Pub Date : 2024-10-14DOI: 10.1016/j.intimp.2024.113278
The cardiotoxicity of Doxorubicin (Dox) limits its clinical application, creating an urgent need to investigate its underlying mechanism and develop effective therapies. Senescence plays an important role in Dox-induced cardiotoxicity (DIC). Recently, Neuregulin-1 (NRG1) was found to regulate Yes-associated protein (YAP), which was reported to inhibit senescence, suggesting that NRG1 might be used to treat DIC by inhibiting senescence through YAP regulation. We examined the changes and regulatory roles of YAP and senescence in Dox cardiotoxicity and whether NRG1 could reduce DIC in chronic DIC mice and Dox-treated H9c2 cells. Our study revealed that sustained small doses of Dox impaired cardiac function and H9c2 cell viability, induced myocardial senescence, and inhibited YAP expression. Conversely, high levels of YAP inhibited Dox-induced senescence in H9c2 cells, indicating that Dox promotes myocardial senescence by inhibiting YAP. In addition, we found that exogenous NRG1 inhibited the phosphorylation of LATS1 and MST1, thereby inhibiting YAP phosphorylation and promote the nuclear translocation of YAP, inhibiting senescence and attenuating Dox-induced cardiotoxicity. YAP knockdown or inhibition of YAP binding to TEA domain transcription factor protein （TEAD）blocks the protective effects of NRG1. In conclusion, our study suggests that Dox-induced myocardial senescence through YAP inhibition is one of the pathological mechanisms of its cardiotoxicity. Additionally, NRG1 reduces DIC by upregulating YAP to inhibit senescence.
{"title":"Neuregulin-1 reduces Doxorubicin-induced cardiotoxicity by upregulating YAP to inhibit senescence","authors":"","doi":"10.1016/j.intimp.2024.113278","DOIUrl":"10.1016/j.intimp.2024.113278","url":null,"abstract":"<div><div>The cardiotoxicity of Doxorubicin (Dox) limits its clinical application, creating an urgent need to investigate its underlying mechanism and develop effective therapies. Senescence plays an important role in Dox-induced cardiotoxicity (DIC). Recently, Neuregulin-1 (NRG1) was found to regulate Yes-associated protein (YAP), which was reported to inhibit senescence, suggesting that NRG1 might be used to treat DIC by inhibiting senescence through YAP regulation. We examined the changes and regulatory roles of YAP and senescence in Dox cardiotoxicity and whether NRG1 could reduce DIC in chronic DIC mice and Dox-treated H9c2 cells. Our study revealed that sustained small doses of Dox impaired cardiac function and H9c2 cell viability, induced myocardial senescence, and inhibited YAP expression. Conversely, high levels of YAP inhibited Dox-induced senescence in H9c2 cells, indicating that Dox promotes myocardial senescence by inhibiting YAP. In addition, we found that exogenous NRG1 inhibited the phosphorylation of LATS1 and MST1, thereby inhibiting YAP phosphorylation and promote the nuclear translocation of YAP, inhibiting senescence and attenuating Dox-induced cardiotoxicity. YAP knockdown or inhibition of YAP binding to TEA domain transcription factor protein （TEAD）blocks the protective effects of NRG1. In conclusion, our study suggests that Dox-induced myocardial senescence through YAP inhibition is one of the pathological mechanisms of its cardiotoxicity. Additionally, NRG1 reduces DIC by upregulating YAP to inhibit senescence.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142437875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1016/j.intimp.2024.113338
Background
Injection drug use (IDU) leads to immune system dysfunction, thereby increasing the risk of opportunistic infection. There is a critical need to reveal the role of IDU in the immunopathogenesis of HIV infection.
Methods
We performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) derived from healthy control (HC) individuals, HIV-infected patients with IDU (HIV-IDU) and without IDU (HIV-nIDU). In addition, the Gene Set Enrichment Analysis (GSEA) was used to analyze the immunomodulatory effects of differential immune cells.
