Current Medical Science最新文献

{"title":"Nintedanib Inhibits VEGF-Induced Neovascularization in Human Conjunctival Vascular Endothelial Cells.","authors":"Yi Cheng, Tang-Rui Huang, Yi-Ke Yan, Yu-Ting Liao, Hai-Xia Liu","doi":"10.1007/s11596-025-00114-3","DOIUrl":"https://doi.org/10.1007/s11596-025-00114-3","url":null,"abstract":"<p><strong>Objective: </strong>Conjunctival vascularization and fibroblasts are important factors leading to filtering bleb scarring after glaucoma filtering surgery. Previous studies have shown that nintedanib can inhibit the transformation of conjunctival fibroblasts into myofibroblasts, alleviating scar formation. This study aimed to investigate the effect of nintedanib on vascular endothelial growth factor (VEGF)-induced neovascularization of human conjunctival vascular endothelial cells and to reveal the molecular mechanisms involved.</p><p><strong>Methods: </strong>Primary human conjunctival vascular endothelial cells were cultured with VEGF alone or in combination with nintedanib, and cell proliferation and migration were measured via cell counting kit-8 and scratch assays, respectively. The effect of nintedanib on human conjunctival vascular endothelial cell tube formation was also assayed. The phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) were measured via Western blotting.</p><p><strong>Results: </strong>VEGF (120 ng/mL) significantly promoted the proliferation of human conjunctival vascular endothelial cells. Nintedanib inhibited the VEGF-induced proliferation of these cells while also suppressing cell migration (P < 0.0001) and vascularization (P < 0.01). Furthermore, nintedanib reduced ERK1/2 (P < 0.01) and JNK phosphorylation (P < 0.001).</p><p><strong>Conclusion: </strong>Our study provides new evidence that nintedanib inhibits the proliferation, migration, and neovascularization of human conjunctival vascular endothelial cells and downregulates the expression of p-ERK and p-JNK in the MAPK pathway.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mRNA Vaccines in Cancer Immunotherapy: Recent Advances, Clinical Translation, and Future Perspectives.","authors":"Silpa Suman Pati, Shrestha Dhal, Ritesh Pattnaik, Sugato Tripathy, Subrat Kumar","doi":"10.1007/s11596-025-00112-5","DOIUrl":"https://doi.org/10.1007/s11596-025-00112-5","url":null,"abstract":"<p><p>Cancer remains a leading global health burden. mRNA cancer vaccines, which are propelled by their rapid development, manufacturing flexibility, and proven efficacy against infectious diseases, have emerged as a transformative approach in cancer immunotherapy. While offering significant advantages over traditional methods, challenges related to mRNA instability and in vivo delivery efficiency persist. However, technological advancements, particularly in nanoparticle formulations such as lipid nanoparticles (LNPs), have substantially mitigated these concerns. This review comprehensively examines the mechanism of action of mRNA vaccines, focusing on their ability to encode tumor-specific antigens (TSAs), particularly neoantigens, and tumor-associated antigens (TAAs) to elicit potent anti-tumor immune responses. We critically analyzed the promising application of mRNA vaccines as monotherapies and, more significantly, in combination with immune checkpoint inhibitors, chemotherapy, adoptive cell therapies (e.g., CAR-T), and radiation to overcome the immunosuppressive tumor microenvironment. The core of this review synthesizes compelling results from key clinical trials across various cancers (e.g., melanoma, non-small cell lung cancer, and prostate cancer), highlighting significant outcomes such as induced neoantigen-specific T-cell responses, improved recurrence-free survival, and objective tumor regression. We also discuss the groundbreaking potential of personalized neoantigen mRNA vaccines. Current challenges, including tumor heterogeneity, optimal delivery strategies, biomarker identification, and enhancing therapeutic efficacy/safety profiles, are thoroughly evaluated alongside potential solutions. Finally, we explore future directions emphasizing next-generation approaches such as advanced nanovaccines and refined personalized platforms. This review aims to provide a timely and critical analysis of the rapidly evolving landscape of mRNA cancer vaccines, underscoring their immense potential to revolutionize cancer treatment paradigms.