Ni Zhu

Paeoniflorin (PF), a monoterpene glycoside from Paeonia roots, shows low toxicity and broad anti‑inflammatory activity. A systematic review (PubMed, through 2025) with network pharmacology indicates that PF restores mitochondrial function, raises anti‑inflammatory mediators (IL‑10 and arginase‑1), reduces TNF‑α, IL‑1β and IL‑6, and eases oxidative stress. Its effects hinge on intertwined routes, dampening TLR4/MyD88, blocking NF‑κB nuclear entry, lowering MAPK phosphorylation, reshaping JAK‑STAT, and disrupting NLRP3 inflammasome assembly. Network mapping singles out a conserved core module (MAPK1, MAPK3, HSP90AA1, TP53, ESR1, BCL2, HIF1A, IL6, IL10 and FGF2), with HSP90AA1 and ESR1 as disease‑tailored effectors in rheumatoid arthritis and osteoarthritis (OA). PF absorbs fast and gathers in the liver with minimal toxicity, yet oral availability stays poor. Preclinical promise spans OA, colitis, and atherosclerosis, while clinical data remain thin. Synergistic pairing with other agents and structural refinement of PF broaden its reach, though such computational leads need experimental corroboration. Future efforts should improve its bioavailability, develop targeted delivery systems, and conduct rigorous clinical trials to move PF from tradition to evidence‑based medicine.

Background: Ulcerative colitis (UC) and psoriasis (PsO) are two common immune-mediated inflammatory diseases with significant comorbidity, yet whether one directly causes the other or they share common genetic and immunopathological backgrounds remains unclear. This study integrated bioinformatics, animal experiments, and bidirectional Mendelian randomization to systematically identify potential common molecular targets mediating the comorbidity. Methods: Transcriptomic data for UC and PsO were obtained from the Gene Expression Omnibus (GEO) database. Differential expression genes (DEGs) and WGCNA were performed to identify common transcriptomic alterations. Then, machine learning algorithms (SVM, RF, XGBoost, GLM) were used to screen for shared signature genes. The nomogram diagnostic models were constructed, and immune infiltration landscape were analyzed. An acute UC-PsO comorbidity mouse model was established by simultaneous administration of dextran sulfate sodium and imiquimod, and the expression levels of key genes were examined. Finally, bidirectional Mendelian randomization (MR) was performed to assess the genetic causal relationship between UC and PsO. Results: 3,840 DEGs in UC and 4,208 in PsO, with 619 overlapping DEGs, were identified. WGCNA further screened 17 up−regulated and 16 down−regulated co−expressed genes common to both diseases. Cross−validation using four machine learning algorithms finally identified CLDN8 and ABCA12 as the core signature genes shared by UC and PsO. Diagnostic models based on these two genes performed well for both diseases (specific AUC values can be added). Immune infiltration analysis revealed similar inflammatory pathway characteristics between the two diseases. In the UC−PsO comorbidity animal model, the expression changes of CLDN8 and ABCA12 were consistent with those in clinical samples, confirming their functional relevance. Bidirectional MR analysis showed no significant causal effect of UC on PsO nor of PsO on UC, which does not support the direct causation hypothesis but instead supports the shared mechanism hypothesis. Conclusion: CLDN8 and ABCA12 shared molecular signature in UC-PsO comorbidity, however, no direct genetic causal relationship between UC and PsO. Clinically, each disease should be managed according to its own pathology, while targeting common inflammatory pathways involving CLDN8/ABCA12 to enable personalized treatment.

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.

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.

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 multiforme (GBM) is the most malignant intracranial tumor with high mortality rates and invariably poor prognosis due to its limited clinical treatments. There is an urgent need to develop new therapeutic drugs for GBM treatment. As a natural prenylated chalcone compound, Isobavachalcone (IBC)’s favorable pharmacological activities have been widely revealed. However, potential inhibitory effects of IBC on GBM have not been explored. In the present study, we aimed to detect the effects of IBC on GBM and clarify its anti-GBM mechanisms for the first time. 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 both subcutaneous and orthotopic GBM xenograft tumor models in vivo. Mechanistically, IBC may target NOD-like receptor family pyrin domain-containing 3 (NLRP3) transcription factor estrogen receptor α (ESR1 gene) by network pharmacology and molecular docking analysis. Experimentally, IBC alleviated NLRP3 inflammasome-related pyroptosis and inflammation, arrested cell cycle at G1 phase, and induced mitochondria-dependent apoptosis in GBM cells. IBC’s inhibition on NLRP3 could be rescued by the NLRP3 antagonist CY-09 both in vitro and in vivo. These results indicate that IBC is a potential therapeutic drug against GBM and provide a new insight into GBM treatment.

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.

Protein tyrosine phosphatase non‐receptor type 21 (PTPN21) is a member of the non‐receptor tyrosine phosphatase family. We have found that PTPN21 is mutated in relapsed Philadelphia chromosome‐negative acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation. PTPN21 consists of three types of isoforms according to the length of the protein encoded. However, the roles of different isoforms in leukemic cells have not been elucidated. In the study, PTPN21 isoform constitution in five ALL cell lines were identified by transcriptome polymerase chain reaction combined with Sanger sequencing, and the relationship between PTPN21 isoforms and sensitivity to natural killer (NK) cells mediated killing in ALL cell lines were further assessed by knock‐out of different isoforms of PTPN21 using CRISPR‐Cas9 technique. Subsequently, we explored the functional mechanisms through RNA sequencing and confirmatory testing. The results showed that there was no significant change when all PTPN21 isoforms were knocked out in ALL cells, but the sensitivity of NALM6 cells with PTPN21‐CDS_long knock‐out (NALM6‐PTPN21_lk) to NK‐mediated killing was significantly increased. Whole transcriptome sequencing and further validation testing showed that human leukocyte antigen class I (HLA‐I) molecules were significantly decreased, accompanied by a significantly downregulated expression of antigen presenting‐related chaperones in NALM6‐PTPN21_lk cells. Our results uncovered a previously unknown mechanism that PTPN21‐CDS_long and CDS_short isoforms may play opposite roles in NK‐mediated killing in ALL cells, and showed that the endogenous PTPN21‐CDS_long isoform inhibited ALL cells to NK cell‐mediated lysis by regulating the KIR‐HLA‐I axis.