EXCLI Journal最新文献

{"title":"Immunoaffinity proteomics for kidney injury biomarkers in male beagle dogs.","authors":"Wael Naboulsi, Hannes Planatscher, Felix F Schmidt, Andreas Steinhilber, Thomas O Joos, Adeyemi O Adedeji, J Eric McDuffie, Oliver Poetz","doi":"10.17179/excli2023-6621","DOIUrl":"10.17179/excli2023-6621","url":null,"abstract":"<p><p>Drug-induced kidney injury (DIKI) is a cause of drug development failure. Dogs represent a common non-rodent animal model in pre-clinical safety studies; however, biomarker assays for detecting nephrotoxicity in dogs are limited. To identify novel proteins and gain insight into the molecular mechanisms involved in DIKI, we developed an assay to evaluate proteomic changes associated with DIKI in male beagle dogs that received nephrotoxic doses of tobramycin for 10 consecutive days. Label-free quantitative discovery proteomics analysis on representative kidney cortex tissues collected on Day 11 showed that the tobramycin-induced kidney injury led to a significant differential regulation of 94 proteins mostly associated with mechanisms of nephrotoxicity such as oxidative stress and proteasome degradation. For verification of the proteomic results, we developed a multiplex peptide-centric immunoaffinity liquid chromatography tandem mass spectrometry assay (IA LC-MS/MS) to evaluate the association of eight DIKI protein biomarker candidates using kidney cortices collected on Day 11 and urine samples collected on Days -4, 1, 3, 7 and 10. The results showed that most biomarkers evaluated were detected in the kidney cortices and their expression profile in tissue aligned with the label-free data. Cystatin C was the most consistent marker regardless of the magnitude of the renal injury while fatty acid-binding protein-4 (FABP4) and kidney injury molecule-1 (KIM-1) were the most affected biomarkers in response to moderate proximal tubular injury in absence of changes in serum-based concentrations of blood urea nitrogen or creatinine. In the urine, clusterin is considered the most consistent biomarker regardless of the magnitude and time of the renal injury. To our knowledge, this is the most comprehensive multiplex assay for the quantitative analysis of mechanism-based proximal tubular injury biomarkers in dogs.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"180-197"},"PeriodicalIF":4.6,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10938254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131164","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":"Uniting minds and methods: how interprofessional education advances male infertility research.","authors":"Pallav Sengupta, Sulagna Dutta","doi":"10.17179/excli2023-6641","DOIUrl":"https://doi.org/10.17179/excli2023-6641","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"92-94"},"PeriodicalIF":4.6,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10853635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722239","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":"Empowering personalized medicine: unleashing the potential of patient-derived explants in clinical practice.","authors":"Oliwia Piwocka, Wiktoria M Suchorska, Katarzyna Kulcenty","doi":"10.17179/excli2023-6700","DOIUrl":"https://doi.org/10.17179/excli2023-6700","url":null,"abstract":"<p><p>In recent decades, significant progress has been made in understanding the molecular characteristics of cancer and its microenvironment, leading to the development of life-saving treatments. However, patients often experience side effects from standard therapies, highlighting the need for personalized medicine. Personalized medicine aims to customize drug therapy and preventive care based on individual patients' specific requirements. The heterogeneity within tumors and among patients necessitates personalized medicine approaches. Patient-derived organoids (PDOs), xenografts (PDXs), and explants (PDEs) have emerged as valuable models for studying tumor behaviour and drug response. This paper aims to summarize the latest advancements in patient-derived explants, focusing on their potential utility in the clinic. Different methods for culturing PDEs, including the free-floating approach, the grid method, and sponge scaffolds, are discussed. These approaches provide opportunities for long-term viability, oxygen and nutrient supply, and maintenance of tissue integrity. Additionally, various solid tumor models using PDEs are highlighted, together with assays to study PDE viability, characteristics, and response to drug treatment.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"81-91"},"PeriodicalIF":4.6,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10853634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722237","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":"Roles of the quantification of serine in the brain.","authors":"Jia-Meng Li, Ya-Zhi Bai, Shuang-Qing Zhang","doi":"10.17179/excli2023-6857","DOIUrl":"10.17179/excli2023-6857","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"79-80"},"PeriodicalIF":4.6,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10864702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734851","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":"Plasma amino acids in major depressive disorder: between pathology to pharmacology.","authors":"Omar Gammoh, Alaa A A Aljabali, Murtaza M Tambuwala","doi":"10.17179/excli2023-6767","DOIUrl":"10.17179/excli2023-6767","url":null,"abstract":"<p><p>Addressing the formidable challenge posed by the development of effective and personalized interventions for major depressive disorder (MDD) necessitates a comprehensive comprehension of the intricate role that plasma amino acids play and their implications in MDD pathology and pharmacology. Amino acids, owing to their indispensable functions in neurotransmission, metabolism, and immune regulation, emerge as pivotal entities in this