Results
Seven types of cells were identified with specific expressions of maker genes. Specific subsets such as CD14+ monocytes, plasmacytoid dendritic cells (pDCs), plasma cells, and CD8+ T cells displayed a high degree of heterogeneity among HC, HIV-nIDU, and HIV-IDU. We identified signature genes for each subset in distinct groups, including CFP+ CD14+ monocytes, PTPRCAP+ pDCs, IGHD+ plasma cells, and IFITM1+ CD8+T cells from HIV-IDU, whereas these genes were not expressed in such cells from HIV-nIDU. Moreover, considerable heterogeneity in the function of these immune cells was observed across different groups, especially the elevated IFN-α/β signaling for CD14+ monocytes, histone H2A/2B and H3/4 pathway for pDCs, the creation of C4 and C2 activators for plasma cells, and drug metabolism cytochrome p450 for CD8+ T cells in HIV-IDU individuals.
Conclusion
Our comprehensive analyses clarify the heterogeneous characteristics of the immune landscape between HIV-IDU and HIV-nIDU. These insights provide a deeper understanding of the IDU-mediated immunopathogenesis in HIV infection.
{"title":"Single-cell sequencing reveals the heterogeneity of immune landscape in drug users with HIV infection","authors":"","doi":"10.1016/j.intimp.2024.113338","DOIUrl":"10.1016/j.intimp.2024.113338","url":null,"abstract":"<div><h3>Background</h3><div>Injection drug use (IDU) leads to immune system dysfunction, thereby increasing the risk of opportunistic infection. There is a critical need to reveal the role of IDU in the immunopathogenesis of HIV infection.</div></div><div><h3>Methods</h3><div>We performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) derived from healthy control (HC) individuals, HIV-infected patients with IDU (HIV-IDU) and without IDU (HIV-nIDU). In addition, the Gene Set Enrichment Analysis (GSEA) was used to analyze the immunomodulatory effects of differential immune cells.</div></div><div><h3>Results</h3><div>Seven types of cells were identified with specific expressions of maker genes. Specific subsets such as CD14<sup>+</sup> monocytes, plasmacytoid dendritic cells (pDCs), plasma cells, and CD8<sup>+</sup> T cells displayed a high degree of heterogeneity among HC, HIV-nIDU, and HIV-IDU. We identified signature genes for each subset in distinct groups, including <em>CFP</em><sup>+</sup> CD14<sup>+</sup> monocytes, <em>PTPRCAP</em><sup>+</sup> pDCs, <em>IGHD</em><sup>+</sup> plasma cells, and <em>IFITM1</em><sup>+</sup> CD8<sup>+</sup>T cells from HIV-IDU, whereas these genes were not expressed in such cells from HIV-nIDU. Moreover, considerable heterogeneity in the function of these immune cells was observed across different groups, especially the elevated IFN-α/β signaling for CD14<sup>+</sup> monocytes, histone H2A/2B and H3/4 pathway for pDCs, the creation of C4 and C2 activators for plasma cells, and drug metabolism cytochrome p450 for CD8<sup>+</sup> T cells in HIV-IDU individuals.</div></div><div><h3>Conclusion</h3><div>Our comprehensive analyses clarify the heterogeneous characteristics of the immune landscape between HIV-IDU and HIV-nIDU. These insights provide a deeper understanding of the IDU-mediated immunopathogenesis in HIV infection.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142437874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1016/j.intimp.2024.113342
It has been reported that the symptoms of rheumatoid arthritis (RA) can be ameliorated by acupuncture, an external treatment of traditional Chinese medicine. However, the immune mechanism underlying its action is elusive. Accordingly, this study investigated the role and mechanism of manual acupuncture (MA) in collagen-induced arthritis (CIA) in mice. The results demonstrated that MA or NaB treatment reduced Articular Index scores and right paw thickness and alleviated synovial inflammation and cartilage damage. MA or NaB treatment altered the content and relative abundance of short-chain fatty acids, particularly butyric and propionic acids, in feces. Additionally, MA or NaB treatment elevated SCD1, SREBP1, and GPX4 protein expression in synovial tissues and GSH-px contents in serum while decreasing ROS fluorescence intensity and MDA contents in peripheral blood. A linear correlation was found between the relative expression of SCD1 and SREBP1 in synovial tissues and the contents of propionic acids and butyric acids in feces, as well as between the contents of propionic acids and butyric acids. In summary, MA regulates butyric acids to inhibit ferroptosis, therefore suppressing inflammation in RA.
