Biochemistry and Biophysics Reports最新文献

{"title":"Cellular phospho-signaling map of the enigmatic serine/threonine kinase MAST2","authors":"Isha Fathima ,&nbsp;Althaf Mahin ,&nbsp;Pahal Priyanka,&nbsp;Nazah Naurah Vattoth,&nbsp;Ayishath Nishana,&nbsp;Athira Perunelly Gopalakrishnan,&nbsp;Sowmya Soman,&nbsp;Rajesh Raju","doi":"10.1016/j.bbrep.2025.102277","DOIUrl":"10.1016/j.bbrep.2025.102277","url":null,"abstract":"<div><h3>Background</h3><div>MAST2 (Microtubule-Associated Serine/Threonine Kinase 2) is an enigmatic serine/threonine kinase that is considered to bridge microtubule-associated cytoskeletal architecture through its phospho-regulatory networks. Yet, MAST2 remains a dark horse in the human kinome, as the molecular details on its structure, upstream regulators, and downstream phosphorylation targets remain unknown.</div></div><div><h3>Methods and results</h3><div>To interpret MAST2-linked phospho-signaling dynamics, PubMed-indexed articles were curated based on predefined MeSH terms to obtain global cellular phosphoproteomics datasets. Among 105 class I phosphosites in MAST2 identified across cellular phosphoproteomics datasets, 2 phosphosites, S74 and S148, were represented more abundantly compared to other phosphosites, making them predominant and functionally significant. Expression coregulation analysis, aimed at interpreting phosphosites that consistently show either similar or opposite patterns of expression, was performed by computing the expression patterns of phosphosites in parallel with the predominant MAST2 phosphosite. Their frequencies were then ranked across differential datasets to ensure consistency, and Fisher's exact test was performed to assess the likelihood of the coregulation pattern. Potential biases within the datasets were mitigated using additional cutoffs. Interpreting these datasets, we identified the majority of high-confidence coregulated protein phosphosites of both predominant phosphosites to be involved in transcriptional regulation. This is consistent with reports that a nearby Arg89Gln mutation in MAST2 disrupts its transcriptional regulatory activity. Co-occurrence analysis of phosphosites within MAST2 revealed that these predominant sites tend to co-occur positively and share similarity in expression coregulation patterns with phosphosites in other proteins. Finally, novel upstream kinases that potentially phosphorylate the predominant phosphosites of MAST2, as well as potential downstream substrates that are phosphorylated by MAST2, were also identified from the high-confidence coregulation dataset.</div></div><div><h3>Conclusions</h3><div>We propose that phosphorylations at S74 and S148 of MAST2 are functionally similar, and that these phosphosites are candidate regulatory sites influencing the transcriptional regulatory activity of MAST2.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102277"},"PeriodicalIF":2.2,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105743","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":"Illuminating the therapeutic potential of Schisandrin a against rheumatoid arthritis by targeting ferroptosis: An integrated bioinformatics and experimental study","authors":"Zhifang Yang,&nbsp;Xiaojuan Yin,&nbsp;Sha Yang,&nbsp;Huimin Li,&nbsp;Huimin Wen","doi":"10.1016/j.bbrep.2025.102266","DOIUrl":"10.1016/j.bbrep.2025.102266","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and hyperplasia of the synovial membrane. This study aimed to elucidate the anti-inflammatory mechanisms of Schisandrin A (SCHA), a bioactive component from Schisandra chinensis, on RA fibroblast-like synoviocytes (FLSs). Integrated bioinformatics analysis was performed on transcriptomic datasets from RA and normal FLSs as well as SCHA-treated RA FLSs. Enrichment analysis revealed that differentially expressed genes between groups were significantly enriched in the ferroptosis pathway, suggesting SCHA may exert anti-inflammatory effects by inhibiting ferroptosis. Protein-protein interaction network analysis identified Txnrd1, lpcat3 and slc7a11 as key hub genes with pivotal roles in mediating SCHA's effects, and molecular docking and dynamics simulations demonstrated that SCHA directly binds to these proteins with favorable binding affinities through