EXCLI JournalPub Date : 2025-06-18eCollection Date: 2025-01-01DOI: 10.17179/excli2025-8565
Selahattin Bozkurt, Silvia Selinski, Meinolf Blaszkewicz, Jörg Reinders, Jan G Hengstler, Lukas Niggemann, Klaus Golka
{"title":"Follow-up of GSTM1, GSTT1, and NAT2 genotyped patients with knee or hip replacement.","authors":"Selahattin Bozkurt, Silvia Selinski, Meinolf Blaszkewicz, Jörg Reinders, Jan G Hengstler, Lukas Niggemann, Klaus Golka","doi":"10.17179/excli2025-8565","DOIUrl":"10.17179/excli2025-8565","url":null,"abstract":"<p><p>A total of 147 patients, genotyped for glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) and for N-acetyltransferase 2 (NAT2), who had undergone total joint replacement of the knee or hip joint between August 2004 and June 2007, showed with 45% a remarkably lower portion of the <i>GSTM1</i>-negative genotype compared to both a local control (51%), an external control (52%) and the portion reported in the literature for the European population (50%). In contrast, the portions of <i>GSTT1</i>-positive (84%) and slow <i>NAT2</i> (55.1%) patients of the initial collective were unremarkable, compared to both controls. To elucidate a possible impact of this interesting finding on the long-term outcome, the patients were contacted in December 2015. Afterwards, they were interviewed using a self-prepared questionnaire. The average follow-up time was 9 years. At the time of follow-up, 57 patients were deceased, 46 patients did not respond and 12 patients declined the interview. A total of 32 patients participated in the follow-up. The mean age of the followed-up patients was 75.9±8.3 years, whereas the mean age of all patients at the time of surgery was 70.9±9 years. The portions of the <i>GSTM1</i>-negative genotype (15 out of 32; 47%), the <i>GSTT1</i>-positive genotype (24 out of 32; 75%) and the slow <i>NAT2</i> status (17 out of 32; 53%) in the followed-up patients were comparable to those of the initial collective. The follow-up results of the patients after 9 years were unable to clarify the significance of the observed lower portion of <i>GSTM1</i>-negative patients. In view of a recently published omics study reporting a reduced GSTM1 activity in tissue attached on hip implants explanted due to aseptic loosening, the striking portion of the <i>GSTM1</i>-negative genotype in this present study may encourage further investigation into the impact of this gene in patients with hip or knee replacement.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"677-689"},"PeriodicalIF":3.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590810","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 the complexity of ulcerative colitis: insights into cytokine dysregulation and targeted therapies.","authors":"Yuta Shimomori, Yoshihiro Yokoyama, Hiroki Kurumi, Kotaro Akita, Tomoe Kazama, Yuki Hayashi, Kazuhiro Mizukami, Hiroshi Nakase","doi":"10.17179/excli2025-8374","DOIUrl":"10.17179/excli2025-8374","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a chronic or recurrent inflammatory disease of the large intestine. Although the causes of UC are insufficiently understood, a complex interaction of several factors, including genetic factors, environmental factors, and gut microbiota, influences the onset of UC. The pathophysiology of UC involves intestinal barrier dysfunction, abnormal immune responses, and dysregulation of cytokines. Cytokine-targeted therapies have been approved for the treatment of UC, with several targeted therapies being currently available. The induction response rates range from 47.8 % to 73 %, and we often experience difficult-to-treat cases. In this review, we outlined the abnormal immune response and cytokine regulation underlying the complex pathology of UC. Moreover, we summarized the mode of action and the effects at the cellular and genetic levels of targeted therapies. A deeper understanding of the pathophysiology of UC and the effects of treatment is essential for advancing personalized medicine, which remains a key, challenging goal in the future management of UC.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"638-658"},"PeriodicalIF":3.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590811","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}
EXCLI JournalPub Date : 2025-06-06eCollection Date: 2025-01-01DOI: 10.17179/excli2025-8351
Nehmat Ghaboura
