BioFactors最新文献

{"title":"Proteins and Carbon Dioxide Struggle Against Peroxynitrite","authors":"Giovanna De Simone,&nbsp;Alessandra di Masi,&nbsp;Grazia R. Tundo,&nbsp;Andresa Messias,&nbsp;Dario A. Estrin,&nbsp;Massimo Coletta,&nbsp;Paolo Ascenzi","doi":"10.1002/biof.70030","DOIUrl":"https://doi.org/10.1002/biof.70030","url":null,"abstract":"<div>\u0000 \u0000 <p>Nitrosative stress plays a key role in the etiology of several human diseases, such as atherosclerosis, inflammation, cancer, and neurological diseases. Peroxynitrite is one of the most potent biological nitrosative agents, being produced at extremely rapid rates when nitric oxide (^●NO) and superoxide (^●O₂⁻) are combined. Peroxynitrite undergoes self-degradation at a slow rate, yielding ~70% nitrate (NO₃⁻) and H⁺, and ~30% nitrite (NO₂⁻) and dioxygen (O₂). Peroxynitrite degradation can be speeded up by the interaction with either (<i>i</i>) carbon dioxide (CO₂), through the transient formation of 1-carboxylato-2-nitrosodioxidane adduct (ONOOC(O)O⁻), which eventually decays to CO₂ and NO₃⁻ via the intermediate strong oxidants trioxocarbonate (CO₃^●−) and (nitrogen dioxide) ^●NO₂⁻, and/or (<i>ii</i>) proteins, such as thiol peroxidases and heme-proteins by different mechanisms. Under physiological conditions, peroxynitrite detoxification, which brings about different effects on the cellular metabolism, depends on the relative concentration of CO₂ and proteins. In this review, we analyze the intrinsic parameters of processes involved in peroxynitrite scavenging, which are crucial in poorly oxygenated tissues (such as the retina), exploring conditions that alternatively favor one process or the other.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 4","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Bioactive Peptides in Preterm Human Milk: Impact of Maternal Characteristics and Their Association to Neonatal Outcomes”","authors":"","doi":"10.1002/biof.70033","DOIUrl":"https://doi.org/10.1002/biof.70033","url":null,"abstract":"<p>C. Balcells-Esponera, C. Borràs-Novell, M. López-Abad, et al. “Bioactive Peptides in Preterm Human Milk: Impact of Maternal Characteristics and Their Association to Neonatal Outcomes,” <i>BioFactors</i> 50, no. 1 (2024): 135–144, https://doi.org/10.1002/biof.1997.</p><p>In the originally published article, the project code PI20/00294 was omitted from the funding information. The correct text is included below. This has been updated in the online version of this article.</p><p>This manuscript is part of Health Research Projects from Instituto Nacional Carlos III (Ministry of Science and Innovation, Government of Spain) granted to Isabel Iglesias-Platas, with financial support from the National R+D+I Plan (PI17/00107, PI20/00294) of the Subdirección General de Evaluación y Fomento de la Investigación Sanitaria (ISCIII), which was co-founded by the European Union Regional Development Fund (FEDER). Funding was also received from the Spanish Association of Pediatrics (Asociación Española de Pediatría; 1a Beca de Nutrición Dinosaurus-Artiach).</p><p>We apologize for this error.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 4","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589925","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":"Correction to EVs Biodistribution and Antifibrotic Impact in Aged Lung Fibrosis Model","authors":"","doi":"10.1002/biof.70034","DOIUrl":"https://doi.org/10.1002/biof.70034","url":null,"abstract":"<p>I. Amtil-Ouahdi, F. Vergara, C. Rio, C. González-Martínez, A. Jahn, M. A. Forteza-Genestra, A. Gayá, J. Calvo, E. Sala-Llinas, B. A. Navarrete, A. D. Romero-Ortiz, M. Monjo, J. M. Ramis, and F. G. Ortega, “EVs Biodistribution and Antifibrotic Impact in Aged Lung Fibrosis Model,” <i>BioFactors</i> 51 (2025): e70021, https://doi.org/10.1002/biof.70021.</p><p>In the originally published article, author Joana M. Ramis' name was mistakenly published as Johana M. Ramis. We have corrected this in the online version of the article.</p><p>We apologize for this error.