EXCLI Journal最新文献

{"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}

{"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}

{"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}

{"title":"Autoimmune diseases share a common genetic architecture involving the JAK-STAT pathway.","authors":"Iraj Saadat, Mostafa Saadat","doi":"10.17179/excli2024-7684","DOIUrl":"https://doi.org/10.17179/excli2024-7684","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1027-1029"},"PeriodicalIF":3.8,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461526","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":"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}

{"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}

{"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}

{"title":"Deciphering NF-kappaB pathways in smoking-related lung carcinogenesis.","authors":"Riya Thapa, Ehssan Moglad, Ahsas Goyal, Asif Ahmad Bhat, Waleed Hassan Almalki, Imran Kazmi, Sami I Alzarea, Haider Ali, Brian Gregory Oliver, Ronan MacLoughlin, Harish Dureja, Sachin Kumar Singh, Kamal Dua, Gaurav Gupta","doi":"10.17179/excli2024-7475","DOIUrl":"https://doi.org/10.17179/excli2024-7475","url":null,"abstract":"<p><p>One of the main causes of death worldwide is lung cancer, which is largely caused by cigarette smoking. The crucial transcription factor NF-κB, which controls inflammatory responses and various cellular processes, is a constitutively present cytoplasmic protein strictly regulated by inhibitors like IκB proteins. Upon activation by external stimuli, it undergoes phosphorylation, translocates into the nucleus, and modulates the expression of specific genes. The incontrovertible association between pulmonary malignancy and tobacco consumption underscores and highlights a public health concern. Polycyclic aromatic hydrocarbons and nitrosamines, potent carcinogenic compounds present in the aerosol emitted from combusted tobacco, elicit profound deleterious effects upon inhalation, resulting in severe perturbation of pulmonary tissue integrity. The pathogenesis of smoking-induced lung cancer encompasses an intricate process wherein NF-κB activation plays a pivotal role, triggered by exposure to cigarette smoke through diverse signaling pathways, including those associated with oxidative stress and pro-inflammatory cytokines. Unraveling the participation of NF-κB in smoking-induced lung cancer provides pivotal insights into molecular processes, wherein intricate crosstalk between NF-κB and pathways such as MAPK and PI3K-Akt amplifies the inflammatory response, fostering an environment conducive to the formation of lung cancer. This study reviews the critical function of NF-κB in the complex molecular pathways linked to the initiation and advancement of lung carcinogenesis as well as potential treatment targets. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"991-1017"},"PeriodicalIF":3.8,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11382301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282679","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":"Smoking increases risk of complication after musculoskeletal surgery: analysis of single immune parameter to predict complication risk.","authors":"Leyla Tümen, Lena Pollmann-Schweckhorst, Regina Breinbauer, Mohammad M Hammour, Romina H Aspera-Werz, Gunnar Blumenstock, Tina Histing, Maximilian M Menger, Sabrina Ehnert, Andreas K Nüssler","doi":"10.17179/excli2024-7306","DOIUrl":"https://doi.org/10.17179/excli2024-7306","url":null,"abstract":"<p><p>Smoking is the most significant and modifiable risk factor for a range of conditions, including cancer, cardiovascular and respiratory diseases. Furthermore, it significantly reduces bone mass and increases the risk of fragility fractures due to its detrimental effects on bone metabolism and regeneration. Moreover, smoking is a known cause of chronic systemic inflammation, leading to an imbalance of cytokines. Comprehending the pathological mechanisms that underlie cytokine production and its impact on post-surgical healing is essential to prevent post-surgical complications. The present study recruited a total of 1144 patients, including 897 patients, among them non-smokers (<i>N = 413</i>), current smokers (<i>N = 201</i>) and ex-smokers (<i>N = 283</i>). Human proteome profiler arrays were used to screen for smoking-dependent differences in the serum cytokine and protein profiles, after matching samples for age, gender, body mass index (BMI), alcohol use, and diabetes risk. Cytokines and immune checkpoint proteins such as CD28, B7-1, MIG, TGFβ2 and IL-1α/β were quantified by ELISA. Our study demonstrates a comprehensive understanding of the relationship between smoking, the development of complications, the systemic immune inflammation index (SII) and cytokine/protein levels. We found that a comparison of non-smokers, former smokers, and active smokers in our study cohort did not exhibit significantly altered cytokine and protein serum levels although other studies reported differences between smokers and non-smokers. We were unable to identify single blood circulating markers that could predict complications in smokers after trauma. However, we found the ratio of women to men to be inverted between non-smokers and active smokers resulting in a ratio of 0.62 in smokers. Furthermore, we demonstrate a higher complication rate, longer hospitalizations and elevated SII values among smokers, indicating an involvement of the immune system. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"967-990"},"PeriodicalIF":3.8,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11382255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282683","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}