EXCLI Journal最新文献

{"title":"The role of immune dysregulation in the pathogenesis of type 1 diabetes: a paradigm shift in prevention strategies.","authors":"Rajiv G Gopalsamy, Hariharan Govindasamy, Jessiane B de Souza, Deise M R R Silva, Pedro H M Moura, Ronaldy S Santos, Marina Dos S Barreto, Adriana G Guimarães, Lucas A da M Santana, Lysandro P Borges, Eloia E D Silva","doi":"10.17179/excli2025-8233","DOIUrl":"https://doi.org/10.17179/excli2025-8233","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"539-541"},"PeriodicalIF":3.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076981","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":"Synthesis, structural studies, and inhibitory potential of selected sulfonamide analogues: insights from in silico and in vitro analyses.","authors":"Tahira Noor, Daniel C Schultz, Gustavo Seabra, Yuting Zhai, Kwangcheol Casey Jeong, Saleem Ahmed Bokhari, Fahim Ashraf Qureshi, Abdul Rauf Siddiqi, Chenglong Li","doi":"10.17179/excli2024-8118","DOIUrl":"https://doi.org/10.17179/excli2024-8118","url":null,"abstract":"<p><p>Antimicrobial resistance is a growing public health threat worldwide, and the current drug development pipeline has thus far been inadequate in addressing this impending crisis. Further research into antibiotic agents, both existing and novel, is therefore paramount for identifying suitable candidates to combat antibiotic-resistant pathogens. Sulfonamides, the first class of synthetic antibiotics, target dihydropteroate synthase (DHPS), a key bacterial enzyme. While this class of antibiotics has historically demonstrated great utility, their use has diminished due to resistance and undesired side effects. In the present study, we synthesized a selection of four sulfonamide analogues (<b>FQ5</b>, <b>FQ6</b>, <b>FQ7</b> and <b>FQ12</b>), validated their structures through NMR spectroscopy, and evaluated their inhibitory potential through computational docking and MIC assays against four bacterial strains: <i>Staphylococcus aureus</i> ATCC 25923, <i>Pseudomonas aeruginosa</i> ATCC 27853, <i>Escherichia coli</i> ATCC 35401 and <i>Bacillus subtilis</i> ATCC 6633. Each compound exhibited antibacterial activity; <b>FQ5</b> demonstrated the most potent activity, with an MIC of 32, 16, 16, and 16 µg/mL against aforementioned strains, respectively. <b>FQ6</b>, <b>FQ7</b> and <b>FQ12</b>, on the other hand, exhibited moderate activity against <i>P. aeruginosa</i> and <i>E. coli</i> (MIC = 128 µg/mL each) and low activity against <i>S. aureus</i> and <i>B. subtilis</i> (MIC = 256 µg/mL each). Molecular docking studies indicated that <b>FQ5</b> captures multiple hydrogen bonding, ionic, and π-π interactions with key binding pocket residues of DHPS, and <b>FQ5</b> also demonstrated superior predicted drug-likeness in <i>in silico</i> ADMET studies compared to other compounds. <b>FQ5</b> is therefore a favorable starting point for further optimization.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"527-538"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076979","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":"Bacteriophages as potential therapeutic agents in the control of bacterial infections.","authors":"Felipe Gomes Dallepiane, Malena Alejandro Coimbra Nogueira, Lucas Menezes Dos Anjos, Gilberto De Souza Melo, João Paulo De Carli, Bruno Henriques, Gislaine Fongaro, Ariadne Cristiane Cabral Cruz","doi":"10.17179/excli2025-8145","DOIUrl":"https://doi.org/10.17179/excli2025-8145","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"524-526"},"PeriodicalIF":3.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076928","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":"Hypothesis-driven weight of evidence evaluation indicates ethylbenzene lacks endocrine disruption potential by EATS pathways.","authors":"Christopher J Borgert","doi":"10.17179/excli2024-7822","DOIUrl":"https://doi.org/10.17179/excli2024-7822","url":null,"abstract":"<p><p>Ethylbenzene (EB) was placed on List 2 for Tier 1 endocrine screening in the U.S. EPA's two-tiered Endocrine Disruptor Screening Program (EDSP) and was scheduled for evaluation under TSCA. Results of toxicology studies on EB were used to evaluate estrogen, androgen, thyroid, and steroidogenic (EATS) endpoints by a Weight of Evidence (WoE) methodology, as required by U.S. EPA and OECD guidelines for evaluating a chemical's endocrine disruptive potential. The WoE method involved problem formulation, systematic literature search and selection, data quality evaluation, relevance weighting of endpoint data, and application of specific interpretive criteria. Data on EB were sufficient to assess its effects on endpoints