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Targeting the phospholipid repair system of Escherichia coli: New mechanistic insights into the antibacterial activity of sanggenon D from mulberry
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2025-04-11 DOI: 10.1016/j.bbrc.2025.151759
Junhui Lin , Fan Liu , Zhaoxiang Huang , Yuxiao Zou , Zhangchang Yang , Shipei Li , Hong Wang , Daorui Pang
{"title":"Targeting the phospholipid repair system of Escherichia coli: New mechanistic insights into the antibacterial activity of sanggenon D from mulberry","authors":"Junhui Lin ,&nbsp;Fan Liu ,&nbsp;Zhaoxiang Huang ,&nbsp;Yuxiao Zou ,&nbsp;Zhangchang Yang ,&nbsp;Shipei Li ,&nbsp;Hong Wang ,&nbsp;Daorui Pang","doi":"10.1016/j.bbrc.2025.151759","DOIUrl":"10.1016/j.bbrc.2025.151759","url":null,"abstract":"<div><div><em>Escherichia coli</em> possesses a phospholipid repair system that serves as a bacterial resistance mechanism, complicating efforts to prevent and control infections. Sanggenon D, derived from mulberry, exhibits broad-spectrum antibacterial properties against various foodborne pathogens including <em>E. coli</em>. In this study, following treatment with sanggenon D (1.0 × MIC was 705.5 μmol/L), the number of <em>E. coli</em> colonies initially increased and then decreased significantly, which is markedly different from <em>Staphylococcus aureus</em>. These results suggest that sanggenon D may inhibit the phospholipid repair system in <em>E. coli</em>. Consequently, we further analyzed the regulation of protein expression levels involved in the phospholipid repair system and the glycerophospholipid profile after treatment with sanggenon D. The expression of proteins associated with maintaining membrane integrity, phospholipid recycling, and <em>de novo</em> phospholipid synthesis in <em>E. coli</em> was downregulated following treatment with sanggenon D, leading to a decrease in the glycerophospholipid profile. Our findings indicate that sanggenon D, derived from mulberry, may specifically target the phospholipid repair system in <em>E. coli</em>. These results could provide a theoretical basis for the further development of novel preservatives utilizing sanggenon D.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"763 ","pages":"Article 151759"},"PeriodicalIF":2.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823911","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}
引用次数: 0
Molecular surfaces modeling: Advancements in deep learning for molecular interactions and predictions
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2025-04-11 DOI: 10.1016/j.bbrc.2025.151799
Renjie Xia , Wei Li , Yi Cheng , Liangxu Xie , Xiaojun Xu
{"title":"Molecular surfaces modeling: Advancements in deep learning for molecular interactions and predictions","authors":"Renjie Xia ,&nbsp;Wei Li ,&nbsp;Yi Cheng ,&nbsp;Liangxu Xie ,&nbsp;Xiaojun Xu","doi":"10.1016/j.bbrc.2025.151799","DOIUrl":"10.1016/j.bbrc.2025.151799","url":null,"abstract":"<div><div>Molecular surface analysis can provide a high-dimensional, rich representation of molecular properties and interactions, which is crucial for enabling powerful predictive modeling and rational molecular design across diverse scientific and technological domains. With remarkable successes achieved by artificial intelligence (AI) in different fields such as computer vision and natural language processing, there is a growing imperative to harness AI's potential in accelerating molecular discovery and innovation. The integration of AI techniques with molecular surface analysis has opened up new frontiers, allowing researchers to uncover hidden patterns, relationships, and design principles that were previously elusive. By leveraging the complementary strengths of molecular surface representations and advanced AI algorithms, scientists can now explore chemical space more efficiently, optimize molecular properties with greater precision, and drive transformative advancements in areas like drug development, materials engineering, and catalysis. In this review, we aim to provide an overview of recent advancements in the field of molecular surface analysis and its integration with AI techniques. These AI-driven approaches have led to significant advancements in various downstream tasks, including interface site prediction, protein-protein interaction prediction, surface-centric molecular generation and design.