EXCLI Journal最新文献

{"title":"Cyclophosphamide-associated partial proximal tubular dysfunction.","authors":"Rutvikkumar Jadvani, Angel Juarez, Chintan V Shah","doi":"10.17179/excli2025-8622","DOIUrl":"10.17179/excli2025-8622","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"777-778"},"PeriodicalIF":4.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948210","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":"In silico evaluation of Toxoplasma gondii rhoptry neck proteins (TgRONs) for potential immunogenic epitopes.","authors":"Masoud Forouta, Hany M Elsheikha, Amir Karimipour-Saryazdi, Ali Dalir Ghaffari, Fatemeh Ghaffarifar, Hamidreza Majidiani","doi":"10.17179/excli2025-8304","DOIUrl":"10.17179/excli2025-8304","url":null,"abstract":"<p><p>This immunoinformatics-based study utilized a suite of online predictive tools to characterize the structural and immunogenic properties of <i>Toxoplasma gondii</i> rhoptry neck proteins (TgRONs). Full-length amino acid sequences of TgRON2, TgRON4, TgRON4L1, TgRON5, TgRON8, TgRON9, TgRON10, and TgRON13 were retrieved from ToxoDB and subjected to comprehensive analysis. Except for TgRON4L1, all proteins were predicted to be possess antigenic potential, with none identified as allergenic. Solubility predictions indicated that TgRON9 and TgRON10 are the most likely to be expressed as soluble antigens. Aliphatic index values, ranging from 51.17 to 84.63, suggest acceptable thermostability, while negative GRAVY scores across all proteins indicate favorable hydrophilicity. Additionally, multiple post-translational modification sites were identified, underscoring the functional complexity of these antigens. Initial 3D structure modeling showed that 60.21-92.41 % of residues fell within favored regions on Ramachandran plots, with refinement increasing this to 92.27-98.58 %, reflecting substantial improvements in structural quality. Several potential T-cell (CTL and HTL) and B-cell epitopes were predicted for all candidate proteins. Immune simulation models further suggested that these antigens could elicit robust humoral and cellular immune responses when delivered in a three-dose regimen at four-week intervals. These findings offer valuable preliminary insights and support the further investigation of TgRONs, particularly TgRON9 and TgRON10, as promising targets for experimental validation in the development of vaccines against <i>T. gondii</i> infection. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"749-773"},"PeriodicalIF":4.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948183","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":"The impact of artificial intelligence on drug discovery for neuropsychiatric disorders.","authors":"Vickram Agaram Sundaram, Bharath Saravanan, Bhavani Sowndharya Balamurugan, Mathan Muthu Chinnakannu Marimuthu, Kavita Munjal, Hitesh Chopra","doi":"10.17179/excli2025-8378","DOIUrl":"10.17179/excli2025-8378","url":null,"abstract":"<p><p>Artificial intelligence (AI) and machine learning (ML) are transforming medication discovery, particularly in neuropsychiatric illnesses, where traditional drug research presents major obstacles. This paper looks at how artificial intelligence might help advance neuropsychiatric medication development, with an emphasis on early-stage research, drug design, and clinical diagnostics. This review discusses AI's contribution to understanding the blood-brain barrier and its link with the central nervous system, which is an important aspect of medication efficacy in neuropsychiatric treatments. AI-facilitated de novo drug design, using predictive algorithms and deep learning models, speeds up the discovery of new medicinal molecules. AI is employed in brain imaging and diagnosis, boosting the accuracy with which neuropsychiatric diseases are identified. BBB permeability prediction is one of the most important uses of AI in drug discovery, as it improves the selection of CNS-active drugs. Additionally, AI is transforming treatment techniques for neurodevelopmental disorders and assisting in the discovery of novel antidepressant medications through data-driven methodologies. Despite these accomplishments, AI-driven drug discovery still has several constraints, such as data biases, regulatory barriers, and ethical issues. Overcoming these restrictions will be critical to unlocking AI's full potential in neuropsychiatric research. This paper concludes with several future possibilities and opportunities, such as incorporating AI into personalized medicine using sophisticated neural network models and multimodal data fusion techniques. This might increase treatment choices for certain conditions by fine-tuning AI approaches. This paper presents a perspective on AI as a highly transformative instrument for influencing neuropsychiatric drug development, as well as an emerging field that has the potential to impact the modern idea of pharmacology. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"728-748"},"PeriodicalIF":4.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948241","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":"Quercetin mitigates aluminum nanoparticle-induced neurotoxicity: a stereological and molecular study on memory, hippocampal integrity, and MAPK signaling.","authors":"Zahra Esmaili, Mohammad Shabani, Fatemeh Karimi, Moazamehosadat Razavinasab, Meysam Ahmadi-Zeidabadi, Majid Reza Farokhi, Maryam Moosavi","doi":"10.17179/excli2025-8315","DOIUrl":"10.17179/excli2025-8315","url":null,"abstract":"<p><p>Emerging evidence suggests a strong association between aluminum (Al) exposure and the development of Alzheimer's disease (AD). Due to their nanoscale size and increased surface area, Al nanoparticles (ALNP) exhibit greater neurotoxicity than bulk Al, raising concerns about their role in neurodegenerative disorders. While quercetin has been recognized for its neuroprotective effects, its ability to counteract ALNP-induced hippocampal neurodegeneration and dysregulated MAPK signaling remains largely unexplored. This study investigated the potential of quercetin to ameliorate ALNP-induced memory deficits, alterations in hippocampal stereological parameters, and disruptions in caspase-3 and MAPK signaling in male Swiss mice. Mice (SWR/J, aged 8-10 weeks) received ALNP (10 mg/kg, intraperitoneally for 10 days) with or without quercetin at doses of 1, 10, or 100 mg/kg (orally). Memory performance was assessed using the elevated plus maze (EPM), novel object recognition (NOR), and Y-maze tasks, followed by stereological and western blot analyses of the hippocampus. Our findings revealed that quercetin (100 mg/kg) significantly preserved hippocampal volume and neuronal integrity in the dentate gyrus (DG) and Cornu Ammonis 1 (CA1)-key regions involved in memory processing and output signaling. Additionally, quercetin modulated MAPK signaling by enhancing ERK phosphorylation while suppressing ALNP-induced activation of p38 and cleaved caspase-3, suggesting a role in reducing neuroinflammation and apoptosis. This is the first study to demonstrate that quercetin can counteract the neurotoxic effects of ALNP, highlighting its potential as a therapeutic strategy against nanoparticle-induced neurodegeneration in an Alzheimer's-like model. See also the graphical abstract.(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"708-727"},"PeriodicalIF":4.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948281","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":"COVID-19 vaccination, all-cause mortality, and hospitalization for cancer: 30-month cohort study in an Italian province.","authors":"Cecilia Acuti Martellucci, Angelo Capodici, Graziella Soldato, Matteo Fiore, Enrico Zauli, Roberto Carota, Marco De Benedictis, Graziano Di Marco, Rossano Di Luzio, Maria Elena Flacco, Lamberto Manzoli","doi":"10.17179/excli2025-8400","DOIUrl":"10.17179/excli2025-8400","url":null,"abstract":"<p><p>Anecdotal reports suggested an association between SARS-CoV-2 vaccination and some cancers, but no formal assessment has been published. This population-wide cohort analysis was aimed at evaluating the risk of all-cause death and cancer hospitalization by SARS-CoV-2 immunization status. Using National Health System official data, the entire population of the Pescara province, Italy was followed from June 2021 (six months after the first vaccination) to December 2023. Cox models were adjusted for age, gender, previous SARS-CoV-2 infection, and selected comorbidities. Of the 296,015 residents aged ≥11 years, 16.6% were unvaccinated, 83.3% received ≥1 dose, and 62.2% ≥3 doses. Compared with the unvaccinated, those receiving ≥1 dose showed a significantly lower likelihood of all-cause death, and a slightly higher likelihood of hospitalization for cancer (HR: 1.23; 95% CI: 1.11-1.37). The latter association was significant only among the subjects with no previous SARS-CoV-2 infection, and was reversed when the minimum time between vaccination and cancer hospitalization was set to 12 months. The subjects who received SARS-CoV-2 vaccination showed a substantial reduction in all-cause mortality, and a risk of cancer hospitalization that varied by infection status, cancer site, and the minimum lag-time after vaccination. Given that it was not possible to quantify the potential impact of the healthy vaccinee bias and unmeasured confounders, these findings are inevitably preliminary. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"690-707"},"PeriodicalIF":4.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948208","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":"Follow-up of GSTM1, GSTT1, and NAT2 genotyped patients with knee or hip replacement.","authors":"Selahattin Bozkurt, Silvia Selinski, Meinolf Blaszkewicz, Jörg Reinders, Jan G Hengstler, Lukas Niggemann, Klaus Golka","doi":"10.17179/excli2025-8565","DOIUrl":"10.17179/excli2025-8565","url":null,"abstract":"<p><p>A total of 147 patients, genotyped for glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) and for N-acetyltransferase 2 (NAT2), who had undergone total joint replacement of the knee or hip joint between August 2004 and June 2007, showed with 45% a remarkably lower portion of the <i>GSTM1</i>-negative genotype compared to both a local control (51%), an external control (52%) and the portion reported in the literature for the European population (50%). In contrast, the portions of <i>GSTT1</i>-positive (84%) and slow <i>NAT2</i> (55.1%) patients of the initial collective were unremarkable, compared to both controls. To elucidate a possible impact of this interesting finding on the long-term outcome, the patients were contacted in December 2015. Afterwards, they were interviewed using a self-prepared questionnaire. The average follow-up time was 9 years. At the time of follow-up, 57 patients were deceased, 46 patients did not respond and 12 patients declined the interview. A total of 32 patients participated in the follow-up. The mean age of the followed-up patients was 75.9±8.3 years, whereas the mean age of all patients at the time of surgery was 70.9±9 years. The portions of the <i>GSTM1</i>-negative genotype (15 out of 32; 47%), the <i>GSTT1</i>-positive genotype (24 out of 32; 75%) and the slow <i>NAT2</i> status (17 out of 32; 53%) in the followed-up patients were comparable to those of the initial collective. The follow-up results of the patients after 9 years were unable to clarify the significance of the observed lower portion of <i>GSTM1</i>-negative patients. In view of a recently published omics study reporting a reduced GSTM1 activity in tissue attached on hip implants explanted due to aseptic loosening, the striking portion of the <i>GSTM1</i>-negative genotype in this present study may encourage further investigation into the impact of this gene in patients with hip or knee replacement.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"677-689"},"PeriodicalIF":3.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590810","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":"Unraveling the complexity of ulcerative colitis: insights into cytokine dysregulation and targeted therapies.","authors":"Yuta Shimomori, Yoshihiro Yokoyama, Hiroki Kurumi, Kotaro Akita, Tomoe Kazama, Yuki Hayashi, Kazuhiro Mizukami, Hiroshi Nakase","doi":"10.17179/excli2025-8374","DOIUrl":"10.17179/excli2025-8374","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a chronic or recurrent inflammatory disease of the large intestine. Although the causes of UC are insufficiently understood, a complex interaction of several factors, including genetic factors, environmental factors, and gut microbiota, influences the onset of UC. The pathophysiology of UC involves intestinal barrier dysfunction, abnormal immune responses, and dysregulation of cytokines. Cytokine-targeted therapies have been approved for the treatment of UC, with several targeted therapies being currently available. The induction response rates range from 47.8 % to 73 %, and we often experience difficult-to-treat cases. In this review, we outlined the abnormal immune response and cytokine regulation underlying the complex pathology of UC. Moreover, we summarized the mode of action and the effects at the cellular and genetic levels of targeted therapies. A deeper understanding of the pathophysiology of UC and the effects of treatment is essential for advancing personalized medicine, which remains a key, challenging goal in the future management of UC.