Pub 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":"2025-11-18","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 : 2025-11-08DOI: 10.1016/j.biocel.2025.106878
Hao Liao , Xiangping Luo , Liqin Jiang
Bone mineral density (BMD) reduction is heavily involved in osteoporosis. Bone marrow mesenchymal stem cells (BMSCs) are promising candidates in the implantation treatment of bone loss-related diseases. Traditional Chinese herbs and their active components are effective in osteoporosis therapy. The effects of linoleic acid on osteogenesis and osteoporosis have been investigated in this study, revealing multifaceted findings through several analyses and experiments. A total of 41 overlapping disease-drug target genes were obtained between differentially expressed genes in osteoporosis and linoleic acid potential targets. Linoleic acid was shown to enhance BMSC osteogenic differentiation and mineralization in in vitro assays. Additionally, linoleic acid significantly countered bone loss and improved bone microstructure in a mouse model of osteoporosis induced by ovarian varixectomy (OVX) operation. Molecular docking was used to predict the interaction between linoleic acid and the top ten Hub genes. The predicted binding energy of Retinoid X Receptor Alpha (RXRA) is the lowest. Moreover, linoleic acid stimulation increased the expression of RXRA in BMSCs. Functional enrichment and pathway analysis of the overlapping potential targets highlighted their involvement in crucial biological processes and signaling pathways, including the PI3K-AKT signaling. Linoleic acid promoted the phosphorylation of PI3K and AKT. Lastly, the siRNA for RXRA knockdown and PI3K/AKT inhibitor LY294002 exerted opposite effects on BMSCs to linoleic acid, and significantly attenuated the effects of linoleic acid on BMSC osteogenic differentiation and the PI3K/AKT signaling activation, suggesting that the functions of linoleic acid might be mediated by the PI3K/AKT signaling. Moreover, linoleic acid also inhibited osteoclastogenetic differentiation. Conclusively, linoleic acid, the main active compound of Rehmanniae Radix Praeparata (RR), could promote BMSC osteogenic differentiation by enhancing the PI3K/AKT signaling activation.
{"title":"Linoleic acid promotes osteogenic differentiation of bone marrow mesenchymal stem cells and ameliorates ovariectomy (OVX)-induced osteoporosis in mice through the PI3K/AKT pathway","authors":"Hao Liao , Xiangping Luo , Liqin Jiang","doi":"10.1016/j.biocel.2025.106878","DOIUrl":"10.1016/j.biocel.2025.106878","url":null,"abstract":"<div><div>Bone mineral density (BMD) reduction is heavily involved in osteoporosis. Bone marrow mesenchymal stem cells (BMSCs) are promising candidates in the implantation treatment of bone loss-related diseases. Traditional Chinese herbs and their active components are effective in osteoporosis therapy. The effects of linoleic acid on osteogenesis and osteoporosis have been investigated in this study, revealing multifaceted findings through several analyses and experiments. A total of 41 overlapping disease-drug target genes were obtained between differentially expressed genes in osteoporosis and linoleic acid potential targets. Linoleic acid was shown to enhance BMSC osteogenic differentiation and mineralization in <em>in vitro</em> assays. Additionally, linoleic acid significantly countered bone loss and improved bone microstructure in a mouse model of osteoporosis induced by ovarian varixectomy (OVX) operation. Molecular docking was used to predict the interaction between linoleic acid and the top ten Hub genes. The predicted binding energy of Retinoid X Receptor Alpha (RXRA) is the lowest. Moreover, linoleic acid stimulation increased the expression of RXRA in BMSCs. Functional enrichment and pathway analysis of the overlapping potential targets highlighted their involvement in crucial biological processes and signaling pathways, including the PI3K-AKT signaling. Linoleic acid promoted the phosphorylation of PI3K and AKT. Lastly, the siRNA for RXRA knockdown and PI3K/AKT inhibitor LY294002 exerted opposite effects on BMSCs to linoleic acid, and significantly attenuated the effects of linoleic acid on BMSC osteogenic differentiation and the PI3K/AKT signaling activation, suggesting that the functions of linoleic acid might be mediated by the PI3K/AKT signaling. Moreover, linoleic acid also inhibited osteoclastogenetic differentiation. Conclusively, linoleic acid, the main active compound of <em>Rehmanniae Radix Praeparata</em> (RR), could promote BMSC osteogenic differentiation by enhancing the PI3K/AKT signaling activation.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"190 ","pages":"Article 106878"},"PeriodicalIF":2.8,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145490852","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 : 2025-10-31DOI: 10.1016/j.biocel.2025.106876
