Pub Date : 2026-03-19Epub Date: 2026-01-29DOI: 10.1016/j.bbrc.2026.153379
Debashish Chakraborty , Supriya Samal , Smaran Banerjee , Aranya Pal , Indrajit Poirah , Gautam Nath , Asima Bhattacharyya
Extracellular vesicles (EVs) are lipid bilayer-encased nano-size carriers that orchestrate molecular exchanges in the tumor microenvironment (TME) and carry significant information about the tumor development, progression and aggressiveness. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) mediates Helicobacter pylori adhesion to gastric epithelial cells and is markedly upregulated in gastric cancer (GC). This study identified that EVs secreted by H. pylori-infected gastric cancer cells (GCCs) were loaded with CEACAM6. In order to examine the tumorigenic potential of EVs released by H. pylori-infected cells with and without CEACAM6 overexpression, EVs were thoroughly characterised and several functional assays were conducted. CEACAM6 overexpressed cell-derived EVs mimicked the elevated status of CEACAM6 as in their source cells which were found to be further enhanced in EVs collected from infected cells. As revealed by the population-doubling, clonogenicity, wound-healing and matrigel invasion assays, CEACAM6-enriched EVs promoted oncogenic properties of recipient cells while EVs from H. pylori-infected CEACAM6-expressing cells further amplified these tumorigenic abilities. A novel approach of EV-sonication and fractionation identified that CEACAM6 were mainly located in the EV membrane. Interestingly, aligned with the finding of elevated CEACAM6 protein in the H. pylori infection-led metastatic GC tissue samples, sera from those GC patients exhibited significantly high CEACAM6 compared to those from the healthy volunteers. Collectively, these findings highlight CEACAM6-containing EVs as mediators of tumorigenesis. This study also showcases the technical, translational and clinical advantages of considering CEACAM6 as a diagnostic biomarker for the detection of GC in a minimally-invasive manner.
{"title":"CEACAM6-positive extracellular vesicles released during Helicobacter pylori infection promote gastric tumor aggression","authors":"Debashish Chakraborty , Supriya Samal , Smaran Banerjee , Aranya Pal , Indrajit Poirah , Gautam Nath , Asima Bhattacharyya","doi":"10.1016/j.bbrc.2026.153379","DOIUrl":"10.1016/j.bbrc.2026.153379","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) are lipid bilayer-encased nano-size carriers that orchestrate molecular exchanges in the tumor microenvironment (TME) and carry significant information about the tumor development, progression and aggressiveness. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) mediates <em>Helicobacter pylori</em> adhesion to gastric epithelial cells and is markedly upregulated in gastric cancer (GC). This study identified that EVs secreted by <em>H. pylori</em>-infected gastric cancer cells (GCCs) were loaded with CEACAM6. In order to examine the tumorigenic potential of EVs released by <em>H. pylori</em>-infected cells with and without <em>CEACAM6</em> overexpression, EVs were thoroughly characterised and several functional assays were conducted. <em>CEACAM6</em> overexpressed cell-derived EVs mimicked the elevated status of CEACAM6 as in their source cells which were found to be further enhanced in EVs collected from infected cells. As revealed by the population-doubling, clonogenicity, wound-healing and matrigel invasion assays, CEACAM6-enriched EVs promoted oncogenic properties of recipient cells while EVs from <em>H. pylori</em>-infected <em>CEACAM6</em>-expressing cells further amplified these tumorigenic abilities. A novel approach of EV-sonication and fractionation identified that CEACAM6 were mainly located in the EV membrane. Interestingly, aligned with the finding of elevated CEACAM6 protein in the <em>H. pylori</em> infection-led metastatic GC tissue samples, sera from those GC patients exhibited significantly high CEACAM6 compared to those from the healthy volunteers. Collectively, these findings highlight CEACAM6-containing EVs as mediators of tumorigenesis. This study also showcases the technical, translational and clinical advantages of considering CEACAM6 as a diagnostic biomarker for the detection of GC in a minimally-invasive manner.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"805 ","pages":"Article 153379"},"PeriodicalIF":2.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131162","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}
Pub Date : 2026-03-19Epub Date: 2026-01-30DOI: 10.1016/j.bbrc.2026.153383
Minho Kim , Myoung Jun Kim , Sung Kyung Choi , Bitnuri Yu , Un Yung Choi , Sunsook Hwang , Wahn Soo Choi , Jueng Soo You
