JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"β3-AR/β-arrestin2 Interaction Triggers Cardiac Fibrosis Through JNK/c-Jun Pathway in Cardiac Fibroblasts","authors":"Zhongcheng Xu,&nbsp;Min Zhu,&nbsp;Chun Zhou,&nbsp;Juncang Duan,&nbsp;Jian Ding,&nbsp;Jun Liu,&nbsp;Xuan Ying,&nbsp;Jie Wu,&nbsp;Yang Dong,&nbsp;Wenbiao Wang,&nbsp;Zhaohui Qiu","doi":"10.1111/jcmm.71305","DOIUrl":"10.1111/jcmm.71305","url":null,"abstract":"<p>Myocardial fibrosis (MF) is a critical pathological substrate of heart failure (HF), and β3-adrenergic receptor (β3-AR) has been implicated in cardiac remodelling with controversial roles. This study aimed to clarify the pro-fibrotic mechanism of β3-AR in cardiac fibroblasts and its association with β-arrestin2-mediated biased activation. Primary cardiac fibroblasts were isolated from neonatal C57BL/6 mice and subjected to β3-AR overexpression, agonist (BRL37344) stimulation, antagonist (SR59230A) inhibition, JNK inhibitor (SP600125) treatment, or β-arrestin2 knockdown via siRNA. RNA sequencing, immunofluorescence, Western blotting, and coimmunoprecipitation assays were performed to explore molecular mechanisms. RNA sequencing identified 577 upregulated and 231 downregulated genes in β3-AR-activated fibroblasts, enriched in extracellular matrix organisation and inflammatory pathways. Functional experiments confirmed that BRL37344 significantly upregulated fibrosis markers (α-SMA, FN, collagen I/III) and TGF-β1 expression, which was reversed by SP600125. Notably, inhibition of Gi signalling by pertussis toxin (PTX) failed to block β3-AR-induced fibrosis, while β-arrestin2 knockdown abrogated JNK/c-Jun/TGF-β1 pathway activation. Immunofluorescence and coimmunoprecipitation verified colocalisation and direct interaction between β3-AR and β-arrestin2, which was enhanced by BRL37344. Our findings demonstrate that β3-AR promotes cardiac fibrosis through β-arrestin2-mediated biased activation of the JNK/c-Jun/TGF-β1 pathway, independent of classical Gi signalling. This study reveals a novel cell-specific signalling mechanism of β3-AR and provides a potential therapeutic target for developing precision drugs against MF and HF.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 15","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669565","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":"HDAC2-Mediated SMAD7 Stabilisation Activates Wnt/β-Catenin Signalling to Drive DNA Damage Repair and Cisplatin Resistance in Ovarian Cancer","authors":"Yingying He,&nbsp;Meiling Wu,&nbsp;Xiaomin Xu,&nbsp;Kang Zheng,&nbsp;Kening Zhou","doi":"10.1111/jcmm.71300","DOIUrl":"10.1111/jcmm.71300","url":null,"abstract":"<p>To investigate the role of histone deacetylase 2 (HDAC2) in cisplatin resistance in ovarian cancer (OC). Cisplatin-resistant OC cell lines were employed to construct HDAC2 overexpression and knockdown models, and their effects on cell proliferation and apoptosis were examined. Chromatin immunoprecipitation, immunoprecipitation, and dual-luciferase reporter assays were performed to investigate the regulation of SMAD7 protein stability and promoter activity by HDAC2. Expression of DNA damage repair-related genes was detected by qRT-PCR. A xenograft mouse model was established for in vivo validation. HDAC2 was highly expressed in cisplatin-resistant OC cells. Overexpression of HDAC2 enhanced drug resistance and inhibited apoptosis and DNA damage, whereas knockdown of HDAC2 exhibited the opposite effects. Mechanistically, HDAC2 directly deacetylated the SMAD7 protein to prevent its degradation rather than suppressing its transcription via H3K27 deacetylation. The HDAC2/SMAD7 axis promoted drug resistance by activating the Wnt/β-catenin signalling pathway and modulating DNA damage repair-related genes. In vivo experiments confirmed that HDAC2 knockdown significantly inhibited tumour growth and enhanced the sensitivity. HDAC2 enhances cisplatin resistance in OC by deacetylating and stabilising SMAD7 protein, thereby activating the Wnt/β-catenin signalling pathway and promoting DNA damage repair.