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 4","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581840","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":"Fucosterol Promotes Browning in Mouse 3T3-L1 Adipocytes Through HO-1/Nrf2 and AMPK Pathways","authors":"Indyaswan T. Suryaningtyas,&nbsp;Won-Kyo Jung,&nbsp;Jae-Young Je","doi":"10.1002/biof.70035","DOIUrl":"https://doi.org/10.1002/biof.70035","url":null,"abstract":"<div>\u0000 \u0000 <p>Browning of white adipose tissue offers a promising strategy to manage obesity by enhancing thermogenesis and lipid oxidation. Although fucosterol, a phytosterol found in brown seaweeds, has been recognized for its antioxidant and metabolic benefits, its ability to trigger browning has not been previously reported. In this study, we demonstrate for the first time that fucosterol induces adipocyte browning in 3T3-L1 cells. Treatment with fucosterol (10–50 μM) during adipogenic differentiation suppressed lipid accumulation and downregulated adipogenic transcription factors (PPARγ, C/EBPα, SREBP-1), while enhancing lipolysis via increased phosphorylation of HSL and AMPK. Critically, browning markers PRDM16, PGC1α, and UCP1 were robustly upregulated in a dose-dependent manner. Fucosterol also activated the Nrf2/HO-1 antioxidant pathway, as evidenced by increased HO-1 expression and Nrf2 nuclear translocation. Pharmacological inhibition of HO-1 or AMPK reversed these effects, confirming their essential role in fucosterol-induced thermogenic remodeling. Interestingly, despite activation of p38 and ERK MAPKs—often linked to stress signaling—fucosterol reduced pro-inflammatory cytokine levels (IL-6, IL-1β, TNF-α) and elevated antioxidant enzymes (SOD, GPx, CAT), suggesting a non-inflammatory metabolic adaptation. These findings reveal a previously uncharacterized function of fucosterol in promoting adipocyte browning, driven by HO-1/Nrf2 and AMPK pathways, with potential relevance for therapeutic strategies targeting obesity.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 4","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Intake of Oleic Acid-Rich Palm Oil Induces Obesity Without Impairing Hypothalamic Insulin Sensitivity and Redox Activity in Male Wistar Rats","authors":"Aleksandra Ruzicic,&nbsp;Tamara Dakic,&nbsp;Tijana Srdic,&nbsp;Iva Lakic,&nbsp;Sanja Stankovic,&nbsp;Milos Mojovic,&nbsp;Djura Nakarada,&nbsp;Damir Kracun,&nbsp;Jelena Djordjevic","doi":"10.1002/biof.70036","DOIUrl":"https://doi.org/10.1002/biof.70036","url":null,"abstract":"<div>\u0000 \u0000 <p>The debate over the impact of extensive palm oil consumption on human health, driven by its economic affordability, persists due to its high saturated fat content and potential health risks. Conversely, its diverse bioactive compounds offer antioxidant and anti-inflammatory properties. This study seeks to investigate the effects of prolonged palm oil consumption on hypothalamic insulin signaling, inflammation, and oxidative stress markers. Rats were fed either standard chow or a palm oil-enriched diet (POD) for 21 weeks, with the latter diet prepared by soaking standard briquette food in commercially available palm oil. The palm oil used in our study contained slightly more oleic acid than palmitic acid (44.3% and 39.5%, respectively). Prolonged consumption of a diet enriched with 20% of palm oil resulted in obesity in rats, accompanied by concurrent changes in blood lipid content. Additionally, palm oil consumption induced hyperinsulinemia and hyperglycemia, indicating the presence of peripheral insulin resistance. Despite these findings, our study did not reveal differences in hypothalamic insulin resistance between obese and control rats. In the cerebrospinal fluid, insulin concentration remained consistent after palm oil consumption, while glucose levels increased. Hypothalamic gene expression analysis did not show significant changes in the levels of NF-κB, IL-6, IL-1β, and Nrf2 mRNA. Moreover, the activation of insulin receptor and its substrate IRS1, as well as the expression of glucose transporters GLUT1-4 in the rat hypothalamus, remained unaltered. Ex vivo EPR spectroscopy of the obese rat hypothalamus indicated no variations in the total redox status compared to control rats. In summary, our results suggest that long-term consumption of palm oil rich in oleic acid induces obesity but does not significantly impact hypothalamic insulin expression and response, inflammation, or oxidative stress, which at least in part may be attributed to the specific fatty acid composition of the palm oil used. However, the potential contribution of other phytochemicals and bioactive compounds, such as vitamin E, must not be overlooked when interpreting the overall metabolic response to the prolonged palm oil intake.