EXCLI Journal最新文献

{"title":"Recent advances in ß-carotene: Biological activities, therapeutic potential, and delivery strategies.","authors":"Chanung Park, Jae Kwang Kim, Sang Un Park","doi":"10.17179/excli2026-9677","DOIUrl":"10.17179/excli2026-9677","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"1458-1459"},"PeriodicalIF":6.2,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105973","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 diethylene glycol oligomer squalene derivative modulates metabolic gene expression in ob/ob mice.","authors":"Yu Cheng, Munkhzul Ganbold, Elda Nurafnie Binti Ibnu Rasid, Farhana Ferdousi, Hiroko Isoda","doi":"10.17179/excli2026-9373","DOIUrl":"10.17179/excli2026-9373","url":null,"abstract":"<p><p>Obesity-related metabolic dysregulation is widespread and often leads to complications such as liver dysfunction. Squalene has long been studied for its potential anti-obesity effects due to its role in lipid metabolism, oxidative stress reduction, and inflammation modulation. However, squalene's hydrophobic nature has limited its applicability in humans. Recently, an amphiphilic form of squalene, namely diethylene glycol oligomer squalene (di-SQ), has shown promise in improving metabolic functions in preadipocytes. However, the <i>in vivo</i> effects and molecular correlates of di-SQ in obesity remain insufficiently characterized. This study aimed to investigate the metabolic effects of di-SQ in an obese mouse model and to explore transcriptomic changes associated with its administration. Using the leptin-deficient ob/ob mouse model, the study employed microarray analysis, histological examination, and real-time PCR to evaluate the impact of di-SQ on obesity and associated metabolic disturbances. Di-SQ reduced body weight gain without affecting food intake and alleviated hepatic steatosis and epididymal white adipose tissue (eWAT) lipid accumulation in ob/ob mice. In the liver, di-SQ was associated with changes in lipid- and glucose-metabolism-related gene expression, energy balance, and inflammation, potentially involving hepatic <i>Sirt1</i> and <i>Prkaa1</i> expression. In eWAT, di-SQ was associated with reduced lipid accumulation, altered lipid-metabolism- and thermogenesis-related gene expression, and suppressed inflammation, thereby suggesting gene expression patterns consistent with improved insulin signaling. Di-SQ was associated with amelioration of hepatic metabolic dysfunction in ob/ob mice, potentially involving <i>Sirt1</i> and <i>Prkaa1</i>, and showed gene expression patterns consistent with enhanced insulin signaling. These findings support its potential as a novel bioactive molecule derived from natural products for obesity-related metabolic dysregulation. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"1460-1485"},"PeriodicalIF":6.2,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024250","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":"Real-time pharmacovigilance and cardiac risk communication during the COVID-19 vaccination campaign in Israel.","authors":"Yaakov Ophir, Yaffa Shir-Raz","doi":"10.17179/excli2026-9596","DOIUrl":"10.17179/excli2026-9596","url":null,"abstract":"<p><p>During the early phase of the COVID-19 vaccination campaign, the Israeli Ministry of Health (IMOH) informed international health authorities that it had identified \"<i>a large number of myocarditis and pericarditis cases in young individuals soon after Pfizer COVID-19 vaccine</i>.\" This study discloses and analyzes an internal pharmacovigilance dataset obtained from within the IMOH to examine the case-level record associated with this early safety signal and trace how the signal was subsequently communicated to physicians and the public. The anonymized dataset, provided as Supplementary Data File 1, includes 531 hospitalization records and 67 unique deaths reported to Pfizer between March 2021 and May 2022. Reported events spanned cardiac, neurological, inflammatory, and other serious clinical categories and involved a substantial proportion of younger individuals, with 211 of 530 hospitalization records with valid age data (39.8 %) involving patients under 30 years of age. Myocarditis was recorded in two of the nine unique deaths among individuals under 50 years of age (22.2 %), while myocarditis or pericarditis was identified in 250 of 531 hospitalization records (47.1 0 %), rising to 151 of 211 records involving