EXCLI Journal最新文献

{"title":"Plant extracts: a potential approach to combating multidrug-resistant bacteria.","authors":"Sun Sik Kong, Chang Ha Park","doi":"10.17179/excli2026-9282","DOIUrl":"https://doi.org/10.17179/excli2026-9282","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"372-374"},"PeriodicalIF":4.9,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13077163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689116","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 compartmentalization model of nitrate homeostasis: Role of the salivary glands, skeletal muscle, and liver.","authors":"Asghar Ghasemi, Sajad Jeddi, Khosrow Kashfi","doi":"10.17179/excli2026-9229","DOIUrl":"https://doi.org/10.17179/excli2026-9229","url":null,"abstract":"<p><p>Nitric oxide (NO) is a small, bioactive molecule with diverse physiological functions. It is generated both enzymatically by NO synthases (NOS) and non-enzymatically through the nitrate-nitrite-NO reduction pathway. Recent studies have renewed interest in nitrate-based regulation of NO, highlighting a compartmentalization model of nitrate homeostasis. In this model, excess NO is rapidly oxidized to nitrite, which is then oxidized to nitrate, a more stable species that limits oxidative damage. Nitrate is differentially distributed across tissues, allowing both storage and rapid mobilization to maintain NO availability. Human and animal studies show that nitrate concentrations in skeletal muscle, plasma, and liver are approximately 100, 35, and 10 nmol/g, respectively, corresponding to a skeletal muscle-to-plasma-to-liver ratio of ~3:1:0.3. The large skeletal muscle reservoir and its higher muscle-to-plasma gradient support the release of nitrate into the circulation when needed. In contrast, the liver-to-plasma ratio < 1 suggests active hepatic uptake of circulating nitrate. Together, these findings support a compartmentalized system in which nitrate storage and flux contribute to whole-body NO homeostasis. Understanding this model may have implications for exercise physiology, metabolic regulation, and liver pathophysiology - all conditions in which NO biology plays a critical role. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"345-371"},"PeriodicalIF":4.9,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13077174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689134","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":"Acetylsalicylic acid versus clopidogrel in cardiovascular prevention: Does the classic still outperform the contemporary?","authors":"Ian Jhemes Oliveira Sousa, Kerolayne de Melo Nogueira","doi":"10.17179/excli2026-9251","DOIUrl":"https://doi.org/10.17179/excli2026-9251","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"342-344"},"PeriodicalIF":4.9,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13077162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689107","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":"Beyond the pitch: The unaddressed challenges of inadequate uniforms in women's football.","authors":"Rizia Rocha-Silva, Geovana José, Marília Santos Andrade, Claudio Andre Barbosa de Lira","doi":"10.17179/excli2025-9263","DOIUrl":"10.17179/excli2025-9263","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"339-341"},"PeriodicalIF":4.9,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12982871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462914","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":"Comparison of LDH activity and LDH-M to predict death in patients with acetaminophen-induced acute liver failure.","authors":"Debasree Bhadra, Jody A Rule, William M Lee, Mitchell R McGill","doi":"10.17179/excli2025-9174","DOIUrl":"10.17179/excli2025-9174","url":null,"abstract":"<p><p>Liver transplantation is often the only life-saving intervention in acute liver failure (ALF), so it is critical to identify all ALF patients who need a transplant to survive. However, transplantable organs are scarce and recipients face significant life-threatening risks, so it is also important to avoid transplantation when possible. Thus, prognostics that can predict death in ALF with both high sensitivity and specificity are needed. We previously demonstrated total lactate dehydrogenase (LDH) activity may be useful for this purpose. However, LDH is a tetramer of LDH-M and LDH-H, and proteomics indicated only the liver enzyme - LDH-M - increases in non-survivors. LDH-H decreased. Because total LDH comprises both, it is possible that LDH-M could have even better prognostic performance. To test that, we compared total LDH and LDH-M in a subset of samples from our prior study of survivors and non-survivors of acetaminophen (APAP)-induced ALF. The model for end-stage liver disease (MELD) score and the MELD-LDH score were also calculated. Both total LDH and LDH-M values were greater in non-survivors than survivors, but there was no significant difference in prognostic metrics between them. Overall, total LDH performed similarly to or modestly better than both LDH-M and the MELD. The MELD-LDH score also performed somewhat better than the MELD. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"330-338"},"PeriodicalIF":4.9,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12982867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462971","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":"Efficacy and safety of CTLA-4, PD-1 and LAG-3 immune checkpoint inhibitors as monotherapy and combination therapy in advanced melanoma: A systematic review and meta-analysis.","authors":"Osama Omar Khan","doi":"10.17179/excli2025-9096","DOIUrl":"10.17179/excli2025-9096","url":null,"abstract":"<p><p>Advanced unresectable melanoma carries a poor prognosis, with minimal benefit from chemotherapy and limited responsiveness to radiotherapy. The emergence of immune checkpoint inhibitors (ICIs) targeting PD-1, CTLA-4, and LAG-3 has transformed treatment outcomes; however, their comparative efficacy and safety remain unclear. This systematic review and meta-analysis evaluated and compared the efficacy and safety of PD-1 and CTLA-4 monotherapies against traditional systemic therapies, as well as the dual regimens PD-1 + CTLA-4 and PD-1 + LAG-3 against their respective monotherapies, in patients with advanced unresectable melanoma. A comprehensive search of PubMed and the Cochrane CENTRAL database was conducted on March 18, 2025, for randomized controlled trials comparing ICIs against conventional therapies or other ICI regimens. Primary endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade ≥ 3 adverse events (AEs). A random-effects meta-analysis was performed, and risk of bias was assessed using the Cochrane RoB 2.0 tool. Eleven randomized controlled trials (n = 4,111) met the inclusion criteria. The PD-1 + CTLA-4 combination demonstrated the greatest clinical benefit, significantly improving OS (HR = 0.59), PFS (HR = 0.45), and ORR (RR = 3.11) compared with monotherapy, but was associated with a higher incidence of grade ≥ 3 AEs (RR = 2.14). The PD-1 + LAG-3 regimen showed a moderate yet statistically significant advantage in efficacy over PD-1 monotherapy (OS HR = 0.80) while maintaining better tolerability. PD-1 monotherapy demonstrated greater efficacy and a more favorable safety profile than CTLA-4 monotherapy when each was compared with traditional therapy. In conclusion, PD-1 + CTLA-4 offers the most substantial therapeutic improvement but with considerable toxicity, whereas PD-1 + LAG-3 provides a more balanced efficacy-safety profile. PD-1 monotherapy remains the safest option, though less effective than combination strategies. These findings highlight the evolving role of combination immunotherapies and the potential clinical value of LAG-3 as a novel checkpoint target in melanoma management. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"310-329"},"PeriodicalIF":4.9,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12982869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462956","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":"Bridging pathologies: Mechanistic insights into the diabetes-Alzheimer's nexus.","authors":"Aniket Kakkar, Harpreet Singh, Yash Jasoria, Arvind Kumar, Shivani Chopra, Hitesh Chopra, Arun Kumar Mishra","doi":"10.17179/excli2025-9165","DOIUrl":"10.17179/excli2025-9165","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is increasingly recognized as a major risk factor for Alzheimer's disease (AD), with mounting evidence highlighting shared pathophysiological mechanisms. This review explores the intricate biological and molecular links between these two chronic disorders. Key overlapping pathways include impaired insulin signaling, chronic inflammation, oxidative stress, mitochondrial dysfunction, amyloid-beta (Aβ) accumulation, tau hyperphosphorylation, and the formation of advanced glycation end-products (AGEs). Disruption of insulin signaling in the brain contributes to synaptic loss and neurodegeneration, while systemic metabolic disturbances aggravate blood-brain barrier dysfunction and neurovascular damage. Emerging studies also underscore the role of antidiabetic treatments, especially newer agents targeting the gut-brain axis, in modulating AD progression. The review further examines preclinical models, clinical observations, and the development of biomarkers to improve early detection and intervention. Despite growing insights, challenges remain in translating mechanistic knowledge into effective therapies. A multidisciplinary approach integrating metabolic control and neuroprotective strategies is essential for addressing the comorbid burden of T2DM and AD. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"261-289"},"PeriodicalIF":4.9,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12982873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462932","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":"Long-term Western diet feeding impairs hepatic vitamin D metabolism and promotes bone loss in mice.","authors":"Pengcheng Zhou, Mohammad Majd Hammour, Romina H Aspera-Werz, Sabrina Ehnert, Maiju Myllys, Zaynab Hobloss, Reham Hassan, Daniela Gonzalez, Rama Hendawi, Karolina Edlund, Sandra Hans, Matthias W Laschke, Ahmed Ghallab, Jan G Hengstler, Andreas K Nüssler, Tanja C Maisenbacher","doi":"10.17179/excli2025-9085","DOIUrl":"10.17179/excli2025-9085","url":null,"abstract":"<p><p>Obesity and metabolic dysfunction-associated fatty liver disease (MAFLD) are increasingly recognized as risk factors for skeletal fragility, yet the mechanisms linking these conditions to impaired bone health remain poorly defined. The liver is central to vitamin D homeostasis through 25-hydroxylation, while skeletal responsiveness relies on vitamin D receptor (VDR) signaling. Disruption of either process may compromise bone remodeling. In this study, we investigated the long-term effects of Western diet (WD) feeding on hepatic vitamin D metabolism and bone integrity in a mouse model. Male C57BL/6N mice were fed a standard diet (SD) or WD for 48 weeks. WD-fed mice developed obesity, hepatic injury, and trabecular bone deterioration characterized by reduced bone mineral density and increased trabecular separation. Although trabecular architecture was compromised, three-point bending revealed no significant impairment in cortical bone mechanical properties. Histological analyses showed increased bone marrow adiposity and macrophage/monocyte lineage cells. Bone gene expression profiling indicated enhanced osteoclastogenic signaling. Hepatic transcriptomics demonstrated marked downregulation of key 25-hydroxylases (<i>Cyp2r1</i>, <i>Cyp27a1</i>) and vitamin D-binding protein, accompanied by reduced circulating 25‑hydroxyvitamin D. Bone tissue also exhibited decreased VDR protein abundance. Together, these findings suggest that long-term WD-induced obesity and hepatic dysfunction impair hepatic vitamin D metabolism and diminish skeletal vitamin D responsiveness, contributing to bone fragility. Targeting the liver-bone axis and restoring vitamin D homeostasis may provide therapeutic potential for obesity-related bone loss. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"290-309"},"PeriodicalIF":4.9,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12982870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147463011","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":"Epigenetic regulation of PANoptosis: DNA methylation, histone modifications and non-coding RNAs.","authors":"Yogendra Singh, Muhammad Afzal, M Arockia Babu, Surya Nath Pandey, Arcot Rekha, Gaurav Gupta, Imran Kazmi, Sami I Alzarea, Omar Awad Alsaidan, Waleed Hassan Almalki, Salem Salman Almujri","doi":"10.17179/excli2025-9099","DOIUrl":"10.17179/excli2025-9099","url":null,"abstract":"<p><p>PANoptosome (Programmed Necrosis-Apoptosis Optosome) multiprotein complexes mediate the convergence of apoptosis, pyroptosis, and necroptosis. The ability of cells to undergo programmed inflammatory cell death is regulated by the epigenetic control of PANoptotic sensors, adaptors, and effectors, and has pivotal implications for their use in cancer therapies. DNA methylation suppresses the main PANoptotic pathways, such as RIPK3 (Receptor-Interacting Serine/Threonine-Protein Kinase 3), GSDME (Gasdermin E), and CASP8 (Caspase-8) that promote chemoresistance; hypomethylating DNA silencers resume PANoptotic sensitivity. BRD4 (Bromodomain-Containing Protein 4)/p300 (E1A-Associated Protein p300 - Histone Acetyltransferase) -mediated histone acetylation in enhancers (H3K27ac) stimulates ZBP1 (Z-DNA Binding Protein 1), NLRP3 (NOD-Like Receptor Family Pyrin Domain Containing 3), and caspase-8 transcription but inhibits the formation of inflammasomes by HDAC (Histone Deacetylase). PANoptotic regulatory regions become accessible in response to inflammatory signals through the dynamic regulation of accessibility through the SWI/SNF (Switch/Sucrose Non-Fermentable Chromatin Remodeling Complex) and NuRD (Nucleosome Remodeling Complex) and NuRD (Nucleosome Remodeling and Deacetylase Complex) chromatin remodelling complexes. Post-transcriptional regulation is mediated by ncRNAs (ncRNAs) such as miR-223-3p (MicroRNA-223-3p) and lncRNA NEAT1 (Long Non-Coding RNA - Nuclear Enriched Abundant Transcript 1) which converge to regulate the expression of NLRP3, RIPK3, and Gasdermin D (GSDMD). The interaction of DNA methylation, histone modification, and ncRNAs creates quantitative epigenetic thresholds that regulate PANoptotic sensitivity. The rational next step to overcome tumor immunoresistance is epigenetic biomarker stratification in combination with DNA methyltransferase inhibitors (DNMTi), histone deacetylase modulators (HDACi), and PANoptosis agonists, which could help reduce collateral tissue toxicity. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"238-260"},"PeriodicalIF":4.9,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12982872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462943","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":"Eugenol: A promising therapeutic terpenoid against ischemia-reperfusion injury.","authors":"Puneet Kaur Randhawa, Deepti Gupta, Mohd Hanifa, Bivek Bajgai, Sorabh Sehajpal, Sarbeshwar Jaggi, Anjana Bali","doi":"10.17179/excli2025-9036","DOIUrl":"10.17179/excli2025-9036","url":null,"abstract":"<p><p>Ischemic disorders are one of the prime causes of mortality and disability among various individuals across the globe. Although drug treatment/percutaneous coronary interventions may recanalize the obstructed blood vessels, yet reperfusion therapy may aggravate tissue damage and result in ischemia-reperfusion injury. Eugenol, a phenolic monoterpenoid (4-allyl-2-methoxyphenol), has been used extensively in various preclinical studies as an antioxidant compound that ameliorates ischemia-reperfusion injury in several organs, including the heart, brain, kidney, and intestine. This protective effect of eugenol is attributed to its ability to influence various several key signaling pathways. These include the AMPK-mTOR-P70S6K (AMP-activated protein kinase-mammalian target of rapamycin-p70 ribosomal S6 kinase) pathway, AMPK/GSK3β (Glycogen synthase kinase-3 beta) axis, PI3K/Akt (phoshatidylinositol-3 kinase/ protein kinase B) signaling, which help to mitigate oxidative damage and inflammation. It also modulates the activity of the Nrf2 transcription factor, ACE, and the apoptotic pathway, affects histone acetylation, and alters the expression of HMGN1, PPP2Ca, and CD151 genes, demonstrating its wide-ranging therapeutic effects. In this review, we will discuss the preclinical evidences and potential mechanisms of action of eugenol-dependent protective benefits against ischemia-reperfusion injury. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"222-237"},"PeriodicalIF":4.9,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12982868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462964","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}