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remimazolam-Remifentanil versus Propofol-Remifentanil for Spontaneous Ventilation During Fiberoptic Bronchoscopy: A Randomized Controlled Trial.","authors":"Jing-Hao Huang, Hui-Jin Huang, Hong-Xin Gao, Liu-Rong Lin, Xin Ling, Qian Zhou, Xian-Zhong Lin","doi":"10.1007/s11596-025-00111-6","DOIUrl":"https://doi.org/10.1007/s11596-025-00111-6","url":null,"abstract":"<p><strong>Objective: </strong>Optimizing sedation to minimize respiratory depression during fiberoptic bronchoscopy (FOB) presents an ongoing challenge. This trial compared the safety and efficacy of remimazolam-remifentanil versus propofol-remifentanil for maintaining spontaneous ventilation in patients undergoing FOB.</p><p><strong>Methods: </strong>This pre-registered randomized controlled trial enrolled 103 consecutive candidates for FOB (April 2023 to April 2024). After excluding 10 ineligible participants, 93 were enrolled in a two-phase study. In the initial dose-determination phase, 21 participants underwent dose escalation to establish the induction dose of remimazolam (0.35 mg/kg) using the modified Dixon's method. Subsequently, 72 participants were randomly assigned in a 1:1 ratio to remimazolam-remifentanil group (Group R-R) or propofol-remifentanil group (Group P-R) (n = 36 each). Remifentanil was administered by target-controlled infusion (3.0 ng/mL plasma concentration) in both groups. Group R-R received remimazolam 0.35 mg/kg, while Group P-R received propofol 2.0 mg/kg after remifentanil loading. Standardized supplemental doses were administered for inadequate sedation (Modified Observer's Assessment of Alertness/Sedation score >1 or Bispectral index >75). The primary endpoint was the incidence of respiratory depression, defined as SpO₂ <95% or a respiratory rate <8 breaths/min. Secondary outcomes included procedure completion, movement or cough-related interruptions, hemodynamic stability, adverse events, procedural time, and satisfaction ratings from both bronchoscopists and participants.</p><p><strong>Results: </strong>Group R-R demonstrated a significantly lower incidence of respiratory depression (11.1% vs. 33.3%; P = 0.045) and of hypotension requiring vasopressors (16.7% vs. 41.7%; P = 0.020). However, transient involuntary movements (25.0% vs. 8.3%; P = 0.111) and cough (38.9% vs. 22.2%; P = 0.125) were numerically more frequent in Group R-R, though not statistically significant. All procedures were completed successfully without discontinuation. Hypertension, arrhythmias, procedural times, and satisfaction scores were comparable between groups (all P > 0.05).</p><p><strong>Conclusions: </strong>Compared to propofol-remifentanil, remimazolam-remifentanil provides effective moderate sedation for FOB with superior respiratory safety and reduced hypotension requiring vasopressors, despite a numerically higher incidence of transient movement and cough. It thus represents a promising alternative for maintaining spontaneous ventilation during FOB.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Prognostic Scoring Systems for Severe CRS after Anti-CD19 CAR-T-Cells in Acute B-Lymphoblastic Leukemia.","authors":"Sha Ke, Tai-Yuan Zhang, Zhuo-Lin Wu, Wei Xie, Lin Liu, Meng-Yi Du","doi":"10.1007/s11596-025-00109-0","DOIUrl":"https://doi.org/10.1007/s11596-025-00109-0","url":null,"abstract":"<p><strong>Objective: </strong>To develop a novel prognostic scoring system for severe cytokine release syndrome (CRS) in patients with B-cell acute lymphoblastic leukemia (B-ALL) treated with anti-CD19 chimeric antigen receptor (CAR)-T-cell therapy, aiming to optimize risk mitigation strategies and improve clinical management.</p><p><strong>Methods: </strong>This single-center retrospective cohort study included 125 B-ALL patients who received anti-CD19 CAR-T-cell therapy from January 2017 to October 2023. These cases were selected from a cohort of over 500 treated patients on the basis of the availability of comprehensive baseline data, documented CRS grading, and at least 3 months of follow-up. Data on patient demographics, treatment history, laboratory parameters, CAR-T-cell characteristics, safety, and efficacy endpoints were collected. CRS severity was graded according to the 2019 ASTCT consensus criteria. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with CRS severity, and a prognostic model was constructed.</p><p><strong>Results: </strong>The overall incidence of CRS was 67.2%, with 13.6% having grade ≥ 3 (severe) CRS. Higher baseline and post-lymphodepletion minimal residual disease (MRD) levels and neutropenia on day 7 post-infusion were significantly associated with severe CRS. Inflammatory markers (CRP, ferritin, and IL-6) and coagulation dysfunction (APTT) on day 7 post-infusion were also predictive of CRS severity. The prognostic model incorporating these factors demonstrated robust discriminatory ability, with an area under the ROC curve of 0.875.