Hepatocellular carcinoma (HCC) remains a highly lethal malignancy despite therapeutic advances. SMARCB1 exhibits context-dependent functions across different cancer types. While it is frequently inactivated as a tumor suppressor in various malignancies, our previous work demonstrated that SMARCB1 acts as an oncogene in HCC by engaging the NUP210–P300 transcriptional axis. However, the upstream mechanisms that regulate SMARCB1 stability in HCC remain unexplored. Because SMARCB1 undergoes ubiquitin-mediated degradation under hypoxic conditions in other contexts, we investigated whether this regulation occurs in HCC. Cycloheximide (CHX) chase assays revealed that SMARCB1 remained highly stable under hypoxia in HCC cells, suggesting the presence of an active stabilization mechanism. Our screening for post-translational regulators identified USP21 as a deubiquitinase modulating SMARCB1 turnover. TCGA-LIHC analysis showed that USP21 is upregulated in HCC and positively correlated with SMARCB1 expression. Loss- and gain-of-function experiments confirmed that USP21 inhibition promotes SMARCB1 degradation, while USP21 overexpression prevents it. Co-immunoprecipitation demonstrated a physical interaction between USP21 and SMARCB1 that blocks ubiquitin-mediated proteasomal degradation. Combined inhibition of USP21 and P300, a downstream effector of SMARCB1, more effectively suppressed HCC cell proliferation under hypoxia than either treatment alone. Transcriptomic analysis further revealed that USP21-SMARCB1 axis contributes to immune-tolerant features in HCC. USP21 stabilizes SMARCB1 under hypoxic conditions, thereby sustaining its oncogenic and immunosuppressive activities in HCC. Targeting the USP21-SMARCB1 axis may inhibit tumor growth and enhance immunotherapy responsiveness, offering a potential therapeutic strategy for overcoming resistance in HCC treatment.
{"title":"USP21-mediated SMARCB1 stabilization under hypoxia may influence tumor progression and immune response in HCC","authors":"Minho Kim , Myoung Jun Kim , Sung Kyung Choi , Bitnuri Yu , Un Yung Choi , Sunsook Hwang , Wahn Soo Choi , Jueng Soo You","doi":"10.1016/j.bbrc.2026.153383","DOIUrl":"10.1016/j.bbrc.2026.153383","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) remains a highly lethal malignancy despite therapeutic advances. SMARCB1 exhibits context-dependent functions across different cancer types. While it is frequently inactivated as a tumor suppressor in various malignancies, our previous work demonstrated that SMARCB1 acts as an oncogene in HCC by engaging the NUP210–P300 transcriptional axis. However, the upstream mechanisms that regulate SMARCB1 stability in HCC remain unexplored. Because SMARCB1 undergoes ubiquitin-mediated degradation under hypoxic conditions in other contexts, we investigated whether this regulation occurs in HCC. Cycloheximide (CHX) chase assays revealed that SMARCB1 remained highly stable under hypoxia in HCC cells, suggesting the presence of an active stabilization mechanism. Our screening for post-translational regulators identified USP21 as a deubiquitinase modulating SMARCB1 turnover. TCGA-LIHC analysis showed that USP21 is upregulated in HCC and positively correlated with SMARCB1 expression. Loss- and gain-of-function experiments confirmed that USP21 inhibition promotes SMARCB1 degradation, while USP21 overexpression prevents it. Co-immunoprecipitation demonstrated a physical interaction between USP21 and SMARCB1 that blocks ubiquitin-mediated proteasomal degradation. Combined inhibition of USP21 and P300, a downstream effector of SMARCB1, more effectively suppressed HCC cell proliferation under hypoxia than either treatment alone. Transcriptomic analysis further revealed that USP21-SMARCB1 axis contributes to immune-tolerant features in HCC. USP21 stabilizes SMARCB1 under hypoxic conditions, thereby sustaining its oncogenic and immunosuppressive activities in HCC. Targeting the USP21-SMARCB1 axis may inhibit tumor growth and enhance immunotherapy responsiveness, offering a potential therapeutic strategy for overcoming resistance in HCC treatment.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"805 ","pages":"Article 153383"},"PeriodicalIF":2.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117593","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}
Pub Date : 2026-03-19Epub Date: 2026-01-29DOI: 10.1016/j.bbrc.2026.153381
Haoyang Yu , Yu Sun , Songyin Qiu , Haoxuan Li , Caixia Wang , Xuejin Zhao , Zhen Yang , Shaoqiang Wu , Xiangmei Lin , Chunyan Feng
Functional monoclonal antibodies (mAbs) are crucial for the development of effective control and therapeutic strategies against lumpy skin disease (LSD), a cattle disease caused by Lumpy skin disease virus (LSDV) that results in significant economic losses. In this study, the soluble recombinant ORF117 protein of LSDV was expressed in 293F cells. It was then employed as an immunogen to generate two mAbs, designated 11C4 and 28B5. Bio-layer interferometry measurements indicated high binding affinities, with equilibrium dissociation constants (Kd) values of 0.05 nM for 11C4 and 0.8 nM for 28B5. Indirect ELISA revealed half-maximal effective concentration (EC50) value of 6.69 × 10−3μg/mL for 11C4 and 11.22 × 10−3μg/mL for 28B5. Immunofluorescence assays confirmed that both mAbs recognized the native viral ORF117. Competition ELISA demonstrated that the mAbs preferentially binded to viral particles rather than to recombinant ORF117 in a co-incubation system. Neutralization assays showed that 11C4 achieved 45.1 % neutralization of LSDV infection, while 28B5 exhibited comparable activity. Epitope mapping indicated both mAbs recognized novel distinct epitopes. 11C4 targeted the epitope (IFPGDDDETNERNINHREKT) with loop structure, whereas 28B5 bound to a novel distinct region (KKIINERYSNYISIDDDEISDILKDSFISNEEMQI) with helix structure. Structural docking simulations revealed that 11C4 recognized a conserved segment IFPGDDDET among Chordopoxvirinae subfamily, with Asp12 and Glu14 identified as critical residues forantibody binding. This study provided valuable tools to advance the development of diagnostic and therapeutic measures against LSDV and related poxviruses.
