JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Mechanism of Gu-Ben-Hua-Shi (AESS) Formula Regulating Autophagy Through Hippo-YAP Pathway in Restoring the Skin Barrier in Atopic Dermatitis","authors":"Xin Ma,&nbsp;Yiting Huang,&nbsp;Xiao Lv,&nbsp;Xiumei Mo,&nbsp;Junfeng Liu,&nbsp;Fenggen Yan,&nbsp;Siqi Ye,&nbsp;Yu Zhang,&nbsp;Dacan Chen,&nbsp;Jinjing Jia","doi":"10.1111/jcmm.71361","DOIUrl":"https://doi.org/10.1111/jcmm.71361","url":null,"abstract":"<p>Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunction and immune balance disorders. Currently, drugs for repairing the skin barrier in AD are limited. The gu-ben-hua-shi formula (AESS) has been shown to regulate Th1/Th2/Th17/Treg imbalance with good clinical effect. However, its effects on regulating autophagy, repairing the skin barrier, and interacting with Yes-associated protein (YAP) remain unknown. To elucidate the therapeutic effects of AESS on AD and to investigate its mechanism of restoring skin barrier function through the Hippo-YAP pathway. We conducted a single-arm observational study to evaluate the clinical efficacy of the AESS in patients with AD. Network pharmacology was used to predict the potential therapeutic targets and mechanisms. AD mouse models were established by house dust mite stimulation in Nishiki-nezumi Cinnamon/Nagoya mice, and the effects on autophagy and the skin barrier were measured using western blotting, immunofluorescence, mRFP-GFP-LC3 tandem fluorescence assay, and transmission electron microscopy. The effects of AESS serum on an AD-like inflammatory cell model were detected in HaCaT cells stimulated with interferon-γ (IFN-γ)/tumour necrosis factor-α (TNF-α). Activity of the Hippo-YAP signalling pathway was also investigated after YAP knockdown. AESS improved skin rash and barrier function, reduced eosinophil counts, and increased Th1/Th2 and Treg/Th17 ratios in patients with AD. AESS increased autophagy, improved skin barrier function, and inhibited Hippo-YAP signalling pathway activity. YAP knockdown reduces these therapeutic effects. Besides regulating immune imbalance, AESS increases keratinocyte autophagy levels, thereby restoring skin barrier function in AD through the Hippo-YAP signalling pathway.</p><p><b>Trial Registration:</b> The Chinese clinical trial registration website: ITMCTR202500042</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 17","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71361","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148943373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased NETosis in Patients With Heart Failure Is Associated With Macrophage Activation Towards a Proinflammatory Phenotype","authors":"Sawa Kostin,&nbsp;Hector A. Cabrera-Fuentes,&nbsp;Manfred Richter,&nbsp;Florian Krizanic,&nbsp;Oliver Ritter,&nbsp;William A. Boisvert,&nbsp;Klaus T. Preissner,&nbsp;Theodoros Kelesidis,&nbsp;Gerasimos Siasos,&nbsp;Nikolaos Pagonas","doi":"10.1111/jcmm.71306","DOIUrl":"https://doi.org/10.1111/jcmm.71306","url":null,"abstract":"<p>In this study, we tested the hypothesis that there is an interaction between neutrophils (N) undergoing NETosis and the activation of macrophages (Mf) in the myocardium of patients with heart failure (HF). Ventricular biopsies were examined from patients with HF due to dilated (DCM, <i>n</i> = 7), ischemic (ICM, <i>n</i> = 7), or inflammatory (InfCM, <i>n</i> = 7) cardiomyopathy, as well as from 5 control patients. Quantification of CD66b⁺/citrullinated histone 3⁺/myeloperoxidase⁺ neutrophils (N) revealed that 49.4% [IQR, 45–52] of N developed NETosis in InfCM, 45.3% [39–46] in ICM, 41.5% [37–45] in DCM, and 4% [3.8–4.2] in the control group. Quantification of the proportion of CD66b⁺/TNF-α⁺ Mf1 in infCM yielded a value of 78.5% [70–85], which differed significantly (<i>p</i> &lt; 0.05) from that in DCM (53.1% [48.4–54.4]) or ICM (54.5% [51–60]). The proportion of Mf1 in the control group was 3% [1.6–5.5] and differed significantly (<i>p</i> &lt; 0.01) from all HF groups. The proportion of CD66b⁺/CD206⁺ Mf2 was 20.9% [17.9–27.7] in DCM, 21.1% [17.8–22.8] in ICM, and 23.2% [21.2–25.1] in