Osimertinib (OSI) resistance in non-small cell lung cancer (NSCLC) remains a significant challenge. This report explored the precise role of USP28 on OSI resistance in NSCLC and identified a functional downstream effector. OSI-resistant H1975 cells (H1975/OSI) were established by long-term OSI exposure. USP28 and SIRT1 expression levels were analyzed by quantitative PCR, immunoblotting, and immunohistochemistry. Functional assays included cell viability, colony formation, EdU incorporation, apoptosis analysis, and glycolysis assays. The interaction between USP28 and SIRT1 was confirmed by co-immunoprecipitation (Co-IP) assay and SIRT1 protein stability analysis. In vivo validation was performed using H1975/OSI xenograft models. USP28 and SIRT1 were upregulated in H1975/OSI cells and OSI-resistant NSCLC tissues. USP28 overexpression enhanced cell proliferation and glycolysis, suppressed apoptosis, and conferred OSI resistance in H1975 cells, while its depletion exerted opposite effects in H1975/OSI cells. Mechanistically, USP28 stabilized SIRT1 by deubiquitination. SIRT1 knockdown attenuated the effects of USP28 overexpression, while SIRT1 restoration reversed the phenotype alterations upon USP28 depletion. In vivo, USP28 depletion sensitized H1975/OSI xenografts to OSI treatment. Our study indicates that USP28 promotes OSI resistance in NSCLC by deubiquitinating SIRT1. Targeting the USP28/SIRT1 axis may represent a novel therapeutic approach to overcome OSI resistance in EGFR-mutant NSCLC.
{"title":"USP28 Promotes Osimertinib Resistance in H1975 NSCLC Cells by Deubiquitinating and Stabilizing SIRT1.","authors":"Hu-Sen Fan, Xiu-Mei Li, Jia-Qi Gu, Hai-Feng Wang, Zhen-Jiang Zhang","doi":"10.1002/kjm2.70095","DOIUrl":"10.1002/kjm2.70095","url":null,"abstract":"<p><p>Osimertinib (OSI) resistance in non-small cell lung cancer (NSCLC) remains a significant challenge. This report explored the precise role of USP28 on OSI resistance in NSCLC and identified a functional downstream effector. OSI-resistant H1975 cells (H1975/OSI) were established by long-term OSI exposure. USP28 and SIRT1 expression levels were analyzed by quantitative PCR, immunoblotting, and immunohistochemistry. Functional assays included cell viability, colony formation, EdU incorporation, apoptosis analysis, and glycolysis assays. The interaction between USP28 and SIRT1 was confirmed by co-immunoprecipitation (Co-IP) assay and SIRT1 protein stability analysis. In vivo validation was performed using H1975/OSI xenograft models. USP28 and SIRT1 were upregulated in H1975/OSI cells and OSI-resistant NSCLC tissues. USP28 overexpression enhanced cell proliferation and glycolysis, suppressed apoptosis, and conferred OSI resistance in H1975 cells, while its depletion exerted opposite effects in H1975/OSI cells. Mechanistically, USP28 stabilized SIRT1 by deubiquitination. SIRT1 knockdown attenuated the effects of USP28 overexpression, while SIRT1 restoration reversed the phenotype alterations upon USP28 depletion. In vivo, USP28 depletion sensitized H1975/OSI xenografts to OSI treatment. Our study indicates that USP28 promotes OSI resistance in NSCLC by deubiquitinating SIRT1. Targeting the USP28/SIRT1 axis may represent a novel therapeutic approach to overcome OSI resistance in EGFR-mutant NSCLC.</p>","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"e70095"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12782254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144984695","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}
Pub Date : 2026-01-01Epub Date: 2025-06-20DOI: 10.1002/kjm2.70072
Yi-Lung Chen, Agata Chudzicka-Czupała, Cheng-Fang Yen
{"title":"Psychological Capital Moderates the Association Between Social Participation and Depressive Symptoms in Taiwanese University Students.","authors":"Yi-Lung Chen, Agata Chudzicka-Czupała, Cheng-Fang Yen","doi":"10.1002/kjm2.70072","DOIUrl":"10.1002/kjm2.70072","url":null,"abstract":"","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"e70072"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12782241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334753","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}
Pub Date : 2026-01-01Epub Date: 2025-08-12DOI: 10.1002/kjm2.70083
Yu-Han Alice Hsu, Cheng-Che E Lan, Sheng-Yiao Lin
