EXCLI Journal最新文献

{"title":"Targeting metabolic vulnerabilities in breast cancer cells by combining PEDF and doxorubicin: pathway insights from GC/MS-based metabolomics.","authors":"Raziyeh Abooshahab, Hani Al-Salami, Crispin R Dass","doi":"10.17179/excli2025-8508","DOIUrl":"10.17179/excli2025-8508","url":null,"abstract":"<p><p>Breast cancer (BC), characterised by its diverse subtypes and molecular heterogeneity, remains a major challenge in oncology. Despite advances in chemotherapy, such as doxorubicin (Dox), limitations persist due to toxicity and drug resistance. Pigment epithelium-derived factor (PEDF) is a multifunctional protein with unique anti-tumour properties. The aim here was to elucidate metabolic reprogramming in human BC cell lines using a metabolomics approach. Untargeted gas chromatography-quadrupole mass spectrometry (GC/Q-MS) was employed to identify the metabolic alterations in BC cell lines MCF-7 (ER-positive) and MDA-MB-231 (TNBC) following treatment with PEDF, Dox, and their combination (Dox+PEDF) in comparison to untreated controls. Statistical models were employed using a combination of multivariate and univariate analyses, including partial least squares discriminant analysis (PLS-DA) and one-way ANOVA, applied by MetaboAnalyst and SIMCA software. To address the potential for multiple-testing errors, false discovery rate (FDR)-adjusted p-values were calculated to ensure robust statistical reliability. The overall analysis revealed significant metabolic alterations across the treatment groups, with distinct patterns emerging in carbohydrate, lipid, and amino acid metabolisms. In MCF-7 cells, PEDF combined with Dox significantly decreased cystine levels and modulated aspartic acid and lipid-related metabolites, indicating potential shifts in redox homeostasis and membrane composition. In MDA-MB-231 cells, the combination treatment significantly reduced glucose-6-phosphate and lactate levels, suggesting remodeling of glycolytic flux and redox balance. Furthermore, the combination of PEDF and Dox influenced amino acid and lipid metabolism. Pathway enrichment and correlation analyses revealed significant perturbations in glutathione metabolism, energy pathways, and lipid signaling, with notable differences between the two cell lines. Combining Dox and PEDF induced coordinated changes in metabolic networks, suggesting synergistic and antagonistic mechanisms that impact multiple biochemical pathways. These findings underline the importance of combining PEDF with chemotherapy to improve treatment outcomes in BC. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"1037-1055"},"PeriodicalIF":4.9,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079996","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":"Incomplete and mismatching descriptors of scanning electron microscopy (SEM) and SEM microscopes: a case study.","authors":"Jaime A Teixeira da Silva","doi":"10.17179/excli2025-8605","DOIUrl":"10.17179/excli2025-8605","url":null,"abstract":"<p><p>The post-publication scrutiny of the literature occasionally reveals errors that have filtered past the scrutiny of peer reviewers and editors. Microscopes, as used in scanning electron microscopy (SEM), form an integral part of the evidence-based methodology of many biomedical studies. A 2025 preprint (DOI: 10.31219/osf.io/4wqcr) claimed that a body of literature in indexed and ranked journals may have published potentially incorrect microscopy (SEM)-based evidence, noting that in about 2400 cases, the model or maker of SEM microscopes, as indicated in the text (e.g., in the methodology section), do not match information indicated in the figures or micrographs. One possible explanation may be that those analyses and/or equipment may have been outsourced to third-party services, although the outsourcing was not declared. Homing in on a sub-set of that preprint's 2400 cases, looking specifically at 23 of the 94 papers published in the mega open access journal, <i>Heliyon</i>, that were flagged in that exposé, textual descriptors in the methods section were compared against SEM descriptors in figures' micrographs. Only two papers showed an unequivocal discord between textual and figure descriptors related to SEM at the level of model and maker, while 16 of the 23 papers had no methodological description of SEM in the methods section. <i>Heliyon</i> editors need to investigate these omissions and discrepancies, and correct the articles accordingly, wherever applicable. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"1019-1022"},"PeriodicalIF":4.