Jichen He , Wenhao Li , Feng Chen, Guodong Yin, Lin Tang, Qie Fan
Autophagy is a promising therapeutic target for intervertebral disc degeneration (IDD). Previous study has shown down-regulation of activator protein 2α (AP-2α) promoted proliferation and inhibited senescence and apoptosis of rat nucleus pulposus (NP) cells in IDD. This study aimed to investigate the involvement of autophagy in IDD and the regulatory mechanism of AP-2α on autophagy. Rat NP cells were exposed to varying concentrations of H2O2. A rat IDD model was constructed and injected with AP-2α low expression adeno-associated virus. To study the role of AP-2α and autophagy in IDD, we constructed an IDD cell model using H2O2 and treated NP cells with AP-2α low expression adeno-associated virus, autophagy activator rapamycin (RA) and autophagy inhibitor 3MA. In vitro, AP-2α (TFAP2A), LC3 (MAP1LC3A/B), Beclin-1 (BECN1), and p62 (Sequestosome 1, SQSTM1) levels were up-regulated after H₂O₂ treatment. In vivo, IDD increased the apoptosis degree of NP cells, but apoptosis was reduced after knockdown of AP-2α. Additionally, IDD increased AP-2α, LC3 II/I, Beclin-1, and p62 levels, but knockdown of AP-2α unblocked the autophagy flow. In vitro, H₂O₂ treatment increased AP-2α, LC3 II/I, Beclin-1, and p62 levels and NP cell apoptosis. Treatment with RA and its combined knockdown of AP-2α alleviated the dysfunction of autophagy flow and reduced the degree of apoptosis. Treatment with 3MA aggravated the dysfunction of autophagy flow and apoptosis, which can be alleviated by knockdown of AP-2α. Together, AP-2α regulated autophagy to participate in the development of IDD in vivo and rat NP cell model of IDD in vitro.
{"title":"The role of autophagy in intervertebral disc degeneration and the regulation mechanism of AP-2α on autophagy","authors":"Jichen He , Wenhao Li , Feng Chen, Guodong Yin, Lin Tang, Qie Fan","doi":"10.1016/j.biocel.2025.106876","DOIUrl":"10.1016/j.biocel.2025.106876","url":null,"abstract":"<div><div>Autophagy is a promising therapeutic target for intervertebral disc degeneration (IDD). Previous study has shown down-regulation of activator protein 2α (AP-2α) promoted proliferation and inhibited senescence and apoptosis of rat nucleus pulposus (NP) cells in IDD. This study aimed to investigate the involvement of autophagy in IDD and the regulatory mechanism of AP-2α on autophagy. Rat NP cells were exposed to varying concentrations of H<sub>2</sub>O<sub>2</sub>. A rat IDD model was constructed and injected with AP-2α low expression adeno-associated virus. To study the role of AP-2α and autophagy in IDD, we constructed an IDD cell model using H<sub>2</sub>O<sub>2</sub> and treated NP cells with AP-2α low expression adeno-associated virus, autophagy activator rapamycin (RA) and autophagy inhibitor 3MA. <em>In vitro</em>, AP-2α (TFAP2A), LC3 (MAP1LC3A/B), Beclin-1 (BECN1), and p62 (Sequestosome 1, SQSTM1) levels were up-regulated after H₂O₂ treatment. <em>In vivo</em>, IDD increased the apoptosis degree of NP cells, but apoptosis was reduced after knockdown of AP-2α. Additionally, IDD increased AP-2α, LC3 II/I, Beclin-1, and p62 levels, but knockdown of AP-2α unblocked the autophagy flow. <em>In vitro</em>, H₂O₂ treatment increased AP-2α, LC3 II/I, Beclin-1, and p62 levels and NP cell apoptosis. Treatment with RA and its combined knockdown of AP-2α alleviated the dysfunction of autophagy flow and reduced the degree of apoptosis. Treatment with 3MA aggravated the dysfunction of autophagy flow and apoptosis, which can be alleviated by knockdown of AP-2α. Together, AP-2α regulated autophagy to participate in the development of IDD <em>in vivo</em> and rat NP cell model of IDD <em>in vitro</em>.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"190 ","pages":"Article 106876"},"PeriodicalIF":2.8,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426907","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 : 2025-10-30DOI: 10.1016/j.biocel.2025.106875
Jinzhu Ma , Yixuan Ma , Shuyu Wei , Shuangshuang Wu , Yazun Dong , Kaiyue Liu , Hongyan Liu , Simiao Yu , Liquan Yu , Beiyan Wang , Baifen Song