</p><p><strong>Conclusion: </strong>This study developed a novel prognostic scoring system for severe CRS in Chinese B-ALL patients receiving anti-CD19 CAR-T-cell therapy. The model integrates clinical and laboratory parameters to facilitate early identification and management of severe CRS. Further validation in larger, prospective cohorts is warranted.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Expression of ATP6V1D and Its Diagnostic Potential in IgA Nephropathy.","authors":"Liang Peng, Lin Hu, Yi-Qun Peng, Dong-Guang Wang","doi":"10.1007/s11596-025-00088-2","DOIUrl":"https://doi.org/10.1007/s11596-025-00088-2","url":null,"abstract":"<p><strong>Objective: </strong>IgA nephropathy (IgAN) is the most prevalent form of primary glomerular disease. However, its diagnosis is contingent on kidney biopsy. Therefore, noninvasive biomarkers are urgently needed for diagnosis. This study aims to identify novel urinary biomarkers that differentiate IgAN from other common primary glomerular diseases, specifically membranous nephropathy (MN) and minimal change disease (MCD).</p><p><strong>Methods: </strong>The peripheral blood mononuclear cell (PBMC) transcriptome dataset GSE73953 was obtained from the GEO database. Differential gene expression, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Gene Ontology (GO) enrichment, and immune infiltration analyses were performed. Protein-protein interaction (PPI) analysis and lysosome-related genes were used to identify hub genes. The expression of the hub gene ATP6V1D in urine and kidney tissues from individuals with IgAN, healthy controls, MCD and MN patients was assessed using enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunostaining techniques. Spearman's correlation analysis was employed to investigate the relationships between the concentration of ATP6V1D in urine, the concentration of galactose-deficient IgA1 (GD-IgA1), and the clinical data of patients. The receiver operating characteristic (ROC) curve was used to assess the role of urine ATP6V1D levels in distinguishing IgAN from MN and MCD.</p><p><strong>Results: </strong>ATPase was identified as the principal intracellular structure associated with differentially expressed genes (DEGs) between IgAN patients and healthy controls in PBMCs. ATP6V1D was identified as a hub gene at the intersection of lysosome-related and differential genes. ATP6V1D levels were lower in PBMCs, urine, and kidney samples from IgAN patients than in those from healthy individuals, MCD and MN patients. The decreased urinary ATP6V1D levels and increased GD-IgA1 levels in IgAN patients were further validated. These changes were positively correlated with 24-h urine protein levels. Notably, a negative correlation was observed between ATP6V1D and GD-IgA1 levels. ROC curve analysis demonstrated that urinary ATP6V1D (AUC = 0.972) and GD-IgA1 (AUC = 0.952) had significant discriminative power in distinguishing IgAN patients from MCD and MN patients, with no significant difference in predictive performance between the two biomarkers (P > 0.05).</p><p><strong>Conclusions: </strong>The findings underscore the potential utility of the urine ATP6V1D concentration as a biomarker to distinguish IgAN from MN and MCD.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Regulatory Mechanism of MicroRNA-144-3p on Damage to Endometrial Epithelial Cells Exposed to Copper Ions In Vitro.","authors":"Xiao-Rong Fan, Hou-Ze Zhu, Meng-Ying Lei, Peng-Jun Jiang, Hui Zhou, Wei Xia","doi":"10.1007/s11596-025-00110-7","DOIUrl":"https://doi.org/10.1007/s11596-025-00110-7","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the differential expression of microRNA-144-3p in endometrial cells exposed to copper ions in vitro. The specific mechanism by which microRNA-144-3p is involved in Cu²⁺-induced damage to the human endometrial epithelial cells (HEECs) was explored.</p><p><strong>Methods: </strong>HEECs were cultured in copper-containing culture medium to simulate changes in the endometrium after copper intrauterine device (Cu-IUD) implantation. Reverse transcription quantitative PCR (RT-qPCR) was used to detect the differential expression of miR-144-3p in HEECs after Cu²⁺ treatment. MiRNAs, siRNAs and related inhibitors were used to treat HEECs. The expression levels of related downstream genes were then analyzed by RT-qPCR, Western blotting and immunofluorescence to explore the specific mechanism involved.