EXCLI Journal最新文献

{"title":"Interaction between periodontal disease and colorectal cancer: implications of oral microbiota in carcinogenesis.","authors":"Thalles Yurgen Balduino, André Felipe Dos Santos Teles, Gabriel Leonardo Magrin, Marco Aurélio Bianchini","doi":"10.17179/excli2024-7869","DOIUrl":"10.17179/excli2024-7869","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1493-1495"},"PeriodicalIF":3.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11713988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946825","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 abyss of research funding in Brazil.","authors":"Lucindo José Quintans-Júnior, Fábio Guedes Gomes","doi":"10.17179/excli2024-8037","DOIUrl":"10.17179/excli2024-8037","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1491-1492"},"PeriodicalIF":3.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11713987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946792","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":"Psychedelic-assisted therapy - supposedly paradigm-shifting research with poor attempts at hypotheses falsifying and questionable ethics.","authors":"Bor Luen Tang","doi":"10.17179/excli2024-8023","DOIUrl":"10.17179/excli2024-8023","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1487-1490"},"PeriodicalIF":3.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11713989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946826","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":"Current update on the neurological manifestations of long COVID: more questions than answers.","authors":"Maria-Ioanna Stefanou, Evangelos Panagiotopoulos, Lina Palaiodimou, Eleni Bakola, Nikolaos Smyrnis, Marianna Papadopoulou, Christos Moschovos, George P Paraskevas, Emmanouil Rizos, Eleni Boutati, Elias Tzavellas, Stylianos Gatzonis, Annerose Mengel, Sotirios Giannopoulos, Sotirios Tsiodras, Vasilios K Kimiskidis, Georgios Tsivgoulis","doi":"10.17179/excli2024-7885","DOIUrl":"10.17179/excli2024-7885","url":null,"abstract":"<p><p>Since the outbreak of the COVID-19 pandemic, there has been a global surge in patients presenting with prolonged or late-onset debilitating sequelae of SARS-CoV-2 infection, colloquially termed long COVID. This narrative review provides an updated synthesis of the latest evidence on the neurological manifestations of long COVID, discussing its clinical phenotypes, underlying pathophysiology, while also presenting the current state of diagnostic and therapeutic approaches. Approximately one-third of COVID-19 survivors experience prolonged neurological sequelae that persist for at least 12-months post-infection, adversely affecting patients' quality of life. Core neurological manifestations comprise fatigue, post-exertional malaise, cognitive impairment, headache, lightheadedness ('brain fog'), sleep disturbances, taste or smell disorders, dysautonomia, anxiety, and depression. Some of these features overlap substantially with those reported in post-intensive-care syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, and postural-orthostatic-tachycardia syndrome. Advances in data-driven research utilizing electronic-health-records combined with machine learning and artificial intelligence have propelled the identification of long COVID sub-phenotypes. Furthermore, the evolving definitions reflect the dynamic conceptualization of long COVID in both research and clinical contexts. Although the underlying pathophysiology remains incompletely elucidated, neuroinflammatory responses, endotheliopathy, and metabolic imbalances, rather than direct viral neuroinvasion, are implicated in neurological sequelae. Genetic susceptibility has also emerged as a potential risk factor. While major limitations remain with existing definitions, collaborative strategies to standardize diagnostic approaches are needed. Current therapeutic paradigms advocate for multimodal approaches, integrating pharmacological and non-pharmacological interventions along with comprehensive rehabilitation programs. Although preliminary evidence of therapeutic efficacy has been provided by a number of clinical trials, methodological constraints limit the generalizability of this evidence. Preventive measures, notably vaccination, have proven integral for reducing the global burden of long COVID. Considering the healthcare and socioeconomic repercussions incurred by long COVID worldwide, international collaborative initiatives are warranted to address the remaining challenges in diagnosing and managing patients presenting with neurological sequelae. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1463-1486"},"PeriodicalIF":3.8,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028491","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 generative artificial intelligence (AI) on the development of personalized pharmaceuticals and the future of precision medicine.","authors":"Varghese Edwin Hillary, Rajiv Gandhi Gopalsamy, Lucas Alves da Mota Santana, Pamela Chaves de Jesus, Jessiane Bispo de Souza, Deise Maria Rego Rodrigues Silva, Pedro Henrique Macedo Moura, Ronaldy Santana Santos, Marina Dos Santos Barreto, Lysandro Pinto Borges, Eloia Emanuelly Dias Silva","doi":"10.17179/excli2024-7915","DOIUrl":"10.17179/excli2024-7915","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1459-1462"},"PeriodicalIF":3.