Mn2+ is an important trace nutrient element in the body. Macrophages act a significant role on resisting Staphylococcus aureus (S. aureus). Nowadays, it remains unclear whether Mn2+ can regulate the phagocytosis of macrophages against S. aureus through autophagy. Here, after the RAW264.7 cells transfected with the p3 × Flag-CMV10-ube2c plasmids were treated with Mn2+, subsequently infected with S. aureus, then these cells manifested that the expression levels of LC3-II and p62 proteins were significantly increased, and autophagosome formation was enhanced, and the expression level of RhoB phagocytosis-related protein also was significantly increased, the phosphorylation levels of mTOR, p38 and JNK were obviously decreased, while phosphorylation level of ERK was enhanced, the production levels of IL-6 and IL-2, IFN-β, IFN-γ, CAT and NO were significantly elevated, especially the phagocytosis against S. aureus was become obviously stronger. The data indicated that Mn2+ could promote the early autophagy activation and inhibit the degradation of autophagolysosomes in the late stage of autophagy of RAW264.7 cells infected with S. aureus through Ube2C, thereby enhancing the phagocytosis of macrophages against S. aureus. These data provide an important basis for a deeper understanding of the molecular mechanism by which Mn2+ enhances the phagocytosis of macrophages.
{"title":"Mn2+ enhances phagocytosis of macrophages against Staphylococcus aureus by regulating autophagy","authors":"Jinzhu Ma , Yixuan Ma , Shuyu Wei , Shuangshuang Wu , Yazun Dong , Kaiyue Liu , Hongyan Liu , Simiao Yu , Liquan Yu , Beiyan Wang , Baifen Song","doi":"10.1016/j.biocel.2025.106875","DOIUrl":"10.1016/j.biocel.2025.106875","url":null,"abstract":"<div><div>Mn<sup>2+</sup> is an important trace nutrient element in the body. Macrophages act a significant role on resisting <em>Staphylococcus aureus</em> (<em>S. aureus</em>). Nowadays, it remains unclear whether Mn<sup>2+</sup> can regulate the phagocytosis of macrophages against <em>S. aureus</em> through autophagy. Here, after the RAW264.7 cells transfected with the p3 × Flag-CMV10-<em>ube2c</em> plasmids were treated with Mn<sup>2+</sup>, subsequently infected with <em>S. aureus</em>, then these cells manifested that the expression levels of LC3-II and p62 proteins were significantly increased, and autophagosome formation was enhanced, and the expression level of RhoB phagocytosis-related protein also was significantly increased, the phosphorylation levels of mTOR, p38 and JNK were obviously decreased, while phosphorylation level of ERK was enhanced, the production levels of IL-6 and IL-2, IFN-β, IFN-γ, CAT and NO were significantly elevated, especially the phagocytosis against <em>S. aureus</em> was become obviously stronger. The data indicated that Mn<sup>2+</sup> could promote the early autophagy activation and inhibit the degradation of autophagolysosomes in the late stage of autophagy of RAW264.7 cells infected with <em>S. aureus</em> through Ube2C, thereby enhancing the phagocytosis of macrophages against <em>S. aureus</em>. These data provide an important basis for a deeper understanding of the molecular mechanism by which Mn<sup>2+</sup> enhances the phagocytosis of macrophages.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"190 ","pages":"Article 106875"},"PeriodicalIF":2.8,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425757","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 : 2025-10-30DOI: 10.1016/j.biocel.2025.106874
Li-Ping Dang, Rui Lv, Yun-Fei Zuo, Chao Sun
Obesity is a major global health challenge closely associated with various metabolic diseases. A deeper understanding of the mechanisms underlying obesity, particularly the complex relationships between lipid metabolism, inflammation, and endoplasmic reticulum stress (ERS), is crucial for improving treatment strategies. This study proposes the hypothesis that "melatonin (MT) alleviates ERS-mediated inflammation in adipose tissue" and explores its mechanism of action. The results showed that MT effectively reduce ERS and its induced inflammatory response in adipose tissue and adipocytes of mice. Mechanistically, MT regulates the expression of the key ERS gene activating transcription factor 6(ATF6) by reducing the methylation level of the circadian clock gene period1 (PER1). Additionally, the study found that PER1 specifically binds to the promoter region of Atf6, thereby negatively regulating its expression and alleviating ERS. We also reveal that MT can effectively mitigate inflammation pathways mediated by ERS, including macrophage polarization and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation. This research not only uncovers the significant role of MT in regulating obesity-related inflammation but also provides new insights for future intervention strategies targeting obesity and its complications. A deeper understanding of the role and mechanism of MT in regulating ERS can lay the foundation for the development of new drugs for the treatment of obesity and metabolic diseases and provide enormous potential for clinical applications.
