Biomedical reports最新文献

{"title":"Mechanisms of monosodium urate crystal-induced bone destruction in gouty arthritis (Review).","authors":"Liekui Hu, Huizhen Li, Xin Huang, Weikang Sun, Qipeng Yuan, Huanan Li","doi":"10.3892/br.2026.2134","DOIUrl":"10.3892/br.2026.2134","url":null,"abstract":"<p><p>The deformities and disabilities resulting from bone destruction in gouty arthritis impose substantial physical and psychological burdens on patients, underscoring the urgent need to elucidate the mechanisms underlying gout-induced osteolysis. Monosodium urate (MSU) crystals play a central role in the pathogenesis of bone destruction in gouty arthritis, significantly disrupting the activity and function of bone-related cells. Mechanistically, MSU induces bone loss by triggering oxidative stress, amplifying inflammatory cascades, and dysregulating bone remodeling pathways. Understanding these pathological mechanisms is essential for early clinical intervention and the development of targeted therapies to prevent disease progression. The present review systematically examines the multifaceted impact of MSU on bone homeostasis and its molecular interactions in gouty arthritis-associated bone destruction, providing insights to refine diagnostic strategies and advance novel therapeutic approaches.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"24 5","pages":"61"},"PeriodicalIF":2.5,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13040328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607441","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":"Efficacy and safety of antifungal prophylaxis in surgical intensive care unit patients: A systematic review and meta-analysis of randomized controlled trials.","authors":"Ika N Kadariswantiningsih, Maulana A Empitu, Edwin Danardono, Ivan Rahmatullah, Alicia Margaretta Widya, Eko Budi Koendhori, Derren D C H Rampengan, Ekram Arima, Pepy Dwi Endraswari","doi":"10.3892/br.2026.2135","DOIUrl":"10.3892/br.2026.2135","url":null,"abstract":"<p><p>Invasive fungal infections (IFIs) are serious complications among surgical intensive care unit (ICU) patients, leading to substantial morbidity and mortality. Antifungal prophylaxis and pre-emptive strategies are employed to reduce the risk of such infections, although their effectiveness and safety remain subjects of debate. The present systematic review and meta-analysis included randomized controlled trials evaluating antifungal prophylaxis or pre-emptive therapy in surgical ICU patients. Searches in the PubMed, Scopus, Google Scholar and Science Direct databases up to February 2025 identified 11 eligible studies. Pooled analyses demonstrated that antifungal prophylaxis significantly reduced the risk of IFIs [risk ratio (RR)=0.63; 95% CI, 0.50-0.78; P<0.0001]. While azoles were effective, polyenes and echinocandins did not show a significant effect. No significant effect on overall mortality was observed (RR=0.99; 95% CI, 0.75-1.31; P=0.9186), and there was no increased risk of severe adverse events (RR=0.98; 95% CI, 0.70-1.36) or liver dysfunction (RR=0.91; 95% CI, 0.31-2.65). The analysis did not reveal strong evidence of publication bias as evaluated by funnel plots. Overall, the results indicated that antifungal prophylaxis appeared to be effective in reducing the risk of IFIs in surgical ICU patients without elevating the risk of serious side effects. The implementation of this therapy should be targeted toward high-risk populations, considering the antifungal type, local resource availability and antimicrobial management parameters. The evidence of prophylaxis therapy in low-risk population is limited, since the majority of included studies in the present meta-analysis analyzed high-risk populations.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"24 5","pages":"62"},"PeriodicalIF":2.5,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13040432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607491","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":"Peroxiredoxin 4 suppresses ferroptosis in esophageal squamous cell carcinoma by activating the phosphoinositide 3-kinase  signaling pathway.","authors":"Ke Li, Shuning Xu, Hongtao Liu, Tianli Fan, Yiyang Li, Ruili Ren, Yue Xu, Shenglei Li, Ying Liu","doi":"10.3892/br.2026.2133","DOIUrl":"10.3892/br.2026.2133","url":null,"abstract":"<p><p>Peroxiredoxin 4 (PRDX4) has been found to be upregulated and verified to play protective roles against oxidative stress in various tumors. However, its exact function and underlying molecular mechanisms in esophageal squamous cell