{"title":"Disease Modification of Pustular Psoriasis by Secukinumab: A 20-Year Follow-Up of Von Zumbusch-Type Generalized Pustular Psoriasis With Evolution Into Annular Pustular Psoriasis-A Case Report.","authors":"Yu-Han Alice Hsu, Cheng-Che E Lan, Sheng-Yiao Lin","doi":"10.1002/kjm2.70083","DOIUrl":"10.1002/kjm2.70083","url":null,"abstract":"","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"e70083"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12782248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839613","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}
Spontaneous pneumomediastinum (SPM) with pneumorrhachis is rare but generally benign and self-limiting. However, the impact of environmental and seasonal factors on SPM remains unclear. This study investigated their association with SPM onset and clinical outcomes. We conducted a 12-year retrospective review of SPM cases, comparing clinical characteristics and outcomes between patients with and without pneumorrhachis. A case-crossover design was used to assess short-term associations between environmental exposures and SPM incidence, analyzed via conditional logistic regression. A total of 70 consecutive patients were identified, with 9 classified as SPM with pneumorrhachis and 61 as SPM without pneumorrhachis. While both groups were predominantly managed with hospitalization, those with pneumorrhachis had longer hospital stays (median: 7 vs. 3 days, p = 0.002) and were more often associated with severe-grade SPM and identifiable triggers (p < 0.001 and p = 0.009, respectively). No significant environmental exposure differences were observed between groups. Seasonally, SPM incidence was significantly higher in autumn and winter (p < 0.001), consistent with elevated air pollutant levels. Linear regression showed that standardized β coefficients for PM2.5 were higher in autumn and winter (β = 1.15 and β = 1.18), indicating a seasonal association between PM2.5 and SPM onset. Despite experiencing more triggers and longer hospitalization, patients with pneumorrhachis had similarly favorable clinical courses. The seasonal clustering of SPM and its association with elevated PM2.5 levels suggest that air pollution may be a contributing factor, warranting further investigation.
{"title":"Impact of Environmental and Seasonal Factors on Spontaneous Pneumomediastinum With and Without Pneumorrhachis.","authors":"Yu-Wei Liu, Chieh-Ni Kao, Chi-Chang Ho, Shah-Hwa Chou, Pau-Chung Chen, Shu-Hung Huang","doi":"10.1002/kjm2.70096","DOIUrl":"10.1002/kjm2.70096","url":null,"abstract":"<p><p>Spontaneous pneumomediastinum (SPM) with pneumorrhachis is rare but generally benign and self-limiting. However, the impact of environmental and seasonal factors on SPM remains unclear. This study investigated their association with SPM onset and clinical outcomes. We conducted a 12-year retrospective review of SPM cases, comparing clinical characteristics and outcomes between patients with and without pneumorrhachis. A case-crossover design was used to assess short-term associations between environmental exposures and SPM incidence, analyzed via conditional logistic regression. A total of 70 consecutive patients were identified, with 9 classified as SPM with pneumorrhachis and 61 as SPM without pneumorrhachis. While both groups were predominantly managed with hospitalization, those with pneumorrhachis had longer hospital stays (median: 7 vs. 3 days, p = 0.002) and were more often associated with severe-grade SPM and identifiable triggers (p < 0.001 and p = 0.009, respectively). No significant environmental exposure differences were observed between groups. Seasonally, SPM incidence was significantly higher in autumn and winter (p < 0.001), consistent with elevated air pollutant levels. Linear regression showed that standardized β coefficients for PM<sub>2.5</sub> were higher in autumn and winter (β = 1.15 and β = 1.18), indicating a seasonal association between PM<sub>2.5</sub> and SPM onset. Despite experiencing more triggers and longer hospitalization, patients with pneumorrhachis had similarly favorable clinical courses. The seasonal clustering of SPM and its association with elevated PM<sub>2.5</sub> levels suggest that air pollution may be a contributing factor, warranting further investigation.</p>","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"e70096"},"PeriodicalIF":3.