Pub Date : 2025-02-12DOI: 10.1016/j.bbrc.2025.151483
Jéssica Silvino Valente , Ketlin Thassiani Colombelli , Lucas Lins Pereira , Érika Stefani Perez , Bruna Tereza Thomazini Zanella , Aislan Quintiliano Delgado , Matheus Naia Fioretto , Carlos Roberto Padovani , Ivan José Vechetti , Débora Cristina Damasceno , Luis Antonio Justulin Jr. , Maeli Dal-Pai-Silva
We assess the effects of aerobic exercise on the soleus and plantaris muscles in adult rats submitted to maternal protein restriction (MPR) during pregnancy and lactation. Male offspring born from dams fed with control (17%-control) or low protein diets (6%-restricted) were randomly assigned to untrained or aerobic exercise, and morphological, biochemical, molecular, and proteomic analyses were performed. The proteome analysis showed many proteins involved with muscle energy metabolism, with emphasis on the glycolysis (ALDOA, ENO1, PGAM2, and TPI1) and glycogen (PYGM) pathways. MPR decreased ALDOA, TPI1, ENO1, PGAM2, and PYGM expression and increased glycogen content in Soleus (SOL); Plantaris (PL) increased PYGM, ALDOA, GAPDH, PKM, and TPI1 protein expression. Aerobic exercise (AE) normalized the glycemic index in restricted animals and increased the expression of proteins PYGM, ALDOA, ENO1, PGAM2, and TPI1, also decreasing glycogen content in the SOL. In the PL, aerobic exercise increased PYGM, ALDOA, GAPDH, PKM, and TPI1 proteins without a change in muscle glycogen content. Our study demonstrates that MPR and AE promoted differential muscle-specific adaptations, and aerobic exercise can represent a way to attenuate early muscle morphophysiological and metabolic changes in offspring rats submitted to MPR.
{"title":"Aerobic exercise acts differentially on proteins from glucose and glycogen pathways in the SOL and PL muscles of offspring rats submitted to a low-protein maternal diet","authors":"Jéssica Silvino Valente , Ketlin Thassiani Colombelli , Lucas Lins Pereira , Érika Stefani Perez , Bruna Tereza Thomazini Zanella , Aislan Quintiliano Delgado , Matheus Naia Fioretto , Carlos Roberto Padovani , Ivan José Vechetti , Débora Cristina Damasceno , Luis Antonio Justulin Jr. , Maeli Dal-Pai-Silva","doi":"10.1016/j.bbrc.2025.151483","DOIUrl":"10.1016/j.bbrc.2025.151483","url":null,"abstract":"<div><div>We assess the effects of aerobic exercise on the soleus and plantaris muscles in adult rats submitted to maternal protein restriction (MPR) during pregnancy and lactation. Male offspring born from dams fed with control (17%-control) or low protein diets (6%-restricted) were randomly assigned to untrained or aerobic exercise, and morphological, biochemical, molecular, and proteomic analyses were performed. The proteome analysis showed many proteins involved with muscle energy metabolism, with emphasis on the glycolysis (ALDOA, ENO1, PGAM2, and TPI1) and glycogen (PYGM) pathways. MPR decreased ALDOA, TPI1, ENO1, PGAM2, and PYGM expression and increased glycogen content in Soleus (SOL); Plantaris (PL) increased PYGM, ALDOA, GAPDH, PKM, and TPI1 protein expression. Aerobic exercise (AE) normalized the glycemic index in restricted animals and increased the expression of proteins PYGM, ALDOA, ENO1, PGAM2, and TPI1, also decreasing glycogen content in the SOL. In the PL, aerobic exercise increased PYGM, ALDOA, GAPDH, PKM, and TPI1 proteins without a change in muscle glycogen content. Our study demonstrates that MPR and AE promoted differential muscle-specific adaptations, and aerobic exercise can represent a way to attenuate early muscle morphophysiological and metabolic changes in offspring rats submitted to MPR.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"752 ","pages":"Article 151483"},"PeriodicalIF":2.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420316","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 : 2025-02-12DOI: 10.1016/j.bbrc.2025.151462
Roham Riaz , Waqas Younis , Ambreen Malik Uttra , Muhammad Nasir Hayat Malik , Wajiha Manzoor , Sumera Qasim , Umme Habiba Hasan , Muhammad Naveed Mushtaq , Arianne Jung Kluck , Francislaine Aparecida dos Reis Lívero , Arquimedes Gasparotto Junior
Arthritis, characterized by persistent joint inflammation, poses a significant challenge due to its detrimental effects on cartilage function and subchondral bone health. This study investigates the potential pharmacological effects of linalool, a monoterpene alcohol commonly found in essential oils, as a promising treatment for arthritis. In vitro assays, including red blood cell membrane stability and protein denaturation tests, were conducted to preliminarily assess the anti-arthritic potential of linalool. Preclinical evaluations were performed on rats with arthritis induced by formaldehyde and complete Freund's adjuvant, focusing on the therapeutic effects of orally administered linalool over a 28-day period. Linalool treatment resulted in significant improvements in body weight, reduced paw inflammation, and decreased arthritis symptoms. Hematological and biochemical analyses revealed that linalool reduced lipid peroxidation and elevated antioxidant levels in arthritic rats. Reverse transcription-polymerase chain reaction analysis demonstrated a notable downregulation of pro-inflammatory markers such as IL-1β, IRAK, NF-κB, TNF-α, and IL-17, alongside an upregulation of the anti-inflammatory cytokine IL-10, in linalool-treated rats compared to controls. These results suggest that linalool is promising as an alternative therapeutic intervention for inflammatory joint diseases.