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 4","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Effects of SELFormer-Selected β-Citronellol and β-Caryophyllene in Vagotomized Ischemic Stroke Model Through Direct Brain Protection and Gut Microbiota Modulation","authors":"Yu Yue,&nbsp;Chen Li,&nbsp;Ting Zhang,&nbsp;Sunmin Park","doi":"10.1002/biof.70031","DOIUrl":"https://doi.org/10.1002/biof.70031","url":null,"abstract":"<div>\u0000 \u0000 <p>Natural compounds identified via the SELFormer pipeline for cognitive enhancement may exert neuroprotective effects in ischemic stroke (IS) through both direct actions on the central nervous system and potential modulation of the gut microbiota. However, it remains unclear whether such benefits persist under conditions in which gut-brain neural communication is compromised. We aimed to evaluate the neuroprotective potential of β-citronellol (BCT), β-caryophyllene (BCP), and citronellyl acetate (CTA) in an IS model with compromised vagal signaling. Mongolian gerbils received daily oral treatment with dextrin (Control), BCT (100 mg/kg), BCP (20 mg/kg), or CTA (100 mg/kg) for 2 weeks before undergoing subdiaphragmatic vagotomy followed by bilateral common carotid artery occlusion; sham-operated animals treated with dextrin served as Normal-C. During an additional 4 weeks of treatment, we assessed neuronal survival, cognitive function, metabolism, neuroinflammation, and gut microbiota composition and metabolism. BCT demonstrated superior neuroprotection, followed by BCP, with CTA showing modest efficacy compared to the control. BCT and BCP increased hippocampal CA1 neurons and improved memory function. Treatments reduced hippocampal acetylcholinesterase activity, lipid peroxidation, and inflammatory markers (TNF-α and IL-1β) while enhancing cerebral blood flow, glucose metabolism, and lipid profiles. Gut microbiota analysis revealed increased α-diversity and restoration of beneficial bacteria, including <i>Akkermansia</i> and <i>Faecalibacterium</i>, particularly with BCT treatment. BCT and BCP increased butyrate-producing bacteria. These improvements occurred despite vagal nerve disruption, indicating alternative neuroprotective mechanisms through enhanced intestinal barrier integrity and microbiota-derived metabolites. In conclusion, these compounds, especially BCT, protect against neuronal death and cognitive impairment in IS conditions through integrated effects on neuroinflammation, oxidative stress, and non-vagal gut-brain communication pathways. Therefore, BCT and BCP were potential for IS prevention and treatment strategies.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 4","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria-Targeting SIRT3 Activator Effectively Controls Bleomycin-Induced Pulmonary Fibrosis","authors":"Geetanjali Devabattula,&nbsp;Bulti Bakchi,&nbsp;Anamika Sharma,&nbsp;Nagamalli Naga Sidhartha,&nbsp;Amol G. Dikundwar,&nbsp;Venkata Madhavi Yeddanapudi,&nbsp;Chandraiah Godugu","doi":"10.1002/biof.70032","DOIUrl":"https://doi.org/10.1002/biof.70032","url":null,"abstract":"<div>\u0000 \u0000 <p>Pulmonary fibrosis is a debilitating condition characterized by excessive collagen deposition and scar formation. Divergent factors often contribute to mitochondrial dysfunction. Oxidative stress is one of the major triggers for the development of pulmonary fibrosis through downregulation of SIRT3. This study aims to enhance the SIRT3 activity at the organelle level by a targeted drug delivery approach. C12 is a known molecule as a SIRT3 activator and is protective in pulmonary fibrosis in our previous studies. We have designed a mitochondrial-targeted delivery approach by introducing a triphenylphosphonium