infCM. The proportion of Mf2 in the control group was 6.5% [4.8–7.6] and differed significantly (<i>p</i> &lt; 0.01) from all HF groups. Correlation analysis revealed a statistically significant positive correlation (<i>r</i> = +0.79, <i>p</i> &lt; 0.01) between Mf1 and the proportion of NETosis. In contrast, there was no significant correlation between Mf2 and the proportion of NETosis (<i>r</i> = −0.12, <i>p</i> = 0.28). It is concluded that the accumulation of N and Mf cells is a typical feature of chronic myocardial inflammation in HF, regardless of its aetiology. An increased number of N cells undergoing NETosis HF is associated with the activation of myocardial Mf cells and causes these cells to adopt a proinflammatory, Mf1-like phenotype.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 17","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71306","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148943155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Long-Read Multi-Omics of a Patient With GPI Deficiency: A Molecular Case Study of a Candidate Dual-Effect GPI Variant","authors":"Ireneusz Stolarek,&nbsp;Joanna Delimata-Raczek,&nbsp;Natalia Koralewska,&nbsp;Klaudia Sikora,&nbsp;Magdalena Rakoczy,&nbsp;Małgorzata Marcinkowska-Swojak,&nbsp;Luiza Handschuh,&nbsp;Jarosław Czyż,&nbsp;Marek Figlerowicz","doi":"10.1111/jcmm.71338","DOIUrl":"https://doi.org/10.1111/jcmm.71338","url":null,"abstract":"<p>The molecular determinants of phenotypic severity in red cell enzymopathies are often obscured by the disconnect between coding sequence variants and their regulatory landscapes. Here we present a single-patient molecular case study that uses an integrative multi-omic approach—combining short-read WGS, PacBio HiFi long-read sequencing, native CpG methylation profiling, and Iso-Seq full-length transcriptomics—to characterize a severe, transfusion-dependent hemolytic anaemia. We identified a compound heterozygous state in the glucose-6-phosphate isomerase (GPI) gene, with no wild-type allele present. One allele (Haplotype 1) carried a missense variant (p.His191Arg); the other (Haplotype 2) carried a distinct missense variant, c.1414C&gt;T (p.Arg472Cys), previously reported as biochemically unstable. Long-read phasing placed the two variants in trans. Allele-resolved transcript counts showed a directionally consistent but statistically non-significant trend toward higher expression of Haplotype 2 across two Iso-Seq replicates. Notably, the c.1414C&gt;T transition abolishes a local CpG dinucleotide; in a small number of haplotype-2 reads spanning this position, the corresponding cytosine on the wild-type/Haplotype-1 background was methylated. We did not measure GPI protein abundance, enzymatic activity, or stability in this patient, and we do not establish that methylation at this site regulates GPI transcription. On the basis of these correlative observations in a single patient, we propose—as a hypothesis for future testing—that a coding variant might simultaneously perturb protein stability and disrupt a local epigenetic mark, and we outline the experiments required to test whether such a dual effect contributes to disease. This case illustrates the value of integrative long-read multi-omics for generating mechanistic hypotheses about variants of uncertain significance, while underscoring that causal claims require dedicated functional validation.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 17","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71338","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148943003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SFRP2 Potentiates Metastasis of Colon Cancer by Enhancing Snai1 Protein Stability via USP11","authors":"Yanshen Kuang,&nbsp;Xin Liu,&nbsp;Mu Ke,&nbsp;Zhijie Chang,&nbsp;Baoqing Jia,&nbsp;Bing Li,&nbsp;Honggang Qian","doi":"10.1111/jcmm.71318","DOIUrl":"https://doi.org/10.1111/jcmm.71318","url":null,"abstract":"<p>Metastatic colon cancer remains a significant clinical challenge, often associated with poor patient prognosis. Recent studies have identified the secreted frizzled-related protein 