International Journal of Medical Sciences最新文献

{"title":"Validation of Osteoporosis associated SNPs candidates from Decisive Gene Strategy using Taiwan Biobank.","authors":"Pei-Jan Tsai, Sin-Yu Lin, Meng-Chang Lee, Mei-Jung Chen, Chih-Chien Wang, Cheng-Jung Chen, Wei-Teing Chen, Po-Jen Hsiao, Chih-Chien Chiu, Yu-Hsuan Chen, Hsiao-Ting Lin, Hao Su, Sui-Lung Su","doi":"10.7150/ijms.125797","DOIUrl":"10.7150/ijms.125797","url":null,"abstract":"<p><p>Decisive gene strategy (DGS) has been developed and identified 21 single nucleotide polymorphisms (SNPs) associated with osteoporosis (OP). This study aimed to further evaluate whether DGS is a suitable candidate strategy to identify the relationship between SNPs and OP using Taiwan Biobank (TWB). A total of 26,225 samples were retrieved from TWB between 2008 and 2021, comprising 4,749 osteoporosis (T-score ≤ -2.5) and 21,476 controls (T-score ≥ -1.0) based on their T-score of bone mineral density (BMD). Logistic regression analysis was used to examine the association between 21 SNPs from DGS and OP risk by using TWB data. The alignment of 21 SNPs from DGS with TWB genotyping chip found 11 identical SNPs. Among the 11 identical SNPs, seven showed results consistent with prior DGS evidence, including ESR1 rs9340799, OPG rs2073617, VDR rs731236, rs7975232, and rs1544410, IL6 rs1800795, and IGF1 rs5742612 [OR: 1.01, 1.03, 1.06, 1.01, 1.10, 0.72, 1.02; 95% CI= 0.94-1.09, 0.97-1.10, 0.93-1.22, 0.94-1.07, 0.97-1.26, 0.32-1.64, 0.96-1.09, respectively]. Furthermore, OPG T245G rs3134069 showed a borderline nominal association with osteoporosis in TWB [OR: 1.09, 95% CI= 1.00-1.19]), suggesting a potential population-specific signal. Our TWB validation of the 11 identical SNPs supports DGS as an effective methodology and, beyond replication, provides a novel framework for examining the relationship between SNPs and disease.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 10","pages":"3122-3133"},"PeriodicalIF":3.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-Related Differences in Clinical and Surgical Outcomes Following Oblique Lateral Interbody Fusion: A Retrospective Cohort Study.","authors":"Yun-Che Wu, Cheng-Hung Lee, Jun-Sing Wang, Meng-Jen Lee","doi":"10.7150/ijms.127252","DOIUrl":"10.7150/ijms.127252","url":null,"abstract":"<p><strong>Introduction: </strong>We compared patient outcomes following oblique lateral interbody fusion (OLIF) for degenerative lumbar spine conditions among different age groups.</p><p><strong>Materials and methods: </strong>This retrospective cohort study included patients between January 2018 and July 2020. Patients were stratified into three groups based on age at the time of surgery (<65 years, 65 to <75 years, and ≥ 75 years). Preoperative and postoperative patient-reported outcome measures were assessed, including visual analog scale (VAS) for back and leg pain, Oswestry Disability Index (ODI), and EuroQol-5 Dimension (EQ-5D). Postoperative orthopedic events, including screw loosening, cage subsidence, and revision surgery, were recorded. All patients' survival status were followed until March 2023. Cox-proportional hazard models were conducted to examine the associations of age groups with postoperative orthopedic events and all-cause mortality.</p><p><strong>Results: </strong>A total of 170 patients were analyzed (n=77, 68, and 25 for age <65 years, 65 to <75 years, and ≥ 75 years, respectively). VAS, ODI, and EQ-5D significantly improved after OLIF in all groups (all p<0.001). There were no significant differences in rates of postoperative screw loosening (p=0.702), cage subsidence (p=0.095), and revision surgery (p=0.265) across the three age groups. After a median follow up of 4.06 years, the three groups had no significant difference in orthopedic event-free survival (log-rank p=0.302). The findings were consistent after multivariate adjustment.</p><p><strong>Conclusion: </strong>OLIF is a safe and effective surgical option for elderly patients with degenerative lumbar spine conditions.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 10","pages":"3148-3155"},"PeriodicalIF":3.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of Structured Skin Care Using Silicone Barrier Spray Compared with Zinc Oxide Ointment for Incontinence-Associated Dermatitis in Long-Term Care Residents: A Randomized Controlled Trial.","authors":"Po-Chung Chen, Chi-Ming Chu, Po-Jen Hsiao, Hsieh-Chih Tsai","doi":"10.7150/ijms.132180","DOIUrl":"10.7150/ijms.132180","url":null,"abstract":"<p><strong>Background: </strong>Incontinence-associated dermatitis (IAD) is a common and clinically significant condition among the residents of long-term care facilities. Although structured skin care is widely recommended for IAD prevention and management, evidence comparing sprayable silicone barrier films with traditional zinc oxide-based barriers remains limited.