{"title":"Characterization of two monoclonal antibodies that capture and neutralize LSDV via distinct novel epitopes","authors":"Haoyang Yu , Yu Sun , Songyin Qiu , Haoxuan Li , Caixia Wang , Xuejin Zhao , Zhen Yang , Shaoqiang Wu , Xiangmei Lin , Chunyan Feng","doi":"10.1016/j.bbrc.2026.153381","DOIUrl":"10.1016/j.bbrc.2026.153381","url":null,"abstract":"<div><div>Functional monoclonal antibodies (mAbs) are crucial for the development of effective control and therapeutic strategies against lumpy skin disease (LSD), a cattle disease caused by Lumpy skin disease virus (LSDV) that results in significant economic losses. In this study, the soluble recombinant ORF117 protein of LSDV was expressed in 293F cells. It was then employed as an immunogen to generate two mAbs, designated 11C4 and 28B5. Bio-layer interferometry measurements indicated high binding affinities, with equilibrium dissociation constants (Kd) values of 0.05 nM for 11C4 and 0.8 nM for 28B5. Indirect ELISA revealed half-maximal effective concentration (EC<sub>50</sub>) value of 6.69 × 10<sup>−3</sup>μg/mL for 11C4 and 11.22 × 10<sup>−3</sup>μg/mL for 28B5. Immunofluorescence assays confirmed that both mAbs recognized the native viral ORF117. Competition ELISA demonstrated that the mAbs preferentially binded to viral particles rather than to recombinant ORF117 in a co-incubation system. Neutralization assays showed that 11C4 achieved 45.1 % neutralization of LSDV infection, while 28B5 exhibited comparable activity. Epitope mapping indicated both mAbs recognized novel distinct epitopes. 11C4 targeted the epitope (IFPGDDDETNERNINHREKT) with loop structure, whereas 28B5 bound to a novel distinct region (KKIINERYSNYISIDDDEISDILKDSFISNEEMQI) with helix structure. Structural docking simulations revealed that 11C4 recognized a conserved segment IFPGDDDET among <em>Chordopoxvirinae</em> subfamily, with Asp12 and Glu14 identified as critical residues forantibody binding. This study provided valuable tools to advance the development of diagnostic and therapeutic measures against LSDV and related poxviruses.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"805 ","pages":"Article 153381"},"PeriodicalIF":2.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123557","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}
Pub Date : 2026-03-19Epub Date: 2026-01-27DOI: 10.1016/j.bbrc.2026.153355
Sebastian Vogel , Sayuri Kamimura , Eric Nguyen , Meghann Smith , Luis E.F. Almeida , Patricia Zerfas , Kapil Bharti , Christian Combs , Michelly Sampaio de Melo , Zenaide M.N. Quezado
The platelet nucleotide-binding domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome is upregulated in sickle cell disease (SCD) and promotes platelet aggregation. We previously identified Bruton tyrosine kinase (BTK) as a critical regulator of the platelet NLRP3 inflammasome. However, whether NLRP3 contributes to platelet function beyond aggregation in SCD and whether these effects can be modulated through BTK inhibition, has been incompletely understood. Here, we show that platelet secretion, platelet spreading, platelet aggregation, and in vitro thrombus formation in response to collagen are elevated in SCD mice and are reduced following treatment of mice with the NLRP3 inhibitor MCC950 or the BTK inhibitor ibrutinib. The NLRP3 activator nigericin partially reversed the inhibitory effects of ibrutinib across all platelet function assays. Together, we identify the NLRP3 inflammasome as a critical mediator of platelet hyperreactivity in SCD mice, which can be targeted via BTK inhibition.
