Light-induced retinal damage is a significant contributor to age-related macular degeneration (AMD). Qihuang granule (QHG), a traditional Chinese herbal formulation, has been clinically employed in the treatment of retinal diseases, including AMD; however, the precise protective mechanisms remain unclear. This study investigated the protective effects and underlying mechanisms of QHG using a rat model of blue light-induced retinal injury and a human retinal pigment epithelial (ARPE-19) cell model. The results demonstrated that QHG significantly alleviated retinal morphological abnormalities, ultrastructural damage, and apoptosis induced by light exposure. Single-cell RNA sequencing further revealed that specific cell clusters were notably enriched in the PI3K-AKT-mTOR and autophagy-related signaling pathways after QHG treatment, characterized by increased MAP1LC3B (LC3B) expression and decreased SQSTM1 (P62) expression. Validation at the protein and gene levels in vivo confirmed that QHG activated the autophagy pathway by downregulating PI3K, AKT, mTOR, and P62 expression while upregulating LC3B expression. Collectively, this study demonstrates that QHG protects against retinal photodamage by modulating autophagy via the PI3K/AKT/mTOR signaling pathway, providing theoretical support for its clinical application in the treatment of AMD.
{"title":"Integrative single-cell transcriptomic and experimental analyses unveil Qihuang granule's protection against retinal photodamage via PI3K/AKT/mTOR-mediated autophagy","authors":"Zhao Zhang , Xiaoqian Shan , Fengming Liang , Lulu Fang","doi":"10.1016/j.biocel.2025.106881","DOIUrl":"10.1016/j.biocel.2025.106881","url":null,"abstract":"<div><div>Light-induced retinal damage is a significant contributor to age-related macular degeneration (AMD). Qihuang granule (QHG), a traditional Chinese herbal formulation, has been clinically employed in the treatment of retinal diseases, including AMD; however, the precise protective mechanisms remain unclear. This study investigated the protective effects and underlying mechanisms of QHG using a rat model of blue light-induced retinal injury and a human retinal pigment epithelial (ARPE-19) cell model. The results demonstrated that QHG significantly alleviated retinal morphological abnormalities, ultrastructural damage, and apoptosis induced by light exposure. Single-cell RNA sequencing further revealed that specific cell clusters were notably enriched in the PI3K-AKT-mTOR and autophagy-related signaling pathways after QHG treatment, characterized by increased MAP1LC3B (LC3B) expression and decreased SQSTM1 (P62) expression. Validation at the protein and gene levels in vivo confirmed that QHG activated the autophagy pathway by downregulating PI3K, AKT, mTOR, and P62 expression while upregulating LC3B expression. Collectively, this study demonstrates that QHG protects against retinal photodamage by modulating autophagy via the PI3K/AKT/mTOR signaling pathway, providing theoretical support for its clinical application in the treatment of AMD.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"190 ","pages":"Article 106881"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624676","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 : 2026-01-01Epub Date: 2025-11-18DOI: 10.1016/j.biocel.2025.106880
Honglin Feng , Xinyi Cao , Yong You , Kengliang Rao , Hongjia Chen , Qing Chen , Li Chen
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by diffuse lung inflammation and edema, with diffuse alveolar damage as the hallmark pathology. Paxillin plays a crucial role in the signaling pathways that regulate inflammatory responses. However, its involvement in modulating nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation and its impact on lung epithelial integrity remain largely unexplored. Hematoxylin and eosin staining, immunohistochemistry, and Western blot (WB) analysis were performed. In the present study, lipopolysaccharide (LPS) stimulation significantly upregulated paxillin expression and phosphorylation concomitant with NLRP3 inflammasome activation. Co-immunoprecipitation was performed to assess the interaction between paxillin and NLRP3. To further explore the role of paxillin, a lentiviral knockdown approach was used to downregulate its expression. Paxillin knockdown attenuated the NLRP3 inflammasome-mediated inflammatory response in LPS-induced ALI/ARDS, leading to enhanced epithelial cell migration and improved wound healing capacity. In conclusion, paxillin plays a key role in regulating inflammation mediated by NLRP3 inflammasome. Overall, suppression of Paxillin expression provides protection by alleviating LPS-induced inflammation and promoting epithelial repair, thus highlighting its potential as a therapeutic target for ALI/ARDS.