{"title":"Acupuncture ameliorates synovitis in mice with collagen-induced arthritis by repressing ferroptosis via butyric acid","authors":"","doi":"10.1016/j.intimp.2024.113342","DOIUrl":"10.1016/j.intimp.2024.113342","url":null,"abstract":"<div><div>It has been reported that the symptoms of rheumatoid arthritis (RA) can be ameliorated by acupuncture, an external treatment of traditional Chinese medicine. However, the immune mechanism underlying its action is elusive. Accordingly, this study investigated the role and mechanism of manual acupuncture (MA) in collagen-induced arthritis (CIA) in mice. The results demonstrated that MA or NaB treatment reduced Articular Index scores and right paw thickness and alleviated synovial inflammation and cartilage damage. MA or NaB treatment altered the content and relative abundance of short-chain fatty acids, particularly butyric and propionic acids, in feces. Additionally, MA or NaB treatment elevated SCD1, SREBP1, and GPX4 protein expression in synovial tissues and GSH-px contents in serum while decreasing ROS fluorescence intensity and MDA contents in peripheral blood. A linear correlation was found between the relative expression of SCD1 and SREBP1 in synovial tissues and the contents of propionic acids and butyric acids in feces, as well as between the contents of propionic acids and butyric acids. In summary, MA regulates butyric acids to inhibit ferroptosis, therefore suppressing inflammation in RA.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142437799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1016/j.intimp.2024.113309
The development of cancer immunology heavily relies on the interaction between long non-coding RNAs (lncRNAs) and molecular chaperones. By participating in gene regulation, lncRNAs interact with molecular chaperones, which play a critical role in protein folding and stress responses, to influence oncogenic pathways. This interaction has an impact on both the immune cells within the tumor microenvironment and the tumor cells themselves. Understanding these mechanisms provides valuable insights into innovative approaches for diagnosis and treatment. Targeting the lncRNA-chaperone axis has the potential to strengthen anti-tumor immunity and enhance cancer treatment outcomes. Further research is necessary to uncover specific associations, identify biomarkers, and develop personalized therapies aimed at disrupting this axis, which could potentially revolutionize cancer diagnosis and treatment.
{"title":"Correlation between lncRNAs with human molecular chaperons in cancer immunopathogenesis and drug resistance","authors":"","doi":"10.1016/j.intimp.2024.113309","DOIUrl":"10.1016/j.intimp.2024.113309","url":null,"abstract":"<div><div>The development of cancer immunology heavily relies on the interaction between long non-coding RNAs (lncRNAs) and molecular chaperones. By participating in gene regulation, lncRNAs interact with molecular chaperones, which play a critical role in protein folding and stress responses, to influence oncogenic pathways. This interaction has an impact on both the immune cells within the tumor microenvironment and the tumor cells themselves. Understanding these mechanisms provides valuable insights into innovative approaches for diagnosis and treatment. Targeting the lncRNA-chaperone axis has the potential to strengthen anti-tumor immunity and enhance cancer treatment outcomes. Further research is necessary to uncover specific associations, identify biomarkers, and develop personalized therapies aimed at disrupting this axis, which could potentially revolutionize cancer diagnosis and treatment.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142437868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1016/j.intimp.2024.113312
Background
The Ras-responsive element binding protein 1 (RREB1) is a transcription factor involved in various biological processes. Notably, RREB1 plays a role in tumor immunity by regulating tumor-related gene expression, shaping the tumor microenvironment, and modulating immune checkpoints. Given these functions, RREB1 has emerged as a potential regulatory target in tumor immunotherapy. However, a comprehensive pan-cancer analysis evaluating RREB1’s prognostic value and its role in modulating the immune microenvironment remains unexplored, warranting further investigation to better understand its mechanisms across different cancer types and its implications for personalized immunotherapy.
