JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"DDR1 Targeting HOXA6 Facilitates Bladder Cancer Progression via Inhibiting Ferroptosis","authors":"Xin Xie,&nbsp;Hongchao He,&nbsp;Ning Zhang,&nbsp;Xiaojing Wang,&nbsp;Wenbin Rui,&nbsp;Danfeng Xu,&nbsp;Yu Zhu,&nbsp;Ming Tian,&nbsp;Wei He","doi":"10.1111/jcmm.70410","DOIUrl":"https://doi.org/10.1111/jcmm.70410","url":null,"abstract":"<p>Ferroptosis is an important factor affecting the progression of bladder cancer (BC). Previous studies have confirmed that discoidin domain receptor 1 (DDR1) promotes BC progression. However, the regulatory mechanisms of BC ferroptosis are largely unknown. Therefore, this study aimed to investigate the regulatory effects of DDR1 on BC cell ferroptosis. Ferroptosis-sensitive and -resistant BC cells were screened, and reverse-transcription quantitative PCR and western blotting were used to determine the expression of DDR1 in BC cells. In vitro and in vivo assays were performed to analyse the mechanisms of DDR1 in BC ferroptosis. The ferroptosis inducer erastin inhibited DDR1 expression in TCCSUP cells. The ferroptosis inhibitor ferrostatin-1 inhibited BC cell death caused by DDR1 knockdown. DDR1 increased glutathione, glutathione peroxidase 4 and solute carrier family 7 member 11 expression, while decreasing malondialdehyde and Fe²⁺ levels and acyl-CoA synthetase long-chain family member 4 levels and inhibiting epithelial mesenchymal transition and neurofibromin 2-yes-associated protein. These effects were abrogated by the knockdown of homeobox A6 (HOXA6). DDR1 targeting of HOXA6 facilitated BC growth and inhibited BC ferroptosis in vivo. DDR1 promotes BC progression by inhibiting ferroptosis and targeting HOXA6. Thus, DDR1 may serve as a potential therapeutic target for BC.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70410","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646234","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":"Disease-Associated Risk Variants and Expression Levels of the lncRNA, CDKN2B-AS1, Are Associated With the Progression of HCC","authors":"Kuan-Chun Hsueh,&nbsp;Hsiang-Lin Lee,&nbsp;Kuo-Hao Ho,&nbsp;Lun-Ching Chang,&nbsp;Shun-Fa Yang,&nbsp;Ming-Hsien Chien","doi":"10.1111/jcmm.70496","DOIUrl":"https://doi.org/10.1111/jcmm.70496","url":null,"abstract":"<p>The most susceptible loci of hepatocellular carcinoma (HCC) identified by genome-wide association studies are located in non-coding regions. The antisense non-coding RNA at the INK4 locus (ANRIL), also known as cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1), is a long non-coding (lnc)RNA situated within and antisense to genes encoding CDKN2A/B on chromosome 9p21.3. Single-nucleotide polymorphisms (SNPs) within CDKN2B-AS1 are associated with several cancer types, but their impacts on HCC remain unclear. In this study, we investigated the effects of CDKN2B-AS1 SNPs on both the susceptibility to HCC and its clinicopathological development. Five CDKN2B-AS1 SNP loci—rs564398 (T/C), rs1333048 (A/C), rs1537373 (G/T), rs2151280 (A/G) and rs8181047 (G/A)—were analysed using a TaqMan allelic discrimination assay for genotyping in a cohort of 810 HCC patients and 1190 healthy controls. Under the dominant model, HCC patients with at least one minor C-allele of rs564398 showed a lower risk of liver cirrhosis (odds ratio (OR) = 0.677). Additionally, HCC patients with the GT + TT genotype of rs1537373 had a reduced risk of developing large tumours (T3 + T4) and advanced clinical stages (III/IV), particularly in the male population (OR = 0.644 and 0.679). Furthermore, data from The Cancer Genome Atlas revealed that CDKN2B-AS1 expression levels were elevated in HCC tissues compared to normal tissues and were correlated with advanced T stages, high histological grades and poor prognoses. Our findings suggest that CDKN2B-AS1 levels and its polymorphic variants at rs564398 and rs1537373 may influence the clinicopathological development and progression of HCC in a Taiwanese population.