hydrogen bonds and hydrophobic contacts, with stable complex formation confirmed over 100-ns molecular dynamics trajectories. In lipopolysaccharide (LPS)-induced inflamed RA FLSs, SCHA significantly decreased pro-inflammatory cytokines IL-6, TNF-α and IL-1β at both protein and mRNA levels, restored antioxidant enzymes GSH-Px and SOD levels, and reduced lipid peroxidation product MDA, Fe2+ and ROS levels in a dose-dependent manner Transmission electron microscopy confirmed SCHA's dose-dependent protective effects against ferroptosis-induced mitochondrial damage. Our study demonstrates inhibition of ferroptosis via targeting TXNRD1, LPCAT3 and SLC7A11 mediates the anti-inflammatory effects of SCHA on RA FLSs. These findings reveal a novel mechanism for SCHA's therapeutic potential against RA by modulating ferroptosis.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102266"},"PeriodicalIF":2.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105896","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":"Characterization of adalimumab Fab variants with the CH1 domain replaced by the Cα1 domain of IgA","authors":"Rara Sugimoto ,&nbsp;Hitomi Nakamura ,&nbsp;Masato Kiyoshi ,&nbsp;Akiko Ishii-Watabe ,&nbsp;Naoko Oda-Ueda ,&nbsp;Takatoshi Ohkuri","doi":"10.1016/j.bbrep.2025.102269","DOIUrl":"10.1016/j.bbrep.2025.102269","url":null,"abstract":"<div><div>Antibody constant domains (C domains) contribute to structural stability. However, studies focusing on Fab fragments with heterologous constant domains are limited. Here, we engineered an IgA-type Fab (Fab_CH1IgA) by replacing the CH1 domain of an IgG1-type adalimumab Fab with the corresponding Cα1 domain of IgA1. Fab_CH1IgA was expressed in CHO cells at approximately 50 mg L⁻¹ and purified to homogeneity. DSC showed comparable thermal stability, with <em>T</em>_m = 74.8 °C for Fab_CH1IgA and 75.2 °C for the IgG1-type Fab. SPR analysis showed similar antigen-binding kinetics, with <em>K</em>_D = 2.23 n M for Fab_CH1IgA and 1.77 nM for the IgG1-type Fab. Structural analysis identified Pro124 and Tyr211 in the C domain as part of the hydrophobic core-bridging variable and constant domains. Substitution of these residues with their IgG-type counterparts reduced thermal stability, underscoring the critical contribution of V–C domain interactions. Although the sequence identity between the IgG1 and IgA1 constant domains was not particularly high, the CH1 domain in adalimumab Fab could be replaced by the IgA Cα1 domain without markedly compromising stability or activity. These findings highlight cooperative packing at the V–C interface, offering important insights into Fab engineering to enhance function while preserving biophysical integrity, and supporting the design of IgG–IgA chimeric antibodies and novel chimeric Fab formats.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102269"},"PeriodicalIF":2.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105746","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":"Heterologous expression and foldase-assisted refolding of LipGoM, a Pseudomonas lipase from family I","authors":"Elena Lizbeth Garcia-Villegas ,&nbsp;Itzel Anahí Hidalgo-Manzano ,&nbsp;Liliana Pardo-López ,&nbsp;Enrique Rudiño-Piñera","doi":"10.1016/j.bbrep.2025.102256","DOIUrl":"10.1016/j.bbrep.2025.102256","url":null,"abstract":"<div><div>Lipases from <em>Pseudomonas</em> species are valuable biocatalysts, but their heterologous expression is often complicated by the need for different protocols to ensure proper folding and activity. In this study, we successfully produced a soluble and active form of LipGoM, a lipase derived from <em>Pseudomonas</em> sp., that employs a refolding strategy after solubilization in urea. Our findings indicate that refolding LipGoM in the presence of its native foldase, LifGoM, is essential for restoring its enzymatic activity. Furthermore, we identified that optimizing the refolding conditions, specifically pH, ionic strength, protein concentration, and the addition of glycerol, reducing agents, and ions, was critical for success. The lipase-lipid GoM mixture, Lip-Lif GoM, exhibited maximal hydrolytic activity toward <em>p</em>-nitrophenyl-octanoate at 55 °C and pH 8.0, demonstrating notable stability in the presence of detergents and organic solvents. These results demonstrate the indispensable role of its cognate foldase, LifGoM, in activating LipGoM, as well as the significance of buffer composition, particularly glycerol, for the effective refolding of the enzyme and its subsequent activity.