{"title":"NLRP3 inflammasome-mediated platelet hyperreactivity in sickle cell mice is targetable by BTK inhibition","authors":"Sebastian Vogel , Sayuri Kamimura , Eric Nguyen , Meghann Smith , Luis E.F. Almeida , Patricia Zerfas , Kapil Bharti , Christian Combs , Michelly Sampaio de Melo , Zenaide M.N. Quezado","doi":"10.1016/j.bbrc.2026.153355","DOIUrl":"10.1016/j.bbrc.2026.153355","url":null,"abstract":"<div><div>The platelet nucleotide-binding domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome is upregulated in sickle cell disease (SCD) and promotes platelet aggregation. We previously identified Bruton tyrosine kinase (BTK) as a critical regulator of the platelet NLRP3 inflammasome. However, whether NLRP3 contributes to platelet function beyond aggregation in SCD and whether these effects can be modulated through BTK inhibition, has been incompletely understood. Here, we show that platelet secretion, platelet spreading, platelet aggregation, and in vitro thrombus formation in response to collagen are elevated in SCD mice and are reduced following treatment of mice with the NLRP3 inhibitor MCC950 or the BTK inhibitor ibrutinib. The NLRP3 activator nigericin partially reversed the inhibitory effects of ibrutinib across all platelet function assays. Together, we identify the NLRP3 inflammasome as a critical mediator of platelet hyperreactivity in SCD mice, which can be targeted via BTK inhibition.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"805 ","pages":"Article 153355"},"PeriodicalIF":2.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123569","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}
Pub Date : 2026-03-19Epub Date: 2026-01-30DOI: 10.1016/j.bbrc.2026.153380
Wenbin Wang , Yumeng Zhao , Manqi Li , Mingming Wei , Lichuan Wu , Jinrui Wei
Resistance to lenvatinib has become a major obstacle in the clinical treatment of liver cancer, highlighting the significant research value and translational potential of developing synergistic drug combinations. In this study, deep learning models (MARSY and MatchMaker) were employed to predict potential synergistic partners for lenvatinib, with vincristine identified as a promising candidate. In vitro experiments confirmed that the combination synergistically inhibited the proliferation, migration, and clonogenic formation of liver cancer cells: CCK-8 and colony formation assays demonstrated a significant reduction in cell viability and clonogenic ability, while wound healing and Transwell assays indicated effective suppression of cell migration. The synergistic effect was quantitatively validated using the ZIP model. Furthermore, flow cytometry and Western blot analyses confirmed that the combination effectively induced apoptosis. Mechanistic studies revealed that the co-treatment led to excessive accumulation of intracellular reactive oxygen species (ROS), which activated the TNF-α/Caspase-8 signaling pathway, thereby inducing apoptosis in liver cancer cells. The cytotoxicity and pro-apoptotic effects were significantly attenuated by the ROS scavenger NAC. These findings provide a solid preclinical foundation for the further development of this combination therapy and underscore the importance of the “computational prediction-mechanistic validation” strategy in advancing cancer drug discovery.
{"title":"Deep learning predicts and in vitro experiments validates the synergistic anti-liver cancer effect of vincristine and lenvatinib: Mechanism involving apoptosis induction via the TNF-α/Caspase-8 pathway","authors":"Wenbin Wang , Yumeng Zhao , Manqi Li , Mingming Wei , Lichuan Wu , Jinrui Wei","doi":"10.1016/j.bbrc.2026.153380","DOIUrl":"10.1016/j.bbrc.2026.153380","url":null,"abstract":"<div><div>Resistance to lenvatinib has become a major obstacle in the clinical treatment of liver cancer, highlighting the significant research value and translational potential of developing synergistic drug combinations. In this study, deep learning models (MARSY and MatchMaker) were employed to predict potential synergistic partners for lenvatinib, with vincristine identified as a promising candidate. In vitro experiments confirmed that the combination synergistically inhibited the proliferation, migration, and clonogenic formation of liver cancer cells: CCK-8 and colony formation assays demonstrated a significant reduction in cell viability and clonogenic ability, while wound healing and Transwell assays indicated effective suppression of cell migration. The synergistic effect was quantitatively validated using the ZIP model. Furthermore, flow cytometry and Western blot analyses confirmed that the combination effectively induced apoptosis. Mechanistic studies revealed that the co-treatment led to excessive accumulation of intracellular reactive oxygen species (ROS), which activated the TNF-α/Caspase-8 signaling pathway, thereby inducing apoptosis in liver cancer cells. The cytotoxicity and pro-apoptotic effects were significantly attenuated by the ROS scavenger NAC. These findings provide a solid preclinical foundation for the further development of this combination therapy and underscore the importance of the “computational prediction-mechanistic validation” strategy in advancing cancer drug discovery.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"805 ","pages":"Article 153380"},"PeriodicalIF":2.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117446","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}
