Pub Date : 2025-12-23DOI: 10.1016/j.bbrc.2025.153196
Oliver S. Reyes, David A. Leonard, Laura M.L. Hawk
Β-lactamases hydrolyze β-lactam antibiotics and thereby play an important role in antibiotic resistance, a major threat to public health. OXA-66, a class D β-lactamase found in Acinetobacter baumannii, has a bulky tryptophan (W222) occluding the active site. To further explore the effect of this tryptophan on binding, we biosynthetically replaced the tryptophans with 7-fluorotryptophans and carried out protein-observed 19F NMR studies on OXA-66. The resonance corresponding to W222 was assigned and titration of boronic acid inhibitor BA4 resulted in perturbation of the W222 resonance. Enzyme kinetics studies showed that 7FW OXA-66 was able to hydrolyze β-lactams and that mutation of W222 to a smaller phenylalanine resulted in an increase in activity. These studies highlight the impact of W222 in ligand binding to OXA-66.
{"title":"Ligand binding to the class D β-lactamase OXA-66 detected by NMR after 19F-labeling of tryptophan residues","authors":"Oliver S. Reyes, David A. Leonard, Laura M.L. Hawk","doi":"10.1016/j.bbrc.2025.153196","DOIUrl":"10.1016/j.bbrc.2025.153196","url":null,"abstract":"<div><div>Β-lactamases hydrolyze β-lactam antibiotics and thereby play an important role in antibiotic resistance, a major threat to public health. OXA-66, a class D β-lactamase found in <em>Acinetobacter baumannii</em>, has a bulky tryptophan (W222) occluding the active site. To further explore the effect of this tryptophan on binding, we biosynthetically replaced the tryptophans with 7-fluorotryptophans and carried out protein-observed <sup>19</sup>F NMR studies on OXA-66. The resonance corresponding to W222 was assigned and titration of boronic acid inhibitor BA4 resulted in perturbation of the W222 resonance. Enzyme kinetics studies showed that 7FW OXA-66 was able to hydrolyze β-lactams and that mutation of W222 to a smaller phenylalanine resulted in an increase in activity. These studies highlight the impact of W222 in ligand binding to OXA-66.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"797 ","pages":"Article 153196"},"PeriodicalIF":2.2,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838868","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 : 2025-12-23DOI: 10.1016/j.bbrc.2025.153167
Sangyeon Won , Minjoong Kim , Seungyeon Yang , Jiyoon Seo , Minbeom Ko , Eun Kyung Lee , Seung Min Jeong
Cellular senescence is a stable growth arrest commonly triggered in cancer cells by chemotherapy or radiotherapy. Although therapy-induced senescence (TIS) initially suppresses tumor proliferation, the persistence of senescent cells can promote relapse and therapeutic resistance. Here, we identify Sestrin2 as a critical regulator of senescent cancer cell survival following DNA-damaging therapies. Sestrin2 expression is robustly induced in TIS cancer cells in a p53-dependent manner. Genetic depletion of Sestrin2 selectively impairs the viability of senescent, but not proliferating, cancer cells. Mechanistically, Sestrin2 knockdown amplifies SASP gene expression and NF-κB activation, leading to endoplasmic reticulum (ER) stress and apoptotic cell death. Importantly, Sestrin2 depletion consistently enhances the elimination of senescent cancer cells across diverse genotoxic therapies. These findings reveal a pivotal pro-survival role for Sestrin2 in TIS cancer cells and highlight its potential as a therapeutic target to improve the efficacy of DNA-damaging cancer therapies.