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"763 ","pages":"Article 151799"},"PeriodicalIF":2.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833234","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}
引用次数: 0
Understanding the structure and function of HPI, a rubber tree serine protease inhibitor, and its interaction with subtilisin
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2025-04-11 DOI: 10.1016/j.bbrc.2025.151801
Jessica Terrón-Hernández , Homero Gómez-Velasco , Laura Pinzón-Yaya, Alejandra Hernández-Santoyo, Benjamín García-Ramírez, Adela Rodríguez-Romero
{"title":"Understanding the structure and function of HPI, a rubber tree serine protease inhibitor, and its interaction with subtilisin","authors":"Jessica Terrón-Hernández ,&nbsp;Homero Gómez-Velasco ,&nbsp;Laura Pinzón-Yaya,&nbsp;Alejandra Hernández-Santoyo,&nbsp;Benjamín García-Ramírez,&nbsp;Adela Rodríguez-Romero","doi":"10.1016/j.bbrc.2025.151801","DOIUrl":"10.1016/j.bbrc.2025.151801","url":null,"abstract":"<div><div>Protease inhibitors are crucial in regulating enzymatic activity and have extensive applications in medicine, biotechnology, and agriculture. This study characterizes a recombinant protease inhibitor from <em>Hevea brasiliensis</em> (rHPI), highlighting its unique structural features and inhibitory potential. Using Matrix-Assisted Laser Desorption/Ionization (MALDI) analysis, the inhibitor exhibits one distinct peak around 7.54 kDa. Enzymatic assays using N-succinyl-Ala-Ala-Pro-Phe-<em>p</em>-nitroanilide as a substrate confirmed the inhibitor's activity against subtilisin Carlsberg, a widely utilized serine protease in industry and biotechnology. The crystal structure of rHPI, resolved at 1.73 Å, reveals a topology closely resembling eglin c, including a single alpha-helix, two parallel beta-strands, and a distinctive binding loop spanning residues 40–51. Disordered regions at the N- and C-termini contribute to its structural uniqueness. Despite lacking disulfide bonds and featuring an Arg residue instead of Trp at the P′<sub>8</sub> position, rHPI maintains a high affinity for subtilisin. Isothermal titration calorimetry (ITC) showed that this interaction is entropically driven. Molecular docking and dynamics simulations of the rHPI-subtilisin complex revealed the formation of antiparallel β-sheets, hydrogen bonding involving the protein backbone, and a salt bridge between His64 of subtilisin and Asp47 of rHPI. These findings provide valuable insights into the molecular basis of rHPI's inhibitory activity and offer a framework for the rational design of novel subtilisin inhibitors with potential applications in agricultural and industrial settings.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"763 ","pages":"Article 151801"},"PeriodicalIF":2.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825566","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}
引用次数: 0
Single-cell transcriptomics reveals the mechanisms of lung injury induced by galt gene editing in mouse
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2025-04-11 DOI: 10.1016/j.bbrc.2025.151780
Zhihao Li , Ning Wang , Haobo Wang , Lingling Yang , Yong Li , Lantao Gu , Can Fu , Pengpeng Yue , Honghao Yu
