EXCLI JournalPub Date : 2024-09-03eCollection Date: 2024-01-01DOI: 10.17179/excli2024-7552
Gustavo Scheiffer, Karime Zeraik Abdalla Domingues, Daniela Gorski, Alexandre de Fátima Cobre, Raul Edison Luna Lazo, Helena Hiemisch Lobo Borba, Luana Mota Ferreira, Roberto Pontarolo
{"title":"<i>In silico</i> approaches supporting drug repurposing for Leishmaniasis: a scoping review.","authors":"Gustavo Scheiffer, Karime Zeraik Abdalla Domingues, Daniela Gorski, Alexandre de Fátima Cobre, Raul Edison Luna Lazo, Helena Hiemisch Lobo Borba, Luana Mota Ferreira, Roberto Pontarolo","doi":"10.17179/excli2024-7552","DOIUrl":"10.17179/excli2024-7552","url":null,"abstract":"<p><p>The shortage of treatment options for leishmaniasis, especially those easy to administer and viable for deployment in the world's poorest regions, highlights the importance of employing these strategies to cost-effectively investigate repurposing candidates. This scoping review aims to map the studies using <i>in silico</i> methodologies for drug repurposing against leishmaniasis. This study followed JBI recommendations for scoping reviews. Articles were searched on PubMed, Scopus, and Web of Science databases using keywords related to leishmaniasis and <i>in silico</i> methods for drug discovery, without publication date restrictions. The selection was based on primary studies involving computational methods for antileishmanial drug repurposing. Information about methodologies, obtained data, and outcomes were extracted. After the full-text appraisal, 34 studies were included in this review. Molecular docking was the preferred method for evaluating repurposing candidates (n=25). Studies reported 154 unique ligands and 72 different targets, sterol 14-alpha demethylase and trypanothione reductase being the most frequently reported. <i>In silico</i> screening was able to correctly pinpoint some known active pharmaceutical classes and propose previously untested drugs. Fifteen drugs investigated <i>in silico</i> exhibited low micromolar inhibition (IC<sub>50</sub> < 10 µM) of <i>Leishmania</i> spp. <i>in vitro</i>. In conclusion, several <i>in silico</i> repurposing candidates are yet to be investigated <i>in vitro</i> and <i>in vivo</i>. Future research could expand the number of targets screened and employ advanced methods to optimize drug selection, offering new starting points for treatment development. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1117-1169"},"PeriodicalIF":3.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461525","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}
EXCLI JournalPub Date : 2024-09-03eCollection Date: 2024-01-01DOI: 10.17179/excli2024-7088
Julia Skoracka, Kaja Bajewska, Maciej Kulawik, Wiktoria Suchorska, Katarzyna Kulcenty
{"title":"Advances in cartilage tissue regeneration: a review of stem cell therapies, tissue engineering, biomaterials, and clinical trials.","authors":"Julia Skoracka, Kaja Bajewska, Maciej Kulawik, Wiktoria Suchorska, Katarzyna Kulcenty","doi":"10.17179/excli2024-7088","DOIUrl":"10.17179/excli2024-7088","url":null,"abstract":"<p><p>Cartilage tissue, characterized by its limited regenerative capacity, presents significant challenges in clinical therapy. Recent advancements in cartilage regeneration have focused on integrating stem cell therapies, tissue engineering strategies, and advanced modeling techniques to overcome existing limitations. Stem cells, particularly Mesenchymal Stem Cells (MSCs) and induced pluripotent stem cells (iPSCs), hold promise for cartilage repair due to their ability to differentiate into chondrocytes, the key cells responsible for cartilage formation. Tissue engineering approaches, including 3D models, organ-on-a-chip systems, and organoids, offer innovative methods to mimic natural tissue microenvironments and evaluate potential treatments. MSC-based techniques, such as cell sheet tissue engineering, address challenges associated with traditional therapies, including cell availability and culture difficulties. Furthermore, advancements in 3D bioprinting enable the fabrication of complex tissue structures, while organ-on-a-chip systems provide microfluidic platforms for disease modeling and physiological mimicry. Organoids serve as simplified models of organs, capturing some complexity and enabling the monitoring of pathophysiological aspects of cartilage diseases. This comprehensive review underscores the transformative potential of integrating stem cell therapies, tissue engineering strategies, and advanced modeling techniques to improve cartilage regeneration and pave the way for more effective clinical treatments.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1170-1182"},"PeriodicalIF":3.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399889","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}
EXCLI JournalPub Date : 2024-08-29eCollection Date: 2024-01-01DOI: 10.17179/excli2024-7342
Kind-Leng Tong, Ahmad Syadi Mahmood Zuhdi, Pooi-Fong Wong
{"title":"The role of miR-134-5p in 7-ketocholesterol-induced human aortic endothelial dysfunction.","authors":"Kind-Leng Tong, Ahmad Syadi Mahmood Zuhdi, Pooi-Fong Wong","doi":"10.17179/excli2024-7342","DOIUrl":"10.17179/excli2024-7342","url":null,"abstract":"<p><p>Atherosclerotic cardiovascular diseases are the leading causes of morbidity and mortality worldwide. In our previous study, a panel of miRNA including miR-134-5p was deregulated in young acute coronary syndrome (ACS) patients. However, the roles of these ACS-associated miRNAs in endothelial dysfunction, an early event preceding atherosclerosis, remain to be investigated. In the present study, human aortic endothelial cells (HAECs) were treated with 7-ketocholesterol (7-KC) to induce endothelial dysfunction. Following treatment with 20 μg/ml 7-KC, miR-134-5p was significantly up-regulated and endothelial nitric oxide synthase (eNOS) expression was suppressed. Endothelial barrier disruption