cation (TPP⁺) into the C12 molecule to enhance its mitochondrial specificity and efficacy. The newly designed MitoC12 attenuated the BLM-induced acute lung injury and pulmonary fibrosis more effectively than C12 primarily through activation of SIRT3. The cellular uptake studies revealed that MitoC12 concentrated more in mitochondria than the cytosolic fraction. MitoC12 reduced BLM-induced oxidative stress in BEAS-2B cells and inhibited TGF-β-induced pulmonary fibrosis in MRC-5 cells. MitoC12 inhibited the EMT by decreasing the expression of vimentin and N-cadherin and increasing the expression of E-cadherin. Further, the in vivo studies of MitoC12 exhibited a protective effect in BLM-induced pulmonary fibrosis by improving lung function, decreasing inflammation, and restoring lung architecture. MitoC12 reduced the collagen deposition and expression of fibrotic markers such as TGF-β, collagen 1A and 3A, α-SMA, fibronectin, and vimentin. Mechanistically, MitoC12 showed an anti-fibrotic effect through activation of SIRT3 thereby preventing mitochondrial dyshomeostasis through regulating MnSOD and OGG1 functioning. Overall, this study suggests that MitoC12 could be a potential therapeutic option for pulmonary fibrosis emphasizing TPP⁺-conjugated molecules in treating mitochondrial dysfunction-related diseases.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 4","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LINC01783 Promotes Glioma Tumorigenesis by Enhancing GATA3 Expression Through CBP-Mediated H3K27 Acetylation to Suppress PTEN Expression","authors":"Shaocai Hao,&nbsp;Linlin Wang,&nbsp;Shengyu Sun,&nbsp;Hechun Xia","doi":"10.1002/biof.70029","DOIUrl":"https://doi.org/10.1002/biof.70029","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aims to investigate for the first time the functional role and underlying mechanisms of long intergenic non-coding RNA <i>LINC01783</i> in glioma progression and development. Glioma tumor tissues of different grades, normal brain tissues, and glioma cell lines were used. Differential expression of <i>LINC01783</i> and other transcripts was validated in glioma tissues and cell lines using RT-qPCR and western blot assays. Furthermore, the biological functions of <i>LINC01783</i> were assessed both in vitro and in vivo using various functional assays. We found that <i>LINC01783</i> was highly expressed in glioma tumor tissues, especially the high-grade glioma samples and glioma cell lines, with its elevated expression associated with glioma cell stemness and progression, while its knockdown had the opposite effects. Functionally, <i>LINC01783</i> targeted <i>PTEN,</i> and <i>PTEN</i> overexpression significantly suppressed glioma cell proliferation and stemness characteristics, while promoting apoptosis. Mechanistic studies confirmed that <i>GATA3</i> binds to the <i>PTEN</i> promoter and transcriptionally represses <i>PTEN</i> expression, contributing to glioma progression. Additionally, our findings showed that <i>LINC01783</i> enhances GATA3 expression by facilitating H3K27 acetylation through its interaction with <i>CBP</i>, which mediates the acetylation process at the <i>GATA3</i> locus, thereby promoting tumorigenesis in glioma. Collectively, our study provides novel evidence that <i>LINC01783</i> functions as a tumor promoter and contributes to glioma tumorigenesis by enhancing <i>GATA3</i> expression via <i>CBP</i>-mediated H3K27 acetylation, thereby suppressing <i>PTEN</i> expression.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 3","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenolic Ethanolic Extracts of Specialty Sorghum Ameliorate Intestinal Colitis and Inflammation Induced by Dextran Sulfate Sodium in Mice","authors":"Ibtesam Sleem,&nbsp;Abby Rodriguez,&nbsp;Bingqi Chen,&nbsp;Ramasamy Perumal,&nbsp;Jaymi Peterson,&nbsp;Adina L. Santana,&nbsp;Dmitriy Smolensky,&nbsp;Vermont P. Dia","doi":"10.1002/biof.70028","DOIUrl":"https://doi.org/10.1002/biof.70028","url":null,"abstract":"<div>\u0000 \u0000 <p>Recently, sorghum [<i>Sorghum bicolor</i> (L.) Moench] has been given great attention as an excellent source of polyphenols that exhibit protective effects