{"title":"Anti-arthritic and anti-inflammatory activity of linalool against formaldehyde and complete Freund's adjuvant induced arthritis in rats","authors":"Roham Riaz , Waqas Younis , Ambreen Malik Uttra , Muhammad Nasir Hayat Malik , Wajiha Manzoor , Sumera Qasim , Umme Habiba Hasan , Muhammad Naveed Mushtaq , Arianne Jung Kluck , Francislaine Aparecida dos Reis Lívero , Arquimedes Gasparotto Junior","doi":"10.1016/j.bbrc.2025.151462","DOIUrl":"10.1016/j.bbrc.2025.151462","url":null,"abstract":"<div><div>Arthritis, characterized by persistent joint inflammation, poses a significant challenge due to its detrimental effects on cartilage function and subchondral bone health. This study investigates the potential pharmacological effects of linalool, a monoterpene alcohol commonly found in essential oils, as a promising treatment for arthritis. <em>In vitro</em> assays, including red blood cell membrane stability and protein denaturation tests, were conducted to preliminarily assess the anti-arthritic potential of linalool. Preclinical evaluations were performed on rats with arthritis induced by formaldehyde and complete Freund's adjuvant, focusing on the therapeutic effects of orally administered linalool over a 28-day period. Linalool treatment resulted in significant improvements in body weight, reduced paw inflammation, and decreased arthritis symptoms. Hematological and biochemical analyses revealed that linalool reduced lipid peroxidation and elevated antioxidant levels in arthritic rats. Reverse transcription-polymerase chain reaction analysis demonstrated a notable downregulation of pro-inflammatory markers such as IL-1β, IRAK, NF-κB, TNF-α, and IL-17, alongside an upregulation of the anti-inflammatory cytokine IL-10, in linalool-treated rats compared to controls. These results suggest that linalool is promising as an alternative therapeutic intervention for inflammatory joint diseases.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"752 ","pages":"Article 151462"},"PeriodicalIF":2.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420306","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 : 2025-02-11DOI: 10.1016/j.bbrc.2025.151481
Takanori Eguchi , Stuart K. Calderwood
Myeloid zinc finger 1 (MZF1) is a multifaceted transcription factor that can act either as a transcriptional activator or a gene repressor. We examined its production of nuclear bodies (NBs) and subcellular localization. Proteomic and protein–protein interaction analysis were used to identify its cofactors and interactions. These revealed the presence of MZF1-NBs (intranuclear oligomers containing MZF1). MZF-NBs are similar to some other nuclear bodies, notably promyelocytic leukemia (PML) -NBs in terms of size and morphology. However the two structures appear to be different. MZF-NBs and PML-NBs were found to associate in the nucleus. Both MZF1 and PML are SUMO1-SUMOylated in PC-3 cells. Sumoylated MZF1 can interact with proteins containing SUMO-interaction motifs (SIM) through SUMO-SIM interaction. Interactome analysis revealed that its NBs participate in the stress response (TPR and UBAP2L), protein folding (CALR and ANKRD40), transcription, post-translational modification (TRIM33, ACOT7, CAMK2D, and CAMK2G), and RNA binding (ALURBP and CPSF5).