was evidenced by the deregulation of adhesion molecules including the activation of focal adhesion kinase (FAK), down-regulation of VE-cadherin, up-regulation of adhesion molecules (E-selectin and ICAM-1), increased expression of inflammatory genes (<i>IL1B</i>, <i>IL6</i> and <i>COX2</i>) and AKT activation. Knockdown of miR-134-5p in 7-KC-treated HAECs attenuated the suppression of eNOS, the activation of AKT, the down-regulation of VE-cadherin and the up-regulation of E-selectin. In addition, the interaction between miR-134-5p and <i>FOXM1</i> mRNA was confirmed by the enrichment of <i>FOXM1</i> transcripts in the pull-down miRNA-mRNA complex. Knockdown of miR-134-5p increased <i>FOXM1</i> expression whereas transfection with mimic miR-134-5p decreased FOXM1 protein expression. In summary, the involvement of an ACS-associated miRNA, miR-134-5p in endothelial dysfunction was demonstrated. Findings from this study could pave future investigations into utilizing miRNAs as a supplementary tool in ACS diagnosis or as targets for the development of therapeutics.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1073-1090"},"PeriodicalIF":3.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399904","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}
EXCLI JournalPub Date : 2024-08-28eCollection Date: 2024-01-01DOI: 10.17179/excli2024-7737
Muhammad Shaheer Bin Faheem, Omer Farooq
{"title":"Navigating the rise of Fusarium meningitis: perspective on the insights and therapeutic approaches.","authors":"Muhammad Shaheer Bin Faheem, Omer Farooq","doi":"10.17179/excli2024-7737","DOIUrl":"https://doi.org/10.17179/excli2024-7737","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1071-1072"},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461527","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":"Opening avenue for the targeted treatment of lung cancer using xanthohumol loaded nanostructured lipid carriers.","authors":"Shubham Singh, Sangeeta Saxena, Himani Sharma, Gaurav Gupta, Kamal Dua, Sachin Kumar Singh","doi":"10.17179/excli2024-7656","DOIUrl":"https://doi.org/10.17179/excli2024-7656","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1068-1070"},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461528","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}
EXCLI JournalPub Date : 2024-08-27eCollection Date: 2024-01-01DOI: 10.17179/excli2024-7519
Waleed Hassan Almalki, Salem Salman Almujri
{"title":"Oxidative stress and senescence in aging kidneys: the protective role of SIRT1.","authors":"Waleed Hassan Almalki, Salem Salman Almujri","doi":"10.17179/excli2024-7519","DOIUrl":"10.17179/excli2024-7519","url":null,"abstract":"<p><p>Aging leads to a gradual decline in kidney function, making the kidneys increasingly vulnerable to various diseases. Oxidative stress, together with cellular senescence, has been established as paramount in promoting the aging process of the kidney. Oxidative stress, defined as an imbalance between ROS formation and antioxidant defense mechanisms, has been implicated in the kidney's cellular injury, inflammation, and premature senescence. Concurrently, the accumulation of SCs in the kidney also exacerbates oxidative stress via the secretion of pro-inflammatory and tissue-damaging factors as the senescence-associated secretory phenotype (SASP). Recently, SIRT1, a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, has been pivotal in combating oxidative stress and cellular senescence in the aging kidney. SIRT1 acts as a potential antioxidant molecule through myriad pathways that influence diverse transcription factors and enzymes essential in maintaining redox homeostasis. SIRT1 promotes longevity and renal health by modulating the acetylation of cell cycle and senescence pathways. This review covers the complex relationship between oxidative stress and cellular senescence in the aging kidney, emphasizing the protective role of SIRT1. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1030-1067"},"PeriodicalIF":3.8,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399902","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}
EXCLI JournalPub Date : 2024-08-26eCollection Date: 2024-01-01DOI: 10.17179/excli2024-7652
Muthu Thiruvengadam
{"title":"Targeting the YAP/TAZ Hippo signaling pathway for oral cancer treatment.","authors":"Muthu Thiruvengadam","doi":"10.17179/excli2024-7652","DOIUrl":"https://doi.org/10.17179/excli2024-7652","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1023-1026"},"PeriodicalIF":3.8,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461530","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}
EXCLI JournalPub Date : 2024-08-19eCollection Date: 2024-01-01DOI: 10.17179/excli2024-7375
Lucindo José Quintans-Júnior
{"title":"An AI without ethical boundaries?","authors":"Lucindo José Quintans-Júnior","doi":"10.17179/excli2024-7375","DOIUrl":"https://doi.org/10.17179/excli2024-7375","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1018-1019"},"PeriodicalIF":3.8,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11382298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282668","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}
EXCLI JournalPub Date : 2024-08-19eCollection Date: 2024-01-01DOI: 10.17179/excli2024-7591
Carolina Santos Souza Tavares, Raquel Souza Marques, Paulo Ricardo Martins-Filho
{"title":"High prevalence of common mental disorders in mothers of children with congenital Zika syndrome at the end of early childhood.","authors":"Carolina Santos Souza Tavares, Raquel Souza Marques, Paulo Ricardo Martins-Filho","doi":"10.17179/excli2024-7591","DOIUrl":"https://doi.org/10.17179/excli2024-7591","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1020-1022"},"PeriodicalIF":3.8,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11382251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282680","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}