{"title":"Melatonin alleviates endoplasmic reticulum stress and its mediated inflammation in adipocytes via the PER1/ATF6 signal","authors":"Li-Ping Dang, Rui Lv, Yun-Fei Zuo, Chao Sun","doi":"10.1016/j.biocel.2025.106874","DOIUrl":"10.1016/j.biocel.2025.106874","url":null,"abstract":"<div><div>Obesity is a major global health challenge closely associated with various metabolic diseases. A deeper understanding of the mechanisms underlying obesity, particularly the complex relationships between lipid metabolism, inflammation, and endoplasmic reticulum stress (ERS), is crucial for improving treatment strategies. This study proposes the hypothesis that \"melatonin (MT) alleviates ERS-mediated inflammation in adipose tissue\" and explores its mechanism of action. The results showed that MT effectively reduce ERS and its induced inflammatory response in adipose tissue and adipocytes of mice. Mechanistically, MT regulates the expression of the key ERS gene activating transcription factor 6(ATF6) by reducing the methylation level of the circadian clock gene period1 (PER1). Additionally, the study found that PER1 specifically binds to the promoter region of <em>Atf6</em>, thereby negatively regulating its expression and alleviating ERS. We also reveal that MT can effectively mitigate inflammation pathways mediated by ERS, including macrophage polarization and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation. This research not only uncovers the significant role of MT in regulating obesity-related inflammation but also provides new insights for future intervention strategies targeting obesity and its complications. A deeper understanding of the role and mechanism of MT in regulating ERS can lay the foundation for the development of new drugs for the treatment of obesity and metabolic diseases and provide enormous potential for clinical applications.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"190 ","pages":"Article 106874"},"PeriodicalIF":2.8,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426887","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":"2025-10-17","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 : 2025-10-15DOI: 10.1016/j.biocel.2025.106873
Ruoyu Wang , Dan Tang , Lingyu Wu , Longyun Ou , Lin Ding , Jiacheng Jiang , Yunan Wu
Hepatocellular carcinoma (HCC) is a leading cause of cancer fatality worldwide. It is closely linked to the gut-liver axis, which plays a crucial role in nutrient metabolism, immune responses, and the biotransformation of bacterial metabolites. Traditional Chinese Medicine (TCM), as an adjuvant treatment, is important in the treatment course of HCC. This study aimed to explore the effects of Bielong Ruangan decoction (BLRG) on HCC. It is a traditional Chinese medicine formula used for liver fibrosis and cancer. The study focuses on its impact on gut microbiota and associated mechanisms. An orthotopic liver transplantation model was established in mice in the presence or absence of BLRG treatment, and the therapeutic effects of BLRG were evaluated. BLRG significantly inhibited tumor growth in an orthotopic liver transplantation mouse model, by reducing tumor size, liver weight, volume, Ki-67, and serum AFP levels. It also enhanced intestinal barrier functions by lowering serum LPS levels, increasing intestinal mucus thickness, and boosting ZO-1 and occludin mRNA levels. Moreover, BLRG modulated immune responses, decreasing inflammatory cytokines (IL-10 and IL-1β) while increasing anti-tumor cytokines (IFN-α, IFN-γ, and IL-2). A notable shift in gut microbiota composition was observed, accompanied by a decrease in Mucispirillum_sp. and Helicobacter_typhlonius post-treatment. Serum metabolomic profiling confirmed these findings and revealed a positive correlation between Mucispirillum and triglycerides (TG). Fecal Microbiota Transplantation (FMT) experiments further highlighted the gut microbiota's role in mediating BLRG's anti-tumor effects, demonstrating decreased tumor metrics and improved serum AFP levels, intestinal permeability, and immune responses in recipient mice. These results underscore BLRG's potential as an adjunctive therapeutic agent in liver cancer, demonstrating its ability to modulate tumor growth, gut microbiota, and immune responses, thereby potentially reshaping the HCC therapeutic landscape.
