Aspects of molecular medicine最新文献

{"title":"The role of Irisin in modulating hypoxia-related disorders: New insights and implications for cancer therapy","authors":"Ghazaleh Khalili-Tanha ,&nbsp;Alireza Shoari ,&nbsp;Elham Nazari","doi":"10.1016/j.amolm.2025.100068","DOIUrl":"10.1016/j.amolm.2025.100068","url":null,"abstract":"<div><div>Regular physical activity is well-known for its health benefits, including reducing the risk of chronic diseases like cancer. Irisin, a myokine released by skeletal muscles during exercise, has emerged as a key regulator in hypoxia-related disorders.Hypoxia, defined by reduced oxygen availability, is a hallmark of various pathological conditions, especially cancer, where it drives tumor growth, metastasis, and resistance to therapy. Recent studies suggest that irisin can modulate hypoxia-induced pathways, impacting processes such as angiogenesis, inflammation, and metabolic adaptation. By targeting these mechanisms, irisin may enhance the efficacy of cancer treatments, reduce tumor aggressiveness, and potentially overcome therapy resistance. Additionally, irisin's influence on the tumor microenvironment highlights its potential as a therapeutic agent to counteract hypoxia-driven cancer progression. This review summarizes current findings on irisin's role in hypoxia-related disorders, focusing on its molecular mechanisms and potential applications in oncology. Despite promising preclinical studies, further research is necessary to fully understand irisin's therapeutic potential, optimize delivery methods, and validate its safety and efficacy in clinical settings. Exploiting exercise-derived molecules such as irisin may enable novel strategies for cancer treatment and other hypoxia-related diseases.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100068"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the interplay of malarial pathogenesis, host immune response and oxidative stress: Implications for disease progression and therapeutic strategies","authors":"Muzi Nicolas Buthelezi ,&nbsp;Kgaugelo Josephine Masia ,&nbsp;Priscilla Masamba ,&nbsp;Mthokozisi Blessing Cedric Simelane ,&nbsp;Abidemi Paul Kappo","doi":"10.1016/j.amolm.2025.100082","DOIUrl":"10.1016/j.amolm.2025.100082","url":null,"abstract":"<div><div>Despite sustained efforts, malaria elimination in developing countries, particularly in Africa, remains a to be a public burden due to the evolution and emergence of resistance to most of the currently available antimalarials and insecticides. Over time, it has been argued that a thorough understanding of the parasite's biology and pathogenesis is important because it arises from a dynamic interplay between the host and the parasite. The lifecycle of the malarial parasite is complex, involving distinct developmental stages that each express specific antigens, which in turn trigger the immune system to either protect or promote pathophysiology. Malaria pathogenesis is thus a complex interplay of <em>Plasmodum</em>-induced red blood cell alterations and microvascular irregularities that lead to clinical symptoms and disease severity. Immune activation during malarial infection triggers a robust production of reactive oxygen and nitrogen species (ROS/RNS), contributing to oxidative stress, a characteristic seen during malarial infection and believed to exacerbate malarial pathophysiology. Therefore, this manuscript will examine the cellular mechanism underlying malarial pathophysiology, zoom in on oxidative stress, how it is linked to malarial severity and pathophysiology, and how it could be targeted to ameliorate ROS-mediated associated complications in malaria.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100082"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel combination therapy of osimertinib and Tupichinol E in triple-negative breast cancer: Targeting EGFR and CDK4/6 pathways","authors":"Adyasa Samantaray,&nbsp;Debasish Pradhan","doi":"10.1016/j.amolm.2025.100069","DOIUrl":"10.1016/j.amolm.2025.100069","url":null,"abstract":"<div><div>Triple-Negative Breast Cancer (TNBC) is one of the most challenging form of breast cancer that lacks hormone receptors and HER2, limiting targeted treatment options. While a third-generation EGFR inhibitor, Osimertinib, has shown efficacy in various cancers, its role in TNBC is not well established. On the other hand, <em>Tupichinol E</em>, a novel compound, has shown