carcinoma (ESCC) remain unclear. The aim of the present study was to evaluate the roles of PRDX4 in ferroptosis of ESCC cells and elucidate its potential molecular mechanisms. Bioinformatics analysis, western blotting and reverse transcription-quantitative PCR confirmed that PRDX4 was markedly upregulated in ESCC samples and cells. The close association of PRDX4 with lymph node metastasis and TNM staging was identified, and PRDX4 may be an independent prognostic marker for patients with ESCC. Furthermore, PRDX4 depletion inhibited the proliferation and invasion of ESCC cells, whereas PRDX4 overexpression had the opposite effect. Notably, PRDX4 knockdown promoted ferroptosis by increasing malondialdehyde and lipid peroxidation levels, and decreasing glutathione levels, coupled with decreased expression of glutathione peroxidase 4 and solute carrier family 7 member 11, and increased expression of prostaglandin-endoperoxide synthase 2. However, PRDX4 overexpression showed opposite effects, which were partly reversed by the ferroptosis inhibitor, ferrostatin-1 and the inducer erastin. Most crucially, PRDX4 depletion-mediated inactivation of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway could be rescued by 740 Y-P (a PI3K activator), whereas PRDX4 overexpression triggered the activation of the PI3K/AKT signaling pathway, which could be reversed by the PI3K inhibitor LY294002. Collectively, the data suggest that PRXD4 suppresses ferroptosis in ESCC cells by activating the PI3K/AKT signaling pathway, suggesting that targeting PRDX4 may be a novel strategy for treating patients with ESCC.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"24 5","pages":"60"},"PeriodicalIF":2.5,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13040322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607546","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":"Understanding and managing dextrocardia with <i>situs inversus</i>: A case report.","authors":"Nihaal Dinesh, Madhuvan Hithelmane Sreeramaiah, Sai Chakith Matta Ravi, Kalabharathi Hampapura Lakkappa Gowda","doi":"10.3892/br.2026.2132","DOIUrl":"10.3892/br.2026.2132","url":null,"abstract":"<p><p>Dextrocardia with <i>situs inversus</i> is an uncommon congenital disorder in which the heart and other organs in the chest and abdomen are reversed. Although it rarely causes symptoms, it can be linked to heart or systemic disorders and is challenging to diagnose due to its unique architecture. The present report describes the case of a 27-year-old man who presented with sudden breathing problems. A physical examination revealed no heartbeat on the left side and odd cardiac noises. Further electrocardiogram tests revealed classic symptoms of dextrocardia, including right axis deviation and inverted P and T waves in Lead 1. Imaging scans confirmed the diagnosis of dextrocardia with <i>situs inversus totalis</i>, which placed the liver and gallbladder on the left and the spleen on the right. Despite these uncommon structural abnormalities, the patient's heart functioned normally, as shown by echocardiography. The patient was provided with treatment (expectorant and mucolytics) for the breathing symptoms and directed to cardiologists and pulmonologists. The present case emphasizes the significance of conducting a thorough clinical and diagnostic investigation when encountering odd results. The report highlights the importance of practitioners being aware of unusual illnesses, such as <i>situs inversus</i>, to prevent misdiagnoses and unnecessary operations. The case is notable for the absence of structural cardiac damage despite a complete reversal of the internal architecture.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"24 5","pages":"59"},"PeriodicalIF":2.5,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13041194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607523","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":"Near-work activity duration and myopia in children: An updated systematic review and meta-analysis.","authors":"Yanxia Song, Wei Zheng, Xiaoge Yang, Suling Yang, Feifan Du, Haixia Tian","doi":"10.3892/br.2026.2131","DOIUrl":"10.3892/br.2026.2131","url":null,"abstract":"<p><p>The present systematic review and meta-analysis aimed to assess the association between near-work activity and myopia in children, as well as to examine the influence of potential moderators, such as age, region and study design. Multiple databases were systematically searched from inception through to June 2025 for observational studies exploring the connection between near