{"title":"Bielong Ruangan decoction inhibits tumor growth and improves immune response in a hepatocellular carcinoma mouse model through gut microbiota","authors":"Ruoyu Wang , Dan Tang , Lingyu Wu , Longyun Ou , Lin Ding , Jiacheng Jiang , Yunan Wu","doi":"10.1016/j.biocel.2025.106873","DOIUrl":"10.1016/j.biocel.2025.106873","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a leading cause of cancer fatality worldwide. It is closely linked to the gut-liver axis, which plays a crucial role in nutrient metabolism, immune responses, and the biotransformation of bacterial metabolites. Traditional Chinese Medicine (TCM), as an adjuvant treatment, is important in the treatment course of HCC. This study aimed to explore the effects of Bielong Ruangan decoction (BLRG) on HCC. It is a traditional Chinese medicine formula used for liver fibrosis and cancer. The study focuses on its impact on gut microbiota and associated mechanisms. An orthotopic liver transplantation model was established in mice in the presence or absence of BLRG treatment, and the therapeutic effects of BLRG were evaluated. BLRG significantly inhibited tumor growth in an orthotopic liver transplantation mouse model, by reducing tumor size, liver weight, volume, Ki-67, and serum AFP levels. It also enhanced intestinal barrier functions by lowering serum LPS levels, increasing intestinal mucus thickness, and boosting ZO-1 and occludin mRNA levels. Moreover, BLRG modulated immune responses, decreasing inflammatory cytokines (IL-10 and IL-1β) while increasing anti-tumor cytokines (IFN-α, IFN-γ, and IL-2). A notable shift in gut microbiota composition was observed, accompanied by a decrease in <em>Mucispirillum_sp.</em> and <em>Helicobacter_typhlonius</em> post-treatment. Serum metabolomic profiling confirmed these findings and revealed a positive correlation between <em>Mucispirillum</em> and triglycerides (TG). Fecal Microbiota Transplantation (FMT) experiments further highlighted the gut microbiota's role in mediating BLRG's anti-tumor effects, demonstrating decreased tumor metrics and improved serum AFP levels, intestinal permeability, and immune responses in recipient mice. These results underscore BLRG's potential as an adjunctive therapeutic agent in liver cancer, demonstrating its ability to modulate tumor growth, gut microbiota, and immune responses, thereby potentially reshaping the HCC therapeutic landscape.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"190 ","pages":"Article 106873"},"PeriodicalIF":2.8,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313842","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 : 2025-10-14DOI: 10.1016/j.biocel.2025.106872
Haser H. Sutcu , Arthur Thomas--Joyeux , Mikaël Cardot-Martin , Delphine Dugué , François Vianna , Yann Perrot , Mohamed A. Benadjaoud , Marc Benderitter , Céline Baldeyron
DNA integrity and stability are vital for proper cellular activity. Nevertheless, to treat cancer patients, DNA is the main target for inducing tumoral cell death. Nowadays, cancer treatment is improving by the development of new technologies, protocols and strategies. Amongst them, the charged particle radiotherapies are becoming prevalent. However, tumor-neighboring healthy tissues are still exposed to ionizing radiation (IR) and subject to late side effects. Skeletal muscle is one of those tissues most likely to be affected. To decipher the DNA damage response (DDR) of skeletal muscle cells, myogenic cells, we irradiated them with microbeams of protons or α-particles and followed the accumulation of DDR proteins at localized irradiation sites. Thereby, we showed that myoblasts, proliferating myogenic cells, repair local IR-induced DNA damage through both non-homologous end-joining and homologous recombination with different recruitment dynamics depending on the characteristics of ionizing particles (type, energy deposition and time after irradiation), whereas myotubes, post-mitotic myogenic cells, display globally reduced DNA damage response.