{"title":"Paxillin mediates lung epithelial injury by activating NLRP3 inflammasomes in an acute respiratory distress syndrome mouse model","authors":"Honglin Feng , Xinyi Cao , Yong You , Kengliang Rao , Hongjia Chen , Qing Chen , Li Chen","doi":"10.1016/j.biocel.2025.106880","DOIUrl":"10.1016/j.biocel.2025.106880","url":null,"abstract":"<div><div>Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by diffuse lung inflammation and edema, with diffuse alveolar damage as the hallmark pathology. Paxillin plays a crucial role in the signaling pathways that regulate inflammatory responses. However, its involvement in modulating nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation and its impact on lung epithelial integrity remain largely unexplored. Hematoxylin and eosin staining, immunohistochemistry, and Western blot (WB) analysis were performed. In the present study, lipopolysaccharide (LPS) stimulation significantly upregulated paxillin expression and phosphorylation concomitant with NLRP3 inflammasome activation. Co-immunoprecipitation was performed to assess the interaction between paxillin and NLRP3. To further explore the role of paxillin, a lentiviral knockdown approach was used to downregulate its expression. Paxillin knockdown attenuated the NLRP3 inflammasome-mediated inflammatory response in LPS-induced ALI/ARDS, leading to enhanced epithelial cell migration and improved wound healing capacity. In conclusion, paxillin plays a key role in regulating inflammation mediated by NLRP3 inflammasome. Overall, suppression of Paxillin expression provides protection by alleviating LPS-induced inflammation and promoting epithelial repair, thus highlighting its potential as a therapeutic target for ALI/ARDS.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"190 ","pages":"Article 106880"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565531","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 : 2025-12-01Epub Date: 2025-09-16DOI: 10.1016/j.biocel.2025.106863
Wei Huang , Guanhua Deng , Qinghua Zhang, Fengquan Lv, Dehuan Xie, Chen Ren, Shasha Du, Peixin Tan
<div><h3>Background</h3><div>Radiation induced lung injury (RILI) is a common complication in patients undergoing thoracic radiotherapy. At present, there are no effective early diagnostic biomarkers, and clinical treatment methods are very limited, which poses a huge challenge to the management of cancer patients. Oxidative stress has been recognized as a key mediator of aging and disease. Therefore, this study integrated multiple omics data in mice and advanced bioinformatics and machine learning methods to systematically analyze the molecular features associated with oxidative stress, and screened for clinically relevant biomarkers and molecular mechanisms of RILI. This study aims to provide a timely and practical theoretical basis for the early diagnosis and targeted intervention of RILI.</div></div><div><h3>Method</h3><div>We implemented a comprehensive approach that integrated both bulk RNA and single-cell RNA sequencing analyses, utilizing advanced bioinformatics methodologies. These encompassed techniques aimed at eliminating batch effects to facilitate smooth data integration, executing differential expression analyses, and applying weighted gene co-expression network analysis (WGCNA). Furthermore, we developed a diagnostic model for RILI utilizing random forest and support vector machine (SVM) algorithms. We also conducted Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). To evaluate immune cell infiltration, we employed Single-Sample Gene-Set Enrichment Analysis (ssGSEA) alongside the CIBERSORT algorithm. We then investigated the expression and interactions of module genes across various cell populations utilizing data derived from single-cell RNA sequencing. Ultimately, the expression of module genes in irradiated lung tissues were validate by reverse transcription–polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC).</div></div><div><h3>Results</h3><div>Our study identified a total of 286 differentially expressed genes (DEGs). Among these, we confirmed 61 genes related to oxidative stress (OSRDEGs). We constructed nine co-expression modules, four of which showed a significant association with RILI, encompassing 53 genes from these modules. A diagnostic model with AUC over 0.9 was constructed and further refined to include five key genes: Stk4, Aaas, Ets1, Sesn2, and Kit, which were validated for accuracy through LASSO regression. The model genes were found to be enriched in crucial pathways, particularly the MAPK signaling pathway. A direct relationship between Ets1 and Kit was found, which extended to 20 functionally similar proteins identified through GeneMANIA. Additionally, we noted significant changes in the infiltration patterns of 13 immune cell types, including Activated B cells and Activated CD4 T cells. Sens2 and Kit were found highly expressed in granulocytes and endothelial cells, respectively. In mouse models of RILI, Sesn2 and Aaas were significantl
{"title":"Integrated bulk and single-cell RNA sequencing identifies oxidative stress signatures of radiation-induced lung injury in mice through machine learning","authors":"Wei Huang , Guanhua Deng , Qinghua Zhang, Fengquan Lv, Dehuan Xie, Chen Ren, Shasha Du, Peixin Tan","doi":"10.1016/j.biocel.2025.106863","DOIUrl":"10.1016/j.biocel.2025.106863","url":null,"abstract":"<div><h3>Background</h3><div>Radiation induced lung injury (RILI) is a common complication in patients undergoing thoracic radiotherapy. At present, there are no effective early diagnostic biomarkers, and clinical treatment methods are very limited, which poses a huge challenge to the management of cancer patients. Oxidative stress has been recognized as a key mediator of aging and disease. Therefore, this study integrated multiple omics data in mice and advanced bioinformatics and machine learning methods to systematically analyze the molecular features associated with oxidative stress, and screened for clinically relevant biomarkers and molecular mechanisms of RILI. This study aims to provide a timely and practical theoretical basis for the early diagnosis and targeted intervention of RILI.</div></div><div><h3>Method</h3><div>We implemented a comprehensive approach that integrated both bulk RNA and single-cell RNA sequencing analyses, utilizing advanced bioinformatics methodologies. These encompassed techniques aimed at eliminating batch effects to facilitate smooth data integration, executing differential expression analyses, and applying weighted gene co-expression network analysis (WGCNA). Furthermore, we developed a diagnostic model for RILI utilizing random forest and support vector machine (SVM) algorithms. We also conducted Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). To evaluate immune cell infiltration, we employed Single-Sample Gene-Set Enrichment Analysis (ssGSEA) alongside the CIBERSORT algorithm. We then investigated the expression and interactions of module genes across various cell populations utilizing data derived from single-cell RNA sequencing. Ultimately, the expression of module genes in irradiated lung tissues were validate by reverse transcription–polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC).</div></div><div><h3>Results</h3><div>Our study identified a total of 286 differentially expressed genes (DEGs). Among these, we confirmed 61 genes related to oxidative stress (OSRDEGs). We constructed nine co-expression modules, four of which showed a significant association with RILI, encompassing 53 genes from these modules. A diagnostic model with AUC over 0.9 was constructed and further refined to include five key genes: Stk4, Aaas, Ets1, Sesn2, and Kit, which were validated for accuracy through LASSO regression. The model genes were found to be enriched in crucial pathways, particularly the MAPK signaling pathway. A direct relationship between Ets1 and Kit was found, which extended to 20 functionally similar proteins identified through GeneMANIA. Additionally, we noted significant changes in the infiltration patterns of 13 immune cell types, including Activated B cells and Activated CD4 T cells. Sens2 and Kit were found highly expressed in granulocytes and endothelial cells, respectively. In mouse models of RILI, Sesn2 and Aaas were significantl","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"189 ","pages":"Article 106863"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087980","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 : 2025-12-01Epub Date: 2025-09-19DOI: 10.1016/j.biocel.2025.106864
