Background: Enteroviruses-infected hand, foot, and mouth disease (HFMD) seriously threatens human health. This study aimed to analyze the research status, hotspots, and frontiers of HFMD. Methods: Publications on HFMD between January 1, 2006, and January 31, 2023, were retrieved from the Web of Science Core database. Bibliometric tools, including CiteSpace, VOSviewer, R package “Bibiometrix,” SCImago Graphica, and Charticulator, were utilized to analyze and visualize the data. Results: A total of 1860 articles from 424 journals, involving 8815 authors from 64 countries and 1797 institutions were analyzed. The number of studies on HFMD has shown an increasing trend over the past 18 years, with an annual increase observed since 2006, which is particularly prominent after 2010. Research in this field has centered on the Asian region. Notably, the research hotspots were mainly focused on vaccines, epidemiology, and pathogenesis of HFMD. Among the researchers in this field, Zhang Yong emerged as the most prolific author, while Xu Wenbo had the most significant influence. The Chinese Academy of Sciences was the most productive institution, and China was the most productive country for HFMD research. Conclusion: By bibliometric analysis, researchers in the HMFD field can efficiently identify and visually represent their research focus and limitations. In the future, it is crucial to maintain ongoing surveillance of HFMD outbreaks and their pathogenic changes. Additionally, future research should extensively explore the molecular mechanisms underlying Enteroviruses-induced HFMD with a focus on developing vaccines and therapies.

Background: Ulcerative colitis (UC), a persistent inflammatory bowel disorder, has witnessed a gradual increase in its global incidence in recent years. This study aims to identify biomarkers linked to PANoptosis in UC, highlighting a pressing requirement to identify novel diagnostic biomarkers and therapeutic targets for improved UC management. Methods: Differentially expressed genes (DEGs) in UC were identified using R software through Gene Expression Omnibus (GEO) GSE87466 and GSE206285 datasets integration. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to uncover co-expression modules. PANoptosis-related hub genes were selected using eight machine learning algorithms, followed by validation of the diagnostic markers with five machine learning algorithms in test datasets GSE38713 and GSE47908. A nomogram incorporating these six genes was subsequently constructed. Comprehensive analyses—including correlation assessment, single-cell profiling, gene set enrichment analysis (GSEA), and immune infiltration evaluation—were performed to characterize their functional relevance. Their expression profiles were further validated through DSS-induced mouse UC model. Results: Six potential biomarkers (ECSCR, IRF1, MMP1, PPARG, S100A8, S100A9) were identified, demonstrating significant upregulation or downregulation in UC. KEGG and GO enrichment analyses indicated these genes are significantly implicated in bacterial infection, immune response, and inflammation pathways. Analysis of immune cell infiltration uncovered distinct shift in immune cell composition in UC patients, correlating with the identified biomarkers. The single-cell analysis indicated that IRF1 was predominantly expressed in smooth muscle cells, while S100A8 and S100A9 showed markedly high expression in neutrophils. In the DSS-induced mouse model, all six biomarkers showed significant expression, which was consistent with their expression patterns in clinical samples. Conclusions: This study effectively discovers six PANoptosis-related biomarkers with potential diagnostic value for UC, emphasizing their role in disease progression and immune regulation, offering new biomarkers for the early diagnosis and personalized treatment of UC.

Mesenchymal stem cells and the derived extracellular microvesicles are potential promising therapy for many disease conditions, including wound healing. Since current therapeutic approaches do not satisfactorily attenuate or ameliorate formation of hypertrophic scars, it is necessary to develop novel drugs to achieve better outcomes. In this study, we investigated the effects and the underlying mechanisms of human umbilical mesenchymal stem cells (HUMSCs)-derived microvesicles (HUMSCs-MVs) on hypertrophic scar formation using a rabbit ear model and a human foreskin fibroblasts (HFF) culture model. The results showed that HUMSCs-MVs reduced formation of hypertrophic scar tissues in the rabbit model based on appearance observation, and hematoxylin and eosin (HE), Masson, and immunohistochemical stainings. HUMSCs-MVs inhibited invasion of HFF cells and decreased the levels of the α-SMA, N-WASP, and cortacin proteins. HUMSCs-MVs also inhibited cell proliferation of HFF cells. The MMP-1, MMP-3, and TIMP-3 mRNA levels were significantly increased, and the TIMP-4 mRNA level and the NF-kB p65/β-catenin protein levels were significantly decreased in HFF cells after HUMSCs-MVs treatment. The p-SMAD2/3 levels and the ratios of p-SMAD2/3/SMAD2/3 were significantly decreased in both the wound healing tissues and HFF cells after HUMSCs-MVs treatment. CD34 levels were significantly decreased in both wound healing scar tissues and HFF cells after HUMSCs-MVs treatment. The VEGF-A level was also significantly decreased in HFF cells after HUMSCs-MVs treatment. The magnitudes of changes in these markers by HUMSCs-MVs were mostly higher than those by dexamethasone. These results suggested that HUMSCs-MVs attenuated formation of hypertrophic scar during wound healing through inhibiting proliferation and invasion of fibrotic cells, inflammation and oxidative stress, Smad2/3 activation, and angiogenesis. HUMSCs-MVs is a potential promising drug to attenuate formation of hypertrophic scar during wound healing.

Glioblastoma (GBM) is the worst and most common malignant intracranial tumor with high mortality rates and almost invariably poor prognosis even after surgery, radiotherapy, chemotherapy and emerging immunotherapies. Therefore, it is important to find new therapeutic drugs for GBM treatment. In the present study, we aimed to explore the effect of one natural chalcone—Isobavachalcone (IBC) on GBM and clarify its anti-cancer mechanisms. It was observed that IBC could inhibit GBM cell proliferation, migration and invasion in vitro and prevent tumor growth without any significant drug toxicity in vivo. Mechanistically, IBC may target NOD-like receptor family pyrin domain-containing 3 (NLRP3) transcription factor estrogen receptor 1 (ESR1) by network pharmacology and molecular docking analysis. Experimentally, IBC reduced NLRP3 inflammasome-related pyroptosis and inflammation, arrested cell cycle at G1 phase, and induced mitochondria-dependent apoptosis in GBM cells. These results indicated that IBC is a potential therapeutic drug against GBM and provide a new insight into GBM treatment.