metabolites and proteins. The results showed that CaOx crystals could induce inflammatory reactions and oxidative stress through Akt, ERK1/2, and P38 MAPK pathways and affect amino acid metabolism and fatty acid β-oxidation to result in kidney injury, thus providing an important direction for the early prevention and treatment of nephrolithiasis.