{"title":"Targeting Sestrin2 impairs survival of senescent cancer cells following DNA-damaging therapies","authors":"Sangyeon Won , Minjoong Kim , Seungyeon Yang , Jiyoon Seo , Minbeom Ko , Eun Kyung Lee , Seung Min Jeong","doi":"10.1016/j.bbrc.2025.153167","DOIUrl":"10.1016/j.bbrc.2025.153167","url":null,"abstract":"<div><div>Cellular senescence is a stable growth arrest commonly triggered in cancer cells by chemotherapy or radiotherapy. Although therapy-induced senescence (TIS) initially suppresses tumor proliferation, the persistence of senescent cells can promote relapse and therapeutic resistance. Here, we identify Sestrin2 as a critical regulator of senescent cancer cell survival following DNA-damaging therapies. Sestrin2 expression is robustly induced in TIS cancer cells in a p53-dependent manner. Genetic depletion of Sestrin2 selectively impairs the viability of senescent, but not proliferating, cancer cells. Mechanistically, Sestrin2 knockdown amplifies SASP gene expression and NF-κB activation, leading to endoplasmic reticulum (ER) stress and apoptotic cell death. Importantly, Sestrin2 depletion consistently enhances the elimination of senescent cancer cells across diverse genotoxic therapies. These findings reveal a pivotal pro-survival role for Sestrin2 in TIS cancer cells and highlight its potential as a therapeutic target to improve the efficacy of DNA-damaging cancer therapies.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"797 ","pages":"Article 153167"},"PeriodicalIF":2.2,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838871","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 : 2025-12-23DOI: 10.1016/j.bbrc.2025.153209
Shuai Li , Qinghua Yang , Longao Huang , Cheng Pan , Jiaqi Wang , Qingjun Wei , Hua Jiang
Objective
To investigate the different expression patterns of circular RNAs (circRNAs) in the serum of patients with intervertebral disc degeneration (IDD).
Methods
The circRNA microarrays were utilized to detect differential expression profiles in the serum of patients with IDD. Bioinformatics tools such as Gene Ontology analysis, Venn analysis, and protein-protein interaction (PPI) network construction were employed to identify functional molecules potentially linked to IDD. The interaction among 00, miR-205-5p, and cyclic-AMP (cAMP)-response element-binding protein 1 (CREB1) was validated using qRT-PCR and immunohistochemistry (IHC).
Results
A total of 401 differentially expressed circRNAs were identified, with circRNA_103372 showing a significant down-regulation in nucleus pulposus (NP) tissues and serum of patients with IDD (FC = 3.23, p = 0.007). Subsequently, an interaction network involving circRNA_103372-miR-205-5p-CREB1 was constructed. Furthermore, qRT-PCR validation demonstrated that in degenerated human NP cells, both circRNA_103372 and CREB1 were downregulated, whereas hsa-miR-205-5p was upregulated. Furthermore, IHC confirmed the expression pattern of CREB1 in both rat and human IDD samples, revealing a significant reduction in CREB1 expression.
Conclusions
Serum circRNA_103372 is significantly down-regulated in patients with IDD and may be a novel, non-invasive circulating biomarker for IDD.
目的探讨椎间盘退变（IDD）患者血清中环状rna （circRNAs）的不同表达模式。方法应用circRNA芯片检测IDD患者血清中circRNA的差异表达谱。利用生物信息学工具，如基因本体分析、维恩分析和蛋白质-蛋白质相互作用（PPI）网络构建，鉴定可能与IDD相关的功能分子。通过qRT-PCR和免疫组化（IHC）验证了00、miR-205-5p和环amp （cAMP）反应元件结合蛋白1 （CREB1）之间的相互作用。结果共鉴定出401个差异表达的circrna，其中circRNA_103372在IDD患者髓核（NP）组织和血清中表达显著下调（FC = 3.23, p = 0.007）。随后，构建了涉及circRNA_103372-miR-205-5p-CREB1的相互作用网络。此外，qRT-PCR验证表明，在退化的人NP细胞中，circRNA_103372和CREB1均下调，而hsa-miR-205-5p上调。此外，免疫组化证实了CREB1在大鼠和人IDD样本中的表达模式，显示CREB1表达显著降低。结论circRNA_103372在IDD患者血清中显著下调，可能是一种新的、无创的IDD循环生物标志物。