2 (SFRP2) as a key player in this malignancy, showing its overexpression in metastatic cases. This research aimed to elucidate the molecular mechanisms by which SFRP2 influences colon cancer progression. We employed in vitro assays to assess the effects of SFRP2 on cell migration and invasion, revealing that SFRP2 significantly enhances these processes without affecting cell proliferation. Mechanistically, we found that SFRP2 interacts with Snai1, a transcription factor known to promote epithelial-mesenchymal transition (EMT), thereby stabilizing Snai1 protein levels. Furthermore, SFRP2 was shown to inhibit Snai1 ubiquitination through the deubiquitinase USP11, leading to increased Snai1 activity. Notably, Snai1 also positively regulates SFRP2 transcription, establishing a feedback loop that amplifies their expression. Our findings indicate that the SFRP2-Snai1 axis promotes colon cancer cell migration and invasion via the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway. In vivo experiments further confirmed that the SFRP2-Snai1 interaction significantly enhances metastatic potential. Collectively, these results suggest that targeting the SFRP2-Snai1 signalling pathway may provide a novel therapeutic strategy for metastatic colon cancer.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 17","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148943123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3 Promotes Lipid Deposition and Pulmonary Fibrosis by Destabilizing PLIN2 in a m6A-Dependent Manner","authors":"Qiping Liu,&nbsp;Rui Xu,&nbsp;Xianzhi Du","doi":"10.1111/jcmm.71239","DOIUrl":"10.1111/jcmm.71239","url":null,"abstract":"<p>Idiopathic pulmonary fibrosis (IPF) is a lethal lung disorder that is associated with aberrant lipid metabolism. N6-methyladenosine (m6A) methylation is involved in IPF progression. However, whether METTL3, a m6A methyltransferase, modulates lipid metabolism in IPF remains unknown. In this study, we aimed to investigate the effects of METTL3 on fibrosis and lipid accumulation and identify the molecular mechanism. PF mouse model was generated by bleomycin. WI-38 cells were stimulated with TGF-β1 to mimic the IPF-caused damage. Lipids were observed using Nile Red staining and marker detection. Fibrosis was evaluated using Masson's Trichrome staining and marker detection. The molecular mechanism was analysed by methylated RNA immunoprecipitation and dual-luciferase reporter assay. We found that METTL3 is highly expressed in IPF mice and TGF-β1-induced WI-38 cells. Knockdown of METTL3 inhibited lipid accumulation and fibrosis In Vitro and In Vivo. Additionally, interference with METTL3 suppressed the m6A methylation of PLIN2, enhanced its stability, and increased its expression. Knockdown of PLIN2 reversed the inhibition of lipid accumulation and fibrosis caused by METTL3 silence. In conclusion, interfering with METTL3 attenuates IPF progression by suppressing lipid deposition, which is associated with the increased stability of PLIN2 suggesting a promising therapeutic target for IPF.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 17","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71239","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: Up-regulation of KISS1 as a Novel Target of Let-7i in Melanoma Serves as a Potential Suppressor of Migration and Proliferation In Vitro","authors":"","doi":"10.1111/jcmm.71364","DOIUrl":"10.1111/jcmm.71364","url":null,"abstract":"<p><b>RETRACTION:</b> H. A. Alkafaji, A. Raji, H. S. Rahman, A. O. Zekiy, A. Adili, M. Jalili, T. Hojjatipour, A. Cid-Arregui, N. Shomali, S. Tarzi, R. Tamjidifar, R. Heshmati, F. Marofi, M. Akbari, A. Hasanzadeh, M. Deljavanghodrati, M. Jarahian, S. S. Shotorbani, “Up-regulation of KISS1 as a Novel Target of Let-7i in Melanoma Serves as a Potential Suppressor of Migration and Proliferation In Vitro”, <i>Journal of Cellular and Molecular Medicine</i> 25, no. 14 (2021): 6864-6873, https://doi.org/10.1111/jcmm.16695.