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12782255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144877672","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 \"Response to Integration of the Comprehensive Physical Examination and Diagnostic Tools in Clinical Cardiology\".","authors":"","doi":"10.1002/kjm2.70164","DOIUrl":"https://doi.org/10.1002/kjm2.70164","url":null,"abstract":"","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"e70164"},"PeriodicalIF":3.1,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Factors Related to Parental Intention to Vaccinate Young Adolescent Boys Against Human Papillomavirus in Taiwan.","authors":"Yu-Min Chen, Yu-Ping Chang, Cheng-Fang Yen","doi":"10.1002/kjm2.70160","DOIUrl":"https://doi.org/10.1002/kjm2.70160","url":null,"abstract":"","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"e70160"},"PeriodicalIF":3.1,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to \"Inhibition of the Numb/Notch Signaling Pathway Increases Radiation Sensitivity in Human Nasopharyngeal Carcinoma Cells\".","authors":"","doi":"10.1002/kjm2.70153","DOIUrl":"https://doi.org/10.1002/kjm2.70153","url":null,"abstract":"","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"e70153"},"PeriodicalIF":3.1,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hu Shan, Rui Zhang, Yu-Er Li, Rui Li, Shao-Bo Ge, Jin Liu, Shi-Yuan Yao, Xia Yang, Tao Zhang, Ming Zhang
Airway epithelial injury plays a critical role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Mitochondrial dysfunction is implicated in this injury, while the underlying mechanism remains incompletely understood. RNA sequencing was conducted to identify key genes involved in mitochondrial dysfunction in airway epithelial injury induced by cigarette smoke extract (CSE). We identified 1981 significantly up-regulated and 4952 down-regulated differentially expressed genes (DEGs) in CSE-treated airway epithelial cells. A protein-protein interaction network constructed from the DEGs revealed that several key genes were involved in CSE-induced airway epithelial injury. Additionally, PDCD5 was identified as a hub gene potentially linked to mitochondrial dysfunction. PDCD5 expression was significantly increased in the airway epithelium of COPD patients and the corresponding experimental mice. The mRNA and protein expression levels of PDCD5 were significantly increased in concentration- and time-dependent manners in airway epithelial cells treated with CSE. PDCD5 silencing significantly attenuated CSE-induced mitochondrial reactive oxygen species (ROS) accumulation, mitochondrial membrane potential loss, and intracellular ATP depletion. Transmission electron microscopy revealed that PDCD5 siRNA treatment ameliorated CSE-induced mitochondrial structural damage. Moreover, PDCD5 knockdown significantly reduced intracellular ROS accumulation, attenuated apoptosis increases, and inhibited cell viability decline in airway epithelial cells treated with CSE. Our findings demonstrate that PDCD5 contributes to airway epithelial cell damage through the mitochondrial pathway and participates in the pathogenesis of COPD, implicating it as a potential diagnostic biomarker and therapeutic target for COPD.
{"title":"PDCD5 Contributes to Airway Epithelial Cell Damage via Mitochondrial Pathway and Participates in COPD Pathogenesis.","authors":"Hu Shan, Rui Zhang, Yu-Er Li, Rui Li, Shao-Bo Ge, Jin Liu, Shi-Yuan Yao, Xia Yang, Tao Zhang, Ming Zhang","doi":"10.1002/kjm2.70165","DOIUrl":"https://doi.org/10.1002/kjm2.70165","url":null,"abstract":"<p><p>Airway epithelial injury plays a critical role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Mitochondrial dysfunction is implicated in this injury, while the underlying mechanism remains incompletely understood. RNA sequencing was conducted to identify key genes involved in mitochondrial dysfunction in airway epithelial injury induced by cigarette smoke extract (CSE). We identified 1981 significantly up-regulated and 4952 down-regulated differentially expressed genes (DEGs) in CSE-treated airway epithelial cells. A protein-protein interaction network constructed from the DEGs revealed that several key genes were involved in CSE-induced airway epithelial injury. Additionally, PDCD5 was identified as a hub gene potentially linked to mitochondrial dysfunction. PDCD5 expression was significantly increased in the airway epithelium of COPD patients and the corresponding experimental mice. The mRNA and protein expression levels of PDCD5 were significantly increased in concentration- and time-dependent manners in airway epithelial cells treated with CSE. PDCD5 silencing significantly attenuated CSE-induced mitochondrial reactive oxygen species (ROS) accumulation, mitochondrial membrane potential loss, and intracellular ATP depletion. Transmission electron microscopy revealed that PDCD5 siRNA treatment ameliorated CSE-induced mitochondrial structural damage. Moreover, PDCD5 knockdown significantly reduced intracellular ROS accumulation, attenuated apoptosis increases, and inhibited cell viability decline in airway epithelial cells treated with CSE. Our findings demonstrate that PDCD5 contributes to airway epithelial cell damage through the mitochondrial pathway and participates in the pathogenesis of COPD, implicating it as a potential diagnostic biomarker and therapeutic target for COPD.