work and myopia in children. Random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Analyses of heterogeneity, subgroup differences, meta-regressions and assessments of publication bias were conducted. A total of 33 studies (43 comparisons) were included. The pooled analysis revealed a significant association between increased near-work exposure and a higher risk of myopia in children (OR, 1.084; 95% CI, 1.060-1.108), although substantial heterogeneity was observed across studies (I²=85.2%). The 95% prediction interval (1.010-1.163) indicated that future studies would likely observe a similar positive association. Subgroup analyses demonstrated that the effect was consistent across continents, with the strongest correlation observed in Asian populations (OR, 1.177; 95% CI, 1.116-1.240) and the weakest in North America (OR, 1.098; 95% CI, 0.859-1.403). These patterns were confirmed by mixed-effects analysis. Meta-regression revealed no statistically significant moderators, and leave-one-out sensitivity analyses supported the stability of the results. Visual inspection of the funnel plot and quantitative tests pointed to minor publication bias, but the effect remained statistically significant after adjustment. In conclusion, higher levels of near-work activity are significantly linked to an increased risk of myopia in children. These findings highlight the importance of limiting prolonged near-work behaviors during childhood as part of comprehensive strategies to reduce myopia risk.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"24 5","pages":"58"},"PeriodicalIF":2.5,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13041198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607446","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":"Chalinasterol attenuates ethanol-induced hepatic lipid accumulation by activating β-oxidation.","authors":"Ji Hye Kim, Min Young Kim, Sejong Oh, Dong Hun Lee","doi":"10.3892/br.2026.2130","DOIUrl":"10.3892/br.2026.2130","url":null,"abstract":"<p><p>Alcoholic liver disease is a global health burden and, during its earliest stage, alcoholic steatosis, it is still reversible. Ethanol promotes hepatic lipid accumulation by enhancing lipogenesis and suppressing fatty acid oxidation. The present study investigated whether chalinasterol (CA), a natural compound derived from the seaweed <i>Capsosiphon fulvescens</i>, can attenuate ethanol-induced hepatic steatosis using <i>in vitro</i> hepatocytes and an <i>in vivo</i> mouse model. This revealed that CA significantly reduced ethanol-induced lipid accumulation. While it did not change the expression levels of lipogenesis-related genes or reduce reactive oxygen species levels, suggesting that its protective effect was not mediated through these pathways, it upregulated β-oxidation gene expression and increased phosphorylated AMP-activated protein kinase (AMPK) protein levels. It also reduced ethanol-induced elevated serum alanine transaminase and aspartate transaminase levels, indicating that CA attenuated early liver injury. Therefore, CA alleviated ethanol-induced hepatic steatosis by enhancing fatty acid oxidation through AMPK-peroxisome proliferator-activated receptor alpha activation, highlighting its potential as a preventive intervention for early-stage ALD.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"24 5","pages":"57"},"PeriodicalIF":2.5,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12996857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484508","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":"Preliminary exploration of the role of CD8⁺ T cells in anti-PD-1 antibody-induced myocarditis in C57BL/6 mice with Lewis lung carcinoma.","authors":"Huachun Chen, Fakai Li, Jun Song, Sheng Wang, Hanwen Xu, Ruoya Lyu, Hui Zhang, Guiyuan Chen, Xiaoyu Wu, Mingxing Ding","doi":"10.3892/br.2026.2129","DOIUrl":"10.3892/br.2026.2129","url":null,"abstract":"<p><p>Globally, ~33% of patients with non-small cell lung cancer receiving anti-PD-1 antibody therapy may experience significant immune-related adverse events (irAEs). Among these, myocarditis is a rare but lethal irAE. The aim of the present study was to preliminarily explore the role of CD8⁺ T cells in anti-PD-1 antibody-induced myocarditis in C57BL/6 mice with Lewis lung carcinoma (LLC). Orthotopic transplantation models were established using wild-type or CD8 knockout (CD8^-/-) C57BL/6 mice. Wild-type and CD8^-/- C57BL/6 mice were separately divided into three groups: Control, LLC and LLC + anti-PD-1. LLC cell suspensions (1x10⁵ cells) with 50 µl Matrigel Matrix