{"title":"Unraveling the Hippo pathway: YAP/TAZ as central players in cancer metastasis and drug resistance.","authors":"Nehmat Ghaboura","doi":"10.17179/excli2025-8351","DOIUrl":"10.17179/excli2025-8351","url":null,"abstract":"<p><p>In regulating cellular plasticity, epithelial to mesenchymal transition (EMT), and tumor progression across a broad range of cancer types, the Hippo signaling pathway depends on YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ binding motif) as core effectors. This pathway can become dysregulated, disrupting tissue homeostasis and promoting oncogenic processes such as metastasis, immune evasion, and therapy resistance. This review explores the multifaceted roles of YAP/TAZ in lung, breast, ovarian, liver, and renal cancers, detailing their interactions with key signaling pathways such as TGF-β, Wnt, and PI3K/AKT and their modulation by mechanical cues like extracellular matrix stiffness and fluid shear stress. Potential YAP/TAZ mediated therapy resistance in EGFR TKI-resistant lung cancer and platinum-resistant ovarian cancer and the impact this has on tumor metabolism as a result of YAP/TAZ controlling tumor mesenchymal stem cells in the hypoxic environment of hepatocellular carcinoma is highlighted. Additionally, we discuss their role in maintaining cancer stem cell traits, creating an immunosuppressive tumor microenvironment, and driving chemoresistance in breast and renal cancers. Small molecule inhibitors, natural compounds (luteolin, apigenin, honokiol), and novel agents (nanoparticles of zinc oxide) are discussed as promising routes for disrupting YAP/TAZ. The review underscores the complexity of YAP/TAZ signaling and the need for patient stratification based on their expression levels to optimize targeted therapies. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"612-637"},"PeriodicalIF":3.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590812","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}
EXCLI JournalPub Date : 2025-05-30eCollection Date: 2025-01-01DOI: 10.17179/2025-8359
Mudasir Maqbool, Yumna Khan, Mohammed M Arab, Saud O Alshammari, Md Sadique Hussain, Fawaz M Almufarriji
{"title":"m6A methylation: a new frontier in epilepsy research and therapeutics.","authors":"Mudasir Maqbool, Yumna Khan, Mohammed M Arab, Saud O Alshammari, Md Sadique Hussain, Fawaz M Almufarriji","doi":"10.17179/2025-8359","DOIUrl":"10.17179/2025-8359","url":null,"abstract":"<p><p>Epilepsy is a highly complex and global neurological disorder, for which available treatments only inadequately control the disease in many patients. Recent advances in molecular research have identified N6-methyladenosine (m6A) RNA modifications as key regulators of neuronal processes that underpin the pathophysiology of epilepsy. This review critically discusses the emerging significance of m6A modifications in epilepsy, focusing on dynamic regulations of m6A \"writers,\" \"erasers,\" and \"readers\" for modulating gene expression, neuronal excitability, and synaptic plasticity in epilepsy. Dysregulation of m6A machinery promotes epilepsy by exacerbating oxidative stress, mitochondrial dysfunction, and neuronal damage. We also discuss the prognostic significance of m6A alterations as a potential biomarker in epilepsy diagnosis and disease progression, along with advanced therapeutic strategies against m6A, including small molecules, RNA editing technologies, and precision medicine. This review highlights the transformational significance of m6A modulation in epilepsy therapy and opens new avenues for personalized therapeutic strategies that may revolutionize the field of drug-resistant epilepsy and improve the prognosis for patients. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"578-611"},"PeriodicalIF":3.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316267","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}
EXCLI JournalPub Date : 2025-05-28eCollection Date: 2025-01-01DOI: 10.17179/2025-8260
Meriem Gaddas, Imen Ben Saida, Helmi Ben Saad
{"title":"Twenty years of inhaled insulin: promise, setbacks, and future directions.","authors":"Meriem Gaddas, Imen Ben Saida, Helmi Ben Saad","doi":"10.17179/2025-8260","DOIUrl":"10.17179/2025-8260","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"573-577"},"PeriodicalIF":3.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316269","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}
EXCLI JournalPub Date : 2025-05-23eCollection Date: 2025-01-01DOI: 10.17179/excli2025-8388
Jan G Hengstler, Agapios Sachinidis
{"title":"Comment to \"The beneficial effect of combination therapy with sulfasalazine and valsartan in the treatment of ulcerative colitis [EXCLI Journal 2021;20:236-247]\".","authors":"Jan G Hengstler, Agapios Sachinidis","doi":"10.17179/excli2025-8388","DOIUrl":"https://doi.org/10.17179/excli2025-8388","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"562-563"},"PeriodicalIF":3.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208078","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}
EXCLI JournalPub Date : 2025-05-22eCollection Date: 2025-01-01DOI: 10.17179/excli2025-8197
Martha Débora Lira Tenório, Pedro Dantas Oliveira, Paulo Ricardo Martins-Filho
{"title":"Lack of association between atopic dermatitis and COVID-19 severity: results from a case-control study.","authors":"Martha Débora Lira Tenório, Pedro Dantas Oliveira, Paulo Ricardo Martins-Filho","doi":"10.17179/excli2025-8197","DOIUrl":"10.17179/excli2025-8197","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"558-561"},"PeriodicalIF":3.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208080","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}