Methods
We analyzed RREB1 expression across 33 cancer types using RNA sequencing data from the TCGA database. RREB1 alterations were further characterized using the cBioPortal database. Clinical and pathological features, along with prognostic significance, were assessed using TCGA clinical data. The involvement of RREB1 in the tumor microenvironment was evaluated using the CIBERSORT and ESTIMATE algorithms. Relationships between RREB1 expression and tumor mutation burden (TMB), as well as microsatellite instability (MSI), were investigated using Spearman’s rank correlation coefficient. GSEA was applied to explore the biological functions of RREB1. Additionally, we assessed the link between RREB1 expression and the efficacy of PD-1/PD-L1 inhibitors. Finally, a series of in vitro experiments were performed to evaluate the impact of RREB1 expression on the malignant behavior of osteosarcoma (OS) and lung cancer cell lines.
Results
RREB1 was overexpressed in several cancer types and correlated with patient prognosis. RREB1 expression was strongly associated with TMB, MSI, and immune cell infiltration, including regulatory T cells, CD8+ T cells, and macrophages. Furthermore, RREB1 expression was linked to immune responses and the efficacy of immunotherapy. In vitro experiments demonstrated that knockdown of RREB1 significantly inhibited the proliferation and migration of OS cells.
Conclusions
RREB1 shows potential as a prognostic marker for certain cancers and may predict the efficacy of immunotherapy. Additionally, RREB1 expression is related to immune-related markers, suggesting its role in prognosis and predicting responses to immune microenvironment therapies in specific tumors.
{"title":"RREB1 could act as an immunological and prognostic biomarker: From comprehensive analysis to osteosarcoma validation","authors":"","doi":"10.1016/j.intimp.2024.113312","DOIUrl":"10.1016/j.intimp.2024.113312","url":null,"abstract":"<div><h3>Background</h3><div>The Ras-responsive element binding protein 1 (RREB1) is a transcription factor involved in various biological processes. Notably, RREB1 plays a role in tumor immunity by regulating tumor-related gene expression, shaping the tumor microenvironment, and modulating immune checkpoints. Given these functions, RREB1 has emerged as a potential regulatory target in tumor immunotherapy. However, a comprehensive pan-cancer analysis evaluating RREB1’s prognostic value and its role in modulating the immune microenvironment remains unexplored, warranting further investigation to better understand its mechanisms across different cancer types and its implications for personalized immunotherapy.</div></div><div><h3>Methods</h3><div>We analyzed RREB1 expression across 33 cancer types using RNA sequencing data from the TCGA database. RREB1 alterations were further characterized using the cBioPortal database. Clinical and pathological features, along with prognostic significance, were assessed using TCGA clinical data. The involvement of RREB1 in the tumor microenvironment was evaluated using the CIBERSORT and ESTIMATE algorithms. Relationships between RREB1 expression and tumor mutation burden (TMB), as well as microsatellite instability (MSI), were investigated using Spearman’s rank correlation coefficient. GSEA was applied to explore the biological functions of RREB1. Additionally, we assessed the link between RREB1 expression and the efficacy of PD-1/PD-L1 inhibitors. Finally, a series of in vitro experiments were performed to evaluate the impact of RREB1 expression on the malignant behavior of osteosarcoma (OS) and lung cancer cell lines.</div></div><div><h3>Results</h3><div>RREB1 was overexpressed in several cancer types and correlated with patient prognosis. RREB1 expression was strongly associated with TMB, MSI, and immune cell infiltration, including regulatory T cells, CD8<sup>+</sup> T cells, and macrophages. Furthermore, RREB1 expression was linked to immune responses and the efficacy of immunotherapy. In vitro experiments demonstrated that knockdown of RREB1 significantly inhibited the proliferation and migration of OS cells.</div></div><div><h3>Conclusions</h3><div>RREB1 shows potential as a prognostic marker for certain cancers and may predict the efficacy of immunotherapy. Additionally, RREB1 expression is related to immune-related markers, suggesting its role in prognosis and predicting responses to immune microenvironment therapies in specific tumors.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142437877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1016/j.intimp.2024.113369
As BAG family members, Bcl-2 associated athanogene family protein 1 (BAG1) and 2 (BAG2) are implicated in multiple cellular processes, including apoptosis, autophagy, protein folding and homeostasis. Although structurally similar, they considerably differ in many ways. Unlike BAG2, BAG1 has four isoforms (BAG1L, BAG1M, BAG1S and BAG1 p29) displaying different expression features and functional patterns. BAG1 and BAG2 play different cellular functions by interacting with different molecules to participate in the regulation of various diseases, including cancer/tumor and neurodegenerative diseases. Commonly, BAG1 acts as a protective factor to predict a good prognosis of patients with some types of cancer or a risk factor in some other cancers, while BAG2 is regarded as a risk factor to promote cancer/tumor progression. In neurodegenerative diseases, BAG2 commonly acts as a neuroprotective factor. In this review, we summarized the differences in molacular structure and biological function between BAG1 and BAG2, as well as the influences of them on pathogenesis of diseases, and explore the prospects for their clinical therapy application by specifying the activators and inhibitors of BAG1 and BAG2, which might provide a better understanding of the underlying pathogenesis and developing the targeted therapy strategies for diseases.