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70496","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646254","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":"Comparative Analysis of Diagnostic Techniques for Helicobacter pylori Infection: Insights for Effective Therapy","authors":"Ahmed Mujtaba,&nbsp;Muhammad Suhail Ibrahim,&nbsp;Sana Parveen,&nbsp;Noreen Sarwar,&nbsp;Suliman A. Alsagaby,&nbsp;Muhammad Ahsan Raza,&nbsp;Mohamed A. Abdelgawad,&nbsp;Mohammed M. Ghoneim,&nbsp;Ahmed H. El-Ghorab,&nbsp;Samy Selim,&nbsp;Waleed Al Abdulmonem,&nbsp;Muzzamal Hussain,&nbsp;Tadesse Fenta Yehuala","doi":"10.1111/jcmm.70487","DOIUrl":"https://doi.org/10.1111/jcmm.70487","url":null,"abstract":"<p>Effective therapy against <i>Helicobacter pylori</i> hinges on a timely and accurate diagnosis. The objective is to assess <i>H. pylori</i> infection in dyspeptic patients and compare various indicative tests. After approval, gastrointestinal biopsies and blood samples of 96 subjects exhibiting gastroduodenal symptoms were collected; both invasive and non-invasive tests were employed to analyse the samples. Results revealed 40 cases (41.67%) positive for <i>H. pylori</i> via histopathology and rapid urease testing, while 46 subjects tested positive for IgA and IgG antibodies via ELISA. Eighteen biopsies showed positivity in the culture test, corroborated by endoscopic examination and biochemical assessments (urease, catalase and oxidase). The isolates showed various degrees of resistance to antibiotics, while polymyxin B showed the highest (100%) followed by amoxicillin (88.90%) and kanamycin (77.78%). Additionally, the <i>CagA</i> gene presence was detected in 18 individuals through molecular methods. Sensitivity and specificity percentages (%) varied among diagnostic methods: histopathology (95/77), rapid urease (100/83.5), gram staining (85.7/90), IgG serology (100/66.6), IgA serology (100/79.5), PCR (100/75), RUT and IgG serology combination (100/79.04), and RUT, Gram staining and IgG serology combination (100/92.4), respectively. PCR emerged as the most reliable test. In the current investigation, other tests also exhibited high sensitivity and specificity values. Thus, employing comparative detection methods rather than relying solely on one methodology is advisable for accurate detection.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70487","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646255","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":"Kindlin-3 Promotes Angiogenesis via Notch Signalling and Is Crucial for Functional Recovery Postmyocardial Infarction","authors":"Yan Sun,&nbsp;Wei Zheng,&nbsp;Xianling Liu,&nbsp;Kai Wang,&nbsp;Di Xu","doi":"10.1111/jcmm.70494","DOIUrl":"https://doi.org/10.1111/jcmm.70494","url":null,"abstract":"<p>Angiogenesis is crucial for minimising ischemic injury postmyocardial infarction (MI), making it a significant target for cardioprotective therapies. While Kindlin-3 has been linked to angiogenesis in breast cancer, its specific function in the context of MI remains largely unexplored. Although Kindlin-3 has been implicated in breast cancer-related angiogenesis, its role in MI remains underexplored. This study investigates the role of Kindlin-3 in promoting angiogenesis, a process critical for cardiac recovery following MI. The study demonstrated a significant upregulation of Kindlin-3 in cardiac microvascular endothelial cells (CMECs) in mice post-MI. Overexpression of Kindlin-3, achieved through cardiotropic adeno-associated virus serotype 9 (AAV9) with the endothelial-specific promoter Tie2, enhanced myocardial angiogenesis, improved cardiac function, decreased cardiomyocyte apoptosis and reduced fibrosis. In vitro, Kindlin-3 overexpression promoted CMECs proliferation, migration, tube formation and the expression of angiogenesis-related genes. Conversely, Kindlin-3 knockdown exerted opposite effects. Mechanistically, Kindlin-3 activated the Notch signalling pathway, as its effects were abrogated by the Notch inhibitor DAPT and β1 integrin knockdown. This study identifies Kindlin-3 as a novel enhancer of angiogenesis and suggests its potential as a therapeutic target for myocardial repair.