EXCLI Journal最新文献

{"title":"Erratum: Ferroptosis and circular RNAs: new horizons in cancer therapy.","authors":"Asif Ahmad Bhat, Neelima Kukreti, Muhammad Afzal, Ahsas Goyal, Riya Thapa, Haider Ali, Moyad Shahwan, Waleed Hassan Almalki, Imran Kazmi, Sami I Alzarea, Sachin Kumar Singh, Kamal Dua, Gaurav Gupta","doi":"10.17179/excli2026-9663","DOIUrl":"10.17179/excli2026-9663","url":null,"abstract":"<p><p>[This corrects the article on p. 570 in vol. 23, PMID: 38887390.].</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"1117-1123"},"PeriodicalIF":6.2,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600455","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":"Integrative analysis of whole-transcriptome sequencing reveals a ceRNA regulatory network centered on P4ha1 in liver cirrhosis treated with Pien Tze Huang.","authors":"Yunxiao Lin, Fan Yang, Yingtian Zhang, Xiaoqin Zhang, Xiangyi Li, Zhiliang Chen, Xianglong Zhao, Yongzhi Wang, Hao Wu, Cong Huai, Qiange Xiao, Wei Bao, Minglei Yang, Ruoyu Chen, Zhongyu Cao, Jinhang Zhu, Zekun Yu, Zexiu Zhang, Shengying Qin","doi":"10.17179/excli2026-9413","DOIUrl":"10.17179/excli2026-9413","url":null,"abstract":"<p><p>Liver cirrhosis represents a terminal stage of chronic liver disease with limited pharmacological options. Pien Tze Huang (PTH), a traditional Chinese medicine with established hepatoprotective properties, has shown therapeutic potential in liver fibrosis, yet its molecular mechanisms in cirrhosis remain poorly understood. Here, we investigated the anti-cirrhotic effects of PTH and underlying mechanisms through whole-transcriptome sequencing in a carbon tetrachloride (CCl₄)-induced mouse model of cirrhosis. PTH treatment significantly attenuated liver injury and other cirrhotic phenotypes, as evidenced by reduced serum transaminases and improved histological features. Transcriptomic analysis identified 1,518 genes dysregulated in cirrhosis and reversed by PTH treatment, with functional enrichment implicating inflammatory and fibrotic pathways including NF-κB, TNF, and IL-17 signaling. Connectivity Map analysis revealed similarity between PTH-induced transcriptional signatures and those of statins and beta-blockers, drugs currently evaluated in cirrhosis clinical trials. Through integrative construction of competing endogenous RNA (ceRNA) networks, we identified a core regulatory module comprising 6 miRNAs, 8 mRNAs, and 27 circRNAs with reversed expression patterns following PTH treatment. Notably, the liver-specific miR-122-5p exhibited the highest network connectivity, targeting <i>P4ha1</i>, a rate-limiting enzyme in collagen biosynthesis. Human proteome data confirmed liver-enriched expression of <i>P4HA1</i>, which is a validated therapeutic target of Lufironil, a Phase II clinical trial drug for cirrhosis. Our findings suggest that PTH ameliorates cirrhosis through multi-pathway regulation of a <i>P4ha1</i>-centered ceRNA network. Functional validation in hepatocytes confirmed that PTH modulates this network via the miR-122-5p/<i>P4HA1</i> axis, alleviating injury-induced miR-122-5p downregulation and consequent <i>P4HA1</i> upregulation. These results provide experimental evidence for a mechanistic basis of PTH's therapeutic application and highlight <i>P4ha1</i> as a promising biomarker for cirrhosis intervention. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"1070-1089"},"PeriodicalIF":6.2,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600805","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":"Acidic pH promotes degranulation and reduces oxidative stress in human primary neutrophils.","authors":"Maximilian Göbel, Yangfan Li, Melike Tombaz, Filiz Sahin, Andreas K Nussler, Sabrina Ehnert","doi":"10.17179/excli2026-9092","DOIUrl":"10.17179/excli2026-9092","url":null,"abstract":"<p><p>Chronic wounds represent an increasing global health burden for both patients and healthcare systems. These non-healing lesions frequently result in amputation and are particularly prevalent among individuals with diabetes. Hallmarks of chronic wounds include a prolonged inflammatory phase characterized by sustained neutrophil infiltration, excessive formation of neutrophil extracellular traps (NETs), and an elevated alkaline tissue pH. Emerging evidence suggests a link between pH and wound healing, with acidic conditions being more favorable for tissue repair. Here, we investigated the pH-dependent modulation of primary neutrophil functions, including viability, reactive