EXCLI Journal最新文献

{"title":"p-Synephrine: an overview of physicochemical properties, toxicity, biological and pharmacological activity.","authors":"Maciej Kulawik, Kaja Bajewska, Anna Kulawik","doi":"10.17179/excli2024-8088","DOIUrl":"https://doi.org/10.17179/excli2024-8088","url":null,"abstract":"<p><p>p-Synephrine is a popular ingredient in dietary supplements. It is also found in trace amounts in living organisms. It is advertised as a weight loss supplement and it is supposed to improve performance in sports. It is contained in plants of the Citrus family, making it widespread in the human diet. Its pharmacological properties include effects on multiple receptors and signaling pathways. Its effects on the alpha and betanergic systems promote doubts about its safety. There are many studies describing a lack of concern when it comes to the potential harmful effects of this compound. On the other hand, several health incidents associated with p-synephrine use have been reported in the scientific literature, making the toxicity of this compound unclear. This review aims to organize the current knowledge about p-synephrine, including physicochemical characteristics, sources of occurrence, pharmacological effects and possible toxic effects. In addition, the presence of three substitution isomers of the hydroxyl group and one chiral carbon atom causes confusion in the literature. Studies conducted on the short-term use of p-synephrine do not indicate its toxicity at low doses for healthy people. Further studies are needed to determine its long-term safety and possible interactions with other chemical compounds. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"381-400"},"PeriodicalIF":3.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076943","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":"Phosphoglycerate dehydrogenase and Alzheimer's disease.","authors":"Quan-Ying Liu, Shuang-Qing Zhang","doi":"10.17179/excli2025-8178","DOIUrl":"10.17179/excli2025-8178","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"401-402"},"PeriodicalIF":3.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751833","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":"Parthanatos and apoptosis: unraveling their roles in cancer cell death and therapy resistance.","authors":"Gaurav Gupta, Muhammad Afzal, Ehssan Moglad, Ahsas Goyal, Waleed Hassan Almalki, Kavita Goyal, Mohit Rana, Haider Ali, Arcot Rekha, Imran Kazmi, Sami I Alzarea, Sachin Kumar Singh","doi":"10.17179/excli2025-8251","DOIUrl":"10.17179/excli2025-8251","url":null,"abstract":"<p><p>Cell death is a fundamental process that needs to be maintained to balance cellular functions and prevent disease. There are several cell death pathways; however, apoptosis and parthanatos are the most prominent and have important roles in cancer biology. As an extremely well-regulated process, apoptosis removes damaged or abnormal cells via caspase activation and mitochondrial involvement. Unlike in the healthy cells, the loss of ability to induce apoptosis in cancer permits tumor cells to survive and multiply out of control and contribute to tumor progression and therapy resistance. On the contrary, parthanatos is a caspase-independent metabolic collapse driven by poly (ADP-ribose) polymerase 1 (PARP1) overactivation, translocation of apoptosis-inducing factor (AIF), and complete DNA damage. Several cancer models are involved with parthanatos. Deoxypodophyllotoxin (DPT) induces parthanatos in glioma cells by excessive ROS generation, PARP1 upregulation, and AIF nuclear translocation. Like in acute myeloid leukemia (AML), the cannabinoid derivative WIN-55 triggers parthanatos, and the effects can be reversed by PARP inhibitors such as olaparib. Developing cancer treatment strategies involving advanced cancer treatment strategies relies on the interplay between apoptosis and parthanatos. However, such apoptosis-based cancer therapies tend to develop resistance, so there is an urgent need to look into alternative pathways like parthanatos, which may not always trigger apoptosis. In overcoming apoptosis resistance, there is evidence that combining apoptosis-inducing agents, such as BH3 mimetics, with PARP inhibitors synergistically enhances cell death. Oxidative stress modulators have been found to promote the execution of parthanatic and apoptotic pathways and allow treatment. In this review, apoptosis and parthanatos are thoroughly compared at the molecular level, and their roles in cancer pathogenesis as related to cancer therapeutic potential are discussed. We incorporate recent findings to demonstrate that not only can parthanatos be used to manage therapy resistance and enhance cancer treatment via the combination of parthanatos and apoptosis but also that immunity and bone deposition can feasibly be employed against long-circulating cancer stem cells to treat diverse forms of metastatic cancers.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"351-380"},"PeriodicalIF":3.