</p><p><strong>Methods: </strong>We conducted a 14-day prospective, randomized controlled trial in a long-term care facility. Forty residents with mild IAD (GLOBIAD Category 1) were randomly assigned in a 1:1 ratio to receive either a silicone-based barrier spray (n = 20) or zinc oxide ointment (n = 20), in addition to standardized cleansing care. IAD severity was assessed using the modified Ghent Global IAD Monitoring Tool (GLOBIAD-M). Secondary outcomes included skin hydration, transepidermal water loss (TEWL), skin pH, and skin temperature, measured at baseline, Day 7, and Day 14. Longitudinal changes were analyzed using generalized estimating equations.</p><p><strong>Results: </strong>The severity of IAD significantly improved over time in both groups (p<0.001), with no significant between-group differences or group-by-time interaction. A modest increase in skin pH toward a more neutral range was observed over time (p=0.036). Although skin hydration, TEWL, and skin temperature did not show significant changes, their overall patterns remained compatible with the clinical improvement observed during follow-up. No adverse events were observed in either group.</p><p><strong>Conclusion: </strong>Within the 14-day study period, sprayable silicone barrier film was well tolerated, with no statistically significant differences in clinical outcomes compared with zinc oxide ointment. The ease of application and the absence of mechanical removal may facilitate routine skin care, making sprayable silicone barrier film a suitable option in long-term care settings.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 10","pages":"3183-3193"},"PeriodicalIF":3.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperbaric Oxygen Therapy for Cognitive Impairment Resulting from Neurological Disorders: Mechanisms of Action and Application Advances.","authors":"Tianjiao Wei, Wenhui Gu, Lisha Ye, Guohua Wang","doi":"10.7150/ijms.128159","DOIUrl":"10.7150/ijms.128159","url":null,"abstract":"<p><p>Cognitive impairment is a common and disabling consequence of various neurological disorders. Due to its high prevalence, high conversion rate, and significant burden, it has increasingly become a major challenge for aging societies worldwide. Existing treatment strategies have limited efficacy in halting disease progression, making effective intervention strategies urgently needed. As a non-invasive physical therapy, hyperbaric oxygen therapy (HBOT) exerts its effects by increasing arterial oxygen partial pressure and improving tissue oxygenation. Historically widely used for treating carbon monoxide poisoning and decompression sickness, HBOT has recently demonstrated potential in alleviating symptoms of neurological disorders. Mechanistically, HBOT modulates the hypoxic microenvironment, promotes angiogenesis, restores neurovascular integrity, enhances neurogenesis and synaptic plasticity, and reduces neuroinflammation and oxidative stress. This paper systematically reviews the mechanisms of action, application progress, and existing limitations of HBOT in neurological disorders causing cognitive impairment. As a promising therapeutic modality, HBOT holds the potential to overcome current treatment limitations and become a key component of comprehensive neurological rehabilitation strategies.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 10","pages":"3194-3210"},"PeriodicalIF":3.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Target-Specific Extracorporeal Shockwave Therapy Modulates TLR4/NF-κB/MMP13 Signaling Within the Joint Microenvironment to Improve Osteochondral Pathology in Patellofemoral Osteoarthritis.","authors":"Shun-Wun Jhan, Kuan-Ting Wu, Wen-Yi Chou, Po-Cheng Chen, Wen-Chiung Huang, Jai-Hong Cheng","doi":"10.7150/ijms.132904","DOIUrl":"10.7150/ijms.132904","url":null,"abstract":"<p><strong>Background: </strong>Patellofemoral joint (PFJ) osteoarthritis (OA) is characterized by cartilage degeneration, subchondral bone remodeling, fat pad fibrosis, and chronic synovial inflammation. This study investigated the therapeutic effects of extracorporeal shockwave therapy (ESWT) applied to different anatomical targets in a rat PFJ OA model.