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102256"},"PeriodicalIF":2.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105895","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":"Royal jelly fermented by Lactobacillus panisapium M1 derived from honeybee queens (Apis mellifera L.) modulates plasmacytoid dendritic cell activation","authors":"Shuhei Nonobe ,&nbsp;Kaori Konishi ,&nbsp;Hideto Okamoto,&nbsp;Hayate Itatani,&nbsp;Takashi Ito,&nbsp;Ayanori Yamaki,&nbsp;Nobuaki Okumura","doi":"10.1016/j.bbrep.2025.102276","DOIUrl":"10.1016/j.bbrep.2025.102276","url":null,"abstract":"<div><div>Fermented royal jelly (fRJ) is generated via the complete bioconversion of the fatty acid 10-hydroxy-2-decenoic acid (10H2DA) into 10-hydroxydecanoic acid (10HDAA). This process occurs through fermentation with the lactic acid bacterium (LAB) <em>Lactobacillus panisapium</em> M1, which was isolated from honeybee queens (<em>Apis mellifera</em> L.). The resultant fRJ contains approximately fivefold higher levels of 10HDAA than RJ and demonstrated enhanced immunostimulatory activity. To further assess the immunological efficacy of fRJ, we performed <em>in vitro</em> assays using Flt3L-induced murine bone marrow-derived plasmacytoid dendritic cells (pDCs). fRJ treatment significantly upregulated activation markers MHC-II, CD86, CD80, and CD40 compared to RJ, with over two-fold higher expression levels. This effect was attributed, in part, to the activity of <em>L. panisapium</em> M1, whereas 10HDAA alone did not reproduce the same response. A pilot open-label clinical trial was conducted in healthy volunteers to evaluate the effect of fRJ on human pDC activation. After four weeks of daily fRJ intake, CD80 expression on peripheral blood pDCs increased by 1.1-fold compared to baseline. These findings suggest that fRJ has the potential to modulate host immune defense through pDC activation.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102276"},"PeriodicalIF":2.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105747","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":"The effect of general anesthetics on neutrophil-like differentiated HL60 cells: sevoflurane activates the mitochondrial function to promote their bactericidal action","authors":"Kosuke Asei,&nbsp;Yuki Nomura,&nbsp;Daichi Fujimoto,&nbsp;Mayu Ooi,&nbsp;Norihiko Obata,&nbsp;Satoshi Mizobuchi","doi":"10.1016/j.bbrep.2025.102272","DOIUrl":"10.1016/j.bbrep.2025.102272","url":null,"abstract":"<div><h3>Background</h3><div>Recent research has suggested that general anesthetics may affect the immune system, but it is unclear how they affect the mitochondria of neutrophils. The effects of general anesthetics on neutrophil-like differentiated HL60 cells mitochondrial function and their production of reactive oxygen species (ROS) were examined in this study.</div></div><div><h3>Methods</h3><div>HL60 cells were differentiated into neutrophil-like cells by treating them with 1 μM all-trans-retinoic acid for 4 days. The differentiated HL60 cells were exposed to propofol (4 μg ml⁻¹), midazolam (0.5 μg ml⁻¹), or sevoflurane (3 %) for 1 h or 5 h. Following the exposure to the anesthetics, we analyzed the production of ROS, bactericidal effects, cell viability, and apoptosis of the neutrophil-like differentiated HL60 cells. We also investigated the effects of these anesthetics on mitochondrial morphology and function of the neutrophil-like differentiated HL60 cells.</div></div><div><h3>Results</h3><div>Administration of propofol or midazolam activated neutrophil-like differentiated HL60 cells mitochondrial respiration and increased ATP production (P &lt; 0.05). However, there was no significant change in production of ROS or cell death. Exposure to sevoflurane activated mitochondrial respiration, ATP production (P &lt; 0.05) and ROS production (P &lt; 0.05). Additionally, exposure to sevoflurane led to a significant increase in phagocytosis. Filamentous mitochondria appeared after treatment with propofol, midazolam, and sevoflurane, while fragmented and filamentous mitochondria were seen in untreated neutrophil-like differentiated HL60 cells.