Chloé Richard , Charlène Pourpe , Guillaume Fourneaux , Gwendal Cueff , Laurent Parry , Cécile Coudy-Gandilhon , Jonas Kindberg , Alina L. Evans , Andrea Miller , Guillemette Gauquelin-Koch , Christophe Tatout , Cécile Polge , Daniel Taillandier , Fabrice Bertile , Etienne Lefai , Lydie Combaret
Muscle atrophy is observed in several pathophysiological situations, including physical inactivity, leading to negative health consequences, without any effective treatment currently available. Conversely, brown bears resist muscle atrophy during hibernation, despite prolonged physical inactivity and fasting. We previously reported that hibernating brown bear serum increases protein content in human myotubes and inhibits proteolysis. To go further, we deciphered here the transcriptional effects of brown bear serum in human myotubes using large-scale transcriptomics. After 48 h, the winter-hibernating bear serum (WBS) induced a specific transcriptomic program, affecting mostly biological pathways related to muscle growth and BMP signalling, compared to the summer-active bear (SBS) serum. WBS predominantly reduced, at mRNA and protein levels, activators and inhibitors of BMP signalling, which is associated with muscle mass maintenance. Moreover, BMP activity was more responsive to a stimulation by BMP7 at supra-physiological concentrations in human myotubes cultured in WBS versus SBS conditions. Meanwhile, WBS also up-regulated expression of genes encoding repressors of the pro-atrophic TGF-β pathway, decreased phosphorylated SMAD3 nuclear protein levels, and down-regulated TGF-β target genes. Furthermore, WBS treatment resulted in reduced TGF-β signalling responsiveness in human myotubes stimulated with TGF-β3 at physiological concentrations. Overall, even though WBS induced larger transcriptomic changes in the BMP compared to TGF-β pathway, the functional consequences were more pronounced for the TGF-β pathway with a marked inhibition. This study suggests that bioactive compounds in WBS may protect human muscle cells during catabolic situations, by regulating the TGF-β/BMP balance. These findings open new perspectives for therapies targeting muscle atrophy.
{"title":"Hibernating brown bear serum modulates the balance of TGF-β and BMP pathways in human muscle cells","authors":"Chloé Richard , Charlène Pourpe , Guillaume Fourneaux , Gwendal Cueff , Laurent Parry , Cécile Coudy-Gandilhon , Jonas Kindberg , Alina L. Evans , Andrea Miller , Guillemette Gauquelin-Koch , Christophe Tatout , Cécile Polge , Daniel Taillandier , Fabrice Bertile , Etienne Lefai , Lydie Combaret","doi":"10.1016/j.biocel.2025.106864","DOIUrl":"10.1016/j.biocel.2025.106864","url":null,"abstract":"<div><div>Muscle atrophy is observed in several pathophysiological situations, including physical inactivity, leading to negative health consequences, without any effective treatment currently available. Conversely, brown bears resist muscle atrophy during hibernation, despite prolonged physical inactivity and fasting. We previously reported that hibernating brown bear serum increases protein content in human myotubes and inhibits proteolysis. To go further, we deciphered here the transcriptional effects of brown bear serum in human myotubes using large-scale transcriptomics. After 48 h, the winter-hibernating bear serum (WBS) induced a specific transcriptomic program, affecting mostly biological pathways related to muscle growth and BMP signalling, compared to the summer-active bear (SBS) serum. WBS predominantly reduced, at mRNA and protein levels, activators and inhibitors of BMP signalling, which is associated with muscle mass maintenance. Moreover, BMP activity was more responsive to a stimulation by BMP7 at supra-physiological concentrations in human myotubes cultured in WBS versus SBS conditions. Meanwhile, WBS