promising anticancer potential in preclinical studies. This study investigates the combined effects of Osimertinib and <em>Tupichinol E</em> on TNBC cell lines, revealing a synergistic reduction in cell viability, increased apoptosis, and cell cycle arrest compared to individual treatments. Furthermore, cyclin-dependent kinases 4 and 6 (CDK4/6), important cell cycle regulators, are essential in transitioning cells from the G1 to S phase via retinoblastoma protein (RB) phosphorylation. Dysregulation of the CDK4/6-RB pathway is a hallmark in many cancers, including hormone receptor-positive breast cancers, and has become a focus of targeted therapies. Our findings not only emphasizes the therapeutic potential of combining Osimertinib with <em>Tupichinol E</em> in TNBC but also underscore the importance of CDK4/6 inhibitors in modulating cell cycle progression, offering a promising avenue for combination therapies in TNBC treatment.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100069"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143518947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatoprotective potential of vanillic acid against isoniazid-rifampicin-induced liver toxicity","authors":"Mohd Islam Ansari,&nbsp;Nazneen Dubey,&nbsp;Aditya Ganeshpurkar","doi":"10.1016/j.amolm.2025.100087","DOIUrl":"10.1016/j.amolm.2025.100087","url":null,"abstract":"<div><div>Liver toxicity induced by antitubercular drugs, such as isoniazid and rifampicin, poses a significant clinical challenge due to oxidative stress and hepatocellular damage. This study evaluated the hepatoprotective potential of vanillic acid in mitigating drug-induced liver injury in rats. Hepatotoxicity was induced by administering isoniazid and rifampicin, followed by treatment with vanillic acid at two different doses (50 mg/kg and 100 mg/kg). Silymarin, a well-known hepatoprotective agent, was used as a reference standard. Biochemical markers, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), superoxide dismutase (SOD), catalase, and bilirubin, were assessed to evaluate liver function and oxidative stress.</div><div>Results revealed significant elevation in AST, ALT, ALP, and bilirubin levels and a reduction in antioxidant enzymes (SOD and catalase) in the isoniazid and rifampicin-treated group, indicating severe liver damage. Co-administration of vanillic acid significantly reduced these elevated markers and restored antioxidant enzyme levels in a dose-dependent manner. The higher dose of vanillic acid (100 mg/kg) exhibited a more pronounced hepatoprotective effect, comparable to silymarin. These findings suggest that vanillic acid exerts its protective effects by enhancing antioxidant defense, reducing oxidative stress, and preserving liver cell integrity.</div><div>This study highlights the therapeutic potential of vanillic acid in preventing drug-induced liver toxicity and underscores its role as a promising candidate for hepatoprotection during antitubercular therapy. Further investigation into its molecular mechanisms and clinical applicability is warranted.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100087"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143883124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational framework for analyzing miRNA-mRNA interactions in sarcopenia: Insights into age-related muscular degeneration","authors":"Sarvesh Sabarathinam ,&nbsp;Akash Jayaraman ,&nbsp;Ramesh Venkatachalapathy ,&nbsp;Subhiksha Shekar","doi":"10.1016/j.amolm.2025.100070","DOIUrl":"10.1016/j.amolm.2025.100070","url":null,"abstract":"<div><h3>Background</h3><div>Sarcopenia, an age-related loss of skeletal muscle mass and function, impairs mobility, fragility, and quality of life. Despite progress in pathophysiology, molecular processes remain unknown. Recent research has investigated miRNAs as biomarkers for sarcopenia diagnosis and therapy. This work analyses differentially expressed genes (DEGs) and predicts miRNA-mRNA interactions using ML methods like XG-Boost and SHAP to find biomarkers.</div></div><div><h3>Objective</h3><div>This work evaluated the function of miRNA-mRNA interactions in sarcopenia pathogenesis and identified possible biomarkers by transcriptome analysis utilizing machine learning.