EXCLI Journal最新文献

{"title":"Validation of NBD-coupled taurocholic acid for intravital analysis of bile acid transport in liver and kidney of mice.","authors":"Ahmed Ghallab, Sebastian Kunz, Celine Drossel, Veronica Billo, Adrian Friebel, Mats Georg, Richard Göttlich, Zaynab Hobloss, Reham Hassan, Maiju Myllys, Abdel-Latief Seddek, Noha Abdelmageed, Paul A Dawson, Erik Lindström, Stefan Hoehme, Jan G Hengstler, Joachim Geyer","doi":"10.17179/excli2024-7707","DOIUrl":"10.17179/excli2024-7707","url":null,"abstract":"<p><p>Fluorophore-coupled bile acids (BA) represent an important tool for intravital analysis of BA flux in animal models of cholestatic diseases. However, addition of a fluorophore to a BA may alter transport properties. We developed and validated a 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole-coupled taurocholic acid (3β-NBD-TCA) as a probe for intravital analysis of BA homeostasis. We compared transport of 3β-NBD-TCA to [3H]-TCA in HEK293 cells stably expressing the mouse hepatic or renal BA carriers mNtcp or mAsbt, respectively. We also studied distribution kinetics intravitally in livers and kidneys of anesthetized wildtype and mOatp1a/1b cluster knockout mice (OatpKO) with and without administration of the Ntcp inhibitor Myrcludex B and the ASBT inhibitor AS0369. In vitro, 3β-NBD-TCA and [3H]-TCA showed comparable concentration- and time-dependent transport via mNtcp and mAsbt as well as similar inhibition kinetics for Myrcludex B and AS0369. Intravital analysis in the livers of wildtype and OatpKO mice revealed contribution of both mNtcp and mOatp1a/1b in the 3β-NBD-TCA uptake from the sinusoidal blood into hepatocytes. Combined deletion of mOatp1a/1b and inhibition of mNtcp by Myrcludex B blocked the uptake of 3β-NBD-TCA from sinusoidal blood into hepatocytes. This led to an increase of 3β-NBD-TCA signal in the systemic circulation including renal capillaries, followed by strong enrichment in a subpopulation of proximal renal tubular epithelial cells (TEC). The enrichment of 3β-NBD-TCA in TEC was strongly reduced by the systemic ASBT inhibitor AS0369. NBD-coupled TCA has similar transport kinetics as [3H]-TCA and can be used as a tool to study hepatorenal BA transport. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1330-1352"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686587","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":"Deoxybouvardin-glucoside induces apoptosis in non-small cell lung cancer cells by targeting EGFR/MET and AKT signaling pathway.","authors":"Na Yeong Lee, Sang Hoon Joo, A-Young Nam, Seung-On Lee, Goo Yoon, Seung-Sik Cho, Yung Hyun Choi, Jin Woo Park, Jung-Hyun Shim","doi":"10.17179/excli2024-7359","DOIUrl":"10.17179/excli2024-7359","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. Its treatment is complicated due to the development of resistance to conventional chemotherapy and targeted therapy. Deoxybouvardin and related cyclic hexapeptides reportedly exhibit antitumor activities, but their mechanisms of action remain unclear. This study aimed to investigate the anticancer mechanisms of deoxybouvardin glucoside (DBG), a glucosidic form of deoxybouvardin from <i>Rubia</i> species, in gefitinib (GEF)-sensitive and -resistant NSCLC HCC827 cells. The effects of DBG treatment on cell proliferation were evaluated using a viability assay. The inhibitory effects of DBG treatment on the activities and phosphorylation of the protein kinases epidermal growth factor receptor (EGFR), MET, and AKTs were assessed using <i>in vitro</i> kinase assay and western blot, respectively. DBG treatment inhibited the growth of HCC827 cells in a concentration- and time-dependent manner. Results of <i>in vitro</i> kinase assay and western blotting showed that DBG treatment significantly inhibited the activities and phosphorylation of the protein kinases EGFR, MET, and AKT. Prediction using molecular docking showed that DBG is located in the ATP-binding pockets of these kinases, supporting the kinase inhibition by DBG treatment. Moreover, DBG treatment induced reactive oxygen species (ROS) generation and cell cycle arrest in the cells. The induction of apoptosis by DBG through caspase activation was confirmed by Z-VAD-FMK treatment. In summary, DBG treatment inhibited the growth of GEF-sensitive and -resistant NSCLC cells by targeting EGFR, MET, and AKTs. Moreover, it induced apoptosis by inducing ROS generation and caspase activation. These results indicate that DBG is a potential therapeutic agent for the treatment of GEF-resistant NSCLC. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1287-1302"},"PeriodicalIF":3.