The SARS-CoV-2 pandemic supercharged global efforts towards cutting-edge vaccination strategies for current threats and emerging viruses. It is imperative to develop and investigate next-generation vaccines such as chimeric Virus-Like Particles (chi-VLPs) vaccines for increased immunogenicity, ease of production, and scalability to supplement the worldwide vaccine supply. This study reports a novel bivalent vaccine design of Chimeric Alphavirus-Coronavirus Virus-Like Particles (ChAC-VLPs), displaying fusion glycoproteins of Chikungunya virus (CHIKV) and a Receptor Binding Domain (RBD) of SARS-CoV-2 on its surface. The uniqueness and versatility of ChAC-VLPs have been demonstrated via various techniques, including Western blot, Immunofluorescence, cryo-EM, and Dynamic Light Scattering (DLS). The multimeric epitope display of immunogenic antigens was validated by cell-based assays. ChAC-VLP immunized mice sera have shown substantial neutralization titers for CHIKV (PRNT50 of 1:25). Similarly, serum antibodies were detected for SARS-CoV-2 RBD as observed by antigen-specific ELISA and validated using Surface Plasmon Resonance (SPR). ChAC-VLP-immunized mice sera at a 1:10 dilution exhibited 80–95 % SARS-CoV-2 pseudovirus neutralization relative to the untreated virus control. In conclusion, this study proposes ChAC-VLPs as a potential hybrid vaccine candidate for CHIKV and SARS-CoV-2 infections and contributes valuable insights into the chi-VLPs domain and its design.
{"title":"Bioengineered chimeric VLPs targeting chikungunya virus and SARS-CoV-2 show high immunogenicity in mice","authors":"Vedita Anand Singh , Sanketkumar Nehul , Ankita Saha , Vishakha Singh , Mandar Bhutkar , Chandra Shekhar Kumar , Manidipa Banerjee , Richard J. Kuhn , Pravindra Kumar , Gaurav Kumar Sharma , Shailly Tomar","doi":"10.1016/j.bbrc.2026.153346","DOIUrl":"10.1016/j.bbrc.2026.153346","url":null,"abstract":"<div><div>The SARS-CoV-2 pandemic supercharged global efforts towards cutting-edge vaccination strategies for current threats and emerging viruses. It is imperative to develop and investigate next-generation vaccines such as chimeric Virus-Like Particles (chi-VLPs) vaccines for increased immunogenicity, ease of production, and scalability to supplement the worldwide vaccine supply. This study reports a novel bivalent vaccine design of Chimeric Alphavirus-Coronavirus Virus-Like Particles (ChAC-VLPs), displaying fusion glycoproteins of Chikungunya virus (CHIKV) and a Receptor Binding Domain (RBD) of SARS-CoV-2 on its surface. The uniqueness and versatility of ChAC-VLPs have been demonstrated via various techniques, including Western blot, Immunofluorescence, cryo-EM, and Dynamic Light Scattering (DLS). The multimeric epitope display of immunogenic antigens was validated by cell-based assays. ChAC-VLP immunized mice sera have shown substantial neutralization titers for CHIKV (PRNT50 of 1:25). Similarly, serum antibodies were detected for SARS-CoV-2 RBD as observed by antigen-specific ELISA and validated using Surface Plasmon Resonance (SPR). ChAC-VLP-immunized mice sera at a 1:10 dilution exhibited 80–95 % SARS-CoV-2 pseudovirus neutralization relative to the untreated virus control. In conclusion, this study proposes ChAC-VLPs as a potential hybrid vaccine candidate for CHIKV and SARS-CoV-2 infections and contributes valuable insights into the chi-VLPs domain and its design.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"805 ","pages":"Article 153346"},"PeriodicalIF":2.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123528","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}
Oral squamous cell carcinoma (OSCC) has been increasingly associated with dysbiosis of the oral microbiome. Among oral pathogens, Prevotella intermedia (P. intermedia) is frequently enriched in patients with OSCC; however, the role of its virulence factors—particularly its deoxyribonuclease (DNase) activity—remains poorly understood.
Methods
We compared the effects of culture supernatants from wild-type P. intermedia OMA14 and DNase-deficient mutant strains (nucA, nucD and nucA nucD) on the migration and invasion of the OSCC cell line SAS, using wound healing and Matrigel invasion assays. Transcriptomic profiling of SAS cells exposed to bacterial supernatants was performed using RNA sequencing (RNA-seq), followed by differential gene expression and pathway enrichment analyses.