{"title":"Comparative analysis of BAG1 and BAG2: Insights into their structures, functions and implications in disease pathogenesis","authors":"","doi":"10.1016/j.intimp.2024.113369","DOIUrl":"10.1016/j.intimp.2024.113369","url":null,"abstract":"<div><div>As BAG family members, Bcl-2 associated athanogene family protein 1 (BAG1) and 2 (BAG2) are implicated in multiple cellular processes, including apoptosis, autophagy, protein folding and homeostasis. Although structurally similar, they considerably differ in many ways. Unlike BAG2, BAG1 has four isoforms (BAG1L, BAG1M, BAG1S and BAG1 p29) displaying different expression features and functional patterns. BAG1 and BAG2 play different cellular functions by interacting with different molecules to participate in the regulation of various diseases, including cancer/tumor and neurodegenerative diseases. Commonly, BAG1 acts as a protective factor to predict a good prognosis of patients with some types of cancer or a risk factor in some other cancers, while BAG2 is regarded as a risk factor to promote cancer/tumor progression. In neurodegenerative diseases, BAG2 commonly acts as a neuroprotective factor. In this review, we summarized the differences in molacular structure and biological function between BAG1 and BAG2, as well as the influences of them on pathogenesis of diseases, and explore the prospects for their clinical therapy application by specifying the activators and inhibitors of BAG1 and BAG2, which might provide a better understanding of the underlying pathogenesis and developing the targeted therapy strategies for diseases.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142437876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1016/j.intimp.2024.113380
Background
Osteoporosis (OP) is a common metabolic bone disease. Low-intensity pulsed ultrasound (LIPUS) can effectively promote bone formation and fracture healing. The Wnt/β-catenin signaling pathway is crucial for regulating bone homeostasis and bone diseases, and its downregulation is one of the main mechanisms of osteoporosis pathogenesis. Interleukin-11 (IL-11), which is regulated by mechanical stress, is a key factor in bone remodeling. Here, we investigated the optimal intervention parameters for LIPUS, the relationships among LIPUS, IL-11, and the Wnt/β-catenin signaling pathway, and the effects of LIPUS on bone loss and potential molecular mechanisms in ovariectomized (OVX) mice.
Methods
Bone marrow mesenchymal stromal cells (BMSCs) were subjected to LIPUS intervention for 0, 10, or 20 min to determine the optimal intervention time. The mediating role of IL-11 in LIPUS intervention was explored through IL-11 knockdown and overexpression. Finally, animal experiments were conducted to investigate the in vivo therapeutic effects of LIPUS.
Results
The optimal intervention time for LIPUS was 20 min. LIPUS promoted IL-11 expression and upregulated the Wnt/β-catenin signaling pathway, thereby promoting osteogenic differentiation and inhibiting adipogenic differentiation of BMSCs. IL-11 mediates the regulation of the Wnt/β-catenin signaling pathway by LIPUS. Additionally, LIPUS effectively improved the bone microstructure in ovariectomized mice, inhibited bone loss, promoted IL-11 expression in bone tissue, and activated the Wnt/β-catenin signaling pathway in the femur.
Conclusion
Low-intensity pulsed ultrasound can regulate BMSCs differentiation and inhibit bone loss by promoting IL-11 expression and activating the Wnt/β-catenin signaling pathway.