</p><p><strong>Results: </strong>MiR-144-3p was significantly upregulated in the Cu²⁺-treated HEECs. The expression of P-NF-κB, MMP9, TGF-β3 and P-SMAD3 was significantly decreased in HEECs treated with 10 μg/mL Cu²⁺. MiR-144-3p regulated the expression of metallothionein 1A (MT1A) and thrombospondin-1 (THBS-1) in Cu²⁺-treated HEECs. The expression of P-NF-κB can be regulated by MT1A, and an inhibitor of P-NF-κB can significantly reduce the expression of MMP9 in Cu²⁺-treated HEECs. The expression of TGF-β3 can be regulated by THBS-1, and a TGF-β3 inhibitor can significantly reduce the expression of SMAD3 in Cu²⁺-treated HEECs. The proliferative capacity of HEECs treated with MMP9 or SMAD3 inhibitors was significantly reduced.</p><p><strong>Conclusions: </strong>The increased Cu²⁺ concentration led to the upregulation of miR-144-3p, further reducing the expression levels of its target genes (MT1A and THBS-1), which in turn downregulated the expression of NF-κB, MMP9, TGF-β3 and SMAD3, ultimately leading to increased endometrial cell damage and decreased cell proliferation.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xiaoke Decoction Inhibits COX-2-Mediated LDLr Pathway Dysfunction and Protects Renal Function in Diabetic Nephropathy Rats.","authors":"Zhi-Qi Tang, Yuan-Xia Liu, Ling-Jia Tao, Jin-Ye Song, Tong-Rui Weng, Teng Fan","doi":"10.1007/s11596-025-00107-2","DOIUrl":"https://doi.org/10.1007/s11596-025-00107-2","url":null,"abstract":"<p><strong>Objective: </strong>Traditional Chinese medicine exhibits positive therapeutic effects as a primary or adjunctive treatment for diabetic nephropathy (DN). This study aimed to evaluate the impact and mechanism of action of Xiaoke decoction (XKD), a traditional Chinese medicine, on renal function in DN rats.</p><p><strong>Methods: </strong>A rat model of DN was established, and the rats were divided into five groups (n = 7 per group): normal control group (NC), DN model group (DN), low-dose XKD treatment group (DN + XKD-L, 1.5 g/kg/d), high-dose XKD treatment group (DN + XKD-H, 6 g/kg/d), and cyclooxygenase-2 (COX-2) inhibitor (NS398) treatment group (DN + NS398, 8 mg/kg/d). Medications were administered via gavage for 12 consecutive weeks, while equal volumes of normal saline were given to the NC and DN groups. A glucometer was used to detect changes in blood glucose (BG). Enzyme-linked immunosorbent assay (ELISA) and an automatic biochemical analyzer were employed to measure levels of insulin, serum creatinine (Scr), blood urea nitrogen (BUN), triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and 24-h urine protein quantity (UP/24 h) in rats. Renal tissue sections from different treatment groups were prepared, with tissue lesions examined via periodic acid-Schiff (PAS) and hematoxylin-eosin (HE) staining. Tissue inflammation and lipid deposition were evaluated using ELISA and Oil Red O staining. Immunohistochemistry and Western blotting were used to detect changes in the expression levels of COX-2 and low-density lipoprotein receptor (LDLr) in tissues, and to clarify the regulatory mechanism of XKD on renal function in DN rats.</p><p><strong>Results: </strong>XKD, particularly at the high dose (XKD-H, 6 g/kg/d), significantly reduced BG, insulin levels, renal weight ratio, Scr, BUN, and UP/24 h in DN rats. DN rats showed significant renal lesions, and XKD gavage (especially XKD-H) markedly improved these pathological changes. In DN rats, XKD significantly decreased the protein expression levels of COX-2 and LDLr, downregulated the levels of inflammatory factors and lipid factors, reduced lipid deposition in renal tissues, and ameliorated structural abnormalities in glomeruli, basement membranes, and renal tubules.</p><p><strong>Conclusions: </strong>XKD alleviates renal tissue damage by regulating the COX-2-mediated LDLr pathway, thereby reducing the release of inflammatory factors and lipid accumulation in DN rats and protecting renal function.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional Roles and Therapeutic Prospects of C1q/TNF-Related Protein 3 (CTRP3) in Human Diseases.","authors":"Qing-Peng Wang, Chen Wang, Yan-Hong Yuan, Yun Yang, Rui Tian, Jiang-Yang Chi, Xin-Zhong Chen","doi":"10.1007/s11596-025-00075-7","DOIUrl":"https://doi.org/10.1007/s11596-025-00075-7","url":null,"abstract":"<p><p>Adipokines, including C1q/tumor necrosis factor (TNF)-related proteins (CTRPs), adiponectin, TNF-α, and leptin, are crucial bioactive molecules that are secreted by adipose tissue and circulate in the bloodstream. To date, 15 members of the CTRP family, which are collectively classified as part of the C1q/TNF superfamily, have been identified. Among these, CTRP3 stands out as a unique adipokine because of its distinct structural and functional properties. Recent research has highlighted the significant role of CTRP3 in the pathogenesis of various diseases. This review aims to comprehensively summarize the involvement and mechanisms of CTRP3 in the development of numerous disorders, as well as its potential therapeutic implications.