{"title":"Comprehensive serum CircRNA profiling identifies CircRNA_103372 as a novel diagnostic biomarker for intervertebral disc degeneration","authors":"Shuai Li , Qinghua Yang , Longao Huang , Cheng Pan , Jiaqi Wang , Qingjun Wei , Hua Jiang","doi":"10.1016/j.bbrc.2025.153209","DOIUrl":"10.1016/j.bbrc.2025.153209","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the different expression patterns of circular RNAs (circRNAs) in the serum of patients with intervertebral disc degeneration (IDD).</div></div><div><h3>Methods</h3><div>The circRNA microarrays were utilized to detect differential expression profiles in the serum of patients with IDD. Bioinformatics tools such as Gene Ontology analysis, Venn analysis, and protein-protein interaction (PPI) network construction were employed to identify functional molecules potentially linked to IDD. The interaction among 00, miR-205-5p, and cyclic-AMP (cAMP)-response element-binding protein 1 (CREB1) was validated using qRT-PCR and immunohistochemistry (IHC).</div></div><div><h3>Results</h3><div>A total of 401 differentially expressed circRNAs were identified, with circRNA_103372 showing a significant down-regulation in nucleus pulposus (NP) tissues and serum of patients with IDD (FC = 3.23, p = 0.007). Subsequently, an interaction network involving circRNA_103372-miR-205-5p-CREB1 was constructed. Furthermore, qRT-PCR validation demonstrated that in degenerated human NP cells, both circRNA_103372 and CREB1 were downregulated, whereas hsa-miR-205-5p was upregulated. Furthermore, IHC confirmed the expression pattern of CREB1 in both rat and human IDD samples, revealing a significant reduction in CREB1 expression.</div></div><div><h3>Conclusions</h3><div>Serum circRNA_103372 is significantly down-regulated in patients with IDD and may be a novel, non-invasive circulating biomarker for IDD.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"797 ","pages":"Article 153209"},"PeriodicalIF":2.2,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838781","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 : 2025-12-23DOI: 10.1016/j.bbrc.2025.153175
Devu B. Kumar , Santhosh Kumar Subramanya , Poonam Thakur
Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by the dopaminergic neuronal loss in the substantia nigra and progressive motor deficits. The non-receptor tyrosine kinase c-Abl is aberrantly activated in PD brains and contributes to α-synuclein pathology, making it an attractive therapeutic target. Although several c-Abl inhibitors have shown neuroprotective effects in preclinical models, most fail in clinical trials due to poor pharmacokinetic profiles and limited brain penetration.
Here, we performed a comparative in silico evaluation of five c-Abl inhibitors—Imatinib, Nilotinib, Ponatinib, Risvodetinib, and PD180970. Binding affinity, target specificity, physicochemical and pharmacokinetic properties, blood–brain barrier permeability, and toxicity profiles were systematically assessed and cross-validated. Molecular docking studies revealed that PD180970 exhibited the strongest binding affinity for the kinase domains of both human and mouse c-Abl. To validate these findings, we performed molecular dynamics (MD) simulations and analyzed root mean square deviations (RMSD), root mean square fluctuation (RMSF), hydrogen bonding, and radius of gyration of ligands, which confirmed the superior stability and binding of PD180970. Target prediction analysis indicated that PD180970 and Ponatinib had the highest selectivity with minimal off-target hits. SwissADME profiling further showed that PD180970 possesses favorable pharmacokinetic characteristics. The BBB permeability and toxicity analysis, using ADMETLab and DeepPK, predicted that PD180970 has enhanced blood–brain barrier permeability and a lower toxicity profile compared to the other inhibitors.
Together, these integrated computational findings indicate PD180970 as a promising next-generation c-Abl inhibitor and support its prioritisation for further preclinical and clinical studies in PD.