also up-regulated expression of genes encoding repressors of the pro-atrophic TGF-β pathway, decreased phosphorylated SMAD3 nuclear protein levels, and down-regulated TGF-β target genes. Furthermore, WBS treatment resulted in reduced TGF-β signalling responsiveness in human myotubes stimulated with TGF-β3 at physiological concentrations. Overall, even though WBS induced larger transcriptomic changes in the BMP compared to TGF-β pathway, the functional consequences were more pronounced for the TGF-β pathway with a marked inhibition. This study suggests that bioactive compounds in WBS may protect human muscle cells during catabolic situations, by regulating the TGF-β/BMP balance. These findings open new perspectives for therapies targeting muscle atrophy.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"189 ","pages":"Article 106864"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096627","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 : 2025-12-01Epub Date: 2025-09-04DOI: 10.1016/j.biocel.2025.106861
Meiqi Sun , Hua Fang , Jiashu Zhang , Mengyao Wang , Peng Jiang , LiLi Ma , Huanyu Jin , Wei Zhang
Silicosis is a fatal occupational lung disease characterized by persistent inflammation and irreversible fibrosis. However, the pathogenesis of silicosis is currently unclear. In this study, a mouse model of silicosis was established by intranasal instillation of silica, and transcriptomic alterations in lung tissues were assessed by mRNA-sequencing. Cholesterol 25-hydroxylase (Ch25h) was upregulated in silicotic lung tissues and alveolar macrophages. Lentivirus-mediated Ch25h knockdown was then employed to assess its functional role in vivo. It was found that Ch25h knockdown alleviated associated pathological changes, including pulmonary injury and fibrosis. Additionally, Ch25h significantly modulated NLRP3 inflammasome activity in vivo and in vitro. Knockdown of Ch25h inhibited the secretion of inflammatory factor (IL-1α, IL-1β, and IL-18), decreased the protein level of cleaved caspase-1 and GSDMD-N in macrophages, and reduced potassium ion efflux and lactate dehydrogenase (LDH) release. Notably, ASC (apoptosis-related spotted protein) oligomerization was suppressed by Ch25h downregulation, suggesting that Ch25h was required for the inflammasome assembly. Our findings suggest that Ch25h may contribute to silicosis development by regulating NLRP3 inflammasome activation and pyroptosis, warranting further investigation as a possible therapeutic target.
{"title":"Resistance to silicosis progression in mice with Ch25h downregulation: The involvement of NLRP3 inflammasome","authors":"Meiqi Sun , Hua Fang , Jiashu Zhang , Mengyao Wang , Peng Jiang , LiLi Ma , Huanyu Jin , Wei Zhang","doi":"10.1016/j.biocel.2025.106861","DOIUrl":"10.1016/j.biocel.2025.106861","url":null,"abstract":"<div><div>Silicosis is a fatal occupational lung disease characterized by persistent inflammation and irreversible fibrosis. However, the pathogenesis of silicosis is currently unclear. In this study, a mouse model of silicosis was established by intranasal instillation of silica, and transcriptomic alterations in lung tissues were assessed by mRNA-sequencing. Cholesterol 25-hydroxylase (Ch25h) was upregulated in silicotic lung tissues and alveolar macrophages. Lentivirus-mediated Ch25h knockdown was then employed to assess its functional role in vivo. It was found that Ch25h knockdown alleviated associated pathological changes, including pulmonary injury and fibrosis. Additionally, Ch25h significantly modulated NLRP3 inflammasome activity in vivo and in vitro. Knockdown of Ch25h inhibited the secretion of inflammatory factor (IL-1α, IL-1β, and IL-18), decreased the protein level of cleaved caspase-1 and GSDMD-N in macrophages, and reduced potassium ion efflux and lactate dehydrogenase (LDH) release. Notably, ASC (apoptosis-related spotted protein) oligomerization was suppressed by Ch25h downregulation, suggesting that Ch25h was required for the inflammasome assembly. Our findings suggest that Ch25h may contribute to silicosis development by regulating NLRP3 inflammasome activation and pyroptosis, warranting further investigation as a possible therapeutic target.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"189 ","pages":"Article 106861"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005125","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}