{"title":"The DNA damage response in myogenic C2C7 cells depends on the characteristics of ionizing particles","authors":"Haser H. Sutcu , Arthur Thomas--Joyeux , Mikaël Cardot-Martin , Delphine Dugué , François Vianna , Yann Perrot , Mohamed A. Benadjaoud , Marc Benderitter , Céline Baldeyron","doi":"10.1016/j.biocel.2025.106872","DOIUrl":"10.1016/j.biocel.2025.106872","url":null,"abstract":"<div><div>DNA integrity and stability are vital for proper cellular activity. Nevertheless, to treat cancer patients, DNA is the main target for inducing tumoral cell death. Nowadays, cancer treatment is improving by the development of new technologies, protocols and strategies. Amongst them, the charged particle radiotherapies are becoming prevalent. However, tumor-neighboring healthy tissues are still exposed to ionizing radiation (IR) and subject to late side effects. Skeletal muscle is one of those tissues most likely to be affected. To decipher the DNA damage response (DDR) of skeletal muscle cells, myogenic cells, we irradiated them with microbeams of protons or α-particles and followed the accumulation of DDR proteins at localized irradiation sites. Thereby, we showed that myoblasts, proliferating myogenic cells, repair local IR-induced DNA damage through both non-homologous end-joining and homologous recombination with different recruitment dynamics depending on the characteristics of ionizing particles (type, energy deposition and time after irradiation), whereas myotubes, post-mitotic myogenic cells, display globally reduced DNA damage response.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"189 ","pages":"Article 106872"},"PeriodicalIF":2.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145309766","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 : 2025-10-06DOI: 10.1016/j.biocel.2025.106870
Hai-yang Liao , Guo-hua Zhang , Jian-xiong Zheng , Jin-yue Lu , Jia-yao Hao , Min Tan , Zhan-dong Wang , Hai-li Shen
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Fibroblast-like synovial cells (FLSs) are the main effector cells in the synovial microenvironment that cause chronic swelling and joint injury, and their enhanced glycolytic metabolism can lead to persistent joint injury. As a key regulatory enzyme in glycolysis, pyruvate kinase M2 (PKM2) plays a crucial role in the pathogenesis of RA. However, the exact mechanism by which PKM2 induces the inflammatory response of RA-FLSs through enhanced glucose metabolism and its impact on the pathogenic behaviour of cells remain unclear. This study detected the expression of PKM2 in synovial tissues and RA-FLSs of patients with RA and explored the effect of PKM2 on collagen-induced arthritis (CIA) rats. The results showed that PKM2 was upregulated in the synovial tissue of RA and RA-FLSs. PKM2 could promote glucose uptake, ATP and lactic acid production, and extracellular acidification rate in RA-FLSs, thereby promoting the release of pro-inflammatory cytokines such as TNF-α, interleukin-1 β (IL-1β), and IL-6. However, inhibiting PKM2 can reverse these changes. In in vivo experiments, inhibition of PKM2 could significantly improve the clinical arthritis symptoms of CIA rats (reduce plantar swelling and arthritis score), down-regulate the expression of pro-inflammatory cytokines, and inhibit bone erosion in CIA rats, reducing inflammatory cell infiltration, synovial hyperplasia and joint destruction. Furthermore, inhibiting PKM2 can suppress the phosphorylated expression of Akt and mTOR proteins, thereby inhibiting glycolytic reprogramming. Our research results indicate that PKM2 mediates glycolytic reprogramming to induce the release of RA-FLSs inflammatory cytokines by activating the Akt/mTOR signaling pathway, thereby promoting the progression of RA. Therefore, PKM2 may be a candidate target for the treatment of RA. Targeting PKM2 to regulate glycolytic reprogramming can provide a new idea for the treatment of RA.