that would be expected to respond to chemicals that operate via EATS modes of action (MoAs) in various screening assays (Tier 1) and toxicity tests (Tier 2) that evaluate reproduction, development, and sub-chronic and chronic toxicity. In those studies, EB produced a pattern of responses inconsistent with the responses that would be expected for hormones and chemicals known to operate via EATS MoAs. Endocrine-sensitive endpoints that respond to EB administration generally do so only at dose levels above its kinetic maximum dose, indicating a lack of relevance to potential effects at lower dose levels in either the test species or humans. This comprehensive WoE evaluation demonstrates that EB lacks the potential to exhibit endocrine disruptive properties and cannot be deemed an endocrine disruptor or potential endocrine disruptor. Because this WoE evaluation was based largely on Tier 2-level studies of the type considered by the U.S. EPA and OECD to be more definitive than results of Tier 1 EDSP screening results, no additional useful information would be obtained by subjecting EB to further endocrine screening. As such, further endocrine screening of EB would be unjustified from animal welfare perspectives. This analysis supports a regulatory decision to halt further testing of EB for endocrine disruption unless unique and compelling data to the contrary arise. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"479-507"},"PeriodicalIF":3.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076842","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":"Exploring the prevalence and risk factors of adolescent mental health issues in the COVID and post-COVID era in the U.K.: A systematic review.","authors":"Kelvin Kanayo Nwabueze, Nnaemeka Akubue, Ademola Onakoya, Stella Chidinma Okolieze, Ikponmwosa J Otaniyen-Igbinoba, Chisom Chukwunonye, Chinelo Grace Okengwu, Temiloluwa Ige, Oluwaseyi Joy Alao, Kelechi Nelson Adindu","doi":"10.17179/excli2025-8325","DOIUrl":"https://doi.org/10.17179/excli2025-8325","url":null,"abstract":"<p><p>Adolescence is a developmental phase largely characterized by rapid biological and non-biological transformations, with a heightened susceptibility to social and environmental influences. Hence, adolescents are particularly vulnerable to external stressors, underscoring the need to safeguard their well-being and prioritize mental health interventions. The coronavirus disease (COVID-19) pandemic caused a global crisis with profound societal disruptions, and led to lasting impact on global public health, disproportionately affecting vulnerable populations, including adolescents. In view of the unique developmental challenges faced by adolescents, it is imperative to assess the growing burden of mental health issues exacerbated by the pandemic. This review synthesizes existing evidence on the emerging mental health challenges faced by adolescents in the United Kingdom (UK) as exacerbated by the COVID-19 pandemic. A systematic literature search was conducted using PubMed, ScienceDirect, MEDLINE, and SpringerNature databases, resulting in the selection of ten high-quality studies. A thematic analysis of the collected data revealed that depression and anxiety were the most frequently reported mental health conditions among adolescents. These conditions were particularly prevalent among adolescents who were from low-income households, those with pre-existing mental health disorders, adolescents experiencing household conflicts, females, and those who provided self-reported data. Several key risk factors were identified, including family and peer relationships, academic pressures such as examinations and grades, financial constraints within households, and the corruptive influence of social media. The findings underscore the urgency of targeted mental health interventions tailored to the specific needs of adolescents in the U.K. By addressing the identified risk factors, mental health professionals, policymakers, and educators can develop more effective strategies to mitigate the psychological impact of the pandemic on this vulnerable population. This study contributes to the evolving body of literature and emphasizes the need for evidence-based policies to foster overall well-being and resilience in adolescents navigating post-pandemic challenges.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"508-523"},"PeriodicalIF":3.