{"title":"Single-cell transcriptomics reveals the mechanisms of lung injury induced by galt gene editing in mouse","authors":"Zhihao Li ,&nbsp;Ning Wang ,&nbsp;Haobo Wang ,&nbsp;Lingling Yang ,&nbsp;Yong Li ,&nbsp;Lantao Gu ,&nbsp;Can Fu ,&nbsp;Pengpeng Yue ,&nbsp;Honghao Yu","doi":"10.1016/j.bbrc.2025.151780","DOIUrl":"10.1016/j.bbrc.2025.151780","url":null,"abstract":"<div><div>Galactosemia, caused by mutations in the <em>GALT</em> gene, leads to multi-organ damage. This study investigates the impact of <em>Galt c.847 + 1G &gt; T mutation</em> on lung tissue using single-cell transcriptomics. We employed CRISPR/Cas9 to generate a <em>Galt</em> gene-edited mouse model with the <em>Galt</em> c. 847 + 1G &gt; T mutation and assessed <em>Galt</em> expression through PCR and Western blotting. Histopathological analysis revealed significant structural lung changes, including alveolar congestion and inflammation. Single-cell RNA sequencing demonstrated a marked reduction in immune cells (NK, T, macrophages, B cells) and an increase in alveolar type II cells, vascular endothelial cells, and myofibroblasts in the GAL mouse. The increased abundance of alveolar type II cells indicated impaired differentiation and repair. Metabolic analysis revealed significant abnormalities linked to <em>Galt c.847 + 1G &gt; T mutation</em>, with disruptions in TGF-β1, FGF, and Mif pathways contributing to cellular dysfunction and exacerbated lung injury. This model provides insights into the molecular mechanisms of lung injury in galactosemia, highlighting significant alterations in lung cell populations and key signaling pathways.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"763 ","pages":"Article 151780"},"PeriodicalIF":2.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829113","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}
引用次数: 0
A network pharmacology approach and experimental validation to investigate the neuroprotective mechanism of quercetin against alcoholic brain injury via the JNK/P38 MAPK signaling pathway
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2025-04-10 DOI: 10.1016/j.bbrc.2025.151789
Yang Zhang , Binchuan Wang , Yingjiang Gu
{"title":"A network pharmacology approach and experimental validation to investigate the neuroprotective mechanism of quercetin against alcoholic brain injury via the JNK/P38 MAPK signaling pathway","authors":"Yang Zhang ,&nbsp;Binchuan Wang ,&nbsp;Yingjiang Gu","doi":"10.1016/j.bbrc.2025.151789","DOIUrl":"10.1016/j.bbrc.2025.151789","url":null,"abstract":"<div><h3>Objective</h3><div>Alcoholic brain damage (ABD) is a progressive neurodegenerative disorder resulting from prolonged and excessive alcohol consumption, characterized by neuronal injury and cognitive decline. Currently, effective therapeutic strategies remain limited. Quercetin, a natural flavonoid, has demonstrated robust antioxidative, anti-inflammatory, and neuroprotective properties, suggesting its potential utility in ABD management. This study aimed to elucidate the molecular mechanisms underlying quercetin's therapeutic effects on ABD, specifically focusing on its regulatory role in the JNK/P38 MAPK signaling pathway, a critical mediator involved in neuroinflammation and apoptosis. Our findings provide mechanistic insights into the protective effects of quercetin and underscore its promise as a novel therapeutic agent targeting neuronal injury pathways associated with alcoholic brain damage.</div></div><div><h3>Methods</h3><div>The components and targets of QE and ABD were identified from multiple databases, and potential targets and pathways were predicted using protein-protein interaction (PPI) network analysis and pathway enrichment analysis. Molecular docking was then employed to validate the predicted results. In vivo, an EtOH-induced ABD rat model was established, while in vitro, EtOH-induced BV2 microglial cells were used to investigate the anti-inflammatory and anti-apoptotic effects of QE. The potential mechanisms of QE were further validated through both in vivo and in vitro experiments.