EXCLI Journal最新文献

{"title":"Candesartan cilexetil as a repurposed therapeutic candidate for nasopharyngeal carcinoma: Integrated in vitro and in silico analyses.","authors":"Chawalit Ngernsombat, Utid Suriya, Somsiri Udompaisarn, Natta Panomchoeng, Tavan Janvilisri","doi":"10.17179/excli2025-9094","DOIUrl":"https://doi.org/10.17179/excli2025-9094","url":null,"abstract":"<p><p>Nasopharyngeal carcinoma (NPC) is prevalent in East and Southeast Asia and is often diagnosed at advanced stages, where current treatment options are limited and associated with high relapse rates and toxicity. Repurposing clinically approved drugs provides a rapid, cost-effective strategy to identify new therapeutic interventions. Here, we investigated candesartan cilexetil (CC), an angiotensin II type 1 receptor (AT1R) blocker widely used for hypertension (13), for its potential anti-cancer effects in NPC. <i>In vitro</i> assays were performed to assess cell viability, proliferation, clonogenic survival, migration, cell-cycle distribution, and epithelial-mesenchymal transition (EMT) marker expression. Molecular mechanisms were examined via immunoblotting of AT1R and downstream MAPK and PI3K-AKT pathways. <i>In silico</i> molecular dynamics (MD) simulations were conducted to characterize CC-AT1R binding. We found that CC significantly decreased NPC cell viability and proliferation in a concentration-dependent manner, while exhibiting lower cytotoxicity toward immortalized nasopharyngeal epithelial cells. CC inhibited colony formation, induced G0/G1 cell-cycle arrest, and suppressed migration. EMT markers were differentially regulated, with consistent downregulation of vimentin and Slug but paradoxical cadherin changes, indicating context-dependent EMT modulation. Mechanistically, CC downregulated AT1R expression, reduced phosphorylation of p38 MAPK, and enhanced AKT phosphorylation, suggesting compensatory survival signaling. MD simulations confirmed stable CC-AT1R binding, identifying key residues critical for ligand stabilization. Therefore, CC exerts multi-faceted inhibitory effects on NPC cells through AT1R blockade and downstream modulation of oncogenic pathways. The integration of <i>in vitro</i> and <i>in silico</i> analyses highlights CC as a promising repurposed therapeutic candidate for NPC and supports further preclinical evaluation. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"204-221"},"PeriodicalIF":4.9,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12946440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world data of tirzepatide in obesity management: a multicenter study by the Italian Society of Obesity - Campania Region.","authors":"Luigi Barrea, Ludovica Verde, Martina Galasso, Renato Patrone, Lucia Digitale, Alessandro Limardi, Marcello Orio, Giovanni Ragozzino, Luigi Digitale, Vittorio Salvatore, Antonella Savoia, Silvia Savastano, Annamaria Colao, Giovanna Muscogiuri","doi":"10.17179/excli2025-9067","DOIUrl":"https://doi.org/10.17179/excli2025-9067","url":null,"abstract":"<p><p>Obesity is a growing public health concern, closely linked to metabolic and cardiovascular complications. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has shown substantial weight loss effects in clinical trials; however, real-world data, especially at lower doses, remain limited. This study aimed to evaluate the short-term effects of tirzepatide 2.5 mg and 5.0 mg on weight, metabolic parameters, and tolerability in adults with obesity in a real-world outpatient setting. This retrospective multicenter study included 70 adults with obesity but without type 2 diabetes, treated with tirzepatide between January and June 2025 in the Campania Region, Italy. Anthropometric and biochemical parameters were assessed at baseline. Follow-up data were collected at dose transitions: from 2.5 mg to 5.0 mg, and from 5.0 mg to 7.5 mg, allowing assessment of the effects of the 2.5 mg and 5.0 mg doses. Seventy participants were included (mean age 50.7 ± 10.2 years; 60 % female; BMI 37.5 ± 6.8 kg/m2). Treatment led to dose-dependent reductions in body weight, BMI, and waist circumference (p < 0.001 for all vs baseline and between doses). Significant improvements were observed in total cholesterol (p = 0.006 between doses), LDL cholesterol (p = 0.001), triglycerides (p < 0.001), prediabetes prevalence (p < 0.001 vs baseline; p = 0.002 between doses), fasting plasma glucose (p < 0.001 vs baseline; p < 0.001 between doses), insulin (p < 0.001 vs baseline; p < 0.001 between doses), HoMA-IR (p < 0.001 vs baseline; p < 0.001 between doses), AST (p = 0.012 vs baseline; p = 0.006 between doses), and ALT (p < 0.001 vs baseline; p = 0.007 between doses). Amylase increased significantly only at 5.0 mg (p = 0.016), while lipase remained unchanged. Renal function (eGFR) improved at both doses (p = 0.025 for 2.5 mg; p = 0.005 for 5.0 mg). Gastrointestinal adverse events were mild and similar between doses. In this real-world cohort, tirzepatide at 2.5 mg and 5.0 mg led to substantial improvements in weight and metabolic health, with good tolerability. These findings support its use in routine obesity care and justify further longitudinal research. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"191-203"},"PeriodicalIF":4.9,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12946444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the prenatal origins of the myeloproliferative neoplasms.","authors":"Stephen E Langabeer","doi":"10.17179/excli2025-9181","DOIUrl":"https://doi.org/10.17179/excli2025-9181","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"189-190"},"PeriodicalIF":4.9,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12946437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethnicity matters: The case for regional reference intervals in polycystic ovary syndrome (PCOS) diagnostics.","authors":"Pallav Sengupta, Sulagna Dutta","doi":"10.17179/excli2025-9011","DOIUrl":"10.17179/excli2025-9011","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"186-188"},"PeriodicalIF":4.9,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12901958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146200618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redefining the role of exercise: beyond medicine and polypill.","authors":"Kayvan Khoramipour, Susana López-Ortiz, Alejandro Santos-Lozano","doi":"10.17179/excli2025-9114","DOIUrl":"https://doi.org/10.17179/excli2025-9114","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"170-173"},"PeriodicalIF":4.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12946443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semaglutide and tirzepatide: Oral cavity effects of weight-loss therapies.","authors":"Maria Eduarda Bernardo, Felipe Gomes Dallepiane, Mario Escobar, Ariadne Cristiane Cabral Cruz, Cesar Augusto Magalhães Benfatti","doi":"10.17179/excli2025-9065","DOIUrl":"https://doi.org/10.17179/excli2025-9065","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"167-169"},"PeriodicalIF":4.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12946442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A cross-sectional exploratory study of rat sarcoma (Ras) activation in non-obese women with and without polycystic ovary syndrome.","authors":"Sara Anjum Niinuma, Haniya Habib, Ashleigh Suzu-Nishio Takemoto, Thozhukat Sathyapalan, Stephen L Atkin, Alexandra E Butler","doi":"10.17179/excli2025-9005","DOIUrl":"10.17179/excli2025-9005","url":null,"abstract":"<p><p>Studies in obese polycystic ovary syndrome (PCOS) have shown growth factors that activate rat sarcoma (Ras) proteins, which regulate intracellular signaling pathways, differ in PCOS; however, it is difficult to account for obesity, insulin resistance, and systemic inflammation that are linked to many of the features found in PCOS. This study explores Ras signaling proteins and related growth factors in non-obese women with and without PCOS. Somascan proteomic analysis of circulating KRas, Ras GTPase-activating protein-1 (RASA1), and 45 growth factor-related proteins that signal through Ras was undertaken in a non-obese population of women with (n=44) and without (n=78) PCOS, groups matched for age and body mass index (BMI), without insulin resistance (HOMA-IR) or systemic inflammation (normal CRP; C-reactive protein). There was an increase in the free androgen index (FAI, p<0.0001) and anti-Müllerian hormone (AMH, p<0.0001) in PCOS. Cohen's <i>d</i> showed a moderate effect size for 3 proteins, of which Vascular endothelial growth factor-A (VEGFA) and EGFR were increased and EGFR1 was decreased in PCOS (all FDR p<0.05). EGFR and VEGF pathways interact closely and when EGFR signaling decreases, VEGFA may increase to maintain angiogenic balance, suggesting that in non-obese PCOS there may be a signal for compensatory angiogenesis in a dysfunctional endothelial environment. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"174-185"},"PeriodicalIF":4.