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076840","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":"Coronary microvascular dysfunction: pathophysiology, diagnosis, and therapeutic strategies across cardiovascular diseases.","authors":"Vincenzo Scarica, Riccardo Rinaldi, Francesco Maria Animati, Matteo Manzato, Rocco A Montone","doi":"10.17179/excli2025-8285","DOIUrl":"https://doi.org/10.17179/excli2025-8285","url":null,"abstract":"<p><p>Ischemic heart disease (IHD) is a leading cause of morbidity and mortality worldwide, presenting with acute and chronic coronary syndromes. Although coronary atherosclerosis is a major cause of IHD, many patients with angina or myocardial ischemia do not have obstructive coronary heart disease and impairment of the coronary microcirculation has been increasingly implicated as a relevant cause of IHD. Therefore, coronary microvascular dysfunction (CMD) refers to a term covering a wide spectrum of structural and functional alterations which affect the coronary microcirculation leading to myocardial ischemia and angina. The advent of non-invasive and invasive functional tests has exponentially broadened the ability to recognize CMD and delineate related clinical and biochemical features. Despite major advances in diagnosing and stratifying this condition, therapeutic strategies remain limited and poorly defined. In this review, we will provide an overview of the pathophysiology and the diagnostic evaluation of CMD across the spectrum of cardiovascular diseases. Furthermore, we will discuss the novel therapeutic strategies available for these patients in the perspective of a personalized medicine approach.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"454-478"},"PeriodicalIF":3.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076929","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":"Erratum: Nargenicin A1 attenuates lipopolysaccharide-induced inflammatory and oxidative response by blocking the NF-κB signaling pathway.","authors":"Da Hye Kwon, Gi-Young Kim, Hee-Jae Cha, Suhkmann Kim, Heui-Soo Kim, Hye-Jin Hwang, Yung Hyun Choi","doi":"10.17179/excli2025-8358","DOIUrl":"https://doi.org/10.17179/excli2025-8358","url":null,"abstract":"<p><p>[This corrects the article on p. 968 in vol. 20, PMID: 34267609.].</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"452-453"},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709176","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 possible approach to overcome the systemic toxicity of azathioprine (AZA) through nanoemulgel.","authors":"Bikash Kumar Sah, Faiz Ahmad, Sachin Kumar Singh, Ankit Kumar","doi":"10.17179/excli2025-8223","DOIUrl":"https://doi.org/10.17179/excli2025-8223","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"450-451"},"PeriodicalIF":3.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076926","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":"Using novel oxidative phosphorylation inhibitors to attenuate drug resistance in human gliomas.","authors":"Chia-Kuang Tsai, Chin-Yu Lin, Yung-Lung Chang, Fu-Chi Yang, Chung-Hsing Chou, Yu-Chian Huang, Dueng-Yuan Hueng","doi":"10.17179/excli2025-8193","DOIUrl":"https://doi.org/10.17179/excli2025-8193","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is an aggressive brain tumor with a poor prognosis, worsened by resistance to temozolomide (TMZ). TMZ-induced DNA damage is counteracted by the repair enzyme O-6-methylguanine-DNA methyltransferase (MGMT), promoting tumor recurrence. Targeting oxidative phosphorylation (OXPHOS), essential for cellular energy production, offers a potential therapeutic strategy to overcome TMZ resistance and improve GBM treatment outcomes. Gboxin, a small-molecule drug, selectively inhibits OXPHOS by targeting complex V, with minimal toxicity to normal cells. It accumulates in the mitochondria of GBM cells, exploiting their high membrane potential and pH, thereby inhibiting cell proliferation. This study evaluates Gboxin's efficacy in TMZ-resistant (TMZ-R) GBM. Results show that Gboxin suppresses the growth of both TMZ-sensitive and TMZ-R GBM cells by inhibiting proliferation, inducing apoptosis, and reducing OXPHOS activity. These findings were confirmed in an <i>in vivo</i> model, highlighting Gboxin as a promising therapeutic for both TMZ-sensitive and TMZ-R GBM. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"433-449"},"PeriodicalIF":3.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076983","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":"From genes to epigenes: DNA methylation in the pathogenesis of Moyamoya disease.","authors":"Md Sadique Hussain, Vikas Jakhmola, Gyas Khan, Gaurav Gupta","doi":"10.17179/excli2025-8206","DOIUrl":"10.17179/excli2025-8206","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"430-432"},"PeriodicalIF":3.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751718","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}