</p><p><strong>Methods: </strong>PFJ OA was induced in rats and treated with ESWT targeted to either the tibial side (SWT) or femoral side (SWF). Micro-computed tomography, histological staining, and immunohistochemistry were used to assess structural changes, fibrosis, and inflammation. Molecular assessments showed the direct and indirecd effects of ESWT on the key inflammatory mediators, including IL-1β, NF-κB, RAGE, TLR4, and MyD88, and significantly reduced MMP13 expression in joint tissues.</p><p><strong>Results: </strong>ESWT significantly attenuated osteophyte formation, cystic changes, and sclerosis in the femoral and patellar bone. SWT showed superior improvement in bone volume fraction, trabecular thickness, and patellar bone integrity. Histologically, ESWT reduced cartilage degradation, fat pad fibrosis, and synovial inflammation. Molecular analyses revealed downregulation of pro-inflammatory mediators and MMP13, with SWT producing greater effects than SWF.</p><p><strong>Conclusions: </strong>ESWT effectively mitigates structural damage, inflammation, and catabolic signaling in PFJ OA. Targeting the tibial side enhances therapeutic outcomes, highlighting ESWT as a promising non-invasive treatment strategy for PFJ OA.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 10","pages":"3134-3147"},"PeriodicalIF":3.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Role of Red Yeast Rice in the Prevention and Treatment of Alzheimer's Disease.","authors":"Qining Quan, Ronghua Pan, Haolin Liu, Lizhong Zheng, Rui Zhang","doi":"10.7150/ijms.135847","DOIUrl":"10.7150/ijms.135847","url":null,"abstract":"<p><p>Red Yeast Rice (RYR) fermented from <i>Monascus</i> is a traditional fermented product with both dietary and medicinal uses and is widely used for lipid regulation. Clinically, it is utilized to lower blood lipid levels and manage hyperlipidemia. Contemporary research indicates that RYR is abundant in secondary metabolites, such as monacolin K, <i>Monascus</i> pigments, and γ-aminobutyric acid, which contribute to its lipid-lowering, blood sugar-reducing, anti-inflammatory, neuroprotective, and antihypertensive properties. These metabolites may play a significant role in the prevention and treatment of Alzheimer's disease (AD) through mechanisms that include cholesterol-dependent pathways, anti-neuroinflammation, antioxidant activity, neuroprotection, modulation of intestinal flora, inhibition of high-risk factors for AD, and suppression of AD-related β-amyloid peptide deposition and tau protein hyperphosphorylation. Consequently, RYR demonstrates potential for a multi-component synergistic approach to preventing and treating AD. However, current research on the use of RYR for AD prevention and treatment remains limited. This review focuses on the primary functional substances in RYR, elucidates the anti-AD effects and mechanisms of each metabolite, analyzes the advantages of its multi-component and multi-target properties, and provides a foundation for the further development of RYR.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 10","pages":"3101-3111"},"PeriodicalIF":3.7,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of GDF-15 in Acute Heart Failure: from Mechanistic Insights to Clinical Applications.","authors":"Paisit Kosum, Nonthikorn Theerasuwipakorn, Siriporn C Chattipakorn, Nipon Chattipakorn","doi":"10.7150/ijms.138771","DOIUrl":"10.7150/ijms.138771","url":null,"abstract":"<p><p>Acute heart failure (AHF) is a clinical syndrome characterized by the rapid or gradual onset of symptoms and signs of heart failure that are severe enough to require urgent evaluation and treatment. It may represent <i>de novo</i> heart failure or acute decompensation of pre-existing chronic heart failure. Natriuretic peptides remain the cornerstone biomarkers for diagnosis and risk assessment, but predominantly reflect hemodynamic stress and incompletely capture inflammation, oxidative injury, cellular damage, and multiorgan dysfunction. Growth differentiation factor-15 (GDF-15), a stress-responsive cytokine of the transforming growth factor-beta superfamily, may complement natriuretic peptides by reflecting these non-hemodynamic pathways. We conducted a targeted PubMed search from database inception to January 2025 and identified 16 original mechanistic and clinical studies relevant to GDF-15 in AHF. In cultured cardiomyocytes, biomechanical stretch increased GDF-15 expression approximately 24.8-fold, while recombinant GDF-15 reduced ischemia/reperfusion-related necrosis and apoptosis through