{"title":"Comparative In silico evaluation of c-Abl inhibitors for Parkinson's disease therapy","authors":"Devu B. Kumar , Santhosh Kumar Subramanya , Poonam Thakur","doi":"10.1016/j.bbrc.2025.153175","DOIUrl":"10.1016/j.bbrc.2025.153175","url":null,"abstract":"<div><div>Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by the dopaminergic neuronal loss in the substantia nigra and progressive motor deficits. The non-receptor tyrosine kinase c-Abl is aberrantly activated in PD brains and contributes to α-synuclein pathology, making it an attractive therapeutic target. Although several c-Abl inhibitors have shown neuroprotective effects in preclinical models, most fail in clinical trials due to poor pharmacokinetic profiles and limited brain penetration.</div><div>Here, we performed a comparative in silico evaluation of five c-Abl inhibitors—Imatinib, Nilotinib, Ponatinib, Risvodetinib, and PD180970. Binding affinity, target specificity, physicochemical and pharmacokinetic properties, blood–brain barrier permeability, and toxicity profiles were systematically assessed and cross-validated. Molecular docking studies revealed that PD180970 exhibited the strongest binding affinity for the kinase domains of both human and mouse c-Abl. To validate these findings, we performed molecular dynamics (MD) simulations and analyzed root mean square deviations (RMSD), root mean square fluctuation (RMSF), hydrogen bonding, and radius of gyration of ligands, which confirmed the superior stability and binding of PD180970. Target prediction analysis indicated that PD180970 and Ponatinib had the highest selectivity with minimal off-target hits. SwissADME profiling further showed that PD180970 possesses favorable pharmacokinetic characteristics. The BBB permeability and toxicity analysis, using ADMETLab and DeepPK, predicted that PD180970 has enhanced blood–brain barrier permeability and a lower toxicity profile compared to the other inhibitors.</div><div>Together, these integrated computational findings indicate PD180970 as a promising next-generation c-Abl inhibitor and support its prioritisation for further preclinical and clinical studies in PD.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"797 ","pages":"Article 153175"},"PeriodicalIF":2.2,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801867","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}
CCR4-NOT complex is involved in transcription, translation, and mRNA degradation. As of yet, it is unknown if CCR4-NOT has additional functions beyond those. It is possible to predict unknown functions of genes by using co-expressed network analysis. Here we show that all CCR4-NOT subunits highly co-express with modulators of small nuclear noncoding RNA biogenesis, predicting that CCR4-NOT regulates the maturation of small nuclear noncoding RNA. In agreement with this, knockdown of CNOT1 decreased the expression levels of small nuclear non-coding RNAs independent of the canonical function of CCR4-NOT complex. However, the reduced expression was rescued by the co-suppression of RBM7, mediating exosomal degradation of misprocessed small RNA. These results suggest that CNOT1 contributes to small nuclear non-coding RNA maturation.
{"title":"CNOT1 contributes to small nuclear non-coding RNA maturation","authors":"Chisato Umehara , Reika Sakurai , Hiroaki Sako , Tadashi Yamamoto","doi":"10.1016/j.bbrc.2025.153185","DOIUrl":"10.1016/j.bbrc.2025.153185","url":null,"abstract":"<div><div>CCR4-NOT complex is involved in transcription, translation, and mRNA degradation. As of yet, it is unknown if CCR4-NOT has additional functions beyond those. It is possible to predict unknown functions of genes by using co-expressed network analysis. Here we show that all CCR4-NOT subunits highly co-express with modulators of small nuclear noncoding RNA biogenesis, predicting that CCR4-NOT regulates the maturation of small nuclear noncoding RNA. In agreement with this, knockdown of CNOT1 decreased the expression levels of small nuclear non-coding RNAs independent of the canonical function of CCR4-NOT complex. However, the reduced expression was rescued by the co-suppression of RBM7, mediating exosomal degradation of misprocessed small RNA. These results suggest that CNOT1 contributes to small nuclear non-coding RNA maturation.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"797 ","pages":"Article 153185"},"PeriodicalIF":2.2,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838709","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 : 2025-12-23DOI: 10.1016/j.bbrc.2025.153187
João Carlos Tolentino , Alfredo Maurício Batista de Paula , Lorena dos Reis Pereira Queiroz , Eloa Mangabeira Santos , Sandy Karolline Souza Santos , Maria Rafaela Pereira Lacerda , Wilson Bambirra Jr. , Maria Tereza Scardua , Donald Fernandes , Sérgio Henrique Sousa Santos , Lucyana Conceição Farias , André Luiz Sena Guimarães
Collagen-stimulating fillers, such as calcium hydroxyapatite (CaHA), poly-l-lactic acid (PLLA), and polycaprolactone (PCL), are widely used in regenerative medicine for skin rejuvenation. However, their precise molecular mechanisms are still poorly understood. Therefore, this study aimed to investigate the gene expression profiles and molecular interactions associated with CaHA, PLLA, and PCL, focusing on the key regulators: PPARG, VEGFA, BGLAP, and IL6. To this end, a systematic search was performed to identify genes related to the fillers. Scratch assays were conducted to assess cell migration, while RT-PCR of 14 genes and molecular docking analyses examined changes in gene expression and protein-ligand interactions. The results showed that CaHA interacted with PPARG and VEGFA, suggesting roles in metabolic and inflammatory regulation. PLLA significantly increased VEGFA expression in fibroblasts, while PCL modulated IL6 expression, impacting immunological pathways. Scratch assays revealed that PCL significantly increased fibroblast and epithelial cell migration, while PLLA inhibited this migration in both cell lines, increasing the wound area. In conclusion, each filler presents distinct molecular responses, allowing targeted applications in aesthetic and regenerative medicine. Understanding these mechanisms allows for optimized treatment strategies. Further research into their molecular pathways will increase their efficacy and safety.
