EXCLI Journal最新文献

{"title":"Potential of melatonin to reverse epigenetic aberrations in oral cancer: new findings.","authors":"Emilio Gil-Martín, Eva Ramos, Francisco López-Muñoz, Javier Egea, Alejandro Romero","doi":"10.17179/excli2023-6624","DOIUrl":"10.17179/excli2023-6624","url":null,"abstract":"<p><p>It is now an accepted principle that epigenetic alterations cause cellular dyshomeostasis and functional changes, both of which are essential for the initiation and completion of the tumor cycle. Oral carcinogenesis is no exception in this regard, as most of the tumors in the different subsites of the oral cavity arise from the cross-reaction between (epi)genetic inheritance and the huge challenge of environmental stressors. Currently, the biochemical machinery is put at the service of the tumor program, halting the cell cycle, triggering uncontrolled proliferation, driving angiogenesis and resistance to apoptosis, until the archetypes of the tumor phenotype are reached. Melatonin has the ability to dynamically affect the epigenetic code. It has become accepted that melatonin can reverse (epi)genetic aberrations present in oral and other cancers, suggesting the possibility of enhancing the oncostatic capacity of standard multimodal treatments by incorporating this indolamine as an adjuvant. First steps in this direction confirm the potential of melatonin as a countermeasure to mitigate the detrimental side effects of conventional first-line radiochemotherapy. This single effect could produce synergies of extraordinary clinical importance, allowing doses to be increased and treatments not to be interrupted, ultimately improving patients' quality of life and prognosis. Motivated by the urgency of improving the medical management of oral cancer, many authors advocate moving from <i>in vitro</i> and preclinical research, where the bulk of melatonin cancer research is concentrated, to systematic randomized clinical trials on large cohorts. Recognizing the challenge to improve the clinical management of cancer, our motivation is to encourage comprehensive and robust research to reveal the clinical potential of melatonin in oral cancer control. To improve the outcome and quality of life of patients with oral cancer, here we provide the latest evidence of the oncolytic activity that melatonin can achieve by manipulating epigenetic patterns in oronasopharyngeal tissue.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"22 ","pages":"1280-1310"},"PeriodicalIF":3.8,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10792176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485374","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 serine in neurodegenerative diseases.","authors":"Jia-Meng Li, Shuang-Qing Zhang","doi":"10.17179/excli2023-6636","DOIUrl":"10.17179/excli2023-6636","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"22 ","pages":"1278-1279"},"PeriodicalIF":4.6,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10792173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485387","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":"Alpha-ketoglutarate partially alleviates effects of high-fat high-fructose diet in mouse muscle.","authors":"Myroslava V Vatashchuk, Maria M Bayliak, Viktoriia V Hurza, Oleh I Demianchuk, Dmytro V Gospodaryov, Volodymyr I Lushchak","doi":"10.17179/excli2023-6608","DOIUrl":"10.17179/excli2023-6608","url":null,"abstract":"<p><p>Consumption of high-calorie diets leads to excessive accumulation of storage lipids in adipose tissue. Metabolic changes occur not only in adipose tissue but in other tissues, too, such as liver, heart, muscle, and brain. This study aimed to explore the effects of high-fat high-fructose diet (HFFD) alone and in the combination with alpha-ketoglutarate (AKG), a well-known cellular metabolite, on energy metabolism in the skeletal muscle of C57BL/6J mice. Five-month-old male mice were divided into four groups - the control one fed a standard diet (10 % kcal fat), HFFD group fed a high-fat high-fructose diet (45 % kcal fat, 15 % kcal fructose), AKG group fed a standard diet with 1 % sodium AKG in drinking water, and HFFD + AKG group fed HFFD and water with 1 % sodium AKG. The dietary regimens lasted 8 weeks. Mice fed HFFD had higher levels of storage triacylglycerides, lower levels of glycogen, and total water-soluble protein, and higher activities of key glycolytic enzymes, namely hexokinase, phosphofructokinase, and pyruvate kinase, as compared with the control group. The results suggest that muscles of HFFD mice may suffer from lipotoxicity. In HFFD + AKG mice, levels of the metabolites and activities of glycolytic enzymes did not differ from the respective values in the control group, except for the activity of pyruvate kinase, which was significantly lower in HFFD + AKG group compared with the control. Thus, metabolic changes in mouse skeletal muscles, caused by HFFD, were alleviated by AKG, indicating a protective role of AKG regarding lipotoxicity.