{"title":"Discovery of myeloid zinc finger (MZF) 1 nuclear bodies","authors":"Takanori Eguchi , Stuart K. Calderwood","doi":"10.1016/j.bbrc.2025.151481","DOIUrl":"10.1016/j.bbrc.2025.151481","url":null,"abstract":"<div><div>Myeloid zinc finger 1 (MZF1) is a multifaceted transcription factor that can act either as a transcriptional activator or a gene repressor. We examined its production of nuclear bodies (NBs) and subcellular localization. Proteomic and protein–protein interaction analysis were used to identify its cofactors and interactions. These revealed the presence of MZF1-NBs (intranuclear oligomers containing MZF1). MZF-NBs are similar to some other nuclear bodies, notably promyelocytic leukemia (PML) -NBs in terms of size and morphology. However the two structures appear to be different. MZF-NBs and PML-NBs were found to associate in the nucleus. Both MZF1 and PML are SUMO1-SUMOylated in PC-3 cells. Sumoylated MZF1 can interact with proteins containing SUMO-interaction motifs (SIM) through SUMO-SIM interaction. Interactome analysis revealed that its NBs participate in the stress response (TPR and UBAP2L), protein folding (CALR and ANKRD40), transcription, post-translational modification (TRIM33, ACOT7, CAMK2D, and CAMK2G), and RNA binding (ALURBP and CPSF5).</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"752 ","pages":"Article 151481"},"PeriodicalIF":2.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420308","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 : 2025-02-11DOI: 10.1016/j.bbrc.2025.151479
Haipeng Dong , Congwen Zang , Lili Liu , Leqin Guo , Xiangyan Ye , Xiangmiao Li , Chang Zhou , Chuanbo Sun , Miaomiao Yang , Xinshu Wei , Bing Lin , Hong Li , Hanhong Wang , Yifei Qi , Hao Hu , Na Li
Neurodevelopmental disorders (NDDs) are characterized by diverse genetic underpinnings and abnormalities in the structure and function of the central nervous system. While the lung-specific SFTPC gene is critical for pulmonary development and homeostasis, its potential involvement in NDDs has not been previously explored. In this study, we identified compound heterozygous variants of SFTPC in two children diagnosed with NDDs, inherited from carrier parents. Bioinformatic analyses predicted these variants to be deleterious, and patient blood samples confirmed reduced SFTPC protein levels. To investigate the functional impact of these mutations, we generated a Sftpc-knock-in (Sftpc-KI) mouse model carrying the defective alleles. The Sftpc-KI mice exhibited significantly reduced Sftpc expression in both lung and blood samples. Remarkably, despite its lung-specific expression, Sftpc-KI mice displayed pronounced impairments in neurobehavioral performance. Proteomic analyses of the Sftpc-KI mouse brain revealed dysregulated proteins associated with neuroinflammation. Furthermore, primary microglial cells isolated from these mice exhibited heightened expression of M1 activation markers, indicating aberrant microglial activation. Our findings uncover a previously unrecognized connection between lung-specific SFTPC dysfunction and neurodevelopmental disorders, suggesting the existence of a novel brain-lung axis and opening new avenues for research into the molecular mechanisms underlying NDDs.
{"title":"Lung-specific SFTPC mutations lead to neurodevelopmental disorders with neuroinflammation","authors":"Haipeng Dong , Congwen Zang , Lili Liu , Leqin Guo , Xiangyan Ye , Xiangmiao Li , Chang Zhou , Chuanbo Sun , Miaomiao Yang , Xinshu Wei , Bing Lin , Hong Li , Hanhong Wang , Yifei Qi , Hao Hu , Na Li","doi":"10.1016/j.bbrc.2025.151479","DOIUrl":"10.1016/j.bbrc.2025.151479","url":null,"abstract":"<div><div>Neurodevelopmental disorders (NDDs) are characterized by diverse genetic underpinnings and abnormalities in the structure and function of the central nervous system. While the lung-specific SFTPC gene is critical for pulmonary development and homeostasis, its potential involvement in NDDs has not been previously explored. In this study, we identified compound heterozygous variants of SFTPC in two children diagnosed with NDDs, inherited from carrier parents. Bioinformatic analyses predicted these variants to be deleterious, and patient blood samples confirmed reduced SFTPC protein levels. To investigate the functional impact of these mutations, we generated a Sftpc-knock-in (Sftpc-KI) mouse model carrying the defective alleles. The Sftpc-KI mice exhibited significantly reduced Sftpc expression in both lung and blood samples. Remarkably, despite its lung-specific expression, Sftpc-KI mice displayed pronounced impairments in neurobehavioral performance. Proteomic analyses of the Sftpc-KI mouse brain revealed dysregulated proteins associated with neuroinflammation. Furthermore, primary microglial cells isolated from these mice exhibited heightened expression of M1 activation markers, indicating aberrant microglial activation. Our findings uncover a previously unrecognized connection between lung-specific SFTPC dysfunction and neurodevelopmental disorders, suggesting the existence of a novel brain-lung axis and opening new avenues for research into the molecular mechanisms underlying NDDs.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"753 ","pages":"Article 151479"},"PeriodicalIF":2.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427553","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}