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751832","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 nitrate administration modulates sialin gene expression in the main tissues of male Wistar rats with type 2 diabetes.","authors":"Sajad Jeddi, Nasibeh Yousefzadeh, Vajiheh Khorasani, Maryam Zarkesh, Khosrow Kashfi, Asghar Ghasemi","doi":"10.17179/excli2024-8051","DOIUrl":"10.17179/excli2024-8051","url":null,"abstract":"<p><p>The increased sialin gene expression in the main tissues of diabetic rats is associated with decreased nitrate and nitrite levels, suggesting a counterregulatory response for reduced nitric oxide (NO) bioavailability. In this study, we hypothesized that long-term nitrate administration (6 months) would decrease sialin gene expression in rats with type 2 diabetes (T2D). Rats were assigned to two groups (n=10): T2D and T2D+nitrate, receiving nitrate in their drinking water at a concentration of 100 mg/L over 6 months. Samples from the main tissues were collected and used to measure the gene expression of sialin, as well as nitrate and nitrite levels. Nitrate-treated T2D rats had higher nitrate levels in the soleus muscle (SM) (163 %), stomach (83 %), lung (271 %), pancreas (90 %), aorta (61 %), adrenal gland (88 %), brain (145 %), liver (95 %), and heart (87 %). Nitrite levels were also higher in SM (136 %), lung (108 %), pancreas (86 %), kidney (88 %), aorta (33 %), brain (221 %), epididymal adipose tissue (eAT) (52 %), and heart (93 %), of nitrate treated T2D rats (all P<0.05). Nitrate decreased sialin gene expression in the SM (0.21-fold, P<0.001), stomach (0.37-fold, P=0.002), liver (0.21-fold, P<0.001), and eAT (0.47-fold, P=0.016) but it increased it in the intestine (1.99-fold, P<0.001), pancreas (2.01-fold, P=0.006), and the kidney (2.45-fold, P<0.001) of diabetic rats, with no effects in the lung, aorta, adrenal gland, brain, and heart. Nitrate administration restores the compensatory increase in sialin gene expression in tissues of T2D rats. However, this compensatory mechanism is not generalizable to all tissues.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"339-350"},"PeriodicalIF":3.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751722","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 regulatory role and mechanism of TRPV3 on apoptosis and inflammation in osteoarthritis.","authors":"Sahar Ghafari, Amin Moqadami, Mohammad Khalaj-Kondori","doi":"10.17179/excli2024-8109","DOIUrl":"10.17179/excli2024-8109","url":null,"abstract":"<p><p>Osteoarthritis (OA) is one of the most common forms of degenerative joint disease characterized by persistent pain, inflammation of the joints, and restricted range of motion among the elderly worldwide. Interleukin-1 beta (IL-1β) is increased in the injured joints and contributes to the OA pathobiology by inducing chondrocyte apoptosis and inflammation. Transient receptor potential (TRP) ion channels have recently been reported as potential players in the modulation of apoptosis and inflammation. Here, we aimed to understand the regulatory role and effect of TRPV3 on apoptosis and inflammation in osteoarthritis by using C28/I2 chondrocyte cells as a model. Chondrocytes were transfected with TRPV3-specific siRNA for 24 hours and then stimulated with IL-1β in vitro. Cell cycle progression and apoptosis were evaluated with flow cytometry. The levels of TRPV3, apoptotic (Bax, Caspase-3, and Bcl-2), and inflammatory (iNOS, COX-2) genes were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and confirmed with western blot. Treatment of the C28/I2 chondrocyte cells with IL-1β resulted in the over-expression of TRPV3, induction of apoptosis, and over-expression of inflammation indices. Knockdown of TRPV3 significantly reduced the expression of Bax and Caspase 3 proapoptotic factors while increasing the expression of the Bcl-2 antiapoptotic factor in the mRNA and protein levels in the IL-1β-stimulated cells. Its knockdown also decreased the expression of the inflammatory factors iNOS and COX-2 in mRNA and protein levels, confirming that TRPV3 knockdown hinders apoptosis and inflammation in IL-1β-stimulated chondrocytes. In conclusion, we demonstrated that si-TRPV3 treatment significantly mitigates IL-1β-related effects on the C28/I2 chondrocyte cells. These findings suggested that TRPV3 could be an effective target for the treatment of OA. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"325-338"},"PeriodicalIF":3.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751758","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":"Current clinical applications of RNA-LNPs in cancer: a promising horizon for targeted therapies.","authors":"Md Sadique Hussain, Gyas Khan","doi":"10.17179/excli2025-8132","DOIUrl":"10.17179/excli2025-8132","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"321-324"},"PeriodicalIF":3.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603559","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":"Rhoifolin: A promising flavonoid with potent cytotoxic and anticancer properties: molecular mechanisms and therapeutic potential.","authors":"Ceyda Sibel Kiliç, Mehmet Murat Kisla, Gülin Amasya, Ceyda Tugba Sengel-Türk, Zeynep Ates Alagöz, Ayse Mine Gençler Özkan, Ilker Ates, Safa Gümüsok, Jesús Herrera-Bravo, Javad Sharifi-Rad, Daniela Calina","doi":"10.17179/excli2024-7836","DOIUrl":"10.17179/excli2024-7836","url":null,"abstract":"<p><p>Rhoifolin is a flavonoid found in various plant species, especially within the Rutaceae family, and is considered a dietary component due to its presence in edible plants. Its bioactive properties, such as cytotoxic and anticancer activities, have gained significant attention. This review aims to highlight the general properties and diverse bioactivities of rhoifolin, with a particular focus on its cytotoxic and anticancer effects. This is based on a comprehensive literature search, focusing on the presence of rhoifolin in different plant species and its biological activities, particularly its anticancer properties. Rhoifolin is widely distributed in the plant kingdom, especially in <i>Citrus</i> species. It exhibits a variety of bioactivities, including strong cytotoxic and anticancer effects. Recent studies have shown that rhoifolin can induce apoptosis and inhibit cancer cell proliferation, making it a promising candidate for anticancer therapies. Rhoifolin's diverse bioactivities, particularly its cytotoxic and anticancer properties, position it as a potential therapeutic agent. Further detailed investigations into its molecular mechanisms and well-designed clinical studies are needed to fully understand and utilize its therapeutic potential. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"289-320"},"PeriodicalIF":3.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603807","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":"Phyto-derived interferons: a promising frontier in antiviral therapy development.","authors":"Baskar Venkidasamy, Ashok Kumar Balaraman, Muthu Thiruvengadam","doi":"10.17179/excli2024-7998","DOIUrl":"10.17179/excli2024-7998","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"286-288"},"PeriodicalIF":3.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751834","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":"Breast cancer preclinical models: a vital resource for comprehending disease mechanisms and therapeutic development.","authors":"Ravneet Kaur, Anuradha Sharma, Nalaka Wijekoon","doi":"10.17179/excli2024-7973","DOIUrl":"10.17179/excli2024-7973","url":null,"abstract":"<p><p>A significant obstacle in translating innovative breast cancer treatments from bench to bed side is demonstrating efficacy in preclinical settings prior to clinical trials, as the heterogeneity of breast cancer can be challenging to replicate in the laboratory. A significant number of potential medicines have not progressed to clinical trials because preclinical models inadequately replicate the complexities of the varied tumor microenvironment. Consequently, the variety of breast cancer models is extensive, and the selection of a model frequently depends on the specific inquiry presented. This review aims to present an overview of the existing breast cancer models, highlighting their advantages, limitations, and challenges in the context of innovative drug discovery, thereby offering insights that may be advantageous to future translational studies. Conventional monolayer cultures are critical for elucidating the different breast cancer types and their behavior, have limitations in adequately replicating tumor environments. The 3D models such as patient-derived xenografts, cell-derived xenografts and genetically engineered models offer better insights by maintaining tumor microenvironments and cellular heterogeneity. Results can be further enhanced when compared with breast epithelial cells, a negative control to determine early stages by investigating differences between healthy and cancerous mammary cells. While cell lines such as MCF-7, MDA-MB-231 etc are useful <i>in vitro</i> models, they exhibit genetic variations that may affect drug responses over time. Additionally, animal models, particularly rodents, are instrumental in breast cancer research due to their biological resemblances to humans and the relative ease of genetic modification, however, witness a low occurrence of tumors. This review thus concludes that different preclinical models have their associated benefits and pitfalls. Therefore, specific preclinical models can be created by altering the gene expression at the genetic level or could be selected as per specific experimental needs which will enable successful translation of preclinical findings into clinical trials can be possible. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"267-285"},"PeriodicalIF":3.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603472","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":"Mechanisms underpinning the effect of exercise on the non-alcoholic fatty liver disease: review.","authors":"Mohamed Bekheit, Blessed Kamera, Laura Colacino, Anne Dropmann, Mirela Delibegovic, Fatema Almadhoob, Nemany Hanafy, Giovanna Bermano, Seddik Hammad","doi":"10.17179/excli2024-7718","DOIUrl":"10.17179/excli2024-7718","url":null,"abstract":"<p><p>Non-alcoholic Fatty Liver Disease (NAFLD) - whose terminology was recently replaced by metabolic liver disease (MAFLD) - is an accumulation of triglycerides in the liver of >5 % of its weight. Epidemiological studies indicated an association between NAFLD and reduced physical activity. In addition, exercise has been shown to improve NAFLD independently of weight loss. In this paper, we aim to systematically review molecular changes in sedentary experimental NAFLD models vs. those subjected to exercise. We utilized the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and standard review techniques. Studies were considered for inclusion if they addressed the primary question: the mechanisms by which exercise influenced NAFLD. This review summarized experimental evidence of improvements in NAFLD with exercise in the absence of weight loss. The pathways involved appeared to have AMPK as a common denominator. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"238-266"},"PeriodicalIF":3.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603560","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}