{"title":"PPARG, VEGFA, BGLAP, and IL6 are key molecular regulators in skin regeneration","authors":"João Carlos Tolentino , Alfredo Maurício Batista de Paula , Lorena dos Reis Pereira Queiroz , Eloa Mangabeira Santos , Sandy Karolline Souza Santos , Maria Rafaela Pereira Lacerda , Wilson Bambirra Jr. , Maria Tereza Scardua , Donald Fernandes , Sérgio Henrique Sousa Santos , Lucyana Conceição Farias , André Luiz Sena Guimarães","doi":"10.1016/j.bbrc.2025.153187","DOIUrl":"10.1016/j.bbrc.2025.153187","url":null,"abstract":"<div><div>Collagen-stimulating fillers, such as calcium hydroxyapatite (CaHA), poly-<span>l</span>-lactic acid (PLLA), and polycaprolactone (PCL), are widely used in regenerative medicine for skin rejuvenation. However, their precise molecular mechanisms are still poorly understood. Therefore, this study aimed to investigate the gene expression profiles and molecular interactions associated with CaHA, PLLA, and PCL, focusing on the key regulators: PPARG, VEGFA, BGLAP, and IL6. To this end, a systematic search was performed to identify genes related to the fillers. Scratch assays were conducted to assess cell migration, while RT-PCR of 14 genes and molecular docking analyses examined changes in gene expression and protein-ligand interactions. The results showed that CaHA interacted with PPARG and VEGFA, suggesting roles in metabolic and inflammatory regulation. PLLA significantly increased VEGFA expression in fibroblasts, while PCL modulated IL6 expression, impacting immunological pathways. Scratch assays revealed that PCL significantly increased fibroblast and epithelial cell migration, while PLLA inhibited this migration in both cell lines, increasing the wound area. In conclusion, each filler presents distinct molecular responses, allowing targeted applications in aesthetic and regenerative medicine. Understanding these mechanisms allows for optimized treatment strategies. Further research into their molecular pathways will increase their efficacy and safety.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"797 ","pages":"Article 153187"},"PeriodicalIF":2.2,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838865","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 : 2025-12-23DOI: 10.1016/j.bbrc.2025.153204
Hye Min Kim , Min Ji Bae , Chang Geun Lee , Wol Soon Jo , Yong Uk Kye , HyoJin Kim , Yeong-Rok Kang , Seung Jin Han , Sang-Gu Hwang , Jeong-Hwa Baek
Radiotherapy and chemotherapy are central components of lung cancer treatment. However, the development of therapeutic resistance significantly limits their efficacy. Here, we identified SLC16A3 as a potential biomarker associated with radioresistance and chemoresistance in lung cancer. Transcriptomic and protein analyses revealed significantly higher SLC16A3 expression in radioresistant R–H460 cells than in parental H460 cells, and immunohistochemistry further confirmed higher SLC16A3 expression in human lung tumors than in healthy tissues. Silencing SLC16A3 significantly reduced cell survival and promoted caspase-3-dependent apoptosis, which was further enhanced by ionizing radiation or cisplatin treatment. Phospho-kinase array profiling demonstrated activation of the p38-MAPK pathway upon SLC16A3 inhibition, and pharmacological blockade of p38 (SB203580) attenuated apoptosis, confirming that SLC16A3 knockdown-induced apoptosis is p38-dependent. Collectively, these findings uncover a previously unrecognized SLC16A3-p38-caspase signaling axis that promotes therapeutic resistance and highlight SLC16A3 as a promising therapeutic target for overcoming radioresistance and chemoresistance in lung cancer.