Coelonin is a dihydrophenanthrene compound derived from the traditional Chinese medicine Bletilla striata (Thunb.) Reichb.f., which exhibits significant anti-inflammatory activity and effectively inhibits lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells. Although previous studies have demonstrated the protective effect of Bletilla striata against LPS-induced acute lung injury (ALI), the potential protective role and underlying molecular mechanisms of its major active component, Coelonin, in ALI remain unclear. In this study, an LPS-induced mouse ALI model was established to systematically evaluate the protective effects of Coelonin on ALI. Furthermore, transcriptomic analysis was utilized to investigate the anti-inflammatory mechanisms mediated by Coelonin through the regulation of non-coding RNA (ncRNA)-associated inflammatory pathways. The results indicated that Coelonin significantly ameliorated LPS-induced pathological damage in lung tissues and markedly reduced the levels of inflammatory markers in bronchoalveolar lavage fluid (BALF). In vitro experiments using the murine alveolar macrophages (MH-S) cell line further confirmed the anti-inflammatory activity of Coelonin. Transcriptome analysis revealed that Coelonin markedly upregulates the expression of the ncRNA Gm27505, which was previously found to be downregulated in a mouse model of Alzheimer's disease. To date, there have been no reports on the biological functions of Gm27505. Bioinformatics analysis and real-time quantitative fluorescence PCR (qPCR) confirmed that this ncRNA is primarily localized within the nucleus. Overexpression of Gm27505 in MH-S cells significantly downregulated the expression of inflammation-related genes such as Il6, Tnfα, Il27, and Ccl3 induced by LPS stimulation. Moreover, overexpression of Gm27505 promoted macrophage polarization toward the M2 phenotype while suppressing M1 polarization. These findings suggest that the ncRNA Gm27505 plays an important biological role and is critically involved in the regulation of inflammatory responses. Coelonin may alleviate LPS-induced ALI in mice by up-regulating Gm27505 expression and modulating macrophage polarization. Therefore, Gm27505 may represent a potential target for the prevention and treatment of ALI, providing new research directions for future therapeutic strategies against related diseases.
{"title":"Coelonin, an active component extract from Bletilla striata (Thunb.) Reichb.f., alleviates lipopolysaccharide-induced acute lung injury by increasing the expression of non-coding RNA Gm27505 and inhibiting the M1 polarization of macrophages caused by inflammatory responses","authors":"Run-ze Qin , Su-yu Peng , Zi-xin Huang , Bo-fei Zhang , Ruo-nan Tang , Yu-cong Zhao , Fu-sheng Jiang , Xiao-hua Xu , Jie-li Pan , Mei-ya Li","doi":"10.1016/j.biocel.2025.106871","DOIUrl":"10.1016/j.biocel.2025.106871","url":null,"abstract":"<div><div>Coelonin is a dihydrophenanthrene compound derived from the traditional Chinese medicine <em>Bletilla striata</em> (Thunb.) Reichb.f., which exhibits significant anti-inflammatory activity and effectively inhibits lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells. Although previous studies have demonstrated the protective effect of <em>Bletilla striata</em> against LPS-induced acute lung injury (ALI), the potential protective role and underlying molecular mechanisms of its major active component, Coelonin, in ALI remain unclear. In this study, an LPS-induced mouse ALI model was established to systematically evaluate the protective effects of Coelonin on ALI. Furthermore, transcriptomic analysis was utilized to investigate the anti-inflammatory mechanisms mediated by Coelonin through the regulation of non-coding RNA (ncRNA)-associated inflammatory pathways. The results indicated that Coelonin significantly ameliorated LPS-induced pathological