Results
Supernatants from the nucA nucD mutant strain significantly enhanced SAS cells migration and invasion compared with those from the OMA14 strain. RNA-seq revealed marked transcriptomic reprogramming, including upregulation of genes related to extracellular matrix degradation, epithelial–mesenchymal transition (EMT), and inflammatory signaling. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses confirmed the enrichment of EMT, cytokine signaling, and tumor-promoting pathways.
Conclusions
Our findings demonstrate a dual role of bacterial DNase activity in SAS cell. Although DNases contribute to immune evasion via neutrophil extracellular trap degradation, their absence enhances tumor invasion by promoting proinflammatory and EMT-related transcriptional programs. These results highlight the complex interplay between microbial nucleases, extracellular DNA, and host signaling, providing novel insights into the contribution of the oral microbiome to OSCC pathogenesis.
{"title":"Supernatants from DNase-deficient Prevotella intermedia strains enhance oral squamous cell carcinoma cell migration and invasion by activating inflammatory and epithelial–mesenchymal transition pathways","authors":"Fumi Seto-Tetsuo , Naoki Katase , Yuko Sasaki , Hideharu Yukitake , Mariko Naito","doi":"10.1016/j.bbrc.2026.153304","DOIUrl":"10.1016/j.bbrc.2026.153304","url":null,"abstract":"<div><h3>Introductions</h3><div>Oral squamous cell carcinoma (OSCC) has been increasingly associated with dysbiosis of the oral microbiome. Among oral pathogens, <em>Prevotella intermedia</em> (<em>P. intermedia</em>) is frequently enriched in patients with OSCC; however, the role of its virulence factors—particularly its deoxyribonuclease (DNase) activity—remains poorly understood.</div></div><div><h3>Methods</h3><div>We compared the effects of culture supernatants from wild-type <em>P. intermedia</em> OMA14 and DNase-deficient mutant strains (<em>nucA</em>, <em>nucD</em> and <em>nucA nucD</em>) on the migration and invasion of the OSCC cell line SAS, using wound healing and Matrigel invasion assays. Transcriptomic profiling of SAS cells exposed to bacterial supernatants was performed using RNA sequencing (RNA-seq), followed by differential gene expression and pathway enrichment analyses.</div></div><div><h3>Results</h3><div>Supernatants from the <em>nucA nucD</em> mutant strain significantly enhanced SAS cells migration and invasion compared with those from the OMA14 strain. RNA-seq revealed marked transcriptomic reprogramming, including upregulation of genes related to extracellular matrix degradation, epithelial–mesenchymal transition (EMT), and inflammatory signaling. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses confirmed the enrichment of EMT, cytokine signaling, and tumor-promoting pathways.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrate a dual role of bacterial DNase activity in SAS cell. Although DNases contribute to immune evasion via neutrophil extracellular trap degradation, their absence enhances tumor invasion by promoting proinflammatory and EMT-related transcriptional programs. These results highlight the complex interplay between microbial nucleases, extracellular DNA, and host signaling, providing novel insights into the contribution of the oral microbiome to OSCC pathogenesis.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"805 ","pages":"Article 153304"},"PeriodicalIF":2.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131146","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}
Although hormones are well-established contributors to prostate and breast cancers, their role in gastric cancer remains poorly understood. Clinical observations have revealed a strong correlation between female hormone levels and the risk of developing gastric cancer, particularly in women with high estrogen levels during pregnancy or lactation, who tend to have worse prognoses. However, the precise mechanisms by which estrogen (E2) and its receptors drive gastric cancer progression are not fully elucidated. Our study demonstrates that estrogen receptor ERβ, but not ERα, promotes the proliferation of E2-responsive gastric cancer cells. Genetic ablation of ERβ significantly suppresses the growth of subcutaneous tumors in mice. RNA-seq analysis identified PIK3R2, a PI3K regulatory subunit, as the most significantly E2-regulated gene, and luciferase reporter assays further validated PIK3R2 as a direct transcriptional target of ERβ. Clinically, PIK3R2 is significantly upregulated in gastric cancer, with elevated expression levels correlating with poor prognosis specifically in female patients, whereas no significant prognostic association was observed in male patients. These findings underscore the critical role of the ERβ/PIK3R2 signaling axis in estrogen-related gastric cancer, providing a potential therapeutic strategy for this subset of patients.
