Biomolecules最新文献

{"title":"Copper Chelation by Penicillamine Protects Against Doxorubicin-Induced Cardiomyopathy by Suppressing FDX1-Mediated Cuproptosis.","authors":"Mohammad El-Nablaway, Hany M A Sonpol, Yaser Hosny Ali Elewa, Mohamed A M Ali, Mohamed Adel, Eman Serry Zayed, Maha Alhelf, Manar A Didamoony, Amal Fahmy Dawood, Eman M Embaby, Khaled S El-Bayoumi, Wesam S El-Saeed","doi":"10.3390/biom15091320","DOIUrl":"10.3390/biom15091320","url":null,"abstract":"<p><strong>Background: </strong>The cardiotoxic effects of doxorubicin (DOX), a powerful chemotherapeutic drug, are widely recognized. Cuproptosis, a unique copper-dependent form of controlled cell death, may be involved in DOX-induced cardiomyopathy, according to recent findings. This study employs both in vivo and in silico procedures to investigate the protective effects of the copper chelator penicillamine (PEN) and the role of cuproptosis in DOX-related cardiotoxicity.</p><p><strong>Methods: </strong>Thirty-two adult Sprague Dawley rats were allocated into four groups (<i>n</i> = 8): control, DOX, DOX+PEN, and PEN. Cardiac function was assessed via echocardiography. Serum cardiac biomarkers (LDH, CK-MB, CTnI), oxidative stress markers (SOD, GPX, MDA), and expression levels of cuproptosis-related genes (FDX1, LIAS, SLC31A1, ATP7A) were evaluated. Histopathological examinations and immunohistochemical staining for FDX1, SLC31A1, and DLAT were performed. Molecular docking simulated PEN's interaction with cuproptosis-related proteins. Network pharmacology and molecular docking studies were also conducted to identify core molecular targets and simulate PEN's binding interactions with key cuproptosis regulators.</p><p><strong>Results: </strong>DOX administration induced significant cardiac dysfunction, oxidative stress, and upregulation of cuproptosis markers. PEN treatment mitigated these effects, improved cardiac function, reduced fibrosis, and suppressed the expression of cuproptosis-related <i>genes</i> and proteins. Docking results confirmed strong interactions between PEN and cuproptosis-regulatory proteins. Network pharmacology revealed 14 key overlapping targets linking PEN with cuproptosis and DOX-induced cardiotoxicity.</p><p><strong>Conclusion: </strong>This study provides experimental evidence implicating cuproptosis in DOX-induced cardiomyopathy. PEN exerts cardioprotection, potentially by targeting this pathway, offering a promising therapeutic strategy.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasminogen Activator Inhibitor-1 in Skin Malignancies: Therapeutic Implications of Its Inhibition.","authors":"Taku Fujimura, Yusuke Muto, Yoshihide Asano","doi":"10.3390/biom15091317","DOIUrl":"10.3390/biom15091317","url":null,"abstract":"<p><p>Plasminogen activator inhibitor-1 (PAI-1), a key regulator of fibrinolysis, has emerged as a critical stromal factor that contributes to tumor progression in various malignancies, including skin cancers. Beyond its classical role in inhibiting plasminogen activators, PAI-1 exerts pleiotropic effects within the tumor microenvironment, promoting immunosuppression, angiogenesis, and extracellular matrix remodeling. This review highlights the tumor-promoting functions of PAI-1 in melanoma, cutaneous squamous cell carcinoma, cutaneous angiosarcoma and cutaneous T-cell lymphoma, with a particular focus on its modulation of tumor-associated macrophages, cancer-associated fibroblasts, and endothelial cells. We also discuss recent preclinical and clinical studies targeting PAI-1, including TM5614, a novel oral PAI-1 inhibitor currently under investigation in phase II /III trials. By summarizing the multifaceted roles of PAI-1 and its impact on the immune and stromal landscape of skin malignancies, this review provides a rationale for PAI-1 as a promising therapeutic target and calls for further clinical validation of PAI-1-directed therapies.