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Konjac Oligosaccharide Alleviates Constipation in Mice via 5-HT4R/cAMP/PKA/p-CREB Pathway Activation.","authors":"Guang-Jun Sun, Ming Li, Xiao-Yu Zhang, Jin-Shuang Liu, Ai-Zhen Lin, Qiong Cai","doi":"10.1007/s11596-025-00102-7","DOIUrl":"https://doi.org/10.1007/s11596-025-00102-7","url":null,"abstract":"<p><strong>Background: </strong>Konjac oligosaccharide (KOS), which is produced through the degradation of konjac glucomannan via enzymatic, chemical, or physical treatments, has been found to have laxative effects. The current study aimed to elucidate the mechanisms underlying the laxative effect of KOS.</p><p><strong>Methods: </strong>KOS was administered by gavage to wild-type and 5-hydroxytryptamine 4 receptor (5-HT4R)-knockout C57BL/6 mice subjected to loperamide-induced constipation for four weeks. Following treatment, feces, blood, small intestine, colonic tissue, and intestinal contents were collected. Constipation-related parameters, gastrointestinal hormones, and Ca²⁺ concentrations were evaluated. Histopathological changes were examined via hematoxylin and eosin staining. Immunofluorescence staining, Western blotting, and immunohistochemical staining were performed to detect the 5-HT4R/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway. Isolated smooth muscle cells (SMCs) were treated with KOS and GR113808 (a 5-HT4R antagonist), morphologically observed under an inverted microscope, and identified by α-SMA immunofluorescence staining. Cell viability was assessed via CCK-8 assays. 5-HT4R/cAMP/PKA/p-CREB pathway activity in SMCs was detected via Western blotting.</p><p><strong>Results: </strong>KOS alleviated loperamide-induced constipation in mice. KOS activated the 5-HT4R/cAMP/PKA/p-CREB pathway in loperamide-induced constipated mice. The protective effect of KOS was significantly diminished in 5-HT4R^-/- mice. KOS promoted the proliferation of SMCs by activating the 5-HT4R/cAMP/PKA/p-CREB signaling pathway.</p><p><strong>Conclusion: </strong>KOS improves loperamide-induced constipation by activating the 5-HT4R/cAMP/PKA/p-CREB signaling pathway.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD44v6 CAR-T Cells Target DNMT3A-Mutant AML: Synergistic Enhancement by Decitabine.","authors":"Hui-Min Li, Yi-Mei Que, Xiao-Ya Cai, Ping-Fan Lu, Li-Man Lin, Min Xiao, Li Zhu, Deng-Ju Li","doi":"10.1007/s11596-025-00097-1","DOIUrl":"https://doi.org/10.1007/s11596-025-00097-1","url":null,"abstract":"<p><strong>Objective: </strong>Acute myeloid leukemia (AML) is a highly heterogeneous disease, and molecular events such as DNMT3A gene mutations are associated with poor prognosis in AML patients. Consequently, there is an urgent need for a novel therapeutic approach for AML.</p><p><strong>Methods: </strong>DNMT3A mRNA and protein expression were confirmed in DNMT3A-mutant AML cells via RT-qPCR and Western blotting. Cell proliferation and apoptosis were assessed via CCK-8 and Annexin V/PI staining, respectively. Flow cytometry was used to analyze surface antigens and CD44v6 CAR-T-cell transfection efficiency. CD44v6-directed CAR plasmids were constructed, and lentiviruses were packaged. Methylation-specific PCR was used to evaluate differences in promoter methylation, whereas ELISA was used to measure cytokine secretion.</p><p><strong>Results: </strong>In this study, we found that the DNMT3A-mutant group presented significantly increased expression of CD44v6 on the cell surface. Methylation of the CD44 promoter region was lower in the mutant group than in the control group. CD44v6 CAR-T cells exhibited specific cytotoxicity against DNMT3A-mutant AML cells. Furthermore, pretreatment with low concentrations of decitabine significantly enhanced the killing effect of CD44v6 CAR-T cells on DNMT3A-mutant AML cells (P < 0.05). Additionally, decitabine treatment upregulated the expression of CD44v6 on the surface of DNMT3A-mutant AML cells (P < 0.05).</p><p><strong>Conclusion: </strong>CD44v6 is a promising CAR-T-cell therapy target in AML patients with DNMT3A mutations. Notably, treatment with decitabine resulted in increased CD44v6 expression on the cell surface of DNMT3A-mutant AML cells. This increase in CD44v6 expression facilitates improved recognition and targeting by CD44v6 CAR-T cells.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}