{"title":"ERβ-PIK3R2 axis promotes estrogen-driven gastric cancer progression","authors":"Jingyi Yin , Lingmeng Li , Yinan Niu, Ling Zhang, Liyu Huang","doi":"10.1016/j.bbrc.2026.153271","DOIUrl":"10.1016/j.bbrc.2026.153271","url":null,"abstract":"<div><div>Although hormones are well-established contributors to prostate and breast cancers, their role in gastric cancer remains poorly understood. Clinical observations have revealed a strong correlation between female hormone levels and the risk of developing gastric cancer, particularly in women with high estrogen levels during pregnancy or lactation, who tend to have worse prognoses. However, the precise mechanisms by which estrogen (E2) and its receptors drive gastric cancer progression are not fully elucidated. Our study demonstrates that estrogen receptor ERβ, but not ERα, promotes the proliferation of E2-responsive gastric cancer cells. Genetic ablation of ERβ significantly suppresses the growth of subcutaneous tumors in mice. RNA-seq analysis identified PIK3R2, a PI3K regulatory subunit, as the most significantly E2-regulated gene, and luciferase reporter assays further validated PIK3R2 as a direct transcriptional target of ERβ. Clinically, PIK3R2 is significantly upregulated in gastric cancer, with elevated expression levels correlating with poor prognosis specifically in female patients, whereas no significant prognostic association was observed in male patients. These findings underscore the critical role of the ERβ/PIK3R2 signaling axis in estrogen-related gastric cancer, providing a potential therapeutic strategy for this subset of patients.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"805 ","pages":"Article 153271"},"PeriodicalIF":2.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096061","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}
Pub Date : 2026-03-19Epub Date: 2026-02-03DOI: 10.1016/j.bbrc.2026.153402
Hee-Won Kim , Jungsoo Kim , Jeong-Heon Ko , Jeong Gu Kang
RALY, a heterogeneous nuclear ribonucleoprotein, binds to nascent RNA and participates in multiple aspects of RNA metabolism, including transport, splicing, transcription, and translation. Recent studies have revealed that RALY is overexpressed in various cancers, such as breast, uterine, and liver cancers. This overexpression has been associated with poor patient survival and uncontrolled carcinoma cell proliferation. In this study, we demonstrate that RALY functions as a key regulator of cell proliferation, migration, and invasion in the hepatocellular carcinoma (HCC) cell lines Hep3B and HepG2. Mechanistically, RALY promotes epithelial–mesenchymal transition (EMT) through regulation of the transcription factor Snail. RALY directly binds to Snail mRNA, thereby enhancing its stability. In addition, RALY modulates the TGF-β signaling pathway to promote Snail transcription. Together, our findings establish a functional link between RALY and EMT and reveal a previously unrecognized role of RALY in cancer cell metastasis. Accumulating evidence, including the results presented here, suggests that RALY represents a potential therapeutic target for cancer treatment.
{"title":"RALY promotes Epithelial-mesenchymal transition in Hepatocellular carcinoma by regulating Snail","authors":"Hee-Won Kim , Jungsoo Kim , Jeong-Heon Ko , Jeong Gu Kang","doi":"10.1016/j.bbrc.2026.153402","DOIUrl":"10.1016/j.bbrc.2026.153402","url":null,"abstract":"<div><div>RALY, a heterogeneous nuclear ribonucleoprotein, binds to nascent RNA and participates in multiple aspects of RNA metabolism, including transport, splicing, transcription, and translation. Recent studies have revealed that RALY is overexpressed in various cancers, such as breast, uterine, and liver cancers. This overexpression has been associated with poor patient survival and uncontrolled carcinoma cell proliferation. In this study, we demonstrate that RALY functions as a key regulator of cell proliferation, migration, and invasion in the hepatocellular carcinoma (HCC) cell lines Hep3B and HepG2. Mechanistically, RALY promotes epithelial–mesenchymal transition (EMT) through regulation of the transcription factor Snail. RALY directly binds to Snail mRNA, thereby enhancing its stability. In addition, RALY modulates the TGF-β signaling pathway to promote Snail transcription. Together, our findings establish a functional link between RALY and EMT and reveal a previously unrecognized role of RALY in cancer cell metastasis. Accumulating evidence, including the results presented here, suggests that RALY represents a potential therapeutic target for cancer treatment.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"805 ","pages":"Article 153402"},"PeriodicalIF":2.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131196","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}
Pub Date : 2026-03-19Epub Date: 2026-01-23DOI: 10.1016/j.bbrc.2026.153336
Helmut Spielvogel, Eveline Schreiber, Teresa Siegert, Christoph Alexiou