damage in lung tissues and markedly reduced the levels of inflammatory markers in bronchoalveolar lavage fluid (BALF). <em>In vitro</em> experiments using the murine alveolar macrophages (MH-S) cell line further confirmed the anti-inflammatory activity of Coelonin. Transcriptome analysis revealed that Coelonin markedly upregulates the expression of the ncRNA Gm27505, which was previously found to be downregulated in a mouse model of Alzheimer's disease. To date, there have been no reports on the biological functions of Gm27505. Bioinformatics analysis and real-time quantitative fluorescence PCR (qPCR) confirmed that this ncRNA is primarily localized within the nucleus. Overexpression of Gm27505 in MH-S cells significantly downregulated the expression of inflammation-related genes such as <em>Il6</em>, <em>Tnfα</em>, <em>Il27,</em> and <em>Ccl3</em> induced by LPS stimulation. Moreover, overexpression of Gm27505 promoted macrophage polarization toward the M2 phenotype while suppressing M1 polarization. These findings suggest that the ncRNA Gm27505 plays an important biological role and is critically involved in the regulation of inflammatory responses. Coelonin may alleviate LPS-induced ALI in mice by up-regulating Gm27505 expression and modulating macrophage polarization. Therefore, Gm27505 may represent a potential target for the prevention and treatment of ALI, providing new research directions for future therapeutic strategies against related diseases.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"189 ","pages":"Article 106871"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330724","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 : 2025-12-01Epub Date: 2025-09-23DOI: 10.1016/j.biocel.2025.106867
Linshan Xie , Rong Xu , Huining Liu , Man Na , Qikai Qin , Fei Xu , Raymond C. Stevens , Yan Liu
The biased agonism of glucagon-like peptide-1 receptor (GLP-1R) plays a key role in the efficacy and side effects of drugs used to treat type II diabetes mellitus and obesity. Despite its therapeutic potential, the mechanisms underlying GLP-1R biased agonism remain poorly understood. In this study, we investigate the role of the extracellular domain (ECD) in GLP-1R signaling bias through saturation mutagenesis at seven key sites. We examined 126 mutations and identified several that selectively abolished β-arrestin recruitment while retaining cAMP production. Additionally, we employed a large language model (LLM) to interpret the functional impacts of these mutations, uncovering correlations between sequence features and signaling outcome. These findings provide new insight into the "two-domain" model of class B1 G protein-coupled receptors (GPCRs), highlighting the ECD's role in biased agonism and offering novel information for designing more effective and selective GLP-1R agonists.
{"title":"Characterizing the role of extracellular domain in GLP-1R biased agonism","authors":"Linshan Xie , Rong Xu , Huining Liu , Man Na , Qikai Qin , Fei Xu , Raymond C. Stevens , Yan Liu","doi":"10.1016/j.biocel.2025.106867","DOIUrl":"10.1016/j.biocel.2025.106867","url":null,"abstract":"<div><div>The biased agonism of glucagon-like peptide-1 receptor (GLP-1R) plays a key role in the efficacy and side effects of drugs used to treat type II diabetes mellitus and obesity. Despite its therapeutic potential, the mechanisms underlying GLP-1R biased agonism remain poorly understood. In this study, we investigate the role of the extracellular domain (ECD) in GLP-1R signaling bias through saturation mutagenesis at seven key sites. We examined 126 mutations and identified several that selectively abolished β-arrestin recruitment while retaining cAMP production. Additionally, we employed a large language model (LLM) to interpret the functional impacts of these mutations, uncovering correlations between sequence features and signaling outcome. These findings provide new insight into the \"two-domain\" model of class B1 G protein-coupled receptors (GPCRs), highlighting the ECD's role in biased agonism and offering novel information for designing more effective and selective GLP-1R agonists.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"189 ","pages":"Article 106867"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151893","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 : 2025-12-01Epub Date: 2025-11-28DOI: 10.1016/j.biocel.2025.106877