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686581","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 paradigm shift in the detection of bloodborne pathogens: conventional approaches to recent detection techniques.","authors":"Sonali Khanal, Manjusha Pillai, Deblina Biswas, Muhammad Torequl Islam, Rachna Verma, Kamil Kuca, Dinesh Kumar, Asim Najmi, Khalid Zoghebi, Asaad Khalid, Syam Mohan","doi":"10.17179/excli2024-7392","DOIUrl":"10.17179/excli2024-7392","url":null,"abstract":"<p><p>Bloodborne pathogens (BBPs) pose formidable challenges in the realm of infectious diseases, representing significant risks to both human and animal health worldwide. The review paper provides a thorough examination of bloodborne pathogens, highlighting the serious worldwide threat they pose and the effects they have on animal and human health. It addresses the potential dangers of exposure that healthcare workers confront, which have affected 3 million people annually, and investigates the many pathways by which these viruses can spread. The limitations of traditional detection techniques like PCR and ELISA have been criticized, which has led to the investigation of new detection methods driven by advances in sensor technology. The objective is to increase the amount of knowledge that is available regarding bloodborne infections as well as effective strategies for their management and detection. This review provides a thorough overview of common bloodborne infections, including their patterns of transmission, and detection techniques.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1245-1275"},"PeriodicalIF":3.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686480","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":"Fisetin-loaded nanoemulsion ameliorates lung cancer pathogenesis via downregulating cathepsin-B, galectin-3 and enolase in an <i>in vitro</i> setting.","authors":"Ayeh Bani Saeid, Keshav Raj Paudel, Gabriele De Rubis, Samir Mehndiratta, Sofia Kokkinis, Sukriti Vishwas, Stewart Yeung, Gaurav Gupta, Sachin Kumar Singh, Kamal Dua","doi":"10.17179/excli2024-7583","DOIUrl":"10.17179/excli2024-7583","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1238-1244"},"PeriodicalIF":3.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686583","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":"Ultrastructural alterations and mitochondrial dysfunction in skeletal muscle of peripheral artery disease patients: implications for early therapeutic interventions.","authors":"Dylan Wilburn, Emma Fletcher, Evlampia Papoutsi, William T Bohannon, Gleb Haynatzki, Bernd Zechmann, Yuqian Tian, Iraklis I Pipinos, Dimitrios Miserlis, Panagiotis Koutakis","doi":"10.17179/excli2024-7592","DOIUrl":"10.17179/excli2024-7592","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Peripheral artery disease (PAD) is an atherosclerotic condition that impairs blood flow to the lower extremities, resulting in myopathy in affected skeletal muscles. Improving our understanding of PAD and developing novel treatment strategies necessitates a comprehensive examination of cellular structural alterations that occur in the muscles with disease progression. Here we aimed to employ electron microscopy to quantify skeletal muscle ultrastructural alterations responsible for the myopathy of PAD. Fifty-two participants (22 controls, 10 PAD Stage II, and 20 PAD Stage IV) were enrolled. Gastrocnemius biopsies were obtained to determine mitochondrial respiration and oxidative stress. Skeletal muscle sarcomere, mitochondria, lipid droplets, and sarcoplasm were assessed using transmission electron microscopy and focused ion beam scanning electron microscopy. Controls and PAD Stage II patients underwent walking performance tests: 6-minute walking test, 4-minute walking velocity, and maximum graded treadmill test. We identified several prominent ultrastructural modifications in PAD gastrocnemius, including reduced sarcomere dimensions, alterations in mitochondria number and localization, myofibrillar disorientation, changes in lipid droplets, and modifications in mitochondria-lipid droplet contact area. These changes correlated with impaired mitochondrial respiration and increased ROS production. We observed progressive deterioration in mitochondrial parameters across PAD stages. Stage II PAD showed impaired mitochondrial function and structure, while stage IV exhibited further deterioration, more pronounced structural alterations, and a decrease in mitochondrial content. The walking performance of Stage II PAD patients was significantly reduced. Our findings suggest that pathological mitochondria play a key role in the skeletal muscle dysfunction of PAD patients and represent an important target for therapeutic interventions aimed at improving clinical and functional outcomes in this patient population. Our data indicate that treatments should be implemented early and may include therapies designed to preserve and enhance mitochondrial biogenesis and respiration, optimize mitochondrial-lipid droplet interactions, or mitigate oxidative stress. &lt;b&gt;Translational Perspective&lt;/b&gt;: Peripheral artery disease (PAD) is characterized by skeletal muscle and mitochondrial dysfunction. Ultrastructural