<div><div>Nanoparticles can be divided into several different classes. Within these classes, iron oxide-based nanoparticles exhibiting superparamagnetic properties occupy a special place because, in contrast to a majority of organic nanoparticles, they are magnetically accumulable and can be visualized in magnetic resonance imaging (MRI).</div><div>In the course of extensive research over several years, the Section for Experimental Oncology and Nanomedicine (SEON) at the University Hospital of Erlangen has developed and fabricated superparamagnetic iron-oxide nanoparticles (SPION) termed SEON<sup>Dex30</sup>. These particles consist of an iron oxide core of magnetite that over time partially oxidizes to maghemite, and an outer layer of cross-linked polysaccharide molecules (dextran). These SPIONs are intended to be employed in a clinical trial with the aim of providing evidence that they are superior to currently obtainable iron oxide nanoparticle medicinal products approved as MRI contrast media for liver imaging in terms of application safety, long-term tolerance and imaging quality.</div><div>In order for a clinical trial center to be able to resort to SEON<sup>Dex30</sup> as an Investigational Medicinal Product (IMP) for human use, the particles must be manufactured according to Good Manufacturing Practice (GMP) guidelines. GMP-compliant development and production of nanomedicines requires in-depth knowledge of regulatory requirements and product-specific process technology as well as the availability of trained specialist staff, built-to-order manufacturing equipment and officially approved production areas.</div><div>In the event that academic and clinical institutions lack the required financial, organisational and human resources to establish their own pharmaceutical production environment, it would seem reasonable to resort to specialised pharmaceutical companies that are able and willing to offer adequate procurement, manufacturing, quality control, certification and distribution services.</div><div>Beyond the use of superparamagnetic nanoparticles as MRI contrast medium, further areas of application are being explored by SEON. In addition to dextran, other biocompatible and toxicologically safe materials such as proteins, lipids and polymers may also be used as coating agents. Functionalisation is achieved by attachment of active pharmaceutical ingredients (APIs) to the coated particle surface via chemical bonding techniques, resulting in the formation of API-loaded nanoparticles for magnetically-based accumulation, controlled drug release, targeted cancer therapies and several other application fields.</div><div>The requirements on quality of starting materials, technology, production processes and quality inspections for finished SEON<sup>Dex30</sup> IMPs as described in this report may be seen as representative for other iron oxide-based nanoparticle medicinal products for human use to be developed and manufactured in the future.</d
{"title":"GMP-compliant batch manufacturing of dextran-coated iron oxide nanoparticles: A process development case study","authors":"Helmut Spielvogel, Eveline Schreiber, Teresa Siegert, Christoph Alexiou","doi":"10.1016/j.bbrc.2026.153336","DOIUrl":"10.1016/j.bbrc.2026.153336","url":null,"abstract":"<div><div>Nanoparticles can be divided into several different classes. Within these classes, iron oxide-based nanoparticles exhibiting superparamagnetic properties occupy a special place because, in contrast to a majority of organic nanoparticles, they are magnetically accumulable and can be visualized in magnetic resonance imaging (MRI).</div><div>In the course of extensive research over several years, the Section for Experimental Oncology and Nanomedicine (SEON) at the University Hospital of Erlangen has developed and fabricated superparamagnetic iron-oxide nanoparticles (SPION) termed SEON<sup>Dex30</sup>. These particles consist of an iron oxide core of magnetite that over time partially oxidizes to maghemite, and an outer layer of cross-linked polysaccharide molecules (dextran). These SPIONs are intended to be employed in a clinical trial with the aim of providing evidence that they are superior to currently obtainable iron oxide nanoparticle medicinal products approved as MRI contrast media for liver imaging in terms of application safety, long-term tolerance and imaging quality.</div><div>In order for a clinical trial center to be able to resort to SEON<sup>Dex30</sup> as an Investigational Medicinal Product (IMP) for human use, the particles must be manufactured according to Good Manufacturing Practice (GMP) guidelines. GMP-compliant development and production of nanomedicines requires in-depth knowledge of regulatory requirements and product-specific process technology as well as the availability of trained specialist staff, built-to-order manufacturing equipment and officially approved production areas.</div><div>In the event that academic and clinical institutions lack the required financial, organisational and human resources to establish their own pharmaceutical production environment, it would seem reasonable to resort to specialised pharmaceutical companies that are able and willing to offer adequate procurement, manufacturing, quality control, certification and distribution services.</div><div>Beyond the use of superparamagnetic nanoparticles as MRI contrast medium, further areas of application are being explored by SEON. In addition to dextran, other biocompatible and toxicologically safe materials such as proteins, lipids and polymers may also be used as coating agents. Functionalisation is achieved by attachment of active pharmaceutical ingredients (APIs) to the coated particle surface via chemical bonding techniques, resulting in the formation of API-loaded nanoparticles for magnetically-based accumulation, controlled drug release, targeted cancer therapies and several other application fields.</div><div>The requirements on quality of starting materials, technology, production processes and quality inspections for finished SEON<sup>Dex30</sup> IMPs as described in this report may be seen as representative for other iron oxide-based nanoparticle medicinal products for human use to be developed and manufactured in the future.</d","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"805 ","pages":"Article 153336"},"PeriodicalIF":2.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131170","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}
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