{"title":"Pyruvate kinase M2 (PKM2) regulates rheumatoid arthritis by mediating glycolysis reprogramming through the Akt/mTOR pathway","authors":"Hai-yang Liao , Guo-hua Zhang , Jian-xiong Zheng , Jin-yue Lu , Jia-yao Hao , Min Tan , Zhan-dong Wang , Hai-li Shen","doi":"10.1016/j.biocel.2025.106870","DOIUrl":"10.1016/j.biocel.2025.106870","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Fibroblast-like synovial cells (FLSs) are the main effector cells in the synovial microenvironment that cause chronic swelling and joint injury, and their enhanced glycolytic metabolism can lead to persistent joint injury. As a key regulatory enzyme in glycolysis, pyruvate kinase M2 (PKM2) plays a crucial role in the pathogenesis of RA. However, the exact mechanism by which PKM2 induces the inflammatory response of RA-FLSs through enhanced glucose metabolism and its impact on the pathogenic behaviour of cells remain unclear. This study detected the expression of PKM2 in synovial tissues and RA-FLSs of patients with RA and explored the effect of PKM2 on collagen-induced arthritis (CIA) rats. The results showed that PKM2 was upregulated in the synovial tissue of RA and RA-FLSs. PKM2 could promote glucose uptake, ATP and lactic acid production, and extracellular acidification rate in RA-FLSs, thereby promoting the release of pro-inflammatory cytokines such as TNF-α, interleukin-1 β (IL-1β), and IL-6. However, inhibiting PKM2 can reverse these changes. In in vivo experiments, inhibition of PKM2 could significantly improve the clinical arthritis symptoms of CIA rats (reduce plantar swelling and arthritis score), down-regulate the expression of pro-inflammatory cytokines, and inhibit bone erosion in CIA rats, reducing inflammatory cell infiltration, synovial hyperplasia and joint destruction. Furthermore, inhibiting PKM2 can suppress the phosphorylated expression of Akt and mTOR proteins, thereby inhibiting glycolytic reprogramming. Our research results indicate that PKM2 mediates glycolytic reprogramming to induce the release of RA-FLSs inflammatory cytokines by activating the Akt/mTOR signaling pathway, thereby promoting the progression of RA. Therefore, PKM2 may be a candidate target for the treatment of RA. Targeting PKM2 to regulate glycolytic reprogramming can provide a new idea for the treatment of RA.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"189 ","pages":"Article 106870"},"PeriodicalIF":2.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253430","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}
This study aimed to elucidate the regulatory role of the muscle-specific gene ATP1B4 in skeletal muscle metabolism and mitophagy in diabetic sarcopenia (DS) rats.
Methods
Differentially expressed genes were screened from the GEO dataset GSE7014, and ATP1B4 was identified as a candidate gene associated with DS. A DS rat model was established via high-fat diet feeding and streptozotocin injection. ATP1B4 expression was modulated through lentiviral overexpression or knockdown. Additionally, PI3K/AKT/mTOR pathway activators (SC79, leucine) and inhibitors (LY294002, MK-2206) were administered. Protein expression of ATP1B4, phosphorylated PI3K/AKT/mTOR components, and autophagy markers (LC3-II, DRP1, ATG9, MFN2) was assessed via Western blotting, immunohistochemistry, and immunofluorescence. Skeletal muscle function and structure were evaluated using behavioral tests (treadmill and inclined plane) and histopathological staining (H&E, Masson, PAS).