changes in skeletal muscle myofibers and mitochondria morphology can provide significant information on the PAD pathophysiology. Here, we investigated skeletal muscle and mitochondria morphological and functional changes at the sarcomere level and across the disease progression and have found that sarcomere lengths and mitochondria count and function are associated with disease progression, indicating loss of skeletal muscle contractile and metabolic function. Ultrastructural changes in the PAD skeletal muscle can provide significant information in the dev","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1208-1225"},"PeriodicalIF":3.8,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686585","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":"Optimized therapeutic potential of Sijunzi-similar formulae for chronic atrophic gastritis via Bayesian network meta-analysis.","authors":"Meilan Huang, Shiman Luo, Jiayue Yang, Huiling Xiong, Xiaohua Lu, Xiao Ma, Jinhao Zeng, Thomas Efferth","doi":"10.17179/excli2024-7618","DOIUrl":"https://doi.org/10.17179/excli2024-7618","url":null,"abstract":"<p><p>Chronic atrophic gastritis (CAG) is considered as a significant risk factor for triggering gastric cancer incidence, if not effectively treated. <i>Sijunzi</i> decoction (SD) is a well-known classic formula for treating gastric disorders, and <i>Sijunzi</i>-similar formulae (SF) derived from SD have also been highly regarded by Chinese clinical practitioners for their effectiveness in treating chronic atrophic gastritis. Currently, there is a lack of meta-analysis for these formulae, leaving unclear which exhibits optimal efficacy. Therefore, we employed Bayesian network meta-analysis (BNMA) to evaluate the efficacy and safety of SF as an intervention for CAG and to establish a scientific foundation for the clinical utilization of SF. The result of meta-analysis demonstrated that the combination of SF and basic therapy outperformed basic therapy alone in terms of clinical efficacy rate, eradication rate of H. pylori, and incidence of adverse events. As indicated by the SUCRA value, <i>Chaishao Liujunzi</i> decoction (CLD) demonstrated superior efficacy in enhancing clinical effectiveness and ameliorating <i>H. pylori</i> infection, and it also showed remarkable effectiveness in minimizing the occurrence of adverse events. Comprehensive analysis of therapeutic efficacy suggests that CLD is most likely the optimal choice among these six formulations, holding potential value for optimizing clinical treatment strategies. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1185-1207"},"PeriodicalIF":3.8,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461529","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":"Pitfalls in the use of sex chromosome sequence markers for internal quality control of next-generation sequencing.","authors":"Danielle Patchell, Stephen E Langabeer","doi":"10.17179/excli2024-7387","DOIUrl":"10.17179/excli2024-7387","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1183-1184"},"PeriodicalIF":3.8,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399903","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":"AI illuminates paths in oral cancer: transformative insights, diagnostic precision, and personalized strategies.","authors":"Devesh U Kapoor, Pushpendra Kumar Saini, Narendra Sharma, Ankul Singh, Bhupendra G Prajapati, Gehan M Elossaily, Summya Rashid","doi":"10.17179/excli2024-7253","DOIUrl":"10.17179/excli2024-7253","url":null,"abstract":"<p><p>Oral cancer retains one of the lowest survival rates worldwide, despite recent therapeutic advancements signifying a tenacious challenge in healthcare. Artificial intelligence exhibits noteworthy potential in escalating diagnostic and treatment procedures, offering promising advancements in healthcare. This review entails the traditional imaging techniques for the oral cancer treatment. The role of artificial intelligence in prognosis of oral cancer including predictive modeling, identification of prognostic factors and risk stratification also discussed significantly in this review. The review also encompasses the utilization of artificial intelligence such as automated image analysis, computer-aided detection and diagnosis integration of machine learning algorithms for oral cancer diagnosis and treatment. The customizing treatment approaches for oral cancer through artificial intelligence based personalized medicine is also part of this review. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1091-1116"},"PeriodicalIF":3.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399890","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":"<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":"https://doi.org/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 (IC₅₀ < 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}

{"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}