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11714025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946794","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 therapeutic potential of <i>Emblica officinalis</i> natural compounds against hepatocellular carcinoma (HCC): a computational approach.","authors":"Sidra Ilyas, Abdul Manan, Yeojin Choi, Donghun Lee","doi":"10.17179/excli2024-7970","DOIUrl":"10.17179/excli2024-7970","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer related deaths globally. Despite advancements in treatment, drug resistance and adverse side effects have spurred the search for novel therapeutic strategies. This study aimed to investigate how the <i>Emblica officinalis</i> can inhibit key targets involved in HCC progression. Screening of the reported compounds based on ADMET profile and identification of protein targets was done using the literature survey. Protein targets were divided into four major categories including inflammatory, angiogenic, anti-apoptotic as well as proliferative targets. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to reveal the functional roles of genes. The STRING database was used to analyze the protein-protein interactions (PPI) of target genes. Docking was employed to predict the binding affinity of compounds with target proteins. Subsequently, MD simulation was conducted to assess the stability and dynamics of protein-ligand complexes. A total of 22 active compounds with 25 protein targets have been identified. These targets have a major role in controlling biological processes such as apoptosis, signaling and cellular interactions. KEGG pathway analysis showed that cancer, atherosclerosis, PI3K-Akt, EGFR tyrosine kinase inhibitor resistance and MAPK signaling pathways are mainly involved. Molecular docking by Mcule platform demonstrated that emblicanin A, punigluconin, penta-o-galloylglucose and quercetin showed higher binding energy affinities with BCL2, BCL2L1, c-Met, HSP70, EGFR, FGFR1, PTGS2 and TNFα. MD simulation revealed conformational changes, flexibility, interactions and compactness of protein-ligand complex. The stable protein binding interactions suggest the potential of compounds to inhibit the functions of target proteins. These results suggest that compounds derived from <i>E. officinalis</i> may have the therapeutic potential for treating HCC. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1440-1458"},"PeriodicalIF":3.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11713998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946752","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":"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":"Amplifying cancer immunity: AMPK activators and gammadelta T cells unveiled.","authors":"Firoz Anwar, Fahad A Al-Abbasi, Naif Abdullaha R Almalki, Sultan Alhayyani, Amita Verma, Vikas Kumar","doi":"10.17179/excli2024-7784","DOIUrl":"https://doi.org/10.17179/excli2024-7784","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1327-1329"},"PeriodicalIF":3.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767619","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":"Enhancing cancer care with improved checkpoint inhibitors: a focus on PD-1/PD-L1.","authors":"Vickram A S, Saghya Infant Shofia, A Saravanan, Vidhya Lakshmi Sivakumar, Packiyam Thamarai, Manikandan Sivasubramanian, Shivani Chopra, Hitesh Chopra","doi":"10.17179/excli2024-7783","DOIUrl":"https://doi.org/10.17179/excli2024-7783","url":null,"abstract":"<p><p>The emergence of checkpoint inhibitors targeting the PD-1/PD-L1 axis marks a paradigm shift in cancer therapy, offering a novel avenue for enhancing patient outcomes. This review examines the structural and functional dynamics of PD-1 and PD-L1 while exploring the clinical implications of current PD-1/PD-L1 monoclonal antibodies. Highlighting recent advancements, this paper delves into the promising results from combination therapies that present a multifaceted attack on tumor progression. Despite the success observed across various cancer types, challenges such as immune resistance remain. Future considerations are discussed with an emphasis on the need for further clinical studies, aiming to refine and broaden the curative potential of PD-1/PD-L1 inhibitors in oncology. This review postulates that ongoing research and innovative approaches could significantly enhance cancer care, making immunotherapy an even more central strategy in the fight against cancer. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1303-1326"},"PeriodicalIF":3.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767623","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}