{"title":"SLC16A3 as a novel therapeutic target for overcoming radioresistance and chemoresistance in lung cancer","authors":"Hye Min Kim , Min Ji Bae , Chang Geun Lee , Wol Soon Jo , Yong Uk Kye , HyoJin Kim , Yeong-Rok Kang , Seung Jin Han , Sang-Gu Hwang , Jeong-Hwa Baek","doi":"10.1016/j.bbrc.2025.153204","DOIUrl":"10.1016/j.bbrc.2025.153204","url":null,"abstract":"<div><div>Radiotherapy and chemotherapy are central components of lung cancer treatment. However, the development of therapeutic resistance significantly limits their efficacy. Here, we identified SLC16A3 as a potential biomarker associated with radioresistance and chemoresistance in lung cancer. Transcriptomic and protein analyses revealed significantly higher SLC16A3 expression in radioresistant R–H460 cells than in parental H460 cells, and immunohistochemistry further confirmed higher SLC16A3 expression in human lung tumors than in healthy tissues. Silencing SLC16A3 significantly reduced cell survival and promoted caspase-3-dependent apoptosis, which was further enhanced by ionizing radiation or cisplatin treatment. Phospho-kinase array profiling demonstrated activation of the p38-MAPK pathway upon SLC16A3 inhibition, and pharmacological blockade of p38 (SB203580) attenuated apoptosis, confirming that SLC16A3 knockdown-induced apoptosis is p38-dependent. Collectively, these findings uncover a previously unrecognized SLC16A3-p38-caspase signaling axis that promotes therapeutic resistance and highlight SLC16A3 as a promising therapeutic target for overcoming radioresistance and chemoresistance in lung cancer.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"797 ","pages":"Article 153204"},"PeriodicalIF":2.2,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877358","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 : 2025-12-23DOI: 10.1016/j.bbrc.2025.153181
Yang Liu, Xinxin Li, Zhengshuo Cui, Han Guo, Xueying Chen, Zihang Zhang, Jieqiong Tang, Wen Zhao, Huina Zhang
Epidemiological research has identified links between dental caries and cardiovascular diseases, yet the underlying mechanisms remain insufficiently elucidated. Given the pivotal role of endothelial dysfunction in cardiovascular diseases, the cariogenic pathogen Streptococcus mutans (S.m), and the significance of bacterial extracellular vesicles (EVs) in host-microbe interactions, we investigated the impact of S.m-derived extracellular vesicles (S.m EVs) on endothelial function. Oral administration of S.m was found to impair endothelial-dependent relaxation (EDR) in vivo. Isolated S.m EVs directly lead to diminished EDR in a dose- and time-dependent manner. Mechanistically, S.m EVs inhibited Akt and eNOS phosphorylation while promoting p38 MAPK phosphorylation and endothelin-1 expression. Further study demonstrates that the Akt/eNOS pathway and the p38 MAPK/endothelin-1axis were involved in S.m EVs-impaired endothelial function. These findings reveal the adverse effects and mechanisms of S.m EVs on endothelial function, establishing a mechanistic link between caries and cardiovascular diseases.