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 15","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669562","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":"Neurofilament Light Chain (Nfl) Level in Serum as a Suitable In Vivo Biomaker for Axonal Damage in a Murine Viral Model of Multiple Sclerosis","authors":"A. Segna,&nbsp;R. Wannemacher,&nbsp;K. Rohn,&nbsp;V. Sippel,&nbsp;M. A. Steiner,&nbsp;F. Lühder,&nbsp;A. Flügel,&nbsp;W. Baumgärtner,&nbsp;K. Hülskötter","doi":"10.1111/jcmm.71304","DOIUrl":"https://doi.org/10.1111/jcmm.71304","url":null,"abstract":"<p>Neurofilament light chain (Nfl) is a protein of the cytoskeleton predominantly found in large calibre myelinated axons and a suitable in vivo biomarker for monitoring neurodegenerative processes. Axonal damage results in Nfl release into the cerebrospinal fluid and the blood stream. Axonal damage is a frequent finding in Theiler's murine encephalomyelitis virus (TMEV)-infected SJL mice, a viral model for multiple sclerosis. Following the hypothesis that TMEV-associated axonal damage is reflected by serum Nfl (sNfl) levels, histopathological findings were compared with sNfl levels at 7, 14, 42 and 147/85 days post infection (dpi) in TMEV-susceptible SJL and -resistant C57BL/6 mice. Axonal damage was evaluated by immunohistochemistry for β-amyloid precursor protein (βAPP) and synaptophysin (syn). Both markers were significantly increased at 42 and 85 dpi in the spinal cord of SJL mice, whereas no axonopathy was observed in the spinal cord of C57BL/6 mice. Similarly, significantly increased sNfl values were only observed in SJL mice at 42 and 85 dpi but not in C57BL/6 mice. Results show a positive correlation between histochemically detected axonal damage and sNfl in TMEV-infected SJL mice. Thus, sNfl represents a potential marker for in vivo monitoring of axonal damage in this animal model.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 15","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71304","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617241","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":"Monocyte Single-Cell-Type Gene Expression Analysis Differentiates Kawasaki Disease From Viral Infection With High Specificity","authors":"Nelson L. S. Tang,&nbsp;Tsz-Ki Kwan,&nbsp;Assunta C. H. Ho,&nbsp;Hugh Simon Lam,&nbsp;Geoffrey Mok,&nbsp;Dan Huang,&nbsp;Suk-Ling Ma,&nbsp;Kwong-Sak Leung","doi":"10.1111/jcmm.71303","DOIUrl":"https://doi.org/10.1111/jcmm.71303","url":null,"abstract":"<p>Kawasaki disease (KD) and viral infection (VD) share similar clinical features but require distinct treatments. A practical biomarker to distinguish them is therefore clinically important. Previous blood transcriptome studies identified many differentially expressed genes, but large gene panels are impractical for routine laboratories. A ratio-based Direct Leukocyte Single-cell-type Transcript Abundance (DIRECT LS-TA) assay was recently developed to quantify monocyte gene expression directly in whole blood using a monocyte-specific target gene relative to monocyte reference genes (<i>PSAP</i> or <i>CTSS</i>). Interferon-stimulated genes <i>IFI27, IFI44L</i>, and <i>SIGLEC1</i> can be measured by this approach. In this study, three ratio biomarkers (<i>IFI27/PSAP, IFI44L/PSAP, SIGLEC1/PSAP</i>) and a conventional interferon (IFN) score derived from eight genes were calculated from public blood transcriptome datasets (GSE73461 and GSE68004) and compared between KD and VD. VD patients showed markedly elevated IFN-related biomarkers, with all three ratios significantly higher in VD and <i>IFI27/PSAP</i> giving the largest increase. <i>IFI27/PSAP</i> achieved the highest diagnostic performance (AUC 0.90), slightly exceeding the conventional IFN score (AUC 0.89). These findings suggest that absent or minimal IFN activation argues against VD and supports KD, and that this simple ratio assay could serve as a clinically useful exclusion test.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 15","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71303","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148616579","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":"Exosome-Mediated Delivery of PROTACs for Targeted Protein Degradation in Cancer, Neurodegenerative, Infectious, and Inflammatory Diseases","authors":"Sruti Bagchi Ghosh,&nbsp;Rumpa Banerjee,&nbsp;Hailah M. Almohaimeed,&nbsp;Amany I. Almars,&nbsp;Tahani Ahmad ALMatrafi,&nbsp;Fayez M. Saleh,&nbsp;Zuhair M. Mohammedsaleh,&nbsp;Kranti Kiran Reddy Ealla,&nbsp;Ajoy Kumer,&nbsp;Bikram Dhara","doi":"10.1111/jcmm.71297","DOIUrl":"https://doi.org/10.1111/jcmm.71297","url":null,"abstract":"<p>Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that hijack the ubiquitin-proteasome system to drive catalytic, sub-stoichiometric degradation of disease-associated proteins, offering a mechanistic advantage over occupancy-driven inhibitors and access to ‘undruggable’ targets. However, their clinical translation is constrained by high molecular weight, poor solubility, low oral bioavailability, inefficient membrane permeability, nonspecific biodistribution, off-target degradation, and the concentration-dependent ‘hook effect.’ Exosomes, nanoscale extracellular vesicles with innate biocompatibility, low immunogenicity, prolonged circulation, and the ability to cross barriers such as the blood–brain barrier, offer a biologically integrated platform to overcome these limitations. This review traces the evolution of PROTAC technology, delineates the challenges of conventional delivery, and evaluates the rationale for exosomal encapsulation, including cargo protection, intracellular trafficking, endosomal escape, and release kinetics. We examine natural and engineered exosomes spanning source selection, active loading strategies, and surface functionalization for tissue-specific homing and synthesize therapeutic applications across viral infections, cancer, neurodegenerative disorders, and inflammatory diseases. Proof-of-concept studies, such as camel milk-derived exosomes delivering the BRD4-targeting PROTAC ARV-825, demonstrate enhanced permeability, lower IC₅₀ values, and improved oral bioavailability. Finally, we discuss key hurdles to clinical translation: scalable production, purification, and standardization, and outline future directions for exosome-mediated targeted protein degradation.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 15","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71297","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617239","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":"Pretreatment With BTK Inhibitors Improved the Sensitivity of DLBCL Cells to CAR-T Cells in a Coculture System by Downregulating the Polarisation of M2 Macrophages","authors":"Yao Qi,&nbsp;Xuemei Fan,&nbsp;Jia Wang,&nbsp;Xin Li,&nbsp;Juan Mu,&nbsp;Rui Cui,&nbsp;Qi Deng","doi":"10.1111/jcmm.71296","DOIUrl":"https://doi.org/10.1111/jcmm.71296","url":null,"abstract":"<p>The tumour microenvironment (TME) of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) patients is associated with resistance of DLBCL cells to CD19 CAR-T cells. How to improve TME in DLBCL and improve the efficacy of CAR-T cell therapy remains to be further explored. We observed the sensitivity of HBL-1/U2932 cells pretreated with BTK inhibitors (BTKi) to CAR-T cells with flow cytometry (FCM). The effect of pretreatment of BTKi on the polarisation state of alternative activated M2 macrophages was observed with FCM, real-time PCR and Western blot method. The effect of Notch1 agonist on expressions of Arg-1 protein, iNOS protein, Notch1 protein and RBP-J protein in alternative activated M2 macrophages was observed by Western blot method. Then the expression consistency of Notch-1 and RBP-J in activated M2 macrophages was observed by siRNA transfection of Notch-1. The cytotoxicity of CD19 CAR-T cells on HBL-1/U2932 cells pretreated with ibrutinib/orelabrutinib was higher than that of HBL-1/U2932 cells unpretreated with ibrutinib/orelabrutinib. Cytotoxicity of CAR-T cells to HBL-1 cells in coculture system with alternative activated M2 macrophages was very low. This drug resistance could be reversed by replacing the M2 macrophages (M2 macrophages after 48 h pretreatment with BTKi) in coculture system. Pretreatment with BTKi could down-regulate the expression of CD206 and IL-10 in activated M2 macrophages. And pretreatment with BTKi down-regulated the expression of Arg-1 and upregulated the expression of iNOS in activated M2 macrophages. The upregulation polarisation of M2 macrophages by Notch1 agonist could be reversed by BTKi. Expression of RBP-J protein decreased in alternative activated M2 macrophages by siRNA silencing Notch 1. Pretreatment with BTKi could down-regulate the polarisation of M2 macrophages and reverse the resistance of DLBCL cells which were cocultured with alternative activated M2 macrophages to CAR-T cells. This effect might be achieved by downregulating the Notch-RBP-J pathway.