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Role of Reactive Oxygen Species in Lung Cancer Development: Nanomedicine as a Therapeutic Strategy.","authors":"Manuel Olazábal-Morán, Elena Pérez, Adrián Esteban-Arranz, Antonio Garrido","doi":"10.3390/biom15091316","DOIUrl":"10.3390/biom15091316","url":null,"abstract":"<p><p>Lung cancer remains a leading cause of mortality worldwide, driven by increased tobacco use, industrialization, and air pollution. Despite advancements in diagnostics and treatments, effective therapies are still lacking. Reactive oxygen species (ROS) play a dual role in cancer development, regulating key signaling pathways and activating cell death pathways, making them a promising target for new drugs. Research shows that wild-type NRF2/KEAP1 lung tumors, which account for about 60% of lung malignancies, are sensitive to ROS induction, and mutated <i>EGFR1</i> lung tumors exhibit high ROS levels. Proteolysis-targeting chimeras (PROTACs) have emerged as a promising alternative to small molecule inhibitors (SMIs) for cancer treatment, addressing limitations like undruggability and drug resistance. However, these face challenges such as limited cell penetration and potential toxic side effects. Nanotechnology has introduced \"nano-PROTACs,\" enhancing tissue accumulation, membrane permeability, and controlled release. In this review, the keystones of ROS in lung cancer will be summarized. Also, a potential therapy for tumors with wild-type NRF2 involving the delivery of ROS inductor nano-PROTAC will be designed. This potential therapy could suppose a potential therapeutic strategy for lung cancer patients with these genetic characteristics.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coming Clean and Avoiding Bubble Trouble-Using Detergents Wisely in the Purification of Membrane Proteins for Cryo-EM Studies.","authors":"Bowen Chen, Peter Harrison, Vasileios Kargas, Naomi Pollock, Robert C Ford, Stephen M Prince, Richard F Collins","doi":"10.3390/biom15091315","DOIUrl":"10.3390/biom15091315","url":null,"abstract":"<p><p>Detergent solubilisation remains the most commonly used but potentially problematic method to extract membrane proteins from lipid bilayers for Cryo-EM studies. Although recent advances have introduced excellent alternatives-such as amphipols, nanodiscs and SMALPs-the use of detergents is often necessary for intermediate steps. In this paper, we share our experiences working with detergent-solubilised samples within the modern Cryo-EM structural pipeline from the perspective of an EM specialist. Our aim is to inform novice users about potential challenges they may encounter. Drawing on specific examples from a variety of biological membrane systems, including Magnesium channels, lipopolysaccharide biosynthesis, and the human major facilitator superfamily transporters, we describe how the intrinsic properties of detergent-extracted samples can affect protein purification, Cryo-EM grid preparation (including the formation of vitreous ice) and the reconstitution of proteins into micelles. We also discuss how these unique characteristics can impact different stages of structural analysis and lead to complications in single-particle averaging software analysis. For each case, we present our insights into the underlying causes and suggest possible mitigations or alternative approaches.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological and Therapeutic Potential of <i>Chrysopogon zizanioides</i> (Vetiver): A Comprehensive Review of Its Medicinal Applications and Future Prospects.","authors":"Conjeevaram J Gunasekar, Amin F Majdalawieh, Imad A Abu-Yousef, Sham A Al Refaai","doi":"10.3390/biom15091312","DOIUrl":"10.3390/biom15091312","url":null,"abstract":"<p><p><i>Chrysopogon zizanioides</i> (Linn.) Nash, commonly known as vetiver, has been an integral component of traditional medicinal systems across India and Asia for centuries. The roots and essential oils of this aromatic grass have been widely utilized for their anti-inflammatory, analgesic, anticancer, antioxidant, antimicrobial, and wound-healing properties. Recent scientific investigations have provided substantial evidence supporting these traditional claims, revealing a diverse array of bioactive phytochemicals with significant pharmacological potential. Preclinical studies have demonstrated the efficacy of <i>C. zizanioides</i> extracts in mitigating inflammation, alleviating pain, combating microbial infections, and even exhibiting anticancer and antidiabetic effects. This review provides a comprehensive analysis of the current literature on the therapeutic properties of <i>C. zizanioides</i>, summarizing