</div></div><div><h3>Methods</h3><div>High-throughput mRNA sequencing datasets (GSE111006, GSE111010, and GSE111016) from GEO database were combined, pre-processed, and normalized using TPM and DESeq2 methods. XG-Boost regression analysis used 80/20 training and testing sets. SHAP analysis was used to evaluate model data and find significant DEGs. PPI networks were created using the STRING database, while miRNA-mRNA interactions were predicted using Encori and displayed with Cytoscape. The degree scores of miRNA-mRNA interactions were utilized to find biomarkers<strong>.</strong></div></div><div><h3>Results</h3><div>XG-Boost and SHAP analysis revealed 20 influential DEGs linked to sarcopenia. With 97% accuracy, the model predicted accurately. PPI network research identified six hub genes: NTRK2, PCK1, DSP, SCD, MMRN1, and EDIL3. MiRNA-mRNA interaction analysis found miR-186–5p as the highest-degree biomarker candidate (36). MiR-186–5p was linked to muscle metabolism, hypertrophy, and exercise response.</div></div><div><h3>Conclusion</h3><div>The study found miR-186–5p to be a promising biomarker for sarcopenia using an integrated machine learning technique. The findings show that miR-186–5p may be a diagnostic and therapeutic target for sarcopenia, revealing its pathogenesis and enabling tailored treatments. Experimental research is needed to prove its therapeutic value.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100070"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular docking interaction of bioactive molecules from Kigelia africana (lam.) benth., revealed potential inhibitors of penicillin-binding protein 2 (PBP2)","authors":"Palani Manogar ,&nbsp;Sitrarasu Vijaya Prabhu ,&nbsp;Palanisamy Durairaj ,&nbsp;Martin Mark John Abel ,&nbsp;Nagamuthu Prakash ,&nbsp;Sivaraman Jayanthi","doi":"10.1016/j.amolm.2024.100051","DOIUrl":"10.1016/j.amolm.2024.100051","url":null,"abstract":"","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"4 ","pages":"Article 100051"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000182/pdfft?md5=52b1abb36022b4193e9727077be8b68c&pid=1-s2.0-S2949688824000182-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141842853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide linkage and association of novel genes and pathways with type 2 diabetes in Italian families","authors":"Mutaz Amin ,&nbsp;Claudia Gragnoli","doi":"10.1016/j.amolm.2024.100046","DOIUrl":"10.1016/j.amolm.2024.100046","url":null,"abstract":"<div><h3>Background</h3><p>Type 2 diabetes mellitus (T2D) stands as one of the most prevalent chronic diseases globally, posing substantial health and economic burdens on society. Within the spectrum of T2D, familial cases emerge as a distinct entity characterized by a strong familial clustering of the disease. This phenomenon has long suggested that genetics contributes substantially to T2D susceptibility, motivating extensive research into the genetic determinants of familial T2D.</p></div><div><h3>Methods</h3><p>We recruited 212 multigenerational Italian families with multiple cases of T2D. The families were genotyped using genomic array (≥ 600k) derived from the UK Biobank Axiom Array platform. Informative markers were tested via Pseudomarker for linkage to and linkage disequilibrium (i.e., linkage joint to association) with T2D across the following models: dominant with complete penetrance (D1), dominant with incomplete penetrance (D2), recessive with complete penetrance (R1), and recessive with incomplete penetrance (R2).</p></div><div><h3>Results</h3><p>We identified a total of 566 variants reaching genome-wide significant (P &lt; 0.00005) linkage and/or association to/with the risk of T2D in Italian families. Of the 355 genes identified in our study, 341 (96%) are novel and have not been reported with T2D or any of its related phenotypes (i.e., obesity, metabolic syndrome, insulin resistance, polycystic ovary syndrome, and hyperglycemia).</p></div><div><h3>Conclusion</h3><p>Our study constitutes the first familial T2D-linkage and association study in the Italian population. However, the functional relevance of the novel variants and genes reported in our study remains to be explored.