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 15","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71296","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617240","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":"Mitochondrial Dysfunction at the Crossroads of Necroptosis: Mechanisms, Molecular Mediators, and Therapeutic Opportunities","authors":"Fengxin Wang,&nbsp;Haiying Rui,&nbsp;Dandan Qin,&nbsp;Huaxiang Yu,&nbsp;Dan Zou,&nbsp;Wenyi Zou,&nbsp;Yuting Li,&nbsp;Ran Li,&nbsp;Yuguo Chen,&nbsp;Li Xue","doi":"10.1111/jcmm.71252","DOIUrl":"10.1111/jcmm.71252","url":null,"abstract":"<p>The conceptual landscape of cell death has evolved beyond the traditional dichotomy of apoptosis and necrosis to encompass diverse regulated pathways including necroptosis, autophagy, ferroptosis, and pyroptosis. Necroptosis, a caspase-independent inflammatory form of programmed cell death, has emerged as a critical driver of the pathogenesis of cardiovascular disorders, neurodegenerative diseases, and cancer. Concurrently, our understanding of mitochondrial biology has undergone a paradigm shift: mitochondria are no longer viewed merely as bioenergetic powerhouses, but as dynamic signalling hubs that orchestrate metabolic reprogramming, cellular homeostasis, and ultimate cell fate decisions. In this regard, a growing body of evidence suggests that mitochondrial dysfunction is a central rheostat that enables necroptotic execution. This review delineates the mechanistic interplay between necroptosis and mitochondrial dysfunction and systematically analyzes the key molecular mediators and pathological pathways through which mitochondrial dysregulation drives necroptotic activation. Furthermore, this review identifies actionable therapeutic targets and translational strategies for modulating necroptosis in related diseases.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 14","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71252","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603377","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":"Correction to ‘Irisin Attenuates Ventilator-Induced Diaphragmatic Dysfunction by Inhibiting Endoplasmic Reticulum Stress Through Activation of AMPK’","authors":"","doi":"10.1111/jcmm.71260","DOIUrl":"10.1111/jcmm.71260","url":null,"abstract":"<p>\u0000 <span>Zhang, J.</span>, <span>Tu, R.</span>, <span>Guan, F.</span>, <span>Feng, J.</span>, <span>Jia, J.</span>, <span>Zhou, J.</span>, <span>Wang, X.</span>, and <span>Liu, L.</span>. “ <span>Irisin Attenuates Ventilator-Induced Diaphragmatic Dysfunction by Inhibiting Endoplasmic Reticulum Stress Through Activation of AMPK</span>,” <i>Journal of Cellular and Molecular Medicine</i> <span>28</span>, no. <span>9</span> (<span>2024</span>): e18259, https://doi.org/10.1111/jcmm.18259.\u0000 </p><p>In Ju Zhang et al. [<span>1</span>], the images of the Con group and the Irisin + MV12h group in Figure 6G overlapped due to a technical error during image preparation. The correct figure is shown below. The authors confirm all results and conclusions of this article remain unchanged.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 14","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71260","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603342","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":"Genetic Evaluation and Pregnancy Outcomes in Foetuses With Overgrowth at a Tertiary Referral Center","authors":"Xiaoqing Wu,&nbsp;Qingmei Shen,&nbsp;Xiaorui Xie,&nbsp;Yuqin Chen,&nbsp;Bin Liang,&nbsp;Meiying Wang,&nbsp;Danhua Guo,&nbsp;Na Lin,&nbsp;Liangpu Xu","doi":"10.1111/jcmm.71162","DOIUrl":"10.1111/jcmm.71162","url":null,"abstract":"<p>Fetal overgrowth is defined as one or more biometric parameters exceeding the 90th–97th percentile or 2 standard deviations above the mean for gestational age. This study aimed to evaluate genetic findings in foetuses diagnosed with sonographic overgrowth. We retrospectively analysed 78 singleton pregnancies that underwent invasive prenatal diagnosis between 2018 and 2024. Fetal overgrowth was defined based on biparietal diameter (BPD), head circumference (HC), and/or abdominal circumference (AC), and cases were categorized into three groups according to the pattern of enlargement: head enlargement (Group A, <i>n</i> = 49), abdominal enlargement (Group B, <i>n</i> = 12), and combined head and abdominal enlargement (Group C, <i>n</i> = 17). All foetuses underwent conventional karyotyping and single nucleotide polymorphism array analysis, and were further