Meiqi Sun , Hua Fang , Jiashu Zhang , Mengyao Wang , Peng Jiang , LiLi Ma , Huanyu Jin , Wei Zhang
{"title":"Corrigendum to “Resistance to silicosis progression in mice with Ch25h downregulation: The involvement of NLRP3 inflammasome” [Int. J. Biochem. Cell Biol. 189 (2025) 106861]","authors":"Meiqi Sun , Hua Fang , Jiashu Zhang , Mengyao Wang , Peng Jiang , LiLi Ma , Huanyu Jin , Wei Zhang","doi":"10.1016/j.biocel.2025.106877","DOIUrl":"10.1016/j.biocel.2025.106877","url":null,"abstract":"","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"189 ","pages":"Article 106877"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684571","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 : 2025-12-01Epub Date: 2025-09-23DOI: 10.1016/j.biocel.2025.106866
Yongwei Du , Fangtian Xu , Shengwang Miao , Bo Zhou , Jianwen Mo , Zhen Liu
<div><h3>Background</h3><div>Ferroptosis occurs in osteoblasts in a diabetic environment, which impairs osteoblast number and function, promotes osteoblast death, destroys bone homeostasis, and eventually contributes to type 2 diabetic osteoporosis (T2DOP). Chromobox protein homolog 7 (CBX7) deficiency plays a positive role in bone formation and skeletal development. Besides, CBX7 interference has been reported to protect against disease development by inhibiting ferroptosis. This study focuses on determining whether CBX7 is involved in the progression of T2DOP by regulating osteoblast ferroptosis and explore the underlying mechanism.</div></div><div><h3>Methods</h3><div>The bone tissues of 28 patients with T2DOP (the research group) and severe bone trauma (the control group) were collected, and CBX7 expression in bone tissues was detected through RT-qPCR and western blotting. Mouse pre-osteoblast MC3T3-E1 cells were treated with high glucose (HG; 25 mM) for 72 h to establish an <em>in vitro</em> model of T2DOP. The effects of CBX7 knockdown or overexpression on ferroptosis in HG-treated MC3T3-E1 cells were assessed by examining the levels of intracellular Fe<sup>2 +</sup> , lipid peroxidation, ROS, MDA, 4‑HNE, GSH, and ferroptosis regulatory proteins SLC7A11 and GPX4. The osteogenic differentiation of HG-treated MC3T3-E1 cells after knocking down or overexpressing CBX7 was assessed by performing ALP and ARS staining and measuring the levels of osteogenesis markers (ALP, RUNX2, and OCN). Whether CBX7 knockdown affects osteoblast differentiation and ferroptosis by regulating the Nrf2 pathway was validated by using the Nrf2 inhibitor ML385. Furthermore, Sprague Dawley (SD) rats were fed a high-fat diet and injected with streptozotocin to induce type 2 diabetes (T2DM), followed by the induction of T2DOP for 2 months and subsequently the determination of the anti-osteoporotic, anti-ferroptotic, and pro-osteogenic effects of CBX7 deficiency <em>in vivo</em>.</div></div><div><h3>Results</h3><div>CBX7 expression was markedly increased in the bone tissues of T2DOP patients compared to control patients. HG stimulation enhanced CBX7 expression, intracellular Fe<sup>2+</sup>, lipid peroxidation, ROS, MDA, and 4‑HNE levels but attenuated GSH, SLC7A11, and GPX4 levels in MC3T3-E1 cells. These effects of HG were reversed by CBX7 knockdown but were intensified by CBX7 overexpression. CBX7 silencing antagonized while CBX7 overexpression enhanced the inhibitory effects of HG treatment on the osteogenic differentiation of MC3T3-E1 cells. CBX7 knockdown promoted Nrf2 expression and nuclear translocation in HG-treated MC3T3-E1 cells and CBX7 showed potential protein interaction with Nrf2. The inhibition of CBX7 depletion on HG-induced ferroptosis in MC3T3-E1 cells and its promotion on the osteogenic differentiation of MC3T3-E1 cells were abrogated by ML385. Additionally, CBX7 silencing ameliorated bone mass loss and bone microstructure destruction, reduced MDA and i
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