{"title":"Streptococcus mutans-derived extracellular vesicles disrupt endothelial function via eNOS and endothelin-1 modulation","authors":"Yang Liu, Xinxin Li, Zhengshuo Cui, Han Guo, Xueying Chen, Zihang Zhang, Jieqiong Tang, Wen Zhao, Huina Zhang","doi":"10.1016/j.bbrc.2025.153181","DOIUrl":"10.1016/j.bbrc.2025.153181","url":null,"abstract":"<div><div>Epidemiological research has identified links between dental caries and cardiovascular diseases, yet the underlying mechanisms remain insufficiently elucidated. Given the pivotal role of endothelial dysfunction in cardiovascular diseases, the cariogenic pathogen <em>Streptococcus mutans</em> (<em>S.m</em>), and the significance of bacterial extracellular vesicles (EVs) in host-microbe interactions, we investigated the impact of <em>S.m</em>-derived extracellular vesicles (<em>S.m</em> EVs) on endothelial function. Oral administration of <em>S.m</em> was found to impair endothelial-dependent relaxation (EDR) <em>in vivo</em>. Isolated <em>S.m</em> EVs directly lead to diminished EDR in a dose- and time-dependent manner. Mechanistically, <em>S.m</em> EVs inhibited Akt and eNOS phosphorylation while promoting p38 MAPK phosphorylation and endothelin-1 expression. Further study demonstrates that the Akt/eNOS pathway and the p38 MAPK/endothelin-1axis were involved in <em>S.m</em> EVs-impaired endothelial function. These findings reveal the adverse effects and mechanisms of <em>S.m</em> EVs on endothelial function, establishing a mechanistic link between caries and cardiovascular diseases.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"797 ","pages":"Article 153181"},"PeriodicalIF":2.2,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838708","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}
To address the growing emergence of multi-resistant phytopathogenic bacteria, innovative solutions are being explored in the field of plant health. Among them, bacteriocins, antimicrobial peptides or proteins secreted by bacteria, characterized by a highly specific spectrum of activity and involved in intra-specific competition, are gaining increasing interest. Bacteriocins can confer a positive selective advantage in both natural and agricultural environments, thereby contributing to microbiome modulation. Bacteriocin-producing rhizobacteria and lactic acid bacteria are already used as biocontrol agents against phytopathogenic bacteria, as well as plant growth stimulators. Bacteriocins can be produced in situ by using avirulent strains, or ex situ through industrial synthesis and applied as biopesticides. Nowadays, genetic engineering enables production of chimeric bacteriocins and their direct production in transgenic plants, avoiding the need for repeated treatments and limiting emergence of resistances. The selection of promising bacteriocins can be guided by omics-based approaches, notably metagenomics, which involve the direct extraction and sequencing of DNA from environmental samples and provides access to the genetic diversity in complex soil or plant-associated microbiomes. Combined with open-access databases and recently developed integrated tools, this approach not only facilitates the identification of known structures of bacteriocins, but also enables the prediction of potentially active peptides even those never experimentally characterized. Bacteriocin-based strategies, at the crossroads of molecular biology, microbial ecology and agronomy, hold significant potential for promoting sustainable agriculture through highly specific pathogen targeting. However, their large-scale implementation still faces several challenges, including standardization of strain screening protocols, compliance with regulatory frameworks and farmer acceptance.
{"title":"Bacteriocins in plant pathology: current knowledge, application, challenges and perspectives","authors":"Eva Caly-Simbou , Stéphane Ramin-Mangata , Stéphane Poussier , Yann Pecrix","doi":"10.1016/j.bbrc.2025.153203","DOIUrl":"10.1016/j.bbrc.2025.153203","url":null,"abstract":"<div><div>To address the growing emergence of multi-resistant phytopathogenic bacteria, innovative solutions are being explored in the field of plant health. Among them, bacteriocins, antimicrobial peptides or proteins secreted by bacteria, characterized by a highly specific spectrum of activity and involved in intra-specific competition, are gaining increasing interest. Bacteriocins can confer a positive selective advantage in both natural and agricultural environments, thereby contributing to microbiome modulation. Bacteriocin-producing rhizobacteria and lactic acid bacteria are already used as biocontrol agents against phytopathogenic bacteria, as well as plant growth stimulators. Bacteriocins can be produced <em>in situ</em> by using avirulent strains, or <em>ex situ</em> through industrial synthesis and applied as biopesticides. Nowadays, genetic engineering enables production of chimeric bacteriocins and their direct production in transgenic plants, avoiding the need for repeated treatments and limiting emergence of resistances. The selection of promising bacteriocins can be guided by <em>omics</em>-based approaches, notably metagenomics, which involve the direct extraction and sequencing of DNA from environmental samples and provides access to the genetic diversity in complex soil or plant-associated microbiomes. Combined with open-access databases and recently developed integrated tools, this approach not only facilitates the identification of known structures of bacteriocins, but also enables the prediction of potentially active peptides even those never experimentally characterized. Bacteriocin-based strategies, at the crossroads of molecular biology, microbial ecology and agronomy, hold significant potential for promoting sustainable agriculture through highly specific pathogen targeting. However, their large-scale implementation still faces several challenges, including standardization of strain screening protocols, compliance with regulatory frameworks and farmer acceptance.