</div></div><div><h3>Results</h3><div>KEGG analysis indicated that the JNK/P38 MAPK signaling pathway is likely associated with the protective effects of QE against ABD. Molecular docking results demonstrated that QE effectively binds to key proteins. QE significantly reduced brain tissue damage in ABD rats, and molecular biology analyses revealed that QE inhibited the protein expression of inflammatory cytokines in ABD and reduced oxidative stress levels in BV2 cells. Additionally, QE markedly decreased the protein expression levels of phosphorylated JNK and P38.</div></div><div><h3>Conclusion</h3><div>The study results indicate that QE significantly mitigates the progression and severity of alcoholic brain damage (ABD), with its anti-inflammatory and neuroprotective effects associated with the downregulation of the JNK/P38 MAPK pathway.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"763 ","pages":"Article 151789"},"PeriodicalIF":2.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143821364","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}
引用次数: 0
Effect of endolysin XZ.700 on monocyte differentiation into osteoclasts and foreign body giant cells
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2025-04-10 DOI: 10.1016/j.bbrc.2025.151796
Jianfeng Jin , Sterre R. van Gils , Behrouz Zandieh-Doulabi , Ton Schoenmaker , Jenneke Klein-Nulend , Peter A. Nolte
{"title":"Effect of endolysin XZ.700 on monocyte differentiation into osteoclasts and foreign body giant cells","authors":"Jianfeng Jin ,&nbsp;Sterre R. van Gils ,&nbsp;Behrouz Zandieh-Doulabi ,&nbsp;Ton Schoenmaker ,&nbsp;Jenneke Klein-Nulend ,&nbsp;Peter A. Nolte","doi":"10.1016/j.bbrc.2025.151796","DOIUrl":"10.1016/j.bbrc.2025.151796","url":null,"abstract":"<div><div>Periprosthetic joint infections due to biofilm formation are a major concern in orthopaedic and dental implant surgery. Current treatment options use antibiotics, but antibiotic-resistant bacteria in the biofilm cause treatment failure. Bacteriophage-derived endolysin XZ.700 is highly promising to fight anti-microbial resistance, since it exhibits potent anti-biofilm activity and low cell toxicity. However, whether it affects immunomodulatory cell formation is currently unknown. Therefore, this study aimed to determine whether endolysin XZ.700 affects monocyte differentiation into osteoclasts and/or foreign body giant cells <em>in vitro</em>.</div><div>Formation of multinucleated osteoclasts and foreign body giant cells from CD14<sup>+</sup> monocytes cultured without/with endolysin XZ.700 (25, 50, 75 μg/ml) was assessed after 7, 14, and 21 days, as well as differentiation, multinucleation, and cell activation-related gene expression.</div><div>Endolysin XZ.700 decreased formation of osteoclasts with 3–5 nuclei/cell, but increased those with &gt;10 nuclei/cell after 21 days, resulting in overall inhibition of total osteoclast formation. The formation of foreign body giant cells with 3–5 nuclei/cell, but not 6–10 or &gt;10 nuclei/cell, was significantly decreased by endolysin XZ.700 at all time points. Only 25 μg/ml endolysin XZ.700 decreased total foreign body giant cell formation after 21 days. Endolysin XZ.700 downregulated differentiation-related gene expression, but upregulated cytokine-related gene expression in monocytes differentiating into osteoclasts or foreign body giant cells.</div><div>In conclusion, the biofilm-reducing agent endolysin XZ.700 decreases the formation of immunomodulatory cells, i.e. foreign body giant cells and osteoclasts, indicating that it might be highly promising as a novel antimicrobial, with short term administration as the safest mode of treatment.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"764 ","pages":"Article 151796"},"PeriodicalIF":2.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847607","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}