Human carbonic anhydrase (CA) isoenzymes IX and XII are overexpressed in cancer cells, contributing to tumor microenvironment acidification and representing important targets for cancer therapy. In this study, we identified compound V35 (ZINC09419065) as a selective inhibitor of CA IX and CA XII with enhanced binding stability and selectivity compared to standard inhibitors. We analyzed conserved regions in CA I, CA II, CA IX, and CA XII to investigate their isozyme selectivity, revealing critical selectivity determinants at positions 95, 141, and 203. Molecular docking results indicated that V35 interacts robustly with CA XII, forming a metal ion coordination complex with Zn via HIS94, HIS96, HIS119, and THR199, similar to the interaction pattern of standard inhibitor SLC-0111. Molecular dynamics (MD) simulations conducted over 500 ns under hypoxic conditions showed that V35 has high binding stability, with root mean square deviation (RMSD) and fluctuation (RMSF) values comparable to SLC-0111, demonstrating its conformational stability in CA XII. Binding free energy calculations using the MMGBSA method showed that V35 achieves binding free energy of −44.17 kcal/mol with CA XII, closely matching SLC-0111 (−49.41 kcal/mol). Density functional theory (DFT) calculations further highlighted V35’s electrostatic potential distribution, supporting its isozyme selectivity. Post-dynamics analysis indicated that the ester functional groups and the inward movement of HIS64 stabilize V35’s interactions in CA XII, a feature absent in CA I.
人类碳酸酐酶（CA）同工酶 IX 和 XII 在癌细胞中过度表达，导致肿瘤微环境酸化，是癌症治疗的重要靶点。在这项研究中，我们发现化合物 V35（ZINC09419065）是一种 CA IX 和 CA XII 的选择性抑制剂，与标准抑制剂相比，它的结合稳定性和选择性更强。我们分析了 CA I、CA II、CA IX 和 CA XII 的保守区域，研究了它们的同工酶选择性，发现了位于 95、141 和 203 位的关键选择性决定因素。分子对接结果表明，V35 与 CA XII 有很强的相互作用，通过 HIS94、HIS96、HIS119 和 THR199 与 Zn 形成金属离子配位复合物，与标准抑制剂 SLC-0111 的相互作用模式相似。在缺氧条件下进行了 500 ns 的分子动力学（MD）模拟，结果表明 V35 具有很高的结合稳定性，其均方根偏差（RMSD）和波动值（RMSF）与 SLC-0111 相当，证明了它在 CA XII 中的构象稳定性。使用 MMGBSA 方法进行的结合自由能计算显示，V35 与 CA XII 的结合自由能为 -44.17 kcal/mol，与 SLC-0111（-49.41 kcal/mol）接近。密度泛函理论（DFT）计算进一步突出了 V35 的静电位分布，支持其同工酶选择性。后动力学分析表明，酯官能团和 HIS64 的内向运动稳定了 V35 在 CA XII 中的相互作用，而 CA I 中不存在这一特征。
{"title":"Molecular dynamics simulation reveals structural insights into isozyme selectivity of carbonic anhydrase XII inhibitors in hypoxic tumor microenvironment","authors":"Venkatesan Saravanan , Sathiya Priya Palani , Bharath Kumar Chagaleti , Quan-Ze Gao , Anjana Gopi Valsaladevi , Kathiravan Muthu Kumaradoss","doi":"10.1016/j.bbrc.2025.151471","DOIUrl":"10.1016/j.bbrc.2025.151471","url":null,"abstract":"<div><div>Human carbonic anhydrase (CA) isoenzymes IX and XII are overexpressed in cancer cells, contributing to tumor microenvironment acidification and representing important targets for cancer therapy. In this study, we identified compound V35 (ZINC09419065) as a selective inhibitor of CA IX and CA XII with enhanced binding stability and selectivity compared to standard inhibitors. We analyzed conserved regions in CA I, CA II, CA IX, and CA XII to investigate their isozyme selectivity, revealing critical selectivity determinants at positions 95, 141, and 203. Molecular docking results indicated that V35 interacts robustly with CA XII, forming a metal ion coordination complex with Zn via HIS94, HIS96, HIS119, and THR199, similar to the interaction pattern of standard inhibitor SLC-0111. Molecular dynamics (MD) simulations conducted over 500 ns under hypoxic conditions showed that V35 has high binding stability, with root mean square deviation (RMSD) and fluctuation (RMSF) values comparable to SLC-0111, demonstrating its conformational stability in CA XII. Binding free energy calculations using the MMGBSA method showed that V35 achieves binding free energy of −44.17 kcal/mol with CA XII, closely matching SLC-0111 (−49.41 kcal/mol). Density functional theory (DFT) calculations further highlighted V35’s electrostatic potential distribution, supporting its isozyme selectivity. Post-dynamics analysis indicated that the ester functional groups and the inward movement of HIS64 stabilize V35’s interactions in CA XII, a feature absent in CA I.