oxygen species (ROS) production, NET formation, and exocytosis. Neutrophils cultured in media with pH values ranging from 6.1 to 8.4 exhibited no significant differences in viability. In contrast, acidic conditions suppressed ROS production and NET formation in a pH-dependent manner, whereas alkaline conditions caused responses comparable to those observed at physiological pH (7.4). Furthermore, levels of antioxidant enzymes were markedly increased under acidic conditions following phorbol 12-myristate 13-acetate (PMA) stimulation. Notably, alkaline pH promoted granule polarization in neutrophils, thereby impairing exocytosis. In contrast, acidic conditions (pH < 7.0) reduced granule polarization and enhanced the release of granule-associated proteins upon PMA stimulation. Pharmacological inhibition of degranulation confirmed that these effects were mediated by neutrophil exocytosis. In summary, extracellular pH critically modulates neutrophil effector functions and may contribute to the distinct healing dynamics observed in acute versus chronic wounds. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"1090-1106"},"PeriodicalIF":6.2,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600474","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":"Ultra-processed food exposure and health outcomes: Current evidence, controversies, and future perspectives.","authors":"Monica Dinu, Sofia Lotti, Farzaneh Asoudeh, Deb Junyi Zhang, Barbara Colombini, Sarah Gauci, Daniela Martini, Wolfgang Marx","doi":"10.17179/excli2026-9423","DOIUrl":"10.17179/excli2026-9423","url":null,"abstract":"<p><p>Ultra-processed food (UPF) exposure has increased markedly worldwide and is now a major contributor to total energy intake in many countries. Evidence from large prospective cohort studies suggests that higher UPF exposure is associated with adverse health outcomes, including overweight and obesity, type 2 diabetes, cardiovascular disease, selected cancers, depression, and increased all-cause mortality. Short-term experimental studies further indicate that diets rich in UPFs can promote excess energy intake and weight gain, supporting biological plausibility. Several mechanisms have been proposed, including poor nutrient quality, high glycemic load, altered food structure and satiety signaling, exposure to additives and contaminants, gut microbiome perturbations, and displacement of minimally processed foods. Nevertheless, the field remains debated. Major controversies concern the Nova classification system, substantial heterogeneity within the UPF category, challenges in reproducible classification, and the extent to which observed associations reflect processing itself rather than nutrient profile, dietary patterns, or broader food environments. These issues hinder causal inference and sustain ongoing debate over whether UPFs act as independent etiological factors or function as markers of unhealthy diets. Policy responses vary internationally, ranging from explicit inclusion of UPFs in dietary guidelines to predominantly nutrient-based or hybrid frameworks. This narrative review summarizes current evidence linking UPF exposure to health outcomes, critically examines methodological and conceptual limitations, and discusses implications for future research and public health policy. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"1037-1069"},"PeriodicalIF":6.2,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600816","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":"HDAC inhibitors as ferroptosis sensitizers in cancer: Epigenetic regulation of redox balance and iron metabolism.","authors":"Mubarak A Alamri, Muhammad Afzal, Surya Nath Pandey, Obaid Afzal, Mohamed Ahmed Akela, A Rekha","doi":"10.17179/excli2026-9414","DOIUrl":"10.17179/excli2026-9414","url":null,"abstract":"<p><p>The evasion of programmed cell death significantly contributes to therapeutic failure in cancer, with resistance to apoptosis being the most prevalent form of resistance in multidrug-refractory diseases. Ferroptosis, an iron-dependent, non-apoptotic form of regulated cell death characterized by the lethal accumulation of lipid peroxides, represents a pharmacologically significant vulnerability in cancers that are resistant to apoptosis and tolerant to drugs. The resistance to ferroptosis, induced by the aberrant overexpression of the epigenetic enzyme histone deacetylases (HDACs) and the sustained transcriptional activity of key antiferroptotic