引用次数: 0
Regulation of alkyl hydroperoxidase D by AhpdR in the antioxidant enzyme system of Pseudomonas aeruginosa
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2025-04-10 DOI: 10.1016/j.bbrc.2025.151797
Xue-Jie Xu, Rui Cui, Yuan-yuan Liu, Wei-rong Liu, Zan-li Wang, Chao-meng Li, Ye-xuan Ju
{"title":"Regulation of alkyl hydroperoxidase D by AhpdR in the antioxidant enzyme system of Pseudomonas aeruginosa","authors":"Xue-Jie Xu,&nbsp;Rui Cui,&nbsp;Yuan-yuan Liu,&nbsp;Wei-rong Liu,&nbsp;Zan-li Wang,&nbsp;Chao-meng Li,&nbsp;Ye-xuan Ju","doi":"10.1016/j.bbrc.2025.151797","DOIUrl":"10.1016/j.bbrc.2025.151797","url":null,"abstract":"<div><div>An overabundance of reactive oxygen species (ROS) can disrupt the initial redox equilibrium within cells, resulting in metabolic issues, cellular harm, and potentially death. <em>Pseudomonas aeruginosa</em> is a widespread gram-negative environmental pathogen that causes serious infectious diseases in humans. <em>P. aeruginosa</em> has developed various antioxidant defense systems. In this study, we analyzed the transcription factor AhpdR, encoded by PA0268, which regulates the alkyl hydroperoxide D (AhpD, encoded by PA0269) and is involved in the antioxidant enzyme system of <em>P. aeruginosa</em>. Our experimental results demonstrated that the deletion of PA0268 significantly increase the mRNA transcription levels of various genes of the operon <em>ahpD</em>-PA0270-PA0271 in <em>P. aeruginosa</em>. Moreover, the absence of PA0268 increased AhpD protein expression. Sensitivity assays showed that AhpD was likely to play a role in resisting hydrogen peroxide at low concentrations of hydrogen peroxide, whereas <em>P. aeruginosa</em> seemed to use other more efficient antioxidant strategies to resist higher concentrations of hydrogen peroxide. These findings indicate that <em>P. aeruginosa</em> possesses the transcription factor PA0268, which is involved in alkyl hydroperoxide reductase systems and two-tiered defense pathways against hydrogen peroxide, involving AhpD and KatA. Furthermore, <em>ahpD</em> and PA0270-PA0271 genes may play novel roles in cellular activities against ROS.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"763 ","pages":"Article 151797"},"PeriodicalIF":2.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143821363","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}
引用次数: 0
Corrigendum to “mRNA encoding antibodies against hemagglutinin and nucleoprotein prevents influenza virus infection in vitro” [Biochem. Biophys. Res. Commun. 738 (2024) 150945]
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2025-04-10 DOI: 10.1016/j.bbrc.2025.151783
Y.A. Zabrodskaya , N.V. Gavrilova , E.A. Elpaeva , A.A. Lozhkov , V.V. Vysochinskaya , O.A. Dobrovolskaya , O.V. Dovbysh , E.L. Zimmerman , P.N. Dav , A.V. Brodskaia , E.I. Sakhenberg , A.A. Shaldzhyan , A.A. Demaev , M.A. Maslov , A.V. Vasin
{"title":"Corrigendum to “mRNA encoding antibodies against hemagglutinin and nucleoprotein prevents influenza virus infection in vitro” [Biochem. Biophys. Res. Commun. 738 (2024) 150945]","authors":"Y.A. Zabrodskaya ,&nbsp;N.V. Gavrilova ,&nbsp;E.A. Elpaeva ,&nbsp;A.A. Lozhkov ,&nbsp;V.V. Vysochinskaya ,&nbsp;O.A. Dobrovolskaya ,&nbsp;O.V. Dovbysh ,&nbsp;E.L. Zimmerman ,&nbsp;P.N. Dav ,&nbsp;A.V. Brodskaia ,&nbsp;E.I. Sakhenberg ,&nbsp;A.A. Shaldzhyan ,&nbsp;A.A. Demaev ,&nbsp;M.A. Maslov ,&nbsp;A.V. Vasin","doi":"10.1016/j.bbrc.2025.151783","DOIUrl":"10.1016/j.bbrc.2025.151783","url":null,"abstract":"","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"762 ","pages":"Article 151783"},"PeriodicalIF":2.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838873","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}
引用次数: 0
FAK regulates trophoblast functions of invasion and proliferation through Rap1 pathway in early-onset preeclampsia FAK 通过 Rap1 通路调节早期子痫前期滋养细胞的侵袭和增殖功能