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"22 ","pages":"1264-1277"},"PeriodicalIF":4.6,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10792174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139486938","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 application of bioglass to treat osteoarthritis.","authors":"Saurav Kumar Jha, Bhupendra Kumar, Keshav Raj Paudel, Amitabha Bandyopadhyay","doi":"10.17179/excli2023-6613","DOIUrl":"10.17179/excli2023-6613","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"22 ","pages":"1232-1234"},"PeriodicalIF":4.6,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10792177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485471","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":"Promising influences of hesperidin and hesperetin against diabetes and its complications: a systematic review of molecular, cellular, and metabolic effects.","authors":"Amirhossein Mirzaei, Ali Mirzaei, Shakiba Najjar Khalilabad, Vahid Reza Askari, Vafa Baradaran Rahimi","doi":"10.17179/excli2023-6577","DOIUrl":"10.17179/excli2023-6577","url":null,"abstract":"<p><p>Hesperidin and hesperetin, two flavonoids with potential therapeutic value, have been extensively studied in the context of diabetes management. The main objective of this research is to ascertain their potential as therapeutic options for managing diabetes and its complications. The present study utilized a systematic review methodology and comprehensively explored relevant literature from databases, including PubMed, Scopus, and Web of Science, from inception until July 2023. The review summarized the outcomes related to the molecular, cellular, and metabolic effects of hesperidin and hesperetin in diabetes and its complications. Hesperetin exhibits a potential treatment for preventing diabetes and its associated complications through modulation of inflammatory cytokine release and expression via the pathway of signaling through Toll-like receptor/Myeloid differentiation factor 88/Nuclear factor-kappa B. Hesperidin shows promise as a biomolecule for treating diabetic neuropathy, primarily through activation of nuclear factor erythroid 2-related factor 2 (Nrf-2), as an antioxidant-response element signaling, leading to neuroprotective effects. Both compounds demonstrated the ability to normalize blood glucose levels and reduce serum and liver lipid levels, making them potential candidates for managing hypoglycemia and hypolipidemia in diabetes. Hesperidin also showed potential benefits against diabetic nephropathy by suppressing transforming growth factor-β1-integrin-linked kinase-Akt signaling and enhancing renal function. Furthermore, hesperidin's antioxidant, anti-inflammatory, and anti-depressant effects in diabetic conditions expanded its potential therapeutic applications. This systematic review provides substantial evidence supporting the consideration of hesperidin and hesperetin for diabetes and its complications. It offers exciting possibilities for developing novel, cost-effective treatment options to enhance diabetes management and patient outcomes.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"22 ","pages":"1235-1263"},"PeriodicalIF":4.6,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10792178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485377","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":"Interplay between lncRNA/miRNA and Wnt/ß-catenin signaling in brain cancer tumorigenesis.","authors":"Farzad Rahmani, Abdulridha Mohammed Al-Asady, Reyhane Hanaie, Mehrdad Zandigohar, Homeira Faridnejad, Mahya Payazdan, Pegah Safavi, Mikhail Ryzhikov, Seyed Mahdi Hassanian","doi":"10.17179/excli2023-6490","DOIUrl":"10.17179/excli2023-6490","url":null,"abstract":"<p><p>Brain cancers are among the most aggressive malignancies with high mortality and morbidity worldwide. The pathogenesis of brain cancers is a very complicated process involving various genetic mutations affecting several oncogenic signaling pathways like Wnt/β-catenin axis. Uncontrolled activation of this oncogenic signaling is associated with decreased survival rate and poor prognosis in cancer patients. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) were shown to play important roles in regulating cell proliferation, differentiation, and apoptosis by regulating the expression of their target genes. Aberrant expression of these non-coding RNAs (ncRNAs) was reported in many human cancers, including glioblastoma, medulloblastoma, meningioma, and pituitary adenoma. Multiple lncRNAs were shown to participate in brain tumor pathogenesis by targeting Wnt signaling regulatory miRNAs. SNHG7/miR-5095, PCAT6/miR-139-3p, SNHG6/miR-944, SNHG1/ miR-556-5p, SNHG17/ miR-506-3p, LINC00702/miR-4652-3p, DLGAP1-AS1/miR-515-5p, HOTAIR/miR-1, HOTAIR/miR-206, CRNDE/miR-29c-3p, AGAP2-AS1/ miR-15a/b-5p, CLRN1-AS1/miR-217, MEG3/miR-23b-3p, and GAS5/miR-27a-5p are identified lncRNA/miRNA pairs that are involved in this process. Therefore, recognition of the expression profile and regulatory role of ncRNAs on the Wnt signaling may offer a novel approach to the diagnosis, prognosis, and treatment of human cancers. This review summarizes previous data on the modulatory role of lncRNAs/miRNAs on the Wnt/β-catenin pathway implicated in tumor growth, EMT, metastasis, and chemoresistance in brain cancers.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"22 ","pages":"1211-1222"},"PeriodicalIF":4.6,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10776877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416734","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 studies on myricetin and its biological and pharmacological activities.","authors":"Priscilla Nadalin, Jae Kwang Kim, Sang Un Park","doi":"10.17179/excli2023-6571","DOIUrl":"10.17179/excli2023-6571","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"22 ","pages":"1223-1231"},"PeriodicalIF":4.6,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10839238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691595","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":"Prevalence and impact of tobacco use disorder on in-hospital mortality in patients hospitalized with non-group 1 pulmonary hypertension: a nationwide propensity score-matched analysis, 2019.","authors":"Rupak Desai, Zainab Gandhi, Saher Taj Shiza, Akhil Jain, Hiren Koshiya, Bibi Alli-Ramsaroop, Agatha Olawunmi Akinsete, Eko Wilson, Pranathi Rudra, Mohan Sai Sunith Vegesna, Madiha Bari, Ankit Vyas, Bisharah Rizvi, Salim Surani","doi":"10.17179/excli2023-6409","DOIUrl":"10.17179/excli2023-6409","url":null,"abstract":"<p><p>Numerous studies indicated that patients with tobacco use disorder (TUD) are inversely associated with mortality in what is known as the smoker's paradox. However, limited studies have been conducted on the impact of TUD on the in-hospital mortality rates of patients with secondary pulmonary hypertension (PH, Non-Group 1 PH). Using the 2019 National Inpatient Sample, we identified PH and divided it into TUD and non-TUD to compare the comorbidities and in-hospital mortality between the two after 1:1 propensity-score matching. Of 1,129,440 PH hospitalizations, 12.1 % had TUD. After matching (n=133545, each group), TUD had lower median age (62 vs. 63), higher females (49 vs. 46.6 %), blacks (25.9 vs. 25.3 %), lower household income (40.8 vs. 32.7 %), Medicaid (22.4 vs. 14.8 %), non-elective (93.5 vs. 89.8 %), rural (9.3 vs. 6.7 %), urban non-teaching (17.2 vs 15.8 %) admissions. All CV comorbidities and other substance use were higher in TUD except CHF and valvular heart disease, TUD+ cohort and lower mortality (3.3 vs. 4.2 %, OR 0.78, p<0.001), higher routine discharges (53.8 vs. 51.3 %, p<0.001) and lower total charges ($47155 vs. 51909, p<0.001) than non-TUD. Although PH patients with TUD had a higher comorbidity burden, they had lower in-hospital mortality rates along with lower total charges of hospitalization, mandating real-world data to validate these results. See also the Graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"22 ","pages":"1200-1210"},"PeriodicalIF":4.6,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10776876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416735","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":"<i>In vitro</i> screening of topical formulation excipients for epithelial toxicity in cancerous and non-cancerous cell lines.","authors":"Farzaneh Forouz, Yousuf Mohammed, Hamid S A Shobeiri Nejad, Michael S Roberts, Jeffrey E Grice","doi":"10.17179/excli2023-6072","DOIUrl":"10.17179/excli2023-6072","url":null,"abstract":"<p><p>Chemical excipients used in topical formulations may be toxic to living skin cells. Here, we compared the <i>in vitro</i> toxicity of some common solubilizing excipients against human melanoma cells, human keratinocytes (HaCaT) and primary skin fibroblasts (FB) as examples of cancerous, immortalized and primary human skin cells, often used as experimental models representative of <i>in vivo</i> conditions. Two distinct endpoint assays (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet (CV)) were used. The mechanism of cell death after excipient exposure was assessed through Reactive Oxygen Species (ROS) production, cell membrane integrity and cell cycle progression. Results showed that the surfactants, Labrasol®, Labrafil® and Transcutol®, were less toxic than Triton X-100 (a model irritant) in all cell types whereas the oil, Labrafac®, was non-toxic. The human melanoma WM164 cell line showed the greatest sensitivity toward cytotoxicity after chemical exposure, while the other cell lines were more resistant. The relative excipient cytotoxicity responses observed in the MTT and CV assays were comparable and similar trends were seen in their estimated 50 % inhibitory concentration (IC₅₀) values. DNA fragmentation by flow cytometry after exposing the cells to IC₅₀ concentrations of the excipients showed negligible apoptotic populations. ROS production was increased in all cell types after toxic exposure; however, ROS elevation did not lead to apoptosis. The toxicity profiles of each excipient are not only relevant to their use in formulating safe topical products but also in the potential synergistic efficacy in the topical treatment of melanoma.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"22 ","pages":"1173-1199"},"PeriodicalIF":4.6,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10776879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416719","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":"Enrichment analysis and chromosomal distribution of gout susceptible loci identified by genome-wide association studies.","authors":"Mostafa Saadat","doi":"10.17179/excli2023-6481","DOIUrl":"10.17179/excli2023-6481","url":null,"abstract":"<p><p>Gout is an inherited and common inflammatory arthritic disease. Many researchers will identify polymorphic loci of gout susceptibility by conducting genome-wide association studies (GWAS). In the present study, the enrichment analysis and chromosomal distribution were performed using predicted polymorphic loci associated with gout risk. The polymorphic loci associated to gout were obtained from the GWAS database. Overall, this database contains 64,806 gout patients and 2,856,174 controls. Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by using the Enrichr online server. A total of 110 common polymorphic protein-coding loci associated with gout risk were identified and included in the analysis. The results of the KEGG analysis showed that the gout-associated loci were mainly related to ABC transporters, endocrine and other factor-regulated calcium reabsorption, and gastric acid secretion pathways. The gene ontology analysis showed that the biological processes of the gout-associated loci were vascular transport, transport across the blood-brain barrier, positive regulation of transporter activity, and positive regulation of transcription by RNA polymerase II. The top cellular component was the external side of the apical plasma membrane. Statistical analysis revealed that the human chromosome segments 1q22, 4p16.1, 6p21.1-p21.2, 11q13.1-q13.2, 12q13.11-q13.3, and 12q24.1 had significantly bearing higher numbers of gout susceptibility loci.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"22 ","pages":"1146-1154"},"PeriodicalIF":4.6,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10776878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416720","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}