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70494","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638717","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":"Identification of the Hub Gene LDB3 in Stanford Type A Aortic Dissection Based on Comprehensive Bioinformatics Analysis","authors":"Xinyi Liu,&nbsp;Xing Liu,&nbsp;Bin Wan,&nbsp;Yipeng Ge,&nbsp;Haiou Hu,&nbsp;Hong Yu,&nbsp;Meng Zhao,&nbsp;Huadong Li,&nbsp;Junming Zhu","doi":"10.1111/jcmm.70471","DOIUrl":"https://doi.org/10.1111/jcmm.70471","url":null,"abstract":"<p>Stanford type A aortic dissection (TAAD) is a life-threatening disease. This study explored the role of LIM domain binding 3 (LDB3) in TAAD progression. Four datasets from the Gene Expression Omnibus were analyzed to identify TAAD-related hub genes. LDB3 single nucleotide polymorphisms (SNPs) were assessed in the UK Biobank. Western blotting and immunofluorescence detected LDB3 expression in angiotensin II (Ang II) stimulated human aortic vascular smooth muscle cells (HA-VSMC), human samples, and a murine model. Bioinformatics identified tissue inhibitor of metalloproteinase-1 (TIMP1) and LDB3 as TAAD hub genes. TIMP1 was expressed in macrophages, mesenchymal cells, and smooth muscle cells, while LDB3 was mostly expressed in smooth muscle cells. Validation showed TIMP1 was upregulated and LDB3 downregulated in TAAD. Six LDB3 SNPs were associated with aortic aneurysm and dissection in the UK Biobank. In human and murine samples, LDB3 expression was reduced in diseased tissues and co-localized with smooth muscle. Ang II-stimulated HA-VSMC exhibited LDB3 reduction and altered intercellular connections. The aforementioned findings suggest that the newly identified gene LDB3 is crucial in the progression of TAAD.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70471","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638778","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":"Elucidation of Dexmedetomidine-Induced Analgesic Tolerance Mechanisms in Neuropathic Pain With Modulation of SGK1, NR2A, and NR2B Expression via the Spinal SGK1/NF-κB Signalling Pathway","authors":"Wang Huikang,&nbsp;Cao Shiya,&nbsp;Pan Di,&nbsp;Faisal Ayub Kiani,&nbsp;Li Hao,&nbsp;Nan Sha,&nbsp;Lin Xuan,&nbsp;Mahmoud M. Abouelfetouh,&nbsp;Zulfiqar Ahmed,&nbsp;Ding Mingxing,&nbsp;Ding Yi","doi":"10.1111/jcmm.70372","DOIUrl":"https://doi.org/10.1111/jcmm.70372","url":null,"abstract":"<p>Neuropathic pain (NP), resulting from nerve damage, is difficult to manage and often requires long-term treatment. However, prolonged use of pain medications can lead to addiction and reduced effectiveness over time. Understanding drug tolerance is essential for developing improved pain management strategies. Dexmedetomidine (DEX) is effective in targeting the <i>α2</i>-adrenergic receptor, providing relief from pain, especially NP. However, its extended use leads to tolerance and hinders its clinical utility. Herein, we investigated tolerance mechanisms and potential applications of this drug in managing NP. Adult C57BL/6 mice (male) were distributed into DEX Dosage Groups (<i>n</i> = 48), DEX Tolerance Model Groups (<i>n</i> = 32), <i>SGK1</i> Inhibitor GSK650394 Groups (<i>n</i> = 48), and <i>NF</i>-<i>κB</i> Inhibitor PDTC Groups (<i>n</i> = 32) to explore dexmedetomidine's effects on NP and tolerance mechanisms. NP was established via selective ligation of the sciatic nerve branch (SNI), followed by administration of DEX. The results revealed a dose-dependent analgesic effect of DEX, with significant increases in pain thresholds observed compared to the sham group (<i>p</i> &lt; 0.05). Optimal efficacy was found at a dose of 30 μg/kg, indicating its potential as an effective treatment for NP (<i>p</i> &lt; 0.05). However, continuous administration of DEX over 13 days induced analgesic tolerance, evidenced by an initial increase in pain thresholds followed by a gradual decrease (<i>p</i> &lt; 0.05). Despite an initial efficacy in elevating pain thresholds, the analgesic effect of DEX diminished over time, returning to pre-dose levels after 5 days (<i>p</i> &lt; 0.05). Transcriptome sequencing of spinal cord samples from mice receiving multiple