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080052","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":"Exploring the role of mTOR pathway in aging and age-related disorders.","authors":"Komal Raghuvanshi, Disha Raghuvanshi, Dinesh Kumar, Eugenie Nepovimova, Marian Valko, Kamil Kuca, Rachna Verma","doi":"10.17179/excli2025-8384","DOIUrl":"10.17179/excli2025-8384","url":null,"abstract":"<p><p>Aging is a highly intricate biochemical process. There is strong evidence suggesting that organismal aging, age-dependent diseases, and cellular senescence are related to the mammalian target of rapamycin (mTOR) signaling pathway. The signaling pathway of mTOR has become a prominent regulatory hub, managing crucial cellular activities that significantly affect lifespan and longevity. The mTOR is involved in controlling cell growth and metabolism in response to both internal and external energy signals as well as growth factors. The interaction between mTOR and cellular homeostasis is crucial in the aging process. This extensive review summarizes the most recent findings on mTOR inhibitors in the context of aging, highlighting their complex interactions with cellular systems, effect on longevity, and potential as therapeutic approaches for age-related diseases. Rapamycin and rapalogs (analogs of rapamycin), which have been proven to be effective mTOR inhibitors, have the ability to reduce the aging process in several model species while also enhancing metabolic health and stress responses. Despite cellular factors, mTOR inhibitors have revealed a potential path for therapeutics in age-related illnesses. These results suggest mTOR inhibitors as potential therapies to address the complex aspects of age-related diseases. However, obstacles stand in the way of clinical translation. Further research is required to improve dosing protocols, reduce potential side effects, and target mTOR inhibitors precisely at specific tissues. In summary, the mTOR signaling pathway is an important node in the intricate web of aging and its associated disorders.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"992-1015"},"PeriodicalIF":4.9,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12419451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039593","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":"Polyphenols bind G4-Quadruplex structures and act as epigenetic modifiers with anti-cancer effects.","authors":"Marco Antonio Meraz-Rodriguez, Manuel Humberto Cháirez-Ramírez, Karen Griselda de la Cruz-López, Rubén Francisco González-Laredo, Alejandro García-Carrancá","doi":"10.17179/excli2025-8507","DOIUrl":"10.17179/excli2025-8507","url":null,"abstract":"<p><p>G4-quadruplexes (G4s) are non-canonical structures of nucleic acids that develop in guanine rich regions of DNA and RNA. Due to their presence in oncogenic promoters and telomeres, G4s represent attractive targets in anticancer drug designs. G4s have also been the subject of recent research regarding their role as epigenetic modulators, supporting their participation in epigenetic processes that control gene expression. The development of small compounds that preferentially target G4s have led to a better understanding of how G4s control these mechanisms. Natural products have greatly contributed to the development of many successful examples of compounds with excellent anticancer activities. Therefore, it is important to investigate ligands targeting G4-quadruplexes in natural products such as dietary polyphenols and their derivatives. In this review, we provide an overview of the latest research on natural compounds, with especial emphasis on dietary polyphenols, as G4-quadruplex targeted ligands. We also discuss dietary polyphenols' structural chemistry that could facilitate their characterization as G4 ligands, highlighting their potential in the development of anticancer drugs. Finally, we explore polyphenols' potential mechanisms of action in regulating epigenetic machinery through G4 binding, thereby providing insights for the development of safe and effective therapeutical tools against cancer.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"957-991"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080046","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 role of redox-active iron, copper, manganese, and redox-inactive zinc in toxicity, oxidative stress, and human diseases.","authors":"Klaudia Jomova, Suliman Y Alomar, Richard Valko, Eugenie Nepovimova, Kamil Kuca, Marian Valko","doi":"10.17179/excli2025-8449","DOIUrl":"10.17179/excli2025-8449","url":null,"abstract":"<p><p>Given the key importance played by the redox-active metals iron (Fe), copper (Cu), and manganese (Mn) in vital cellular processes, such as DNA synthesis, oxidative phosphorylation, the detoxification of reactive oxygen species (ROS), and angiogenesis, it is not surprising that their dysregulation plays a causative role in many human diseases. The same applies to redox-inactive zinc (Zn), which is involved in numerous biological functions, and serves as a structural element, a catalyst, and a participant in both intracellular and intercellular signaling and in maintaining immune system function. An imbalance in redox active (Fe, Cu, Mn) or redox inactive (Zn) metal ions, whether in excess or deficiency, is harmful and may disrupt the structural, regulatory, and catalytic roles of various antioxidant enzymes (superoxide dismutases (SODs), catalase (CAT), glutathione peroxidases (GPxs)), proteins, receptors, transporters, alter sulfhydryl homeostasis, generate