findings from in vitro assays, cell line studies, animal models, and available clinical studies. The bioactive constituents responsible for these pharmacological effects, including essential oil components and isolated fractions, are discussed, along with their proposed mechanisms of action. These mechanisms involve modulation of oxidative stress, inflammatory pathways, microbial proliferation, and pain perception. Additionally, current research limitations, gaps in knowledge, and future directions for investigating medicinal applications of <i>C. zizanioides</i> are explored. Emerging scientific evidence increasingly validates traditional claims regarding the healing properties of this versatile medicinal grass.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual Perspectives on Peptide-Zinc Complexation: Highlighting Aquatic Sources While Contextualizing Other Natural Origins.","authors":"Lingyu Han, Nuo Dong, Jixin Yang, Bing Hu","doi":"10.3390/biom15091311","DOIUrl":"10.3390/biom15091311","url":null,"abstract":"<p><p>Zinc is an essential mineral for the body, with chelated zinc valued for its superior absorption efficiency and bioavailability. This review systematically examines peptide-zinc interactions, covering fundamental concepts, historical evolution, current insights, clinical relevance, technological innovations, and future outlooks. It delves into chelation mechanisms and structural theories, summarizes historical milestones in bioavailability research-particularly aquatic protein-zinc interactions-and details current studies on chelation efficacy and interaction dynamics. Clinical applications in nutritional supplements, therapeutic potential, and trial progress are discussed, alongside advances in analytical techniques, complex synthesis, and computational modeling. Future directions highlight emerging trends, application prospects, and challenges in bioavailability research, offering a comprehensive framework for subsequent investigations and practical implementations.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PARP1 and PARG Are the Draft Horses for Polycomb-Trithorax Chromatin Regulator Machinery.","authors":"Guillaume Bordet, Alexei V Tulin","doi":"10.3390/biom15091314","DOIUrl":"10.3390/biom15091314","url":null,"abstract":"<p><p>During tissue differentiation, gene expression patterns are committed to the epigenetic cellular memory machinery, including Polycomb and Trithorax groups (PcG and TrxG), which label chromatin with repressive or active histone marks. Histone marks recruit effector proteins that then execute local chromatin repression or activation. The effectors of TrxG have remained largely unknown. Here we report that the Poly (ADP-ribose) Polymerase 1 (PARP1) and Poly (ADP-ribose) Glycohydrolase (PARG) function as critical effectors of TrxG and PcG, respectively. We found that PARP1 binds TrxG-generated histone marks with high affinity in vitro, completely colocalizing with them genome-wide, and controls the expression of loci modified by TrxG. Conversely, PARG preferentially associates with PcG-occupied loci. We propose a model in which TrxG complexes prime chromatin for PARP1 recruitment, leading to poly (ADP-ribose) generation to maintain an open chromatin state essential for transcription.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strand Displacement Chain Reaction (SDCR): New Hybrid Amplification Technique for Fast and Sensitive Detection of Genetic Materials.","authors":"Evgeniya V Smirnova, Ekaterina V Barsova, Dmitriy A Varlamov, Vladimir M Kramarov, Konstantin A Blagodatskikh, Konstantin B Ignatov","doi":"10.3390/biom15091313","DOIUrl":"10.3390/biom15091313","url":null,"abstract":"<p><p>Nucleic acid amplification methods are widely used in science, medicine and forensics for molecular biological assays and for the detection of genetic material. The newly developed strand displacement chain reaction (SDCR) method is a hybrid amplification technique based on polymerase chain reaction (PCR) and isothermal nucleic acid amplification. Here, we compared conventional PCR, the \"gold standard\" for molecular diagnostic assays, with the SDCR method by performing real-time amplification assays using human, bacterial and viral genetic materials. In the assays, SDCR demonstrated very high sensitivity and amplification efficiency. We found that the SDCR method provided an amplification factor above three, which noticeably outperformed that of PCR amplification and enabled a marked reduction in the number of cycles in comparison with PCR. Therefore, the new hybrid amplification technique could be extremely useful for the detection of genetic material and the development of new diagnostic kits.