classified as isolated or non-isolated based on the presence of additional ultrasound findings. Chromosomal abnormalities were identified in 2 cases (2.6%) by karyotyping, including mosaic 47,XYY/45,X and 46,X,add(X)(p22)/45,X, while SNP array detected copy number variants involving chromosome 11 in 2 additional cases, one likely pathogenic and one variant of uncertain significance. Notably, all chromosomal abnormalities were observed in the non-isolated overgrowth group. Overall, 12 cases (15.4%) were classified as isolated and 66 (84.6%) as non-isolated. Associated ultrasound findings included structural anomalies in 18 cases, non-structural abnormalities in 12 cases, soft markers in 28 cases, and multiple coexisting abnormalities in 20 cases. Ventriculomegaly was the most common structural anomaly, particularly among foetuses with head enlargement, while polyhydramnios was the most frequent non-structural finding. Follow-up data were available for 76 cases, with 8 pregnancies resulting in stillbirth or termination and 68 in live births. Foetuses with combined head and abdominal enlargement had a significantly higher incidence of macrosomia compared with those with isolated head or abdominal enlargement (29.4% vs. 4.3% and 8.3%, respectively; <i>p</i> = 0.015). In conclusion, fetal overgrowth is predominantly non-isolated, and chromosomal abnormalities are mainly observed in this subgroup. Concurrent head and abdominal enlargement is associated with increased risks of structural anomalies and macrosomia. Prenatal genetic testing and macrosomia-specific management should be considered for head-abdominal enlargement foetuses.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 14","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13403038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591430","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":"Abelmoschus manihot Polysaccharides Target the AMPK/Nrf2/HO-1 Signalling Pathway to Inhibit Macrophage M1 Polarisation and Hepatic Stellate Cell Activation Improving Liver Fibrosis in Mice","authors":"Shixing Li,&nbsp;Zukuan Chang,&nbsp;Jinzhan Liu,&nbsp;Huilin Lu","doi":"10.1111/jcmm.71294","DOIUrl":"10.1111/jcmm.71294","url":null,"abstract":"<p>Liver fibrosis (LF) is a critical pathological stage in the progression from chronic liver disease to cirrhosis. While <i>Abelmoschus manihot</i> polysaccharides (AMP) demonstrate hepatoprotective potential, the underlying anti-fibrotic mechanisms remain incompletely understood. A carbon tetrachloride-induced LF mouse model was established followed by AMP intervention. Comprehensive assessments included ELISA measurement of serum biochemical indicators (ALT, AST, ALP, TBA, TBil), fibrosis markers (HA, PC III, LN, Hyp) and inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-10). Liver tissue pathological changes were evaluated through haematoxylin–eosin (HE), Masson and Sirius Red staining. In vitro experiments utilised TGF-β1-stimulated JS-1 and LPS/IFN-γ-induced M1-type RAW264.7 macrophages. Experimental techniques encompassed MTT assay, immunofluorescence, qPCR, Western blot and flow cytometry to analyse cellular markers and signalling pathways. The study specifically investigated AMP's regulatory effects on macrophage polarisation and hepatic stellate cell activation, using the AMPK inhibitor (Compound C) to explore potential mechanistic pathways. AMP treatment effectively mitigated CCl₄-induced liver injury by reducing serum markers (ALT, AST, HA, PC III, Hyp) and pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) while increasing anti-inflammatory IL-10. Mechanistically, AMP regulated macrophage polarisation (inhibiting M1 markers iNOS/CD80/CD86 while promoting M2 markers CD206/Arg-1) and suppressed fibrogenesis by downregulating α-SMA, Collagen I and TIMP1 while upregulating MMP13. These effects were mediated through activation of the AMPK/Nrf2/HO-1 pathway, ultimately inhibiting HSCs activation and extracellular matrix (ECM) accumulation. The AMPK inhibitor Compound C attenuates these protective effects. AMP alleviates LF by activating the AMPK/Nrf2/HO-1 pathway, modulating macrophage polarisation and ECM remodelling, demonstrating promising therapeutic potential.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 14","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591428","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}