</p>","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"e70165"},"PeriodicalIF":3.1,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chen Li, Jia-Wen Yang, Yong-Rui Jia, Jie Zhang, Qiao Gou
Radiotherapy effectively eradicates tumor cells but can also trigger pyroptotic damage in vascular endothelial cells. This study investigates the role of interferon regulatory factor 1 (IRF1) in radiation-induced endothelial injury, aiming to provide mechanistic insights for optimizing radiotherapy. Human umbilical vein endothelial cells (HUVECs) were exposed to x-ray irradiation, after which cell viability, lactate dehydrogenase (LDH) release, γ-H2AX foci formation, and the expression of pyroptosis-associated proteins (NLRP3, Cleaved Caspase-1, GSDMD-N, IL-1β, IL-18) were assessed. Expression levels of IRF1, NFE2L1-DT, PELP1, ALKBH5, and Cx43 were quantified. Chromatin enrichment of IRF1 at the NFE2L1-DT promoter and IRF1-NFE2L1-DT interactions were examined, along with NFE2L1-DT or ALKBH5 binding to PELP1. The enrichment of m6A modifications on Cx43 transcripts was also evaluated. X-ray exposure reduced HUVEC viability, elevated LDH release, increased γ-H2AX foci, and upregulated IRF1, along with pyroptosis markers. Silencing IRF1 reversed these changes. Mechanistically, IRF1 directly bound to and increased NFE2L1-DT expression. NFE2L1-DT interacted with PELP1 to enhance the binding of PELP1 to and ALKBH5 mRNA, thus upregulating ALKBH5 expression. ALKBH5-mediated m6A demethylation subsequently downregulated Cx43 expression. Overexpression of NFE2L1-DT or ALKBH5, or silencing Cx43, attenuated the protective effects of IRF1 silencing against radiation-induced damage. These findings indicate that radiation-induced IRF1 upregulation leads to endothelial injury by promoting pyroptosis through the NFE2L1-DT/ALKBH5/Cx43 axis.
{"title":"Molecular Mechanism of the IRF1/NFE2L1-DT/ALKBH5/Cx43 Axis in Radiation-Induced Injury in Vascular Endothelial Cells Through Pyroptosis.","authors":"Chen Li, Jia-Wen Yang, Yong-Rui Jia, Jie Zhang, Qiao Gou","doi":"10.1002/kjm2.70159","DOIUrl":"https://doi.org/10.1002/kjm2.70159","url":null,"abstract":"<p><p>Radiotherapy effectively eradicates tumor cells but can also trigger pyroptotic damage in vascular endothelial cells. This study investigates the role of interferon regulatory factor 1 (IRF1) in radiation-induced endothelial injury, aiming to provide mechanistic insights for optimizing radiotherapy. Human umbilical vein endothelial cells (HUVECs) were exposed to x-ray irradiation, after which cell viability, lactate dehydrogenase (LDH) release, γ-H2AX foci formation, and the expression of pyroptosis-associated proteins (NLRP3, Cleaved Caspase-1, GSDMD-N, IL-1β, IL-18) were assessed. Expression levels of IRF1, NFE2L1-DT, PELP1, ALKBH5, and Cx43 were quantified. Chromatin enrichment of IRF1 at the NFE2L1-DT promoter and IRF1-NFE2L1-DT interactions were examined, along with NFE2L1-DT or ALKBH5 binding to PELP1. The enrichment of m<sup>6</sup>A modifications on Cx43 transcripts was also evaluated. X-ray exposure reduced HUVEC viability, elevated LDH release, increased γ-H2AX foci, and upregulated IRF1, along with pyroptosis markers. Silencing IRF1 reversed these changes. Mechanistically, IRF1 directly bound to and increased NFE2L1-DT expression. NFE2L1-DT interacted with PELP1 to enhance the binding of PELP1 to and ALKBH5 mRNA, thus upregulating ALKBH5 expression. ALKBH5-mediated m<sup>6</sup>A demethylation subsequently downregulated Cx43 expression. Overexpression of NFE2L1-DT or ALKBH5, or silencing Cx43, attenuated the protective effects of IRF1 silencing against radiation-induced damage. These findings indicate that radiation-induced IRF1 upregulation leads to endothelial injury by promoting pyroptosis through the NFE2L1-DT/ALKBH5/Cx43 axis.</p>","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"e70159"},"PeriodicalIF":3.1,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}