against multiple chronic disease models. Ulcerative colitis (UC) is strongly linked to the incidence of colon cancer and other intestinal chronic diseases. This study aimed to determine the ability of sorghum ethanolic phenolic extracts (SEPEs) to mitigate intestinal colitis and inflammation induced by dextran sulfate sodium (DSS) in a mice model. Forty C57BL/6 male mice were randomly assigned to one of the experimental groups: negative control, positive control (DSS only), and three groups given SEPEs containing (100 μg gallic acid eq/mL) from specialty brown sorghum accession SC84 grains (BSG) and leaves (BSL) from the same brown cultivar, and white sorghum grains (WSG). SEPEs-fed groups showed a significant reduction of the inflammatory cytokines including IL-6, TNF-alpha, and IL-1-beta in the plasma and colon, colonic disease activity index values, and fecal hemoglobin content compared to the DSS group (<i>p</i> ≤ 0.001). Furthermore, SEPEs mitigated neutrophil infiltration by inhibiting myeloperoxidase activity in the colon and enhancing intestinal integrity by upregulation of tight junction proteins' production such as ZO-1 and claudin-7. Histopathological results showed an improvement in mucosal structure and colon morphology under SEPE uptake. BSL extract exhibited a better effect against DSS compared to BSG and WSG. Metabolomic and enrichment analyses of plasma showed that SEPEs effectively recovered the disrupted metabolomic profiling in UC via modulating key pathways associated with colitis-related inflammation and oxidative stress such as bile acids metabolism, amino acids metabolism, and taurine and hypotaurine metabolism. SEPEs ameliorate colonic colitis and inflammation by suppressing proinflammatory cytokines production, neutrophil infiltration, and enhancement of intestinal integrity and functionality. Thus, specialty sorghum phenolics represent a potential alternative to mitigate colonic inflammation and colitis.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 3","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Product Daidzin Inhibits Glioma Development via Suppressing the LRP5-Mediated GSK-3β/c-Myc Signaling Pathway","authors":"Yijing Pan,&nbsp;Shunshun Wang,&nbsp;Guoliang Duan,&nbsp;Jiaqin Wu,&nbsp;Fan Feng,&nbsp;Lin Chen,&nbsp;Anzheng Li,&nbsp;Kang Xu,&nbsp;Chunli Wang,&nbsp;Shibing Fan","doi":"10.1002/biof.70025","DOIUrl":"https://doi.org/10.1002/biof.70025","url":null,"abstract":"<div>\u0000 \u0000 <p>Daidzin (DZN) is a natural flavonoid compound derived from soybeans that has recently been recognized for its potential antitumor properties. In traditional Chinese medicine, soybeans and their extracts are extensively used to prevent and treat various diseases. To evaluate the therapeutic efficacy of DZN on human glioblastoma through in vivo and in vitro experiments, and through multi-omics analyses to elucidate potential molecular mechanisms. Cell viability of LN-229 and U-87MG glioblastoma cells was assessed using the CCK-8 assay. Protein and mRNA levels of proliferation and apoptosis-related genes were analyzed via Western blotting and qPCR. Metabolomics and transcriptomics identified key pathways and targets, which were confirmed by in-cell Western blotting and expression correlation analysis. The in vivo antitumor effects of DZN were evaluated in nude mice with LN-229 tumors. DZN treatment reduced cell viability, migration, and survival in a dose-dependent manner, demonstrating strong antitumor effects in both in vitro and in vivo models. Multi-omics analysis identified amino acid metabolism and ubiquitin-mediated proteolysis as key mechanisms. Bioinformatics highlighted LRP5 as a prognostic biomarker in glioblastoma. DZN decreased LRP5 activity, downregulated p-GSK-3<i>β</i>, and promoted c-Myc degradation, thereby inhibiting the Wnt signaling pathway. In vivo, DZN significantly reduced tumor size and Ki67 expression. These findings highlight LRP5 as a promising therapeutic target, with DZN emerging as a potent LRP5 inhibitor and exhibiting significant antitumor effects in glioblastoma.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 3","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}