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12901957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146200611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA-Seq-based investigation of interferon-mediated antiviral activity of chlorophyll a from Tetraselmis sp.","authors":"Nalae Kang, Eun-A Kim, Yeon-Ji Lee, Seong-Yeong Heo, Jun-Ho Heo, Won-Kyu Lee, Yong-Kyun Ryu, Taeho Kim, Soo-Jin Heo","doi":"10.17179/excli2025-8841","DOIUrl":"10.17179/excli2025-8841","url":null,"abstract":"<p><p><i>Tetraselmis</i> sp., a marine microalga amenable to mass cultivation, possesses antiviral properties, partly attributed to chlorophyll a. However, the underlying antiviral mechanisms remain poorly characterized. In this study, we investigated the antiviral activity and mode of action of chlorophyll a derived from <i>Tetraselmis</i> sp. by performing transcriptomic analyses on three experimental groups: untreated, uninfected cells; Zika virus (ZIKV)-infected cells; and chlorophyll a-treated, ZIKV-infected cells. Treatment with 5 µM chlorophyll a induced differential expression of genes associated with interferon-inducible antiviral responses. Gene ontology analysis revealed significant enrichment of biological processes such as \"response to external stimulus\" and \"response to biotic stimulus.\" Notably, Venn diagram analysis of 130 differentially expressed genes (DEGs) demonstrated restoration of key interferon-stimulated genes, including interferon-induced protein with tetratricopeptide repeats (IFIT)1, IFIT2, IFIT3, and IFIT5, which was further validated by quantitative PCR and immunocytochemistry. These findings suggest that chlorophyll a from <i>Tetraselmis</i> sp. exerts antiviral effects primarily through modulation of interferon-mediated pathways. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"150-166"},"PeriodicalIF":4.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12901952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146200686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why does the world continue to struggle with effectively addressing hepatitis E?","authors":"Henrique Borges da Silva Grisard, Gislaine Fongaro","doi":"10.17179/excli2025-9166","DOIUrl":"https://doi.org/10.17179/excli2025-9166","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"131-132"},"PeriodicalIF":4.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12946441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurotoxicity of mancozeb-based commercial fungicide in human neuroblastoma SH-SY5Y cells.","authors":"Evelin G Cuadros-Buenaventura, Lenin Ramírez-Cando, Ronny A Ordoñez Sánchez, Johnny Chimborazo, Santiago J Ballaz","doi":"10.17179/excli2025-9090","DOIUrl":"https://doi.org/10.17179/excli2025-9090","url":null,"abstract":"<p><p>Mancozeb, a polymeric dithiocarbamate complex fungicide with zinc and manganese salts, has the potential to be neurotoxic to humans. Unfortunately, the parent molecule maneb has attracted far too much attention, limiting the available evidence on mancozeb neurotoxicity to preclinical research and non-human cells. We sought to evaluate mancozeb cytotoxicity in neuroblastoma SH-SY5Y cells at lower concentrations than those used for maneb in <i>in vitro</i> investigations in order to quantify its risk for humans. Commercial mancozeb showed concentration- and time-dependent neurotoxicity in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction test (EC₅₀= 5.9 µM and 1.7 µM at 24 h and 72 h respectively). Using the trypan blue exclusion dye, cell death toll reached around 100% after 24- and 72-hour exposure to mancozeb 1 µM and 0.5 µM respectively. Reactive oxygen species generated by mancozeb, which peaked at 4 µM, could be the cause of cell death. The number and length of neurites were concentration-dependently reduced by mancozeb at sub-µM concentrations, and this was accompanied by changes in cell biomechanical characteristics (stiffness) as determined by atomic force microscopy. The uncertainty factor obtained from our cytotoxic studies, when performing risk assessment of mancozeb, varied from 200 to 2000, which may result in detectable neurotoxicity in humans in accordance with international regulatory agencies recommendations. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"133-149"},"PeriodicalIF":4.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12946439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}