patients under 30 (71.6 %). Among younger hospitalized patients, 134 of 211 (63.5 %) had no meaningful medical history identified under the study definition; within this subgroup, 99 of 134 (73.9 %) had myocarditis or pericarditis, of whom 90 (90.9 %) were male. The safety signal was communicated to clinicians and the public only after approximately three to four months, primarily in ways that emphasized its rarity, generally mild clinical course, and lower concern relative to COVID-19 outcomes. The accuracy and completeness of this characterization, together with the implications of the case-level patterns and communication timeline documented in this study, are discussed in the broader contexts of pharmacovigilance, risk communication, and informed consent during large-scale public health interventions. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"1437-1457"},"PeriodicalIF":6.2,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105945","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":"Aging impairs bimanual isometric force smoothness.","authors":"Hajun Lee, Hanall Lee, Jinwon Shin, Eo-Jin Son, Nyeonju Kang","doi":"10.17179/excli2026-9581","DOIUrl":"10.17179/excli2026-9581","url":null,"abstract":"<p><p>Older adults normally showed impaired fine motor control capabilities, as indicated by increased force error and variability during submaximal force control tasks. However, whether aging additionally disrupts temporal smoothness of the force trajectory remains unclear beyond the magnitude of force fluctuation. This study investigated age-related changes in bimanual isometric force smoothness using YANK analysis (i.e., time-derivative of force; d<i>F</i>/d<i>t</i>). Fifteen younger adults (mean ± SD of age = 25.4 ± 2.5 years) and fifteen older adults (mean ± SD of age = 64.9 ± 6.5 years) performed bimanual hand-grip isometric force control at 10 % of maximum voluntary contraction across the vision and no-vision conditions. Force accuracy (relative root-mean-square error; rRMSE), variability (coefficient of variation; CV), smoothness (YANK), and interlimb force coordination (correlation coefficient) were quantified. Receiver operating characteristic (ROC) curve and Pearson's correlation analyses were conducted to evaluate the discriminative ability of each variable and potential relationships between YANK and conventional force control variables. Older adults showed significantly higher YANK values than younger adults in both vision and no-vision conditions, indicating reduced force smoothness. Greater rRMSE, CV, and correlation coefficient values for older adults were observed only in the vision condition. The ROC curve analysis revealed that YANK effectively discriminated between the younger and older adults in both vision and no-vision conditions. For older adults, increased YANK was significantly correlated with greater rRMSE and CV in the vision condition and with greater CV in the no-vision condition, whereas no significant correlations appeared in younger adults. These findings suggest the YANK approach can capture age-related fine motor control deficits that conventional variability measures may overlook. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"1420-1436"},"PeriodicalIF":6.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024237","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":"Mesenchymal stromal cells and paracrine modulation of neuroplasticity in the central nervous system.","authors":"Sacha Krolow E Silva, Iris Virgínia Rondanine Sanches, Juliana Soares Lara de Lima, Luciana Le Sueur-Maluf","doi":"10.17179/excli2026-9599","DOIUrl":"10.17179/excli2026-9599","url":null,"abstract":"<p><p>Mesenchymal stromal cells (MSCs) have been widely investigated in regenerative medicine because of their immunomodulatory, anti-inflammatory, and reparative properties. Current evidence indicates that many of their effects are mediated by paracrine and intercellular mechanisms rather than sustained engraftment or direct neural replacement. This narrative review synthesizes how MSCs and MSC-derived extracellular vesicles (MSC-EVs) may modulate neuroplasticity in the central nervous system (CNS). MSC-mediated effects include trophic and immunomodulatory signaling, mitochondrial transfer via tunneling nanotubes (TNTs), efferocytosis of apoptotic MSCs by host phagocytes, blood-brain barrier stabilization, and secondary modulation of