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"753 ","pages":"Article 151471"},"PeriodicalIF":2.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427558","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 chemotherapy-induced senescence (CIS) can slow tumor progression by halting the cell cycle, recent studies suggest that some cancer cells may escape this state, resume proliferation, and acquire a more aggressive phenotype. This phenomenon may contribute to chemotherapy resistance in colorectal cancer, highlighting the need to identify which treatments can effectively induce senescence. We previously demonstrated that low doses of SN38 (the active form of irinotecan) and etoposide induce senescence in HCT116 colon cancer cells, accompanied by reprogramming of the Hexosamine Biosynthesis Pathway (HBP) and O-GlcNAcylation. Here, we investigated whether other chemotherapeutic agents also induce senescence in these cells and whether changes in HBP and O-GlcNAcylation are hallmark features of CIS. Our results show that doxorubicin and cisplatin induce senescence, while 5-FU and oxaliplatin do not. Senescence induced by doxorubicin and cisplatin was associated with decreased expression of GFAT (the rate-limiting enzyme of the HBP), OGT, and OGA (the enzymes driving O-GlcNAcylation cycling), along with reduced O-GlcNAcylation levels, consistent with our previous findings. This suggests that HBP reprogramming and O-GlcNAcylation changes are hallmarks of CIS. Furthermore, they highlight the differential ability of chemotherapeutic agents to induce senescence in colorectal cancer cells, which could have implications for optimizing treatment strategies and exploring therapeutic approaches to counteract CIS.
{"title":"Comparative analysis of senescence induction by different chemotherapeutic agents in HCT116 colon cancer cells","authors":"Adrien Pioger , Ingrid Loison , Inès Metatla , Nathalie Spruyt, Corinne Abbadie, Vanessa Dehennaut","doi":"10.1016/j.bbrc.2025.151482","DOIUrl":"10.1016/j.bbrc.2025.151482","url":null,"abstract":"<div><div>Although chemotherapy-induced senescence (CIS) can slow tumor progression by halting the cell cycle, recent studies suggest that some cancer cells may escape this state, resume proliferation, and acquire a more aggressive phenotype. This phenomenon may contribute to chemotherapy resistance in colorectal cancer, highlighting the need to identify which treatments can effectively induce senescence. We previously demonstrated that low doses of SN38 (the active form of irinotecan) and etoposide induce senescence in HCT116 colon cancer cells, accompanied by reprogramming of the Hexosamine Biosynthesis Pathway (HBP) and <em>O</em>-GlcNAcylation. Here, we investigated whether other chemotherapeutic agents also induce senescence in these cells and whether changes in HBP and O-GlcNAcylation are hallmark features of CIS. Our results show that doxorubicin and cisplatin induce senescence, while 5-FU and oxaliplatin do not. Senescence induced by doxorubicin and cisplatin was associated with decreased expression of GFAT (the rate-limiting enzyme of the HBP), OGT, and OGA (the enzymes driving <em>O</em>-GlcNAcylation cycling), along with reduced <em>O</em>-GlcNAcylation levels, consistent with our previous findings. This suggests that HBP reprogramming and <em>O</em>-GlcNAcylation changes are hallmarks of CIS. Furthermore, they highlight the differential ability of chemotherapeutic agents to induce senescence in colorectal cancer cells, which could have implications for optimizing treatment strategies and exploring therapeutic approaches to counteract CIS.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"752 ","pages":"Article 151482"},"PeriodicalIF":2.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395623","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 : 2025-02-10DOI: 10.1016/j.bbrc.2025.151469
Jiu Yin , Hui Gou , Jian Qi , Wenli Xing
Background
Infantile hemangioma (IH) is a prevalent vascular tumor in infancy with a complex pathogenesis that remains unclear. This study aimed to investigate the underlying mechanisms of IH using comprehensive bioinformatics analyses and in vitro experiments.
Methods
Using GSE127487, we identified differentially expressed genes (DEGs) in IH patients across three age groups (6, 12, and 24 months). GO and KEGG enrichment analyses were performed to identify biological processes and pathways. Immune cell infiltration, transcription factor target genes, miRNA expression, and metabolic pathways were analyzed. WGCNA classified IH patients into clusters, and machine learning algorithms identified key genes. The role of SH3KBP1, the most abundantly expressed gene in the skin, was investigated using shRNA knockdown and functional assays.