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2025-04-10 DOI: 10.1016/j.bbrc.2025.151788
Tingting Wang , Hai Tong , Ruixin Chen , Youqing Jiang , Chen Zhang , Hongbo Qi , Xue Zhang
{"title":"FAK regulates trophoblast functions of invasion and proliferation through Rap1 pathway in early-onset preeclampsia","authors":"Tingting Wang ,&nbsp;Hai Tong ,&nbsp;Ruixin Chen ,&nbsp;Youqing Jiang ,&nbsp;Chen Zhang ,&nbsp;Hongbo Qi ,&nbsp;Xue Zhang","doi":"10.1016/j.bbrc.2025.151788","DOIUrl":"10.1016/j.bbrc.2025.151788","url":null,"abstract":"<div><div>This investigation examined focal adhesion kinase (FAK)'s role in trophoblast cellular processes during early-onset preeclampsia (EOPE). We analyzed FAK and its phosphorylated form (pY397FAK) expression patterns in both normal (n = 15) and EOPE (n = 15) placental tissues, including first trimester samples, using immunohistochemistry and Western blot techniques. Next, Y15 was used to inhibit FAK activity. CCK-8 detection, Western blotting, wound healing assay, Transwell assays and flow cytometry were employed to systematically evaluate FAK's impact on trophoblast cell line HTR8/SVneo. Through transcriptomic and bioinformatics analyses, we identified Rap1 as a potential downstream mediator of FAK signaling in trophoblasts. In a mouse model of preeclampsia, we found decreased expression of both FAK and Rap1 in placental tissues, supporting our in vitro findings. These results suggest that FAK may contribute to preeclampsia development by regulating trophoblast invasion and proliferation through the Rap1 signaling pathway. Our study provides insights into the molecular mechanisms underlying EOPE and identifies FAK as a potential therapeutic target for preeclampsia treatment.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"763 ","pages":"Article 151788"},"PeriodicalIF":2.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143821293","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}
引用次数: 0
The essential role of E3 ubiquitin ligases in the pathogenesis of neurodevelopmental and psychiatric disorders: Cul3, Cul4, Ube3a, and ZNRF1 E3 泛素连接酶在神经发育和精神疾病发病机制中的重要作用:Cul3、Cul4、Ube3a 和 ZNRF1
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2025-04-10 DOI: 10.1016/j.bbrc.2025.151798
Moeka Ohno , Shuji Wakatsuki , Toshiyuki Araki
{"title":"The essential role of E3 ubiquitin ligases in the pathogenesis of neurodevelopmental and psychiatric disorders: Cul3, Cul4, Ube3a, and ZNRF1","authors":"Moeka Ohno ,&nbsp;Shuji Wakatsuki ,&nbsp;Toshiyuki Araki","doi":"10.1016/j.bbrc.2025.151798","DOIUrl":"10.1016/j.bbrc.2025.151798","url":null,"abstract":"<div><div>The ubiquitin-proteasome system (UPS) is a crucial proteolytic pathway responsible for maintaining cellular homeostasis by degrading specific substrates and misfolded proteins. Protein ubiquitination, a key post-translational modification, is mediated by three enzymes: E1 (activating enzyme), E2 (conjugating enzyme), and E3 (ligase enzyme). Among these, E3 ligase genes have been linked to various neurological disorders, emphasizing the need to understand their molecular mechanisms. This paper reviews recent studies on the substrates of various E3 ubiquitin ligases including Cul3, Cul4, Ube3a, and ZNRF1, and explains how their dysfunction contributes to neuronal impairments and disease phenotypes. By deepening our understanding of these mechanisms, this review aims to facilitate the development of targeted therapies and guide future research into neurodegenerative and neurodevelopmental disorders.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"763 ","pages":"Article 151798"},"PeriodicalIF":2.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825568","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}
引用次数: 0
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