were orthotopically injected into the left lung lobe of wild-type or CD8^-/- C57BL/6 mice. Following needle removal, the incision was sutured. At 10 days post-surgery, mice in the anti-PD-1 groups received an intraperitoneal injection of anti-PD-1 antibody (200 µg). After 3 weeks, all mice were humanely euthanized via intraperitoneal injection of sodium pentobarbital (200 mg/kg). The histopathological examination of tumor, lung and heart tissue was performed by Masson's trichrome and hematoxylin and eosin staining. Reverse transcription-quantitative PCR was carried out to determine the mRNA expression of monocyte chemotactic protein-1, interleukin-6, interferon-γ and tumor necrosis factor-α in myocardial tissue. Flow cytometry was used to analyze the ratio of CD8⁺ and CD4⁺ T cells and macrophages in myocardial tissues. Anti-PD-1 therapy effectively inhibited tumor growth and mitigated lung tissue damage. In wild-type C57BL/6 mouse, treatment with anti-PD-1 was associated with myocardial injury, inflammatory responses and a notable increase in the ratios of CD8⁺ and CD4⁺ T cells and macrophages. However, in CD8^-/- C57BL/6 mice, no significant differences were observed in myocardial histopathology, inflammatory cytokine levels and the ratios of CD4⁺ T cells and macrophages between the control, LLC and LLC + anti-PD-1 groups. Anti-PD-1 therapy did not cause significant damage to myocardial tissue. The presence of CD8⁺ T cells facilitated the development of anti-PD-1-induced myocarditis by activating CD4⁺ T cells, macrophages and inflammatory responses.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"24 5","pages":"56"},"PeriodicalIF":2.5,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12996858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484656","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":"Clinically aggressive early-onset pancreatic ductal adenocarcinoma with KRAS wild-type status: A case report.","authors":"Maria E Avendaño, Cristopher San Martin Abello, Fernán Gómez-Valenzuela, Ian Silva, Ignacio N Retamal, Benjamín García-Bloj, Tomás De Mayo Glaser, Matías Muñoz-Medel, Alex Gómez, Carolina Sánchez, Felipe Pinto, Paola Aravena, Andrea C Sabioncello, Marcelo Garrido Villanueva, Fernando Sigler Chávez, Ignacio Corvalán, Henry Barrios, Mauricio A Sáez, José M Erpel, Patricio A Manque, Juvenal A Rios, Juan A Godoy, Marcelo Garrido","doi":"10.3892/br.2026.2128","DOIUrl":"10.3892/br.2026.2128","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) represents one of the most lethal and challenging gastrointestinal (GI) malignancies. Predominant driver mutations for this cancer include <i>KRAS</i>, which is present in >90% of cases, alongside inactivating mutations in various tumor suppressor genes, such as <i>CDKN2A</i>, <i>TP53</i> and <i>SMAD4</i>. The present case report explores a case of early onset pancreatic cancer in a 45-year-old patient with cancer antigen 19-9 (CA 19-9) levels within the minimal range, a finding typically associated with advanced disease. Specifically, the tumor exhibited an atypical somatic molecular profile, characterized by mutations in the <i>ERBB2</i>, <i>MSH3</i>, <i>MUC1</i>/<i>MUC16</i> genes and the absence of <i>KRAS</i> mutations (<i>KRAS</i> wild type), which is an uncommon occurrence in PDAC. The presence of liver metastases and vascular invasion at diagnosis, coupled with the lack of response to standard FOLFIRINOX treatment, underscored the aggressiveness of the disease and highlighted the need to explore novel targeted therapies. The patient underwent surgery and has maintained a favorable response to date. This case of PDAC in a relatively young patient underscored a distinctive molecular profile that especially lacked <i>KRAS</i> mutations whilst featuring alterations in <i>ERBB2</i>, <i>MSH3</i> and <i>MUC1</i>/<i>MUC16</i>, potentially indicating a unique subgroup with unique biological and treatment responses. Additionally, CA19-9 levels within the minimal range suggest the need to identify alternative novel biomarkers with adequate sensitivity and specificity. This is because in >80% PDAC cases with stage II disease and beyond, CA-19-9 levels are elevated. The rarity of the present case, combined with the rapid progression despite FOLFIRINOX treatment, suggests that additional human epidermal growth factor receptor 2-targeted therapies may be necessary during disease progression.