</p><p>The above article, published online on 6th June 2021 on Wiley Online Library (https://onlinelibrary.wiley.com), has been retracted by agreement between the authors, Editor-in-Chief Stefan N. Constantinescu, the Foundation for Cellular and Molecular Medicine, and John Wiley and Sons Ltd. The article has been retracted because essential information about experimental methods is missing and therefore the Editors do not consider the results to be reproducible.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 17","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Furong Tongmai Capsule Ameliorates Atherosclerosis in ApoE−/− Mice by Modulating Gut Microbiota, Arachidonic Acid Metabolism and Macrophage Polarization","authors":"Shuquan Lv,&nbsp;Hanzhou Li,&nbsp;Yuming Wang,&nbsp;Xiuxiu Sang,&nbsp;Feng Wang,&nbsp;Jing Yang,&nbsp;Lirong Fan,&nbsp;Ziang Ma,&nbsp;Lixin Wang,&nbsp;Yuhong Bian,&nbsp;Huantian Cui","doi":"10.1111/jcmm.71354","DOIUrl":"10.1111/jcmm.71354","url":null,"abstract":"<p>Furong Tongmai capsule (FRTM) is a traditional Chinese medicine formula with reported lipid-lowering and anti-inflammatory activities, but its mechanisms in atherosclerosis (AS) remain unclear. In ApoE^−/− mice fed a high-fat diet, FRTM administration improved serum lipid profiles by reducing total cholesterol, triglycerides and low-density lipoprotein cholesterol and increasing high-density lipoprotein cholesterol. FRTM also attenuated aortic lesion formation, reduced pro-inflammatory cytokines (IL-6, IL-1β and TNF-α), and improved oxidative stress indices. 16S rRNA sequencing showed that FRTM reshaped the gut microbiota, increasing beneficial taxa such as Lactobacillus and Bifidobacterium while decreasing Turicibacter. Functional prediction and untargeted serum metabolomics both suggested that arachidonic acid metabolism was a key pathway affected by FRTM. Furthermore, FRTM was associated with increased p-PPARγ and EP4 expression, decreased p-P65, and increased p-STAT3/STAT3, accompanied by downregulation of M1 markers (iNOS/Nos2) and upregulation of M2 markers (CD206 and ARG1). Faecal microbiota transplantation from FRTM-treated donors partially recapitulated the anti-atherosclerotic and anti-inflammatory effects. Overall, these findings suggest that FRTM may ameliorate AS in a murine model by modulating gut microbiota, arachidonic acid metabolism and macrophage polarization; however, further functional studies are needed to establish causality and assess translational relevance.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 17","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-Derived iPSC-MSC Modelling Reveals Reversible GSK3-Mediated Suppression of Mesenchymal Lineage Differentiation in Legg-Calvé-Perthes Disease","authors":"Binna Seol,&nbsp;Hyung Jin Lim,&nbsp;Cho Lok Song,&nbsp;Jungwoon Lee,&nbsp;Yee Sook Cho","doi":"10.1111/jcmm.71350","DOIUrl":"10.1111/jcmm.71350","url":null,"abstract":"<p>Legg-Calvé-Perthes disease (LCPD) is an idiopathic paediatric osteonecrosis characterized by avascular injury to the femoral head, resulting in structural collapse and early osteoarthritis. Although mesenchymal stem cell (MSC) dysfunction has been implicated, the underlying mechanisms remain unclear due to the absence of human disease models. Here, we generated patient-specific induced pluripotent stem cells (iPSCs) from dermal fibroblasts of LCPD patients and differentiated them into mesenchymal stem cells (iMSCs) to establish an in vitro platform for mechanistic interrogation. LCPD-iMSCs exhibited hallmark disease-associated phenotypes, including concurrent suppression of osteogenic, adipogenic and chondrogenic differentiation, accompanied by enhanced phosphorylation of GSK3α/β, reduced β-catenin abundance and attenuated canonical Wnt signalling. Transcriptomic analyses revealed alterations in extracellular matrix organization, adhesion pathways and PI3K-Akt/MAPK signalling, consistent with a cellular environment predisposed to impaired mesenchymal function. Pharmacological inhibition of GSK3 using lithium chloride restored β-catenin levels, improved osteogenic and adipogenic marker expression, and enhanced matrix deposition, demonstrating functional reversibility of the LCPD phenotype. These findings identify GSK3-mediated β-catenin destabilization as a central regulator of MSC lineage impairment in LCPD and establish a patient-derived iPSC-MSC model as a valuable platform for mechanistic and therapeutic exploration in paediatric osteonecrosis.