glymphatic and interstitial fluid clearance. MSC-EVs additionally deliver proteins, lipids, microRNAs, and long non-coding RNAs that regulate inflammatory and reparative gene-expression programs through well-supported post-transcriptional and emerging epigenetic mechanisms. These processes may promote neurite remodeling, angiogenesis, mitochondrial recovery, and attenuation of neuroinflammation, and may support the clearance of neurotoxic proteins. The evidence is organized into five CNS disorder macrocategories defined by shared pathophysiological processes and overlapping therapeutic targets: cerebrovascular and ischemic/hemorrhagic disorders; neurodegenerative proteinopathies and related disorders; neurotrauma and acute lesions; autoimmune, inflammatory, and emerging disorders; and retinal diseases as CNS-related sensory disorders. Although substantial preclinical evidence and encouraging early clinical signals support continued investigation, adequately powered confirmatory trials are still needed to establish whether MSC-based thera5pies can produce durable disease-modifying effects in neurodegenerative disorders. Translation is further limited by variability in cell sources, manufacturing procedures, doses, delivery routes, potency assays, and patient stratification by disease stage and biological phenotype. A cohesive translational roadmap should therefore combine Good Manufacturing Practice (GMP)-compliant production and mechanism-relevant potency testing with the 2025 International Society for Cell & Gene Therapy (ISCT) reporting framework. Finally, engineered MSC-EVs with modified surfaces or defined cargo may enable more targeted and controllable cell-free strategies for CNS repair. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"1392-1419"},"PeriodicalIF":6.2,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105931","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":"Genetic and molecular advancements in combined hepatocellular-cholangiocarcinoma: Addressing a persistent clinical conundrum.","authors":"Rabab Fatima","doi":"10.17179/excli2026-9655","DOIUrl":"10.17179/excli2026-9655","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"1388-1391"},"PeriodicalIF":6.2,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105958","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":"Can nitric oxide-responsive polymers enable precision therapeutics for ageing?","authors":"Parteek Prasher, Mousmee Sharma","doi":"10.17179/excli2026-9640","DOIUrl":"10.17179/excli2026-9640","url":null,"abstract":"<p><p>Disruptions in nitric oxide homeostasis, characterised by endothelial dysfunction, neurodegeneration, metabolic decline, and chronic inflammation represent a hallmark of the ageing process. These pathological features led to the development of NO-responsive polymeric systems which exploit the endogenous gasotransmitter fluctuations for offering therapeutic and diagnostic applications. This commentary highlights the advances in NO-responsive polymers, which undergo NO-triggered self-assembly or disassembly, fluorescence activation for intracellular NO imaging, NO scavenging, and site-specific drug release. Although critical challenges still persist, including tissue-specific variability in NO levels and validation in clinically relevant ageing models, the contemporary advances in polymer engineering and design aim to translate these intelligent biomaterials towards ageing-targeted precision therapeutics.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"1376-1382"},"PeriodicalIF":6.2,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105851","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":"From gut to lung: Microbiota-derived metabolites reshaping the tumor immune microenvironment.","authors":"Prabesh Baniya, Santosh Lamichhane, Kamal Dua, Keshav Raj Paudel","doi":"10.17179/excli2026-9646","DOIUrl":"10.17179/excli2026-9646","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"1383-1387"},"PeriodicalIF":6.2,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105921","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":"Clinical and pathophysiological perspectives on haemostasis, inflammation, and thrombo-haemorrhagic risk in cirrhosis.","authors":"Alberto Zanetto, Kymentie Ferdinande, Marco Senzolo","doi":"10.17179/excli2026-9622","DOIUrl":"10.17179/excli2026-9622","url":null,"abstract":"<p><p>Haemostasis in cirrhosis is a dynamic