</div></div><div><h3>Conclusion</h3><div>We investigated the effects of three anesthetics on the mitochondrial and bactericidal functions of differentiated HL60 cells. Our results indicate that sevoflurane activates mitochondrial function in differentiated HL60 cells, promotes the production of reactive oxygen species, and enhances bactericidal activity.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102272"},"PeriodicalIF":2.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105897","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":"SNHG16 promotes breast cancer progression by regulating the hsa-let-7b-5p/AURKA axis","authors":"Zipeng Qiao ,&nbsp;Yongjun Tang ,&nbsp;Shengle Li ,&nbsp;Qiufeng Lao ,&nbsp;Yu Xing ,&nbsp;Qingquan Zhang ,&nbsp;Songying Pan ,&nbsp;Chaoyong Bei ,&nbsp;Weiyi Pang ,&nbsp;Hui Liu","doi":"10.1016/j.bbrep.2025.102271","DOIUrl":"10.1016/j.bbrep.2025.102271","url":null,"abstract":"<div><h3>Background</h3><div>Long non-coding RNAs (lncRNAs) play crucial roles in the progression of breast cancer (BC). The lncRNA small nuclear RNA host gene 16 (SNHG16), represents a lncRNA associated with tumor development. This study focuses on SNHG16 and its regulatory role in BC progression, validated through microarray analysis and in vitro experiments.</div></div><div><h3>Method</h3><div>The GEO datasets GSE65194 and GSE61304 were used to identify differentially expressed lncRNAs, GSE41922 and GSE45666 for differentially expressed miRNAs, and GSE29431 and GSE42568 for differentially expressed mRNAs. The TCGA database was used to validate the genes identified in the previous analyses. The regulatory pathways of SNHG16 were identified through differential gene analysis, target gene prediction, functional enrichment analysis, and protein-protein interaction network analysis. RT-qPCR, Western blot, CCK-8, cell migration, and cell knockdown experiments were performed for validation.</div></div><div><h3>Results</h3><div>Our study found that elevated expression levels of SNHG16 were associated with BC cell proliferation and poor prognosis. According to an in vitro knockdown assay, SNHG16 silencing inhibits the progression of BC. SNHG16 was found to positively regulate AURKA levels as a competitive sponge for hsa-let-7b-5p.</div></div><div><h3>Conclusion</h3><div>The activity of the lncRNA SNHG16 can be triggered via the hsa-let-7b-5p/AURKA axes. These findings shed light on the novel molecular mechanisms underlying BC progression.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102271"},"PeriodicalIF":2.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105888","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":"The research progress of α-ketoglutarate in osteoarthritis","authors":"Fanghao Long ,&nbsp;Junlin Xiang ,&nbsp;Yangfan Tan,&nbsp;Jun Zhao,&nbsp;Chi Ma","doi":"10.1016/j.bbrep.2025.102270","DOIUrl":"10.1016/j.bbrep.2025.102270","url":null,"abstract":"<div><div>α-Ketoglutarate (AKG) is a key intermediate in the tricarboxylic acid, (TCA) cycle. AKG is not only involved in cellular energy metabolism but also plays important roles in a variety of physiological and pathological processes such as antioxidant activity, anti-inflammatory effects, immune regulation, and maintenance of mitochondrial function, which have garnered widespread attention. Many experiments have shown that there is a certain correlation between AKG and OA. The purpose of this paper is to comprehensively review the literature to elucidate the mechanisms of AKG in alleviating osteoarthritis (OA), such as autophagy, gut microbiota, cellular senescence, and ferroptosis. We aim to provide theoretical references and evidence for the use of AKG in the prevention and treatment of OA.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102270"},"PeriodicalIF":2.