intricate disorder. Our primary objective entails unraveling the underlying mechanisms and unveiling tailored treatments through a meticulous investigation into the interplay between plasma amino acids, MDD, and pharmacological strategies. By conducting a thorough and exhaustive review of the existing literature, we have identified pertinent studies on plasma amino acids in MDD, thereby uncovering noteworthy disturbances in the profiles of amino acids among individuals afflicted by MDD when compared to their healthy counterparts. Specifically, disruptions in the metabolism of tryptophan, phenylalanine, and tyrosine, which serve as precursors to essential neurotransmitters, have emerged as prospective biomarkers and critical contributors to the pathophysiology of depression. Amnio acids play an essential role in MDD and could represent an attractive pharmacological target, more studies are further required to fully reveal their underlying mechanisms.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"62-78"},"PeriodicalIF":4.6,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10864705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734850","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":"AZU1: a new promising marker for infection in orthopedic and trauma patients?","authors":"Philipp Hemmann, Lisa Kloppenburg, Regina Breinbauer, Sabrina Ehnert, Gunnar Blumenstock, Marie K Reumann, Felix Erne, Johann Jazewitsch, Tobias Schwarz, Heiko Baumgartner, Tina Histing, Mika Rollmann, Andreas K Nüssler","doi":"10.17179/excli2023-6705","DOIUrl":"10.17179/excli2023-6705","url":null,"abstract":"<p><p>Early and reliable detection of infection is vital for successful treatment. Serum markers such as C-reactive protein (CRP) and procalcitonin (PCT) are known to increase with a time lag. Azurocidin 1 (AZU1) has emerged as a promising marker for septic patients, but its diagnostic value in orthopedic and trauma patients remains unexplored. Between July 2020 and August 2023, all patients necessitating inpatient treatment for periprosthetic joint infection (PJI), peri-implant infection (II), soft tissue infection, chronic osteomyelitis, septic arthrodesis, bone non-union with and without infection were enrolled. Patients undergoing elective total joint arthroplasty (TJA) served as the control group. Blood samples were collected and analyzed for CRP, white blood cell count (WBC), PCT, and AZU1. Based on the inclusion and exclusion criteria 222 patients were included in the study (trauma = 38, soft tissue infection = 75, TJA = 33, PJI/II = 39, others = 37). While sensitivity and specificity were comparably high for AZU1 (0.734/0.833), CRP and PCT had higher specificity (0.542/1 and 0.431/1, respectively), and WBC a slightly higher sensitivity (0.814/0.455) for septic conditions. Taken together, the area under the curve (AUC) showed the highest accuracy for AZU1 (0.790), followed by CRP (0.776), WBC (0.641), and PCT (0.656). The Youden-Index was 0.57 for AZU1, 0.54 for CRP, 0.27 for WBC, and 0.43 for PCT. Elevated AZU1 levels effectively distinguished patients with a healthy condition from those suffering from infection. However, there is evidence suggesting that trauma may influence the release of AZU1. Additional research is needed to validate the diagnostic value of this new biomarker and further explore its potential clinical applications.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"53-61"},"PeriodicalIF":4.6,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10864703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734804","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":"Unraveling NEAT1's complex role in lung cancer biology: a comprehensive review.","authors":"Md Sadique Hussain, Obaid Afzal, Gaurav Gupta, Ahsas Goyal, Waleed Hassan Almalki, Imran Kazmi, Sami I Alzarea, Abdulmalik Saleh Alfawaz Altamimi, Neelam Kukreti, Amlan Chakraborty, Sachin Kumar Singh, Kamal Dua","doi":"10.17179/excli2023-6553","DOIUrl":"https://doi.org/10.17179/excli2023-6553","url":null,"abstract":"<p><p>This review delves into the pivotal role of the long non-coding RNA NEAT1 in cancer biology, particularly in lung cancer (LC). It emphasizes NEAT1's unique subcellular localization and active involvement in gene regulation and chromatin remodeling. The review highlights NEAT1's impact on LC development and progression, including cell processes such as proliferation, migration, invasion, and resistance to therapy, positioning it as a potential diagnostic marker and therapeutic target. The complex web of NEAT1's regulatory interactions with proteins and microRNAs is explored, alongside challenges in targeting it therapeutically. The review concludes optimistically, suggesting future avenues for research and personalized LC therapies, shedding light on NEAT1's crucial role in LC. See also the Graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"34-52"},"PeriodicalIF":4.6,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10853633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722240","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":"Impairment of value-based decision-making in morphine-dependent rats is partly related to neural connectivity between the anterior cingulate cortex and basolateral amygdala.","authors":"Zahra Fatahi, Mohammad Fatahi, Abbas Haghparast","doi":"10.17179/excli2023-6442","DOIUrl":"https://doi.org/10.17179/excli2023-6442","url":null,"abstract":"<p><p>Previous studies have established that the amygdala specifically the basolateral amygdala (BLA), has a fundamental role in decision-making. The present study aimed to investigate functional and neural synchronization between the BLA and anterior cingulate cortex (ACC) while making effort-choice decisions regarding pre-morphine dependence and morphine dependence times. A T-maze decision-making task with a differential outlay (great vs. small effort) and benefit (great vs. small reward) was done, and local field potentials from the BLA and ACC were assessed simultaneously. Results illustrated that in pre-morphine dependence time, when the animals made great reward/great effort decisions, there was a neural synchronization between both regions in beta and gamma frequency bands; and also, in delta, theta, beta, and gamma frequencies while expending effort and climbing the barrier. However, in morphine-dependent rats, during low reward/low effort choice and also during expending low effort, there was just a weak neural coherence in gamma frequency. Besides, there was neural synchronization in theta, beta, and gamma frequencies during reaching great reward in pre-morphine dependence time. Nevertheless, during reaching low reward in morphine dependence time, there was a weaker coherence in beta and gamma compared to pre-morphine dependence. These findings showed that functional and neural coherence between the BLA and ACC has a fundamental role in making the effort-based decision and expending effort. Preference for low reward/low effort, and decrease in expending effort in morphine-dependent rats is partly associated with the changes in the neural coherence between the BLA and ACC.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"1-17"},"PeriodicalIF":4.6,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10853632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722238","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":"Myocardial infarct size is reduced by nitrite and nitrate administration: a systematic review and meta-analysis of animal studies.","authors":"Younes Yassaghi, Sajad Jeddi, Khosrow Kashfi, Asghar Ghasemi","doi":"10.17179/excli2023-6740","DOIUrl":"10.17179/excli2023-6740","url":null,"abstract":"<p><p>Ischemic heart disease (IHD) is the leading cause of mortality worldwide and can be complicated by myocardial infarction (MI), leading to cardiac failure. Inorganic nitrite and nitrate, which release nitric oxide (NO), can protect the heart against myocardial injury. This animal systematic review and meta-analysis aims to assess whether the administration of nitrite/nitrate decreases myocardial infarct size. We systematically searched PubMed, Scopus, and Web of Science databases until October 2023; 15 eligible animal studies (35 study arms for in-vivo and 10 for in-vitro studies) published between 1989 and 2023 were included. <i>In-vivo</i> studies were conducted on rats, mice, cats, and dogs, and <i>in-vitro</i> studies on rats and mice with an overall exposure of 0.03 to 12713 mg/kg to nitrate/nitrite administrated before, after, or during ischemia mainly by intravenous single bolus or by oral over 270 days. All <i>in-vitro</i> studies used nitrite/nitrate before ischemia, with the concentration ranging between 0.34 to 201 μM. MI was induced by occlusion of the left anterior diagonal or left circumflex arteries in <i>in-vitro</i> studies and by isoproterenol in <i>in-vivo</i> studies. Infarct size was measured by direct staining of the sliced heart sections. In <i>in-vivo</i> studies, nitrite (overall effect size (ES)=-17.0 %, 95 % confidence interval (CI)=-21.3, -12.8, P<0.001) and nitrate (overall ES= -9.6 %, 95 % CI=-15.7, -3.4, P=0.002) reduced myocardial infarct size. In <i>in-vitro</i> studies, nitrite (overall ES=-15.8 %, 95 % CI=-25.5, -6.2, P=0.001) reduced the infarct size. Sensitivity analysis showed that the overall effect of nitrite on myocardial infarct size was unaffected by doses or health conditions in <i>in-vivo</i> and <i>in-vitro</i> studies. In conclusion, our meta-analysis showed that nitrite/nitrate administration can effectively reduce myocardial infarct size. However, these results should be approached with caution because of the limitations of animal studies and the existing high heterogeneity.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"18-33"},"PeriodicalIF":4.6,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10864704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734849","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":"Embelin: A multifaceted anticancer agent with translational potential in targeting tumor progression and metastasis.","authors":"Adithya Jayaprakash Kamath, Alda Sara Chandy, Aina Ann Joseph, Jaggiah N Gorantla, Asawari Dilip Donadkar, Lekshmi R Nath, Javad Sharifi-Rad, Daniela Calina","doi":"10.17179/excli2023-6590","DOIUrl":"10.17179/excli2023-6590","url":null,"abstract":"<p><p>Embelin, a natural para-benzoquinone product, is derived from plants of the Embelia genus, particularly <i>Embelia ribes</i> Burm.f. A staple in traditional medicinal formulations for centuries, Embelin's pharmacological actions are attributed to the hydroxyl benzoquinone present in its structure. Its therapeutic potential is bolstered by unique physical and chemical properties. Recently, Embelin, recognized as a non-peptidic, cell-permeable small inhibitor of the X-linked inhibitor of apoptosis protein (XIAP), has garnered significant attention for its anticancer activity. It demonstrates various anticancer mechanisms, such as apoptosis induction, cell cycle arrest, and autophagy, in different cancer types. Additionally, Embelin modulates several signal transduction pathways, including NF-κB, PI3Kinase/AKT, and STAT3, effectively inhibiting the proliferation of diverse cancer cell lines. This literature review illuminates the anticancer potential of Embelin, detailing its mechanisms of action and prospective clinical applications, based on relevant scientific literature from the past decade sourced from various electronic databases. See also the Graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"22 ","pages":"1311-1329"},"PeriodicalIF":4.6,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10792175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485371","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}