process characterised by a fragile equilibrium. Haemostatic alterations become more pronounced during acute decompensation and acute-on-chronic liver failure, conditions driven by increasing systemic inflammation. When compounded by bacterial infection or acute kidney injury, additional alterations may emerge, predisposing to bleeding and thrombosis. Recent data indicate an interplay between haemostasis and inflammation in chronic liver disease, with implications for disease progression and thrombo-haemorrhagic complications. In this review, we discuss evolving knowledge across four interconnected domains. First, we summarise novel insights into the haemostatic status in cirrhosis derived from functional assays assessing platelet aggregation, total thrombus formation, thrombin and plasmin generation. Second, we examine the interplay between haemostasis and inflammation, focusing on immunohaemostasis, immunothrombosis, and coagulation-driven fibrogenesis as contributors to disease progression, with altered gut-liver axis signalling as an important upstream trigger. Third, we review evolving concepts in portal vein thrombosis and venous thromboembolism, highlighting accumulating evidence that portal vein thrombosis may represent a vascular remodelling disorder characterised by endothelial-to-mesenchymal transition, driven by portal hypertension-induced low shear stress, inflammation, infection, and gut-derived inflammatory stimuli, establishing a microenvironment permissive to secondary thrombus formation. Finally, we discuss procedure-related bleeding risk assessment, underscoring the need for a multidimensional framework integrating procedure- and patient-related factors, clinical trajectory, systemic inflammation, and functional haemostatic testing. These advances reinforce an integrated paradigm in which haemostasis, inflammation, and liver disease progression are highly interconnected. Improved understanding of this interface may enhance risk stratification and identify novel therapeutic targets in advanced chronic liver disease. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"1346-1375"},"PeriodicalIF":6.2,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105860","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":"Synthesis, molecular docking and biological evaluation of 2,4-diaminopyrimidines and pyrazoles as aurora kinase inhibitors.","authors":"Kaksha Sankhe, Mrunal Jadhav, Arati Prabhu, Tabassum Khan","doi":"10.17179/excli2026-9347","DOIUrl":"10.17179/excli2026-9347","url":null,"abstract":"<p><p>Aurora kinases (<i>AURKs</i>) constitute a family of serine/threonine protein kinases that regulate cell cycle progression and are frequently overexpressed in various cancers, thereby contributing to tumorigenesis. A series of pyrazoles and 2,4-diaminopyrimidines were designed and synthesized as potential cytotoxic entities in ovarian, brain, and leukemia cancer. Molecular docking studies were conducted on <i>AURKA</i> (PDB IDs: 3UP7) and <i>AURKB</i> (PDB IDs: 4AF3). Compounds exhibiting favorable interaction with the ATP binding site and key residues (Ala213 and Glu211 in <i>AURKA;</i> Ala157 and Glu155 in <i>AURKB</i>) were identified as potential candidates. Compounds 2j, 2l, 2p, 9a, and 10a showed dose-dependent cytotoxicity in SKOV3, C6, and THP1 cell lines. Of them, 2l, 9a, and 10a effectively suppressed the growth of SKOV3, C6, and THP1 cells with IC₅₀ values of 8.63 µM, 0.019 µM and 0.084 µM, respectively. Compounds 2l, 2p, 9a, and 10a showed promising inhibitory activity in <i>AURKA</i> and <i>AURKB</i>. 2p and 10a exhibited comparable potency to the standard Barasertib at 10 µM (2p: 68.14 %, 10a: 55.64 %, Barasertib: 78.42 %) highlighting their potential as novel therapeutic agents. The compounds 2j and 2p displayed potent inhibitory activity in <i>AURKB.</i> At 10µM, these compounds achieved inhibition rates comparable to standard Barasertib (2j: 56.36 %, 2p: 56.39 %, Barasertib: 68.62 %). Molecular docking and ADME prediction studies indicated these compounds to have good drug likeliness scores. The results of this study indicated that 2l, 2p, 9a, and 10a can be used as lead compounds targeting <i>AURK</i> for development as anti-cancer agents. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"1316-1345"},"PeriodicalIF":6.2,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024253","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}