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":"2025-11-27","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 : 2025-11-18DOI: 10.1016/j.biocel.2025.106879
Yi Wu , Fang Wang , Fang-Lin Peng
Type II diabetes is a prevalent chronic disease worldwide, yet no curative treatment currently exists. Compromised insulin release is one of the hallmarks of type II diabetes, to restore insulin release is one standard to screen candidates for therapy. Proton-activated chloride (PAC) channels are pH-sensitive chloride channels that open under acidic conditions, but their potential role in pancreatic β-cell physiology and diabetes has not been fully explored. In this study, we identified PAC on the membrane of pancreatic β-cells and found it to be closely associated with insulin secretory granules. Immunostaining and FRET imaging revealed that PAC is co-localized with Syntaxin 1 A and CaV1.2. Overexpression and knockdown of PAC increased and reduced L type calcium currents and steady capacitance jumps which reflect fast insulin secretion. Furthermore, manipulation of PAC expression significantly altered overall insulin release under high glucose conditions in vitro. Knockout of PAC channels in mice, however, affects body weight, fasting blood glucose levels, and serum insulin levels when constructing a type II diabetes model through high-fat diet feeding, compared to wild-type mice or Pac knockout mice fed a normal diet. Together, these findings reveal a previously unrecognized role for PAC in regulating both phases of insulin secretion and suggest that PAC channels could represent a novel therapeutic target for improving β-cell function and treating diabetes. Given the global burden of type II diabetes, understanding PAC channel function could open new avenues for targeted interventions to restore insulin secretion and improve disease outcomes.
{"title":"Proton activated chloride channel and its regulation of insulin secretion in β cells","authors":"Yi Wu , Fang Wang , Fang-Lin Peng","doi":"10.1016/j.biocel.2025.106879","DOIUrl":"10.1016/j.biocel.2025.106879","url":null,"abstract":"<div><div>Type II diabetes is a prevalent chronic disease worldwide, yet no curative treatment currently exists. Compromised insulin release is one of the hallmarks of type II diabetes, to restore insulin release is one standard to screen candidates for therapy. Proton-activated chloride (PAC) channels are pH-sensitive chloride channels that open under acidic conditions, but their potential role in pancreatic β-cell physiology and diabetes has not been fully explored. In this study, we identified PAC on the membrane of pancreatic β-cells and found it to be closely associated with insulin secretory granules. Immunostaining and FRET imaging revealed that PAC is co-localized with Syntaxin 1 A and CaV1.2. Overexpression and knockdown of PAC increased and reduced L type calcium currents and steady capacitance jumps which reflect fast insulin secretion. Furthermore, manipulation of PAC expression significantly altered overall insulin release under high glucose conditions in vitro. Knockout of PAC channels in mice, however, affects body weight, fasting blood glucose levels, and serum insulin levels when constructing a type II diabetes model through high-fat diet feeding, compared to wild-type mice or <em>Pac</em> knockout mice fed a normal diet. Together, these findings reveal a previously unrecognized role for PAC in regulating both phases of insulin secretion and suggest that PAC channels could represent a novel therapeutic target for improving β-cell function and treating diabetes. Given the global burden of type II diabetes, understanding PAC channel function could open new avenues for targeted interventions to restore insulin secretion and improve disease outcomes.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"190 ","pages":"Article 106879"},"PeriodicalIF":2.8,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565775","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 : 2025-11-18DOI: 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}
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