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"4 ","pages":"Article 100046"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000133/pdfft?md5=3aef99032194eb4bf3cd9f8b59833a30&pid=1-s2.0-S2949688824000133-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141275920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green synthesis of CuO nanoparticles: A promising role of antioxidant and antimicrobial activity by using Tribulus terrestris L","authors":"Manogar Palani ,&nbsp;Snekhaa Kalaiselvan ,&nbsp;John Abel Martin Mark ,&nbsp;Kanagadurga Chandran ,&nbsp;Vinoth Ekhambaram","doi":"10.1016/j.amolm.2024.100049","DOIUrl":"https://doi.org/10.1016/j.amolm.2024.100049","url":null,"abstract":"","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"4 ","pages":"Article 100049"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000169/pdfft?md5=cfacbf66b08c3b23e0d597f141380de5&pid=1-s2.0-S2949688824000169-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-related factors drive high rates of reported antibiotic allergies: A qualitative study","authors":"Renee Berry ,&nbsp;Susan Herrmann ,&nbsp;Michaela Lucas","doi":"10.1016/j.amolm.2024.100052","DOIUrl":"10.1016/j.amolm.2024.100052","url":null,"abstract":"<div><h3>Background</h3><p>Unnecessary antibiotic avoidance due to allergy fears has adverse cost and health implications however, the problem is difficult to resolve because patient and provider-related factors leading to avoidance are multifactorial. We use qualitative research methods to explore patient perspectives of antibiotic allergy and testing to reach the heart of the problem.</p></div><div><h3>Objective</h3><p>To reveal factors leading patients to report antibiotic allergy, and determine what education is required to prevent the cycle of erroneous allergy reporting.</p></div><div><h3>Methods</h3><p>The 29 patients were a sample of convenience recruited from a tertiary public hospital in Western Australia between March 2020 until August 2020; 18 were inpatients and 11 outpatients, with a median age of 64.2 years, and 15 (55%) were female. Semi-structured interviews assessed patients’ understanding and knowledge of three topics: (1) antibiotic allergy, (2) antibiotic allergy testing, and (3) outcomes of testing. Interview transcripts underwent thematic analysis by two researchers, independently.</p></div><div><h3>Results</h3><p>Three main, overlapping themes emerged as influential across topics: (1) Severity of the Index Reaction, (2) Trust in family and health care providers, and (3) Health literacy. Patients were largely unaware of the benefits of confirmatory testing, and the detrimental health consequences of unnecessary avoidance. Patients displayed trust in health care providers’ expertise and assumed that medical records were accurate to prevent prescribing errors.</p></div><div><h3>Conclusions</h3><p>The findings provide evidence for an effective patient education strategy and highlight failures among hospital and primary health providers to recognise the potential harm of unverified antibiotic allergy. Healthcare professionals are influential at multiple steps of a patient's healthcare journey and addressing unconfirmed antibiotic allergy should be taken at each opportunity.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"4 ","pages":"Article 100052"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000194/pdfft?md5=c33bf8df1da47841d8b9caeba3e8d635&pid=1-s2.0-S2949688824000194-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141993534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plants as a source of dietary bioactives: Flavonoids and basis for their health benefits","authors":"Andrea Galatro ,&nbsp;Agustin Lucini Mas ,&nbsp;Melisa Luquet ,&nbsp;Cesar G. Fraga ,&nbsp;Monica Galleano","doi":"10.1016/j.amolm.2024.100048","DOIUrl":"10.1016/j.amolm.2024.100048","url":null,"abstract":"<div><p>Flavonoids are a group of bioactive compounds widely distributed in edible plants. They have gained special attention given strong scientific evidence supporting their health promoting actions. This review summarizes current knowledge on the biosynthetic pathways of flavonoids in plants, the regulation of those pathways, and the conservation of flavonoids in plant road to becoming a food. Additionally, the main dietary sources of flavonoid, evidence from population and clinical studies, and possible mechanisms involved in the beneficial effects of flavonoids on human health are also discussed.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"4 ","pages":"Article 100048"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000157/pdfft?md5=c64a4f91a9fc1c74480b36f391594b49&pid=1-s2.0-S2949688824000157-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141399001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}