Results
Bioinformatic analysis of the GSE7014 dataset identified ATP1B4 as a skeletal muscle-related differentially expressed gene enriched in extracellular matrix and metabolic pathways. In DS rats, ATP1B4 expression was upregulated, coinciding with suppression of PI3K/AKT/mTOR signaling and activation of mitophagy markers (LC3-II, DRP1, ATG9). Overexpression of ATP1B4 exacerbated hyperglycemia, muscle atrophy, collagen accumulation, and glycogen deposition, while knockdown reversed these effects. Activation of the PI3K/AKT/mTOR pathway improved muscle function and histological architecture, normalized autophagy, and reduced pathological features. However, co-overexpression of ATP1B4 eliminated the protective effects of pathway activation. Conversely, dual intervention with ATP1B4 knockdown and PI3K activation restored skeletal muscle integrity and autophagy flux. Importantly, ATP1B4 expression remained unchanged following pathway modulation, supporting its unidirectional upstream regulatory role in DS.
Conclusion
ATP1B4 may aggravate diabetic sarcopenia by acting as an upstream suppressor of the PI3K/AKT/mTOR pathway.
{"title":"ATP1B4 as a candidate upstream regulator of muscle atrophy in diabetic sarcopenia via PI3K/AKT/mTOR-mediated autophagy","authors":"Tingting Duan , Shumin Jia , Dan Zhou , Liqun Zhao","doi":"10.1016/j.biocel.2025.106869","DOIUrl":"10.1016/j.biocel.2025.106869","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to elucidate the regulatory role of the muscle-specific gene ATP1B4 in skeletal muscle metabolism and mitophagy in diabetic sarcopenia (DS) rats.</div></div><div><h3>Methods</h3><div>Differentially expressed genes were screened from the GEO dataset GSE7014, and ATP1B4 was identified as a candidate gene associated with DS. A DS rat model was established via high-fat diet feeding and streptozotocin injection. ATP1B4 expression was modulated through lentiviral overexpression or knockdown. Additionally, PI3K/AKT/mTOR pathway activators (SC79, leucine) and inhibitors (LY294002, MK-2206) were administered. Protein expression of ATP1B4, phosphorylated PI3K/AKT/mTOR components, and autophagy markers (LC3-II, DRP1, ATG9, MFN2) was assessed via Western blotting, immunohistochemistry, and immunofluorescence. Skeletal muscle function and structure were evaluated using behavioral tests (treadmill and inclined plane) and histopathological staining (H&E, Masson, PAS).</div></div><div><h3>Results</h3><div>Bioinformatic analysis of the GSE7014 dataset identified ATP1B4 as a skeletal muscle-related differentially expressed gene enriched in extracellular matrix and metabolic pathways. In DS rats, ATP1B4 expression was upregulated, coinciding with suppression of PI3K/AKT/mTOR signaling and activation of mitophagy markers (LC3-II, DRP1, ATG9). Overexpression of ATP1B4 exacerbated hyperglycemia, muscle atrophy, collagen accumulation, and glycogen deposition, while knockdown reversed these effects. Activation of the PI3K/AKT/mTOR pathway improved muscle function and histological architecture, normalized autophagy, and reduced pathological features. However, co-overexpression of ATP1B4 eliminated the protective effects of pathway activation. Conversely, dual intervention with ATP1B4 knockdown and PI3K activation restored skeletal muscle integrity and autophagy flux. Importantly, ATP1B4 expression remained unchanged following pathway modulation, supporting its unidirectional upstream regulatory role in DS.</div></div><div><h3>Conclusion</h3><div>ATP1B4 may aggravate diabetic sarcopenia by acting as an upstream suppressor of the PI3K/AKT/mTOR pathway.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"189 ","pages":"Article 106869"},"PeriodicalIF":2.8,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193857","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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