Results
Gene expression in IH patients exhibited dynamic changes with age. Cellular processes and signaling pathways were consistent in the early proliferative phase, with gradual resolution in the late phase. Immune infiltration analysis revealed reduced immune cells in patients, while Pericytes were increased. NR5A1 was downregulated, while ZNF112, HSF4, and multiple miRNAs were upregulated with age. Metabolic pathways confirmed differences between proliferative and involution phases. WGCNA identified two clusters: Cluster 1 (angiogenesis and signal transduction) and Cluster 2 (metabolic and synthetic processes). Key genes, including SH3KBP1, were identified using machine learning algorithms. In vitro experiments demonstrated SH3KBP1's crucial role in cell migration and invasion.
Conclusion
This study unravels the gene expression and regulatory mechanisms of IH at different stages, providing new insights into its pathophysiology. SH3KBP1 offers a potential biomarker for future diagnostic and therapeutic strategies.
{"title":"Feature gene selection and functional validation of SH3KBP1 in infantile hemangioma using machine learning","authors":"Jiu Yin , Hui Gou , Jian Qi , Wenli Xing","doi":"10.1016/j.bbrc.2025.151469","DOIUrl":"10.1016/j.bbrc.2025.151469","url":null,"abstract":"<div><h3>Background</h3><div>Infantile hemangioma (IH) is a prevalent vascular tumor in infancy with a complex pathogenesis that remains unclear. This study aimed to investigate the underlying mechanisms of IH using comprehensive bioinformatics analyses and in vitro experiments.</div></div><div><h3>Methods</h3><div>Using GSE127487, we identified differentially expressed genes (DEGs) in IH patients across three age groups (6, 12, and 24 months). GO and KEGG enrichment analyses were performed to identify biological processes and pathways. Immune cell infiltration, transcription factor target genes, miRNA expression, and metabolic pathways were analyzed. WGCNA classified IH patients into clusters, and machine learning algorithms identified key genes. The role of SH3KBP1, the most abundantly expressed gene in the skin, was investigated using shRNA knockdown and functional assays.</div></div><div><h3>Results</h3><div>Gene expression in IH patients exhibited dynamic changes with age. Cellular processes and signaling pathways were consistent in the early proliferative phase, with gradual resolution in the late phase. Immune infiltration analysis revealed reduced immune cells in patients, while Pericytes were increased. NR5A1 was downregulated, while ZNF112, HSF4, and multiple miRNAs were upregulated with age. Metabolic pathways confirmed differences between proliferative and involution phases. WGCNA identified two clusters: Cluster 1 (angiogenesis and signal transduction) and Cluster 2 (metabolic and synthetic processes). Key genes, including SH3KBP1, were identified using machine learning algorithms. In vitro experiments demonstrated SH3KBP1's crucial role in cell migration and invasion.</div></div><div><h3>Conclusion</h3><div>This study unravels the gene expression and regulatory mechanisms of IH at different stages, providing new insights into its pathophysiology. SH3KBP1 offers a potential biomarker for future diagnostic and therapeutic strategies.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"752 ","pages":"Article 151469"},"PeriodicalIF":2.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420264","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 : 2025-02-09DOI: 10.1016/j.bbrc.2025.151445
Silvia Gleitze , Omar A. Ramírez , Ignacio Vega-Vásquez , Emely Stefan , C. Peter Bengtson , Andrea Paula-Lima , Hilmar Bading , Cecilia Hidalgo
The brain constantly adapts to environmental changes by modifying the expression of genes that enable synaptic plasticity, learning and memory. The expression of several of these genes requires nuclear calcium (Ca2+) signals, which in turn requires that Ca2+ signals generated by neuronal activity at the synapses or the soma propagate to the nucleus. Since cytoplasmic Ca2+ diffusion is highly restricted, Ca2+ signal propagation to the nucleus requires the participation of other cellular mechanisms. The inositol trisphosphate receptor (IP3R) and the ryanodine receptor (RyR) channels, both of which reside in the endoplasmic reticulum (ER) membrane, play key roles in cellular Ca2+ signal generation. Yet, their roles in the generation of nuclear and mitochondrial Ca2+ signals induced by neuronal activity require further investigation. Here, the impact of IP3R1 or RyR2 knockdown on gabazine-induced nuclear and mitochondrial Ca2+ signals in neurons was evaluated. To this aim, recombinant adeno-associated viruses (rAAVs) were used to introduce small hairpin RNAs (shRNAs) to knockdown type-1 (IP3R1) and type-2 (RyR2) channel expression in cultured rat hippocampal neurons. Additionally, synaptic contact numbers were assessed through immunocytochemistry. Knockdown of IP3R1 or RyR2 channels significantly reduced their protein contents and the generation of gabazine-induced nuclear and mitochondrial Ca2+ signals, without altering synaptic contact numbers. Our results highlight the contribution of IP3R1 and RyR2 channels to the generation of nuclear and mitochondrial Ca2+ signal induced by neuronal activity, reinforcing the role that these Ca2+ release channels play in hippocampal synaptic plasticity and memory formation.