DEX injections revealed differential gene expression patterns, notably upregulation of <i>SGK1</i>, <i>NR2A</i>, and <i>NR2B</i> subunits (<i>p</i> &lt; 0.05). Inhibiting <i>SGK1</i> mitigated DEX-induced tolerance, suggesting its involvement in tolerance development (<i>p</i> &lt; 0.05). Moreover, <i>NF</i>-<i>κB</i> inhibition reversed DEX-induced tolerance and implicated the <i>SGK1</i>-<i>NF</i>-<i>κB</i> pathway in the mediation of analgesic tolerance. To sum up, these findings revealed the molecular mechanism underlying DEX-induced analgesic tolerance in the NP model and offer potential avenues for future therapeutic interventions.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638722","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":"HOGA1 Suppresses Renal Cell Carcinoma Growth via Inhibiting the Wnt/β-Catenin Signalling Pathway","authors":"Congmin Wang,&nbsp;Yu Liu,&nbsp;Ying Tan,&nbsp;Fuyi Xu,&nbsp;Mingyao Wang,&nbsp;Yiming Tang,&nbsp;Guofeng Nie,&nbsp;Xiaodong Chi,&nbsp;Zhaowei Xu,&nbsp;Yuxue Xu,&nbsp;Baijiao An,&nbsp;Geng Tian,&nbsp;Donglai Qi,&nbsp;Cuifang Yao","doi":"10.1111/jcmm.70490","DOIUrl":"https://doi.org/10.1111/jcmm.70490","url":null,"abstract":"<p>Changes in hydroxyproline metabolism are reported to promote tumorigenesis. HOGA1 is a useful marker for diagnosing primary hyperoxaluria 3, catalysing the final step of mitochondrial hydroxyproline metabolism from 4-hydroxy-2-oxoglutarate (HOG) to glyoxylate and pyruvate; however, its specific mechanism in RCC remains unclear. This study investigated the role of HOGA1 in the pathogenesis of ccRCC. The results showed that HOGA1 was decreased significantly in tumour tissues, with this low expression associated with a poor prognosis in patients with ccRCC. QTL mapping showed that <i>Hoga1</i> was <i>cis</i>-regulated. Gene enrichment analyses showed that <i>Hoga1</i> co-expressed genes were enriched in the Wnt/β-catenin signalling pathway. Furthermore, in vitro and in vivo assays demonstrated that HOGA1 significantly inhibited the proliferation, invasion and migration of renal carcinoma cells via the Wnt/β-catenin–c-Myc/CyclinD1 axis, probably via regulating the level of HOG. In conclusion, this study demonstrates that HOGA1 has a tumour suppressor role by inhibiting the Wnt/β-catenin signalling pathway. This finding provides new insights into the function of HOGA1 in ccRCC.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70490","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638723","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":"Targeting PKC as a Therapeutic Strategy to Overcome Chemoresistance in TNBC by Restoring Aurora Kinase B Expression","authors":"Bing Cheng,&nbsp;Jinxin Chen,&nbsp;Vera Katalina,&nbsp;Guojie Long,&nbsp;Chaoying Wei,&nbsp;Zhitong Niu,&nbsp;Chen Chen,&nbsp;Panpan Wang,&nbsp;Qiang Yu,&nbsp;Wenyu Wang","doi":"10.1111/jcmm.70464","DOIUrl":"https://doi.org/10.1111/jcmm.70464","url":null,"abstract":"<p>Triple-negative breast cancer (TNBC) poses a significant challenge due to its high mortality rates, primarily attributed to resistance against chemotherapy regimens containing taxanes like paclitaxel. Thus, developing combinatorial strategies to override resistance is a pressing need. By taking advantage of a library screening with various kinase inhibitors, we found that the small-molecule inhibitor enzastaurin targeting protein kinase C (PKC) could overcome resistance in TNBC cells. Mechanistically, dual treatment with paclitaxel and enzastaurin resulted in efficient mitotic arrest and subsequent cell death by restoring AURKB expression. Further analysis revealed that the GCN2-p-eIF2α axis was responsible for the posttranscriptional accumulation of AURKB upon combinatorial treatment. Finally, we confirmed that combinatorial regimens synergistically suppressed tumour growth in vivo in mouse models. Moreover, the efficiency of dual treatment was largely determined by AURKB, implying that AURKB could be a potential predictive marker for stratifying patients who may benefit from the combinatorial treatment. Collectively, our study not only unravels a novel underlying mechanism for paclitaxel resistance in TNBC but also provides a new potential combinatorial therapeutic strategy in the clinic.