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Animal Models for Multiple Sclerosis: R-Ras GTPases in Myelin Pathophysiology.","authors":"Gema M Esteban-Ortega, Gonzalo Garcia-Martin, Beatriz Cubelos","doi":"10.3390/biom15091309","DOIUrl":"10.3390/biom15091309","url":null,"abstract":"<p><p>Demyelinating diseases, such as multiple sclerosis, involve oligodendrocyte death, myelin loss, and neuronal death. These processes have been extensively studied, and a causal relationship has been demonstrated between them: destruction of oligodendrocytes results in myelin deficiency, which subsequently leads to neurodegeneration and the consequent loss of sensory, motor, and cognitive functions. Currently, myelinopathies lack fully effective treatments. Available drugs primarily focus on controlling the immune response without directly promoting myelin regeneration or restoring neuronal functionality. Alongside these treatments, pharmaceutical research has increasingly focused on developing therapies that stimulate oligodendroglial lineage differentiation and myelin sheath regeneration. Despite these advances, the lack of suitable preclinical models has been a significant obstacle in evaluating new therapeutic compounds. In this review, we present the main animal models used in the preclinical phase for the study of myelin-related diseases and their role in the development of new therapies. In addition, we highlight the usefulness of R-Ras animal models for assessing the efficacy of compounds that promote oligodendrocyte differentiation.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Vesicle Molecular Profiling by dSTORM Imaging in a Liquid Biopsy Assay Predicts Early Relapse in Colorectal Cancer.","authors":"Gabriele Raciti, Giulia Cavallaro, Raffaella Giuffrida, Cristina Grange, Loredana Leggio, Marco Catania, Nunzio Iraci, Elena Bruno, Luca Antonio Giaimi, Sofia Paola Lombardo, Giulia Chisari, Marzia Mare, Enrica Deiana, Lorenzo Memeo, Benedetta Bussolati, Stefano Forte","doi":"10.3390/biom15091307","DOIUrl":"10.3390/biom15091307","url":null,"abstract":"<p><strong>Background and objectives: </strong>Colorectal cancer (CRC) is the third most diagnosed tumor type and the second leading cause of cancer-related mortality. Despite recent improvements in the clinical management of CRC patients both before and after surgery, disease recurrence remains common, with an incidence of about 20-30% within 5 years. Current tissue biopsy techniques are invasive and inadequate for assessing tumor heterogeneity or capturing real-time disease dynamics. In contrast, liquid biopsy offers a promising, minimally invasive alternative. This study aimed to evaluate extracellular vesicle (EV)-associated protein markers, detected through super-resolution microscopy, as potential indicators of recurrence in CRC patients.</p><p><strong>Methods: </strong>We employed a novel liquid biopsy approach based on the super-resolution imaging (dSTORM) of specific protein markers carried by EVs isolated from the plasma of CRC patients. We analyzed combinations of both surface and intravesicular proteins, including EpCAM, PD-L1, CD81, IL-6, and Cyclin D1.</p><p><strong>Results: </strong>Specific combinations of EV-associated markers were able to distinguish patients with recurrence from those without residual disease. Additionally, we observed correlations between some marker profiles and tumor stage or lymph node involvement. No association was found with mismatch repair system status.</p><p><strong>Conclusions: </strong>To our knowledge, this is the first study to propose the use of EV-bound proteins for recurrence detection in CRC using super-resolution microscopy within a liquid biopsy framework. These findings support the potential of this approach as a non-invasive tool for CRC monitoring.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}