{"title":"Calcium release via IP3R/RyR channels contributes to the nuclear and mitochondrial Ca2+ signals elicited by neuronal stimulation","authors":"Silvia Gleitze , Omar A. Ramírez , Ignacio Vega-Vásquez , Emely Stefan , C. Peter Bengtson , Andrea Paula-Lima , Hilmar Bading , Cecilia Hidalgo","doi":"10.1016/j.bbrc.2025.151445","DOIUrl":"10.1016/j.bbrc.2025.151445","url":null,"abstract":"<div><div>The brain constantly adapts to environmental changes by modifying the expression of genes that enable synaptic plasticity, learning and memory. The expression of several of these genes requires nuclear calcium (Ca<sup>2+</sup>) signals, which in turn requires that Ca<sup>2+</sup> signals generated by neuronal activity at the synapses or the soma propagate to the nucleus. Since cytoplasmic Ca<sup>2+</sup> diffusion is highly restricted, Ca<sup>2+</sup> signal propagation to the nucleus requires the participation of other cellular mechanisms. The inositol trisphosphate receptor (IP<sub>3</sub>R) and the ryanodine receptor (RyR) channels, both of which reside in the endoplasmic reticulum (ER) membrane, play key roles in cellular Ca<sup>2+</sup> signal generation. Yet, their roles in the generation of nuclear and mitochondrial Ca<sup>2+</sup> signals induced by neuronal activity require further investigation. Here, the impact of IP<sub>3</sub>R1 or RyR2 knockdown on gabazine-induced nuclear and mitochondrial Ca<sup>2+</sup> signals in neurons was evaluated. To this aim, recombinant adeno-associated viruses (rAAVs) were used to introduce small hairpin RNAs (shRNAs) to knockdown type-1 (IP<sub>3</sub>R1) and type-2 (RyR2) channel expression in cultured rat hippocampal neurons. Additionally, synaptic contact numbers were assessed through immunocytochemistry. Knockdown of IP<sub>3</sub>R1 or RyR2 channels significantly reduced their protein contents and the generation of gabazine-induced nuclear and mitochondrial Ca<sup>2+</sup> signals, without altering synaptic contact numbers. Our results highlight the contribution of IP<sub>3</sub>R1 and RyR2 channels to the generation of nuclear and mitochondrial Ca<sup>2+</sup> signal induced by neuronal activity, reinforcing the role that these Ca<sup>2+</sup> release channels play in hippocampal synaptic plasticity and memory formation.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"754 ","pages":"Article 151445"},"PeriodicalIF":2.5,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512711","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 : 2025-02-09DOI: 10.1016/j.bbrc.2025.151468
Yuka Takahashi , Trieu Tu San , Md Imran Nur Manik , Shamsul Morshed , Takashi Ushimaru
Atg1/ULK1 protein kinase induces macroautophagy, but not microautophagy, after nutrient starvation and inactivation of target of rapamycin complex 1 (TORC1) protein kinase. Microautophagy is also induced by TORC1 inactivation, but a TORC1-downstream protein kinase responsible for microautophagy induction remains obscure. Here, we show that the Greatwall kinase Rim15, a downstream protein kinase of TORC1, promotes bulk microautophagy induction after TORC1 inactivation. In addition, Rim15 was required for proper induction of microlipophagy (microautophagic degradation of lipid droplet). Endosomal sorting complex required for transport (ESCRT) machinery is recruited onto the vacuolar membrane after TORC1 inactivation for microautophagy. Loss of Rim15 reduced protein levels of subunits (Vps27 and Hse1) of ESCRT-0, a primary ESCRT subcomplex. Consistently, the recruitment of ESCRT-0 onto the vacuolar membrane after rapamycin was reduced in rim15Δ cells. On the other hand, Rim15 was dispensable for ESCRT function in multivesicular body formation. This study reveals that Rim15 specifically regulates function of ESCRT-0 in microautophagy under the control of TORC1 and provides a new insight into lipophagy-related human diseases.