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"797 ","pages":"Article 153203"},"PeriodicalIF":2.2,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838867","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 : 2025-12-23DOI: 10.1016/j.bbrc.2025.153210
Apolline Goudmaeker , Aurélien Warnant , Thomas Baily , Laura Pirard , Martin Deladrière , Jean-François Rees , Yvan Larondelle , Cathy Debier
Piceatannol, a stilbene structurally close to resveratrol, was previously shown to reduce lipolysis in mouse adipocytes both in vitro and in vivo. Here, we investigated the effects of both resveratrol and piceatannol on pig precision-cut adipose tissue slices stimulated with isoproterenol, a beta-adrenergic receptor agonist. Neither polyphenol affected glycerol release by adipocytes when applied at 10 or 100 μM. However, both compounds appeared to reduce glycerol release at 1 mM, suggesting a potential lowering effect on triglyceride hydrolysis at high concentrations. Since polyphenols may react with hydrogen peroxide, a by-product of the glycerol assay, we evaluated potential interferences with the assay. We found a dose-dependent reduction of the dye production by both polyphenols at 50 μM and above, particularly strong in the case of piceatannol. To circumvent this interference, we quantified the production of free fatty acids using gas chromatography-flame ionization detection in isoproterenol-stimulated precision cut adipose tissue slices, as free fatty acid levels are expected to increase concomitantly with glycerol release during the hydrolysis of triglycerides. Analysis confirmed that piceatannol at 1 mM significantly reduced fatty acid release from adipocytes in isoproterenol-stimulated precision cut adipose tissue slices. In contrast, resveratrol effects were no longer significant. In conclusion, this study shows that high concentrations of piceatannol, but not resveratrol, influence fatty acid mobilization in a distinct species and in vitro model. It also highlights the interferences of polyphenols with enzymatic kits commonly used to assess lipolysis, emphasizing the importance of validating such observations through gas chromatography-based free fatty acid analysis.
{"title":"Piceatannol affects fatty acid mobilization during isoproterenol-induced lipolysis in pig precision-cut adipose tissue slices","authors":"Apolline Goudmaeker , Aurélien Warnant , Thomas Baily , Laura Pirard , Martin Deladrière , Jean-François Rees , Yvan Larondelle , Cathy Debier","doi":"10.1016/j.bbrc.2025.153210","DOIUrl":"10.1016/j.bbrc.2025.153210","url":null,"abstract":"<div><div>Piceatannol, a stilbene structurally close to resveratrol, was previously shown to reduce lipolysis in mouse adipocytes both <em>in vitro</em> and <em>in vivo</em>. Here, we investigated the effects of both resveratrol and piceatannol on pig precision-cut adipose tissue slices stimulated with isoproterenol, a beta-adrenergic receptor agonist. Neither polyphenol affected glycerol release by adipocytes when applied at 10 or 100 μM. However, both compounds appeared to reduce glycerol release at 1 mM, suggesting a potential lowering effect on triglyceride hydrolysis at high concentrations. Since polyphenols may react with hydrogen peroxide, a by-product of the glycerol assay, we evaluated potential interferences with the assay. We found a dose-dependent reduction of the dye production by both polyphenols at 50 μM and above, particularly strong in the case of piceatannol. To circumvent this interference, we quantified the production of free fatty acids using gas chromatography-flame ionization detection in isoproterenol-stimulated precision cut adipose tissue slices, as free fatty acid levels are expected to increase concomitantly with glycerol release during the hydrolysis of triglycerides. Analysis confirmed that piceatannol at 1 mM significantly reduced fatty acid release from adipocytes in isoproterenol-stimulated precision cut adipose tissue slices. In contrast, resveratrol effects were no longer significant. In conclusion, this study shows that high concentrations of piceatannol, but not resveratrol, influence fatty acid mobilization in a distinct species and <em>in vitro</em> model. It also highlights the interferences of polyphenols with enzymatic kits commonly used to assess lipolysis, emphasizing the importance of validating such observations through gas chromatography-based free fatty acid analysis.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"797 ","pages":"Article 153210"},"PeriodicalIF":2.2,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145853739","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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