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105750","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":"Development of injectable cuttlebone derived nanohydroxyapatite hydrogel for osteoblast cell encapsulation","authors":"Premjit Arpornmaeklong ,&nbsp;Akapong Kongjaroen ,&nbsp;Surisa Kangwarnwiboon ,&nbsp;Onkanya Vajatieng ,&nbsp;Komsan Apinyauppatham ,&nbsp;Supakorn Boonyuen ,&nbsp;Sarute Ummartyotin","doi":"10.1016/j.bbrep.2025.102268","DOIUrl":"10.1016/j.bbrep.2025.102268","url":null,"abstract":"<div><div>This study focused on creating bioactive, injectable hydrogels for bone regeneration, utilizing cuttlebone derived nanohydroxyapatite (CB-nHA) and quercetin (QT), a natural flavonoid, to enhance their capacity. It explored how different ratios of CB-nHA and chitosan/collagen, along with QT, in calcium carbonate (CaCO₃-QT) microcapsules influenced the injectability and osteoconductive properties of thermosensitive chitosan/collagen hydrogels. The hydrogels were prepared with varying concentrations of CB-nHA (0 %, 5 %, 10 %, and 15 % w/v) and chitosan/collagen ratios (7:1 and 14:1 w/w). Their microstructure, mechanical, and physical properties, rheological and injectability tests were examined to identify optimal hydrogel's formulations. Additionally, cytotoxicity and osteoconductivity of the hydrogel were evaluated using encapsulated human fetal osteoblasts (hFOB) obtained from ATCC (USA). It was found that higher concentrations of CB-nHA and chitosan reduced pore size and degradation while increasing complex modulus and injection force. The CaCO₃-QT promoted cell growth by effectively storing and releasing QT. The optimal formulation, a 5 % CB-nHA and 1 % CaCO₃-QT hydrogel with a 7:1 chitosan/collagen ratio, was injectable and exhibited a pore size of 116 ± 47 μm. The hydrogel encapsulated cells demonstrated high viability and extensive intercellular connections, with ALP activity levels significantly higher than those in the groups with 0 % CB-nHA and CaCO₃ alone (p &lt; 0.05). In conclusion, the CB-nHA and CaCO₃-QT enhanced the osteoconductive property of the injectable hydrogel. A thermosensitive hydrogel composed of 5 % CB-nHA, 1 % CaCO₃-QT, and a 7:1 ratio of chitosan to collagen is a bioactive and injectable carrier for osteoblasts and QT to enhance bone regeneration.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102268"},"PeriodicalIF":2.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105889","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":"VH032 suppresses glioma proliferation by inhibiting the VHL/HIF-1α/VEGF pathway","authors":"Yi Zhang ,&nbsp;Xin-yu Zhu ,&nbsp;Jia-rong Gu ,&nbsp;Peng Wang ,&nbsp;Yu-jun Wen ,&nbsp;Shao-zhang Hou ,&nbsp;Jing-yu Yang ,&nbsp;Jin-hai Gu","doi":"10.1016/j.bbrep.2025.102254","DOIUrl":"10.1016/j.bbrep.2025.102254","url":null,"abstract":"<div><h3>Purpose</h3><div>VH032 is a VHL ligand employed for the recruitment of the von Hippel-Lindau (VHL) protein. Recent studies reveal VHL exhibits significant antitumour effects on various tumor cells. Nevertheless, VH032's impacts on glioma cells remain largely unexplored.</div></div><div><h3>Methods</h3><div>The study explored VH032's impact on glioma cell lines U87MG and U251 through a series of experimental assessments. The experiments included cell viability assays, wound healing assays and transwell assays. The apoptotic activity of VH032 was determined via flow cytometry. Finally, a xenograft tumor model composed of nude mice was used to confirm the results.</div></div><div><h3>Results</h3><div>In vitro, the CCK-8 assay indicated that VH032 potently inhibited the proliferation of glioma cells. Wound healing and transwell assays further revealed that the drug significantly impaired glioma cell migration and invasion. Flow cytometry analysis demonstrated an increased rate of apoptosis in the drug-treated cell population. Moreover, the inhibitory effect on the VHL/HIF-1α/VEGF signaling pathway was confirmed, supporting its role in reducing tumour growth. The xenograft mouse study confirmed that VH032 markedly inhibited tumour growth.</div></div><div><h3>Conclusion</h3><div>These findings suggest that VH032 is a novel and promising chemotherapeutic agent for gliomas, acting through the interference of the VHL/HIF-1α/VEGF signaling pathway to suppress migration and invasion of glioma cells.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102254"},"PeriodicalIF":2.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105894","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}