phosphoinositide 3-kinase/Akt signaling and attenuated agonist-induced hypertrophy through SMAD2/3-associated pathways. In animal models, GDF-15 deficiency increased infarct size and cardiomyocyte apoptosis after ischemia/reperfusion and produced greater hypertrophy and an 84% reduction in contractile performance after 2 weeks of pressure overload, compared with a 25% reduction in wild-type mice. Clinical studies generally showed that higher admission or discharge GDF-15 concentrations and increasing serial levels were associated with mortality or heart-failure rehospitalization. For example, serial GDF-15 remained independently associated with adverse outcomes after simultaneous modelling with established biomarkers (adjusted hazard ratio 1.44 per 1-SD increase in log GDF-15), and a multimarker model incorporating GDF-15, NT-proBNP, and troponin I achieved an area under the curve of 0.785. GDF-15 is not currently recommended for routine heart-failure management since assays and thresholds are not standardized and no prospective trial has shown that GDF-15-guided treatment improves outcomes. Its most plausible near-term role is therefore as one component of a multimarker risk-stratification strategy.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 10","pages":"3112-3121"},"PeriodicalIF":3.7,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay between Skin Sympathetic Nerve Activity and Gut Microbiota, the Neurocardiac Axis in Acute Coronary Syndrome.","authors":"Wei-Chung Tsai, Po Peng, Pei-Syuan Jhou, Yi-Chun Tsai, Wei-Wen Hung, Tien-Chi Huang, Li-Fang Chou, Tsung-Hsien Lin, Chien-Hung Lee, Bin-Nan Wu, Shien-Fong Lin, Wei-Chun Hung","doi":"10.7150/ijms.126417","DOIUrl":"10.7150/ijms.126417","url":null,"abstract":"<p><p>Our previous study demonstrated increased skin sympathetic nerve activity (SKNA) in acute coronary syndrome (ACS) patients and its correlation with ventricular arrhythmias. In the current study, we explored specific gut microbial profiles and their relationships with SKNA in ACS patients. Fifteen ACS patients and age- and sex-matched controls were included in this cross-sectional study. Demographic and clinical data were recorded, and SKNA was measured by neuECG. The gut microbial profiles were analyzed by 16S rRNA gene sequencing of the V3-V4 region. Statistically significant differences in alpha diversity (including the Chao 1 index and Faith's phylogenetic diversity) and gut microbial composition were observed between the ACS and control groups. Redundancy analysis and the Mantel test revealed a significant relationship between SKNA and the microbial profiles. The abundance of butyrate-producing bacteria, including <i>Lachnospira</i> and <i>Oscillibacter</i>, was decreased in the ACS group, whereas the abundance of the genus <i>Hungatella</i>, a trimethylamine producer, significantly increased and was positively correlated with the abundance of SKNA. This study is the first to establish an association between SKNA and gut microbial profiles in ACS patients. SKNA may serve as a potential biomarker reflecting the interaction between the nervous system and gut microbiota in ACS.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 10","pages":"3090-3100"},"PeriodicalIF":3.7,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Haloperidol Triggers RAW264.7 Macrophages Injury through Oxidative Stress-Driven Mitochondrial Dysfunction, Genomic Instability, and Apoptotic Cell Death.","authors":"Yen-Ju Lee, Yen-Po Chen, Wan-Yun Hsu, Serena-Haining Shay, Ping-Kun Tsai, Chun-Hung Su, Shih-Pin Chen, Sheng-Wen Wu, Chen-Yu Chiang, Yu-Hsiang Kuan","doi":"10.7150/ijms.135133","DOIUrl":"10.7150/ijms.135133","url":null,"abstract":"<p><strong>Background and objective: </strong>Haloperidol is a widely used first-generation antipsychotic for the management of schizophrenia and acute neurocognitive disorders. However, its potential immunotoxic effects remain poorly understood. This study aimed to investigate the cytotoxic and genotoxic mechanisms of haloperidol in RAW264.7 macrophages, focusing on oxidative stress, mitochondrial dysfunction, and apoptosis.</p><p><strong>Methods: </strong>RAW264.7 macrophages were treated with haloperidol (0-150 μM). Cell viability (MTT), DNA damage (micronucleus and comet assays), ROS production, mitochondrial membrane potential, cytochrome c release, apoptosis (annexin V/PI), death receptor expression and caspase activity were evaluated. N-acetylcysteine (NAC)-based pharmacological rescue was further performed to assess the involvement of ROS in haloperidol-induced cytotoxicity, intracellular ROS generation, and caspase-3 activity.