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 17","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Therapeutic Potential of Purmorphamine Across Disease Models","authors":"Ashis Dhar,&nbsp;Ahnaf Dil Sharar,&nbsp;Saikarthik Papisetty,&nbsp;Mohammad Bydon,&nbsp;F. M. Moinuddin","doi":"10.1111/jcmm.71349","DOIUrl":"10.1111/jcmm.71349","url":null,"abstract":"<p>Purmorphamine (PUR) is a trisubstituted purine compound that selectively activates Smoothened receptor, thereby initiating Sonic Hedgehog (Shh) signalling—a pathway critical for embryonic patterning, neuronal specification and tissue regeneration across multiple organ systems. Dysregulation of Shh signalling has been implicated in degenerative diseases yet therapeutic interventions targeting this pathway remain limited. PUR demonstrates broad therapeutic efficacy across diverse preclinical disease models by activating both canonical GLI-mediated transcription and non-canonical Shh pathways, resulting in neuroprotection, reduced neuroinflammation, enhanced blood–brain barrier integrity and tissue regeneration. In contrast to previous assumptions that Shh pathway activation requires endogenous ligand binding, PUR bypasses this requirement through direct Smoothened engagement, offering a pharmacologically tractable approach to pathway modulation. Preclinical studies demonstrate that PUR enhances motor neuron survival in amyotrophic lateral sclerosis models, protects dopaminergic neurons in Parkinson's disease, reverses behavioural abnormalities in autism spectrum disorder, promotes neurovascular repair following stroke, restores myelin integrity in multiple sclerosis models and drives osteogenic differentiation in bone tissue engineering applications. Beyond its established Smoothened agonist activity, recent evidence identifies PUR as a positive allosteric modulator of the secretin receptor, expanding its therapeutic scope to include cardiovascular applications such as hypertension management through enhanced nitric oxide bioavailability.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 17","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Sulfonamide Intermediate Elicits Therapeutic Effect Against Sepsis by Enhancing Neutrophil Maturation","authors":"Ji Ye Park,&nbsp;Yu Sun Jeong,&nbsp;Myeongsu Shin,&nbsp;Jiwoo Choi,&nbsp;Jiwon Shin,&nbsp;Leezhi Kwon,&nbsp;Kanghyun Lyu,&nbsp;Hwangi Jo,&nbsp;Youngjoo Byun,&nbsp;JaeHyung Koo,&nbsp;Yoe-Sik Bae","doi":"10.1111/jcmm.71346","DOIUrl":"10.1111/jcmm.71346","url":null,"abstract":"<p>Sepsis, a life-threatening condition characterized by systemic inflammation and immune dysregulation, remains a major cause of mortality worldwide. Here, we identify a synthetic sulfonamide intermediate, 1-[5-(2-fluorophenyl)furan-2-yl]-N-(4-methylbenzyl)methanamine (FMM), as a host-directed therapeutic candidate that enhances neutrophil maturation and antimicrobial function via autophagy. In a <i>Pseudomonas aeruginosa</i>-induced sepsis model, FMM administration markedly improved survival and attenuated inflammatory cytokine levels while reducing tissue injury and immune cell apoptosis. Furthermore, FMM promoted bone marrow neutrophil maturation, increased reactive oxygen species generation, and enhanced neutrophil extracellular trap formation. FMM also activated GPCR-mediated G_βγ–PLC signalling, which triggered intracellular calcium and ERK/p38 phosphorylation. Notably, FMM lacked direct bactericidal activity, suggesting its therapeutic effects are mediated by host immune modulation rather than pathogen targeting. Collectively, these findings demonstrate that FMM exerts potent pharmacological effects on neutrophil function and represents a promising lead compound for developing host-directed immunomodulatory therapies for sepsis.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 17","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}