targets, particularly GPX4 and SLC7A11, is enforced through epigenetic mechanisms. This review examines the extant preclinical and translational data, demonstrating that HDAC inhibitors predispose cancer cells to ferroptosis through four mechanistically convergent pathways. These pathways include the transcriptional silencing of SLC7A11 and subsequent glutathione depletion, disruption of intracellular iron homeostasis via ferroportin downregulation, enhancement of mitochondrial ROS-induced lipid peroxidation, and suppression of the HDAC3-NRF2-GPX4 antiferroptotic axis. The specific roles of HDAC1, HDAC3, and HDAC10 in colorectal, lung, gastric, and hematological cancers are elucidated. Additionally, the review discusses hybrid molecules of HDAC-ferroptosis, combination strategies with GPX4 inhibitors, and immunochemotherapy. Considerations such as isoform selectivity, biomarker development, and clinical translation are addressed, highlighting HDAC inhibitor-mediated ferroptosis sensitization as a promising strategy to overcome drug resistance in cancer. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"1014-1036"},"PeriodicalIF":6.2,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600751","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":"Berberine-induced ferroptosis as a novel anti-cancer strategy: Molecular, epigenetic and translational perspectives.","authors":"Neetu Agrawal, Gaurav Gupta, Surya Nath Pandey, A Rekha, Mano Priya Vijayan, Dinesh Kumar Chellappan, Keshav Raj Paudal, Sachin Kumar Singh, Kamal Dua","doi":"10.17179/excli2026-9385","DOIUrl":"10.17179/excli2026-9385","url":null,"abstract":"<p><p>Cancer cells frequently evade therapies that depend on apoptosis, necessitating the exploration of alternative cell death mechanisms. Ferroptosis, an iron-dependent regulated cell death characterized by lethal lipid peroxidation, has emerged as a promising strategy for cancer treatment. Recent studies have identified berberine, an isoquinoline alkaloid derived from Coptis chinensis and Berberis species, as an inducer of ferroptosis in various malignancies through its multitarget effects. This review systematically elucidates the molecular pathways through which berberine induces ferroptosis. These pathways include the inhibition of the System Xc^-/glutathione/glutathione peroxidase 4 antioxidant axis, disruption of iron homeostasis via ferritinophagy, inhibition of mitochondrial complex I, and regulation of the upstream regulators p53, nuclear factor erythroid 2-related factor 2, and Gli1/signal transducer and activator of transcription 3 axis. Evidence specific to various cancer types, including nasopharyngeal, lung, colorectal, gastric, hepatocellular, pancreatic, prostate cancer, and osteosarcoma, was critically evaluated. Translational strategies, such as combination therapy, nanodelivery systems, and machine learning-directed structural optimization, have been examined. Additionally, the challenges of low bioavailability, resistance to ferroptosis, and complex immunological responses are discussed. Preclinical evidence suggests that berberine exhibits significant epigenetic activity, including the inhibition of DNA methyltransferases (DNMT1/DNMT3), histone modifications (H3K9me3 via SETDB1, H3K27me3 via EZH2), and modulation of oncogenic/tumor-suppressor microRNAs (e.g., miR-21, miR-155). These actions enhance its ferroptotic effects and may synergistically increase the sensitivity of cancer cells to lipid peroxidation. Although primarily based on preclinical findings, these epigenetic mechanisms represent a crucial and underexplored aspect of berberine's anticancer potential. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"993-1013"},"PeriodicalIF":6.2,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600498","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":"Therapeutic potential of berberine in cancer treatment: Current update.","authors":"Safwan Hazaa, Yachana Mishra, Vijay Mishra","doi":"10.17179/excli2026-9530","DOIUrl":"10.17179/excli2026-9530","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"991-992"},"PeriodicalIF":6.2,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600834","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":"Doxorubicin-induced cardiotoxicity: Is ferroptosis the primary driver or a downstream amplifier?","authors":"Yogender Goswami, Nisha Sharma, Umashanker Navik","doi":"10.17179/excli2026-9516","DOIUrl":"10.17179/excli2026-9516","url":null,"abstract":"<p><p>Doxorubicin (Dox) is one of the most effective anticancer agents used to treat a wide range of solid tumors as well as hematological malignancies. However, its associated cardiotoxicity poses a major challenge for its therapeutic use. There are numerous studies exploring the underlying cellular mechanisms behind Dox-induced cardiotoxicity. Apart from the well-established apoptosis and necrosis pathways, ferroptosis is a recently identified regulated cell death pathway being studied in the context of drug-induced cardiotoxicity. Under normal physiology, cardiomyocytes maintain a highly regulated iron homeostasis, while the polyunsaturated fatty acid-rich membrane also renders it susceptible to peroxidation, a hallmark of ferroptosis. Dox-induced cardiotoxicity disrupts the coordinated control of iron metabolism, generating reactive oxygen species, propagating lipid peroxidation, and impairing mitochondrial function. Progressive structural damage and functional loss of cardiomyocytes culminate in permanent cardiac cell death. Therefore, targeting regulatory nodes of ferroptosis may be beneficial for ameliorating Dox-induced cytotoxicity. However, it is still not clear whether the ferroptotic process merely acts as an initiator or can further act as an amplifier to upregulate the downstream signaling molecules in this cell death cascade. This review offers an overview of perspectives on the ferroptotic pathway and introduces readers to a novel driver-amplifier concept. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"974-990"},"PeriodicalIF":6.2,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600469","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":"Recent biological and pharmacological activities of naringenin in clinical studies.","authors":"Fares Aljasmi, Cijo George Vazhappilly","doi":"10.17179/excli2026-9460","DOIUrl":"10.17179/excli2026-9460","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"972-973"},"PeriodicalIF":6.2,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13369879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455052","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":"Eschar, enigma, and encephalopathy: a case series of atypical and fatal presentations of scrub typhus in young adults from Northern India.","authors":"Abhijeet Sharma, Yashendra Sethi, Shirobhi Sharma, Akansha Jain, Prakhar Choudhry, Nidhi Uniyal, Pankaj N Choudhry, Shivani Chopra, Hitesh Chopra, Pratik Agarwal","doi":"10.17179/excli2026-9514","DOIUrl":"10.17179/excli2026-9514","url":null,"abstract":"<p><p>Scrub typhus is a re-emerging but often underdiagnosed tropical zoonosis in India. Its clinical heterogeneity, serological overlap with other endemic infections, and frequent absence of pathognomonic signs contribute to delayed diagnosis and high complication rates. Central nervous system, pulmonary, and renal involvement signify severe disease and are associated with considerable morbidity and mortality. We describe three cases of previously healthy young adult males (ages 24-32) who presented with severe, organ-threatening complications of scrub typhus: acute encephalitis syndrome (AES), acute respiratory distress syndrome (ARDS), and acute kidney injury (AKI). All patients had evidence of systemic inflammation, thrombocytopenia, and multiorgan dysfunction. Eschars-although present in all cases-were initially missed or overlooked, delaying causal diagnosis. Serologic cross-reactivity with dengue, chikungunya, and leptospira further complicated early recognition. Despite early initiation of doxycycline upon clinical suspicion, one patient with ARDS succumbed to progressive hypoxemia and multiorgan failure. These cases underscore the protean and fulminant nature of scrub typhus and highlight the diagnostic importance of thorough skin examination in febrile patients with unexplained CNS, pulmonary, or renal involvement. In endemic settings, empiric doxycycline should be considered early, even in the absence of classical signs. Early recognition and treatment remain the most critical determinants of survival. Our experience reinforces that scrub typhus, though elusive, is a potentially treatable cause of severe febrile illness when promptly identified.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"25 ","pages":"957-971"},"PeriodicalIF":6.2,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13369890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455062","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}