</p><p><strong>Results: </strong>Haloperidol induced significant cytotoxicity, with marked effects observed at concentrations ≥50 μM. DNA damage was evidenced by increased micronucleus formation and elevated comet assay parameters. ROS levels were significantly increased, accompanied by mitochondrial membrane depolarization and cytochrome c release. In addition, apoptotic and necrotic cell populations and sub-G1 accumulation were markedly elevated. Mechanistically, both intrinsic and extrinsic apoptotic pathways were activated, as indicated by increased caspase-9, caspase-8, and caspase-3 activities, along with upregulation of Fas and TNFR. NAC pretreatment attenuated haloperidol-induced ROS accumulation, caspase-3 activation, and loss of cell viability, suggesting that ROS accumulation contributes, at least in part, to haloperidol-induced macrophage injury.</p><p><strong>Conclusions: </strong>The present study demonstrates that haloperidol induces cytotoxicity and DNA damage in macrophages through oxidative stress-mediated mitochondrial dysfunction and activation of caspase-dependent apoptotic pathways under high-exposure in vitro conditions. These findings identify macrophages as a potential target of haloperidol toxicity and highlight the importance of considering immune-related effects in safety evaluation.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 10","pages":"3066-3078"},"PeriodicalIF":3.7,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoalantolactone Attenuates LPS-Induced Acute Lung Injury, an Effect Associated with Suppressed MAPK/STAT3 Activation and Epithelial-Mesenchymal Transition.","authors":"Chia-Yang Li, Chung-Wei Liu, Hsin-Han Tseng, Yu-Hsin Tseng, Shu-Chi Wang, Po-Len Liu, Hsin-En Wu, Yuan-Ru Chen, Sheng-I Lee, Tzu-Chieh Lin, Ching-Tang Chang, Xin-Yi Lin, I-Chen Chen","doi":"10.7150/ijms.126267","DOIUrl":"10.7150/ijms.126267","url":null,"abstract":"<p><strong>Background: </strong>Acute lung injury (ALI) is characterized by a high mortality rates and acute inflammation that compromises the epithelial and endothelial barriers of the respiratory system. Isoalantolactone (IsoA) is a natural compound derived from <i>Inula helenium</i> that has been shown to exhibit anti-inflammatory activity. However, its ability to preserve epithelial barrier integrity or modulate mitogen-activated protein kinase/signal transducer and activator of transcription 3 (MAPK/STAT3) signaling and epithelial-mesenchymal transition (EMT) has not been evaluated in ALI.</p><p><strong>Methods: </strong>Human bronchial epithelial cells (HBEC3-KT and BEAS-2B) were stimulated with lipopolysaccharide (LPS) with or without IsoA to assess cytotoxicity and cytokine release. In vivo, female C57BL/6 mice were pretreated with IsoA (10-20 mg/kg, intraperitoneally) or vehicle 1 h before LPS challenge (1 mg/kg, intratracheally). At 4 h, lung tissues and bronchoalveolar lavage fluid (BALF) were collected for histopathology and to measure total protein, cellular composition, and cytokine levels (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], monocyte chemoattractant protein-1 [MCP-1]); leukocyte subsets were quantified by multicolor flow cytometry. Lung homogenates were analyzed using Western blot for phosphorylated/total extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase 1/2 (JNK1/2), p38 MAPKs, STAT3, and EMT markers (E-cadherin, N-cadherin, snail).</p><p><strong>Results: </strong>In LPS-stimulated HBEC3-KT and BEAS-2B cells, IsoA significantly reduced IL-6 secretion. In the murine model of LPS-induced ALI, IsoA administration alleviated lung tissue damage, decreased inflammatory cell infiltration, and reduced IL-6 and TNF-α concentration in BALF and serum. Mechanistically, IsoA attenuated the phosphorylation of ERK, JNK, and p38 MAPKs and suppressed STAT3 activation in lung tissues. Furthermore, IsoA attenuated EMT, as evidenced by decreased N-cadherin and snail expressions and restored E-cadherin expression.</p><p><strong>Conclusions: </strong>IsoA alleviates LPS-induced ALI by reducing MAPK/STAT3 activation and EMT-associated epithelial injury. These findings suggest that IsoA may be a promising candidate for the targeted modulation of inflammatory lung injury, and that further preclinical and translational studies are justified.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 10","pages":"3079-3089"},"PeriodicalIF":3.7,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}