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"24 5","pages":"55"},"PeriodicalIF":2.5,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12998417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484596","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":"Anatomical variations of the maxillary sinuses: A cross-sectional study.","authors":"Soran H Tahir, Razhan Sabah, Yusif Firas, Botan Salih","doi":"10.3892/br.2026.2126","DOIUrl":"10.3892/br.2026.2126","url":null,"abstract":"<p><p>Anatomical variations of the maxillary sinus have important clinical implications, yet factors influencing maxillary sinus volume (MSV) remain debated. The present study evaluated MSV and related anatomical variations in an Iraqi population using multi-slice computed tomography. Sinus dimensions and volume were measured using the Radiant DICOM viewer, and variations including infraorbital nerve (ION) protrusion, septation, Haller cells, and hypoplasia were assessed. Maxillary sinus asymmetry was common. Males demonstrated significantly larger sinus volumes on both sides compared with females (P<0.001). Age had no significant effect on right MSV (P=0.123), whereas left MSV varied across age groups (P=0.025). A key finding was the strong association between ION protrusion and increased MSV bilaterally (P<0.001). Septations, Haller cells, and hypoplasia occurred infrequently but remained relevant anatomical considerations. Overall, the present study revealed substantial anatomical variability in the maxillary sinus and highlighted the importance of preoperative imaging, particularly when ION protrusion is present, to support safe and effective surgical planning.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"24 5","pages":"53"},"PeriodicalIF":2.5,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12997086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484588","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":"Integrated transcriptomic and molecular docking analysis identifies Rhotekin 2 as a promising therapeutic target for overcoming gemcitabine resistance in cholangiocarcinoma.","authors":"Sonexai Kidoikhammouan, Panupong Mahalapbutr, Prasertsri Ma-In, Worachart Lert-Itthiporn, Raksawan Deenonpoe, Utid Suriya, Sopit Wongkham, Wunchana Seubwai","doi":"10.3892/br.2026.2125","DOIUrl":"10.3892/br.2026.2125","url":null,"abstract":"<p><p>Gemcitabine resistance remains a significant problem in cholangiocarcinoma (CCA) treatment. The present study aimed to identify novel molecular targets associated with gemcitabine resistance in CCA using integrated bioinformatics, molecular docking, and experimental validation. Commonly differentially expressed genes (DEGs) were identified based on three public transcriptomic datasets (GSE116118, GSE208659, and GSE140077) from stable gemcitabine-resistant cancer cell lines. Expression levels of selected upregulated genes were validated in Thai patients with CCA using the GEO datasets. Further validation was performed using real-time PCR on parental and gemcitabine-resistant CCA cell lines (KKU-213A/KKU-100 and KKU-213A-GemR/KKU-100-GemR). The 3D structure of the candidate protein was modeled using AlphaFold3 and refined by molecular dynamics simulations. Druggable pockets were predicted using CavityPlus. Virtual screening of 5,396 drug-repurposing compounds was performed using AutoDock Vina to identify potential inhibitors of the candidate protein. In total, 14 DEGs were commonly upregulated in three datasets from stable gemcitabine-resistant cancer cell lines. A total of six genes, including RAB1B, JAG1, PACS1, ANKS6, SF3B4, and RTKN2, were significantly elevated in CCA tissues compared with adjacent normal tissues. Reverse transcription-quatitative PCR confirmed that RTKN2 was significantly overexpressed in two stable gemcitabine-resistant CCA cell lines, KKU-213A-GemR and KKU-100-GemR. Pathway analysis of RTKN2-associated genes revealed enrichment in mitochondrial and metabolic processes, including suppression of the TP53-regulated metabolic pathway. Molecular docking analysis identified several candidate compounds with strong binding affinities to RTKN2 (-10.49 to -11.47 kcal/mol), including NKP608, tegatrabetan, umbralisib, vepdegestrant, and MK-3207. RTKN2 was identified as a novel and druggable molecular target potentially contributing to gemcitabine resistance in CCA. Targeting RTKN2 may offer a promising approach to overcome chemoresistance and improve outcomes for patients with CCA.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"24 5","pages":"52"},"PeriodicalIF":2.5,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12997093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484663","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}