high levels of ROS (e.g., hydroxyl radicals by the Fenton reaction), initiate lipid peroxidation, cause DNA damage, and lead to cell death via mechanisms such as ferroptosis, cuproptosis, cellular senescence, or inflammation. Maintaining redox homeostasis is essential for regulating numerous cellular signaling pathways. Redox-sensitive signaling pathways, such as the nuclear factor kappa B (NF-κB), mitogen-activated protein kinase kinase (MAPK), and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways, form an intricate network that governs cellular responses to redox metal-induced oxidative stress and inflammation. The Nrf2 pathway is primarily responsible for mediating antioxidant defenses, whereas the NF-κB and MAPK pathways play roles in proinflammatory and stress-related responses. Dysregulation of redox-active Fe, Cu, Mn, and redox-inactive Zn can alter epigenetic regulatory mechanisms such as DNA methylation, histone modification, and non-coding RNA expression. The dyshomeostasis of metal ions is closely related to the pathogenesis of lung, renal, and gastrointestinal diseases, neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, and Huntington's disease), psychiatric conditions (schizophrenia), and various cancers. This review summarizes recent findings on the role of iron, copper, manganese, and zinc in maintaining physiological functions, redox homeostasis, and human diseases. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"880-954"},"PeriodicalIF":4.9,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12419454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039564","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":"MAPK/ERK Signaling in Tumorigenesis: mechanisms of growth, invasion, and angiogenesis.","authors":"Jiaying Fei, Yanjun Guo","doi":"10.17179/excli2025-8479","DOIUrl":"10.17179/excli2025-8479","url":null,"abstract":"<p><p>The significance of ERK1/2 in the process of tumorigenesis has attracted considerable interest owing to its essential role in a variety of cellular mechanisms, especially in relation to cancer initiation and progression. The Ras-Raf-MAPK signaling cascade, responsible for the activation of ERK1/2, plays a vital role in the regulation of tumor cell growth, invasion, and the formation of new blood vessels. Recent research has underscored the intricate nature of the mechanisms by which ERK1/2 is activated and the subsequent implications for tumor biology, illustrating both the oncogenic capabilities and the therapeutic hurdles linked to the modulation of this pathway. Despite progress in the comprehension of ERK1/2 signaling, numerous challenges persist, including the emergence of resistance to therapies that target this pathway, alongside the necessity for more selective inhibitors. This review intends to consolidate the most recent scientific discoveries pertaining to ERK1/2 and its regulatory influence within the Ras-Raf-MAPK pathway, offering insights into how these interactions facilitate tumor proliferation and metastasis. By clarifying the connection between ERK1/2 signaling and tumor biology, this article aspires to contribute to the formulation of novel therapeutic approaches aimed at interrupting this pathway in the context of cancer treatment.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"854-879"},"PeriodicalIF":4.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080031","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":"Demystifying the power of essential oils: a review of their antibacterial properties and potential as natural food preservatives.","authors":"Hanen Falleh","doi":"10.17179/excli2025-8439","DOIUrl":"10.17179/excli2025-8439","url":null,"abstract":"<p><p>This review delves into the antimicrobial potential of essential oils (EOs), focusing on their mechanisms of action against foodborne pathogens and their applications as natural food preservatives. EOs, derived from aromatic plants, are complex mixtures of volatile compounds, primarily terpenes, terpenoids, and phenolic compounds, which exhibit potent antimicrobial properties. These bioactive compounds disrupt bacterial cell membranes, increase permeability, and induce leakage of intracellular components, leading to cell death. Additionally, EOs inhibit energy production by depleting ATP levels, disrupting the tricarboxylic acid cycle, and impairing cellular respiration. They also generate reactive oxygen species (ROS), causing oxidative stress and damaging bacterial DNA, proteins, and lipids. Furthermore, EOs interfere with quorum sensing and biofilm formation, reducing bacterial virulence and resistance. Despite their efficacy, challenges such as strong flavors, poor solubility, and environmental sensitivity limit their direct application. To address these issues, encapsulation techniques, such as nanoemulsions and active packaging, have been developed to enhance the stability and controlled release of EOs. For instance, nanoencapsulation of thyme and cinnamon EOs has significantly improved their antimicrobial efficacy in food products like milk and minced meat. By harnessing the multifaceted mechanisms of EOs, this review underscores their potential as sustainable and effective natural preservatives to combat foodborne pathogens and improve food safety. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"828-850"},"PeriodicalIF":4.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12419452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039531","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":"Molecular signature of cadmium-mediated neurodevelopmental disorders in prenatal to postnatal stages.","authors":"Sabiha Sultana Preety, Fahim Rejanur Tasin, Amit Sarder, Debasish Halder, Farjana Yasmin, Chanchal Mandal","doi":"10.17179/excli2025-8322","DOIUrl":"10.17179/excli2025-8322","url":null,"abstract":"<p><p>Cadmium can surpass fetal circulation and the blood-brain barrier due to its similar physicochemical properties to those of other divalent metals and causes diverse neuronal disorders. Previous reports have suggested a possible link between epigenetic alterations and neuronal changes in offspring due to cadmium exposure at different developmental stages. Hypermethylation of the glucocorticoid receptor NR3C1 disturbs the development of the hypothalamic-pituitary-adrenal axis, which in turn is responsible for the abnormal cognitive behavior of neonates. In addition, the upregulation of placental miR-509-3p and miR-193-5p expression was found to be the major cause of impaired development of the central nervous system. In this review, the epigenetic mechanism of cadmium-mediated neurotoxicity is described. Moreover, the journey of cadmium from the maternal body to the fetal body through circulation and to the neonatal body through breast milk is also tracked. The vulnerability of developing fetuses to cadmium is an alarming issue. Different types of epigenetic changes, such as DNA methylation, altered miRNA expression and histone modifications, are induced by cadmium and lead to various types of neurodevelopmental disorders. We hope this narrative review will provide distinct knowledge of the transportation of cadmium and its adverse effects on fetal neurodevelopment. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"797-823"},"PeriodicalIF":4.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12419453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039614","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":"Unveiling the antimicrobial, biofilm inhibition, and photoprotective potential of Bupleurum falcatum L. for dermatological applications.","authors":"Mirjana Milinkovic Sreckovic, Jovana Petrovic, Marija Ivanov, Uros Gasic, Milena Milivojevic, Danijela Stanisavljevic Ninkovic, Dejan Stojkovic","doi":"10.17179/excli2025-8344","DOIUrl":"10.17179/excli2025-8344","url":null,"abstract":"<p><p><i>Bupleurum falcatum</i> L. is known for its therapeutic properties, especially in treating fever, inflammation, and infectious diseases. However, its potential for dermatological applications remains mainly unexplored. Thus, the present study explores antimicrobial potential of <i>B. falcatum</i> against biofilm-associated infections, antibiotic-resistant strains, and UV-induced skin damage. This aligns with the growing interest in natural products as sources of bioactive compounds with skin-protecting features. Herein, we employed maceration (M) and ultrasound-assisted extraction (USA) at 50 Hz and 100 Hz (USA 50 and USA 100) to obtain extracts from aerial parts of the plant. Chemical profiling was performed using UHPLC. Antimicrobial activity, biofilm inhibition, EPS and eDNA production were assessed using microdilution test, crystal violet, Congo red, and eDNA assays, respectively. Cytotoxicity and photoprotective effects were evaluated on human keratinocytes using the MTT assay. Chemical analysis identified 64 compounds, including benzoic and cinnamic acid derivatives, flavonoid glycosides, and saikosaponins. Extracts showed strong antimicrobial activity against <i>Pseudomonas aeruginosa</i> and methicillin-resistant <i>Staphylococcus aureus</i> (MIC as low as 0.5 mg/mL). The M extract displayed moderate biofilm inhibition and reduced eDNA production. Cytotoxicity assays confirmed safety on keratinocytes, while M and USA 100 extracts demonstrated photoprotective effects. <i>B. falcatum</i> extracts showed promising potential in addressing biofilm-associated infections, antibiotic resistance, and UV-induced skin damage. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"779-796"},"PeriodicalIF":4.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948189","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":"Digital escapism amid conflict: media and gaming behaviors in the shadow of war.","authors":"Muddsar Hameed","doi":"10.17179/excli2025-8592","DOIUrl":"10.17179/excli2025-8592","url":null,"abstract":"","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"24 ","pages":"774-776"},"PeriodicalIF":4.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948223","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}