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70464","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638843","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":"Hsa_circ_0004662 Accelerates the Progression of Ulcerative Colitis via the microRNA-532/HMGB3 Signalling Axis","authors":"Chunhua Qiu,&nbsp;Yun Chen,&nbsp;Huan Xia,&nbsp;Jun Duan,&nbsp;Lu Zhang,&nbsp;You Zhang,&nbsp;Ziyang Chen,&nbsp;Li Zhang","doi":"10.1111/jcmm.70430","DOIUrl":"https://doi.org/10.1111/jcmm.70430","url":null,"abstract":"<p>Increasing research has indicated that circular RNAs (circRNAs) are crucial for the development of ulcerative colitis (UC). Thus, we attempted to identify the role of hsa_circ_0004662 in UC progression. Hsa_circ_0004662 expression was determined via qRT-PCR. Lipopolysaccharide (LPS)-induced inflammation in normal colonic epithelial cells (ECs). The hsa_circ_0004662 content was then assessed in a mucosal inflammatory bowel disease (IBD) model. Cell proliferation was examined via CCK-8 and EdU uptake assays. Apoptotic rates were analysed via flow cytometry. The protein content was quantified via Western blotting. Enzyme-linked immunosorbent assay kits were used to detect IL-1β, TNF-α and IL-6, and dual-luciferase reporter (DLR) assays were used to identify interactions between miR-532 and circ_0004662 or HMGB3. An animal model of UC was also developed for confirmation. In this study, we identified the function of hsa_circ_0004662 in promoting UC progression. Hsa_circ_0004662 was upregulated in clinical UC tissues and LPS-induced colonic ECs, and its knockdown inhibited apoptosis, reduced inflammatory cytokine release and promoted cell proliferation in vitro. Mechanistically, hsa_circ_0004662 acted as a molecular sponge for miR-532, which targets HMGB3. The hsa_circ_0004662/miR-532/HMGB3 axis was further validated in a DSS-induced colitis mouse model, where hsa_circ_0004662 knockdown attenuated inflammation and tissue damage. These findings suggested that hsa_circ_0004662 contributes to UC progression through the miR-532/HMGB3 signalling pathway, offering potential targets for UC therapy.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70430","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638777","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":"Protein Disulfide Isomerase Involvement in Dilated Cardiomyopathy Caused by Filamin C Deficiency in Male Mice","authors":"He Xuan,&nbsp;Chenghao Fan,&nbsp;Xue Bai,&nbsp;Anteng Shi,&nbsp;Yu Nie,&nbsp;Shengshou Hu,&nbsp;Hong Lian","doi":"10.1111/jcmm.70493","DOIUrl":"https://doi.org/10.1111/jcmm.70493","url":null,"abstract":"<p>Loss-of-function variants in the <i>FLNC</i> gene, which encodes Filamin C, cause dilated cardiomyopathy with a high risk of life-threatening arrhythmias. Therapies targeting the underlying mechanism of <i>FLNC</i>-related dilated cardiomyopathy remain limited. In this study, we observed that deletion of <i>Flnc</i> in cardiomyocytes of mice led to prominent ventricular dilation, cardiac dysfunction, and cardiac fibrosis. This phenotype closely resembles <i>FLNC</i>-related dilated cardiomyopathy in humans. RNA sequencing analysis revealed activation of protein disulfide isomerase (PDI) in <i>Flnc</i>-deleted cardiac tissues, as confirmed by immunoblotting. Treatment with the specific PDI inhibitor E64FC26 improved cardiac function, reduced cardiac fibrosis, and decreased cardiomyocyte apoptosis in cardiomyocyte-specific <i>Flnc</i>-deleted mice. We provide evidence that PDI is involved in the cardiac remodeling induced by Filamin C deficiency, and that treatment with the PDI inhibitor resulted in beneficial effects in mice with dilated cardiomyopathy caused by <i>Flnc</i> deletion. Our findings suggest that PDI could be a promising therapeutic target for <i>FLNC</i>-related dilated cardiomyopathy.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70493","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638841","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}