{"title":"The Greatwall kinase Rim15 promotes microautophagy and microlipophagy under the control of TORC1","authors":"Yuka Takahashi , Trieu Tu San , Md Imran Nur Manik , Shamsul Morshed , Takashi Ushimaru","doi":"10.1016/j.bbrc.2025.151468","DOIUrl":"10.1016/j.bbrc.2025.151468","url":null,"abstract":"<div><div>Atg1/ULK1 protein kinase induces macroautophagy, but not microautophagy, after nutrient starvation and inactivation of target of rapamycin complex 1 (TORC1) protein kinase. Microautophagy is also induced by TORC1 inactivation, but a TORC1-downstream protein kinase responsible for microautophagy induction remains obscure. Here, we show that the Greatwall kinase Rim15, a downstream protein kinase of TORC1, promotes bulk microautophagy induction after TORC1 inactivation. In addition, Rim15 was required for proper induction of microlipophagy (microautophagic degradation of lipid droplet). Endosomal sorting complex required for transport (ESCRT) machinery is recruited onto the vacuolar membrane after TORC1 inactivation for microautophagy. Loss of Rim15 reduced protein levels of subunits (Vps27 and Hse1) of ESCRT-0, a primary ESCRT subcomplex. Consistently, the recruitment of ESCRT-0 onto the vacuolar membrane after rapamycin was reduced in <em>rim15Δ</em> cells. On the other hand, Rim15 was dispensable for ESCRT function in multivesicular body formation. This study reveals that Rim15 specifically regulates function of ESCRT-0 in microautophagy under the control of TORC1 and provides a new insight into lipophagy-related human diseases.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"752 ","pages":"Article 151468"},"PeriodicalIF":2.5,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395626","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}
Circadian rhythm alterations are related to the onset and severity of various diseases. The expression of the dopamine receptor D3 (DRD3) is regulated by clock genes, and DRD3 functional abnormalities are linked to various neurological diseases. However, the relationship between DRD3 function and circadian machinery is unclear. Here, we demonstrate the influence of DRD3 on the circadian machinery. Although the expression of DRD3 in mouse suprachiasmatic nucleus (SCN) did not show a circadian rhythm, the expression of Per1 mRNA was altered in the SCN of Drd3 knockout (Drd3−/−) mice compared to that in wild-type (WT) mice. These differences were caused by the upregulation of the DRD3–extracellular signal–regulated kinase–cAMP response element binding protein (DRD3–ERK–CREB) signaling pathway in cultured cells and SCN. In addition, Drd3−/− mice demonstrated increased period length of locomotor activity than WT mice only under constant dark conditions. Expression of clock genes in the liver, which does not express DRD3, was affected by the loss of DRD3 only under constant dark conditions, similar to that in the SCN. These results suggest that DRD3 expressed in the SCN regulates the central clock via endogenous ligands and affects peripheral organs. This may provide new evidence to unravel the relationship between dopamine neurotransmission and the circadian clock, which has not yet been fully elucidated.
{"title":"Dopamine receptor D3 affects the expression of Period1 in mouse cells via DRD3–ERK–CREB signaling","authors":"Masaki Matsuda , Takumi Nishi , Yuya Yoshida , Yuma Terada , Chihiro Matsuda-Hayama , Taisei Kumamoto , Kengo Hamamura , Eriko Kohro-Ikeda , Shinobu Yasuo , Satoru Koyanagi , Naoya Matsunaga , Shigehiro Ohdo","doi":"10.1016/j.bbrc.2025.151470","DOIUrl":"10.1016/j.bbrc.2025.151470","url":null,"abstract":"<div><div>Circadian rhythm alterations are related to the onset and severity of various diseases. The expression of the dopamine receptor D3 (DRD3) is regulated by clock genes, and DRD3 functional abnormalities are linked to various neurological diseases. However, the relationship between DRD3 function and circadian machinery is unclear. Here, we demonstrate the influence of DRD3 on the circadian machinery. Although the expression of DRD3 in mouse suprachiasmatic nucleus (SCN) did not show a circadian rhythm, the expression of <em>Per1</em> mRNA was altered in the SCN of <em>Drd3</em> knockout (<em>Drd3</em><sup><em>−/−</em></sup>) mice compared to that in wild-type (WT) mice. These differences were caused by the upregulation of the DRD3–extracellular signal–regulated kinase–cAMP response element binding protein (DRD3–ERK–CREB) signaling pathway in cultured cells and SCN. In addition, <em>Drd3</em><sup><em>−/−</em></sup> mice demonstrated increased period length of locomotor activity than WT mice only under constant dark conditions. Expression of clock genes in the liver, which does not express DRD3, was affected by the loss of DRD3 only under constant dark conditions, similar to that in the SCN. These results suggest that DRD3 expressed in the SCN regulates the central clock via endogenous ligands and affects peripheral organs. This may provide new evidence to unravel the relationship between dopamine neurotransmission and the circadian clock, which has not yet been fully elucidated.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"752 ","pages":"Article 151470"},"PeriodicalIF":2.5,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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