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"638-658"},"PeriodicalIF":3.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590811","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":"Unraveling the Hippo pathway: YAP/TAZ as central players in cancer metastasis and drug resistance.","authors":"Nehmat Ghaboura","doi":"10.17179/excli2025-8351","DOIUrl":"10.17179/excli2025-8351","url":null,"abstract":"<p><p>In regulating cellular plasticity, epithelial to mesenchymal transition (EMT), and tumor progression across a broad range of cancer types, the Hippo signaling pathway depends on YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ binding motif) as core effectors. This pathway can become dysregulated, disrupting tissue homeostasis and promoting oncogenic processes such as metastasis, immune evasion, and therapy resistance. This review explores the multifaceted roles of YAP/TAZ in lung, breast, ovarian, liver, and renal cancers, detailing their interactions with key signaling pathways such as TGF-β, Wnt, and PI3K/AKT and their modulation by mechanical cues like extracellular matrix stiffness and fluid shear stress. Potential YAP/TAZ mediated therapy resistance in EGFR TKI-resistant lung cancer and platinum-resistant ovarian cancer and the impact this has on tumor metabolism as a result of YAP/TAZ controlling tumor mesenchymal stem cells in the hypoxic environment of hepatocellular carcinoma is highlighted. Additionally, we discuss their role in maintaining cancer stem cell traits, creating an immunosuppressive tumor microenvironment, and driving chemoresistance in breast and renal cancers. Small molecule inhibitors, natural compounds (luteolin, apigenin, honokiol), and novel agents (nanoparticles of zinc oxide) are discussed as promising routes for disrupting YAP/TAZ. The review underscores the complexity of YAP/TAZ signaling and the need for patient stratification based on their expression levels to optimize targeted therapies. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"612-637"},"PeriodicalIF":3.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590812","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":"m6A methylation: a new frontier in epilepsy research and therapeutics.","authors":"Mudasir Maqbool, Yumna Khan, Mohammed M Arab, Saud O Alshammari, Md Sadique Hussain, Fawaz M Almufarriji","doi":"10.17179/2025-8359","DOIUrl":"10.17179/2025-8359","url":null,"abstract":"<p><p>Epilepsy is a highly complex and global neurological disorder, for which available treatments only inadequately control the disease in many patients. Recent advances in molecular research have identified N6-methyladenosine (m6A) RNA modifications as key regulators of neuronal processes that underpin the pathophysiology of epilepsy. This review critically discusses the emerging significance of m6A modifications in epilepsy, focusing on dynamic regulations of m6A \"writers,\" \"erasers,\" and \"readers\" for modulating gene expression, neuronal excitability, and synaptic plasticity in epilepsy. Dysregulation of m6A machinery promotes epilepsy by exacerbating oxidative stress, mitochondrial dysfunction, and neuronal damage. We also discuss the prognostic significance of m6A alterations as a potential biomarker in epilepsy diagnosis and disease progression, along with advanced therapeutic strategies against m6A, including small molecules, RNA editing technologies, and precision medicine. This review highlights the transformational significance of m6A modulation in epilepsy therapy and opens new avenues for personalized therapeutic strategies that may revolutionize the field of drug-resistant epilepsy and improve the prognosis for patients. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"578-611"},"PeriodicalIF":3.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316267","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":"Twenty years of inhaled insulin: promise, setbacks, and future directions.","authors":"Meriem Gaddas, Imen Ben Saida, Helmi Ben Saad","doi":"10.17179/2025-8260","DOIUrl":"10.17179/2025-8260","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"573-577"},"PeriodicalIF":3.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316269","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}