{"title":"Low-intensity pulsed ultrasound regulates bone marrow mesenchymal stromal cells differentiation and inhibits bone loss by activating the IL-11-Wnt/β-catenin signaling pathway","authors":"","doi":"10.1016/j.intimp.2024.113380","DOIUrl":"10.1016/j.intimp.2024.113380","url":null,"abstract":"<div><h3>Background</h3><div>Osteoporosis (OP) is a common metabolic bone disease. Low-intensity pulsed ultrasound (LIPUS) can effectively promote bone formation and fracture healing. The Wnt/β-catenin signaling pathway is crucial for regulating bone homeostasis and bone diseases, and its downregulation is one of the main mechanisms of osteoporosis pathogenesis. Interleukin-11 (IL-11), which is regulated by mechanical stress, is a key factor in bone remodeling. Here, we investigated the optimal intervention parameters for LIPUS, the relationships among LIPUS, IL-11, and the Wnt/β-catenin signaling pathway, and the effects of LIPUS on bone loss and potential molecular mechanisms in ovariectomized (OVX) mice.</div></div><div><h3>Methods</h3><div>Bone marrow mesenchymal stromal cells (BMSCs) were subjected to LIPUS intervention for 0, 10, or 20 min to determine the optimal intervention time. The mediating role of IL-11 in LIPUS intervention was explored through IL-11 knockdown and overexpression. Finally, animal experiments were conducted to investigate the in vivo therapeutic effects of LIPUS.</div></div><div><h3>Results</h3><div>The optimal intervention time for LIPUS was 20 min. LIPUS promoted IL-11 expression and upregulated the Wnt/β-catenin signaling pathway, thereby promoting osteogenic differentiation and inhibiting adipogenic differentiation of BMSCs. IL-11 mediates the regulation of the Wnt/β-catenin signaling pathway by LIPUS. Additionally, LIPUS effectively improved the bone microstructure in ovariectomized mice, inhibited bone loss, promoted IL-11 expression in bone tissue, and activated the Wnt/β-catenin signaling pathway in the femur.</div></div><div><h3>Conclusion</h3><div>Low-intensity pulsed ultrasound can regulate BMSCs differentiation and inhibit bone loss by promoting IL-11 expression and activating the Wnt/β-catenin signaling pathway.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142437870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1016/j.intimp.2024.113383
Background
Although efficacy and safety of Upadacitinib and Dupilumab in moderate to severe atopic dermatitis (AD) have been shown in clinical trials, real world data are still limited. The aim of this retrospective study is to indirectly compare the efficacy and safety of Upadacitinib and Dupilumab in patients with moderate to severe AD in real world practice.
Methods
A single-center retrospective cohort study was conducted. The study included patients with moderate to severe AD, who were enrolled from May 2022 to March 2024, to indirectly compare the efficacy and safety of Upadacitinib and Dupilumab over 12 weeks duration.
Results
Eighty-seven patients were included (46 received Upadacitinib and 41 Dupilumab). Compared with week 0, there was a significant decrease in EASI score, ADCT score and NRS score in patients of both groups in weeks 4, 8, and 12. In week 4, the reduction in EASI score, ADCT score and NRS score was significantly greater in patients of Upadacitinib group compared to those in Dupilumab group. Compared to baseline, in week 12, the decrease in IL-4, IL-13, and IL-31 level in the serum of patients in Upadacitinib group was significantly greater than that of patients in Dupilumab group. The total IgE of patients in Dupilumab group decreased significantly, while there was no significant change in patients of Upadacitinib group. Although Upadacitinib group reported more adverse events than Dupilumab group, no serious adverse events were observed.
Conclusions
Both Upadacitinib and Dupilumab groups showed effective trend in patients with moderate to severe AD. Upadacitinib has better efficacy and rapid onset in the treatment of patients with moderate to severe AD.
{"title":"Comparative effectiveness of upadacitinib versus dupilumab for moderate-to-severe atopic dermatitis: A retrospective cohort study","authors":"","doi":"10.1016/j.intimp.2024.113383","DOIUrl":"10.1016/j.intimp.2024.113383","url":null,"abstract":"<div><h3>Background</h3><div>Although efficacy and safety of Upadacitinib and Dupilumab in moderate to severe atopic dermatitis (AD) have been shown in clinical trials, real world data are still limited. The aim of this retrospective study is to indirectly compare the efficacy and safety of Upadacitinib and Dupilumab in patients with moderate to severe AD in real world practice.</div></div><div><h3>Methods</h3><div>A single-center retrospective cohort study was conducted. The study included patients with moderate to severe AD, who were enrolled from May 2022 to March 2024, to indirectly compare the efficacy and safety of Upadacitinib and Dupilumab over 12 weeks duration.</div></div><div><h3>Results</h3><div>Eighty-seven patients were included (46 received Upadacitinib and 41 Dupilumab). Compared with week 0, there was a significant decrease in EASI score, ADCT score and NRS score in patients of both groups in weeks 4, 8, and 12. In week 4, the reduction in EASI score, ADCT score and NRS score was significantly greater in patients of Upadacitinib group compared to those in Dupilumab group. Compared to baseline, in week 12, the decrease in IL-4, IL-13, and IL-31 level in the serum of patients in Upadacitinib group was significantly greater than that of patients in Dupilumab group. The total IgE of patients in Dupilumab group decreased significantly, while there was no significant change in patients of Upadacitinib group. Although Upadacitinib group reported more adverse events than Dupilumab group, no serious adverse events were observed.</div></div><div><h3>Conclusions</h3><div>Both Upadacitinib and Dupilumab groups showed effective trend in patients with moderate to severe AD. Upadacitinib has better efficacy and rapid onset in the treatment of patients with moderate to severe AD.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142437964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1016/j.intimp.2024.113376
Heat stress (HS) induces various pathophysiological responses in the brain, encompassing neuroinflammation and cognitive impairments. Although taurine has been reported to possess anti-inflammatory and cognitive-enhancing properties, its role and mechanisms in HS-induced cognitive impairment remain unclear. This study supplemented mice exposed to HS with taurine to assess its effect on cognitive function in a HS-induced mouse model. The results revealed that taurine ameliorated cognitive deficits following HS in mice and mitigated HS-induced astrocyte and microglia activation as well as blood–brain barrier (BBB) damage in the hippocampus. Mechanistically, Mechanistically, transcriptome sequencing was employed to identify that taurine regulates neuronal PAS domain protein (Npas4) and lipocalin 2 (Lcn2) during HS. Taurine was found to modulate hippocampal inflammation and influence cognitive function by upregulating Npas4 and downregulating Lcn2 after HS. Subsequently, molecular docking and AnimalTFDB database calculations were conducted, revealing that taurine might regulate the expression of Npas4 and Lcn2 by modulating the regulatory transcription factors (TFs) RE1 silencing transcription factor (REST) and nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1). Our findings demonstrate that taurine enhances the recovery of cognitive function through Npas4 and Lcn2 following HS, providing a theoretical basis for the clinical application of taurine in preventing or treating HS-induced cognitive impairment.
{"title":"Protective effects of taurine on heat Stress-Induced cognitive impairment through Npas4 and Lcn2","authors":"","doi":"10.1016/j.intimp.2024.113376","DOIUrl":"10.1016/j.intimp.2024.113376","url":null,"abstract":"<div><div>Heat stress (HS) induces various pathophysiological responses in the brain, encompassing neuroinflammation and cognitive impairments. Although taurine has been reported to possess anti-inflammatory and cognitive-enhancing properties, its role and mechanisms in HS-induced cognitive impairment remain unclear. This study supplemented mice exposed to HS with taurine to assess its effect on cognitive function in a HS-induced mouse model. The results revealed that taurine ameliorated cognitive deficits following HS in mice and mitigated HS-induced astrocyte and microglia activation as well as blood–brain barrier (BBB) damage in the hippocampus. Mechanistically, Mechanistically, transcriptome sequencing was employed to identify that taurine regulates neuronal PAS domain protein (<em>Npas4</em>) and lipocalin 2 (<em>Lcn2</em>) during HS. Taurine was found to modulate hippocampal inflammation and influence cognitive function by upregulating <em>Npas4</em> and downregulating <em>Lcn2</em> after HS. Subsequently, molecular docking and AnimalTFDB database calculations were conducted, revealing that taurine might regulate the expression of <em>Npas4</em> and <em>Lcn2</em> by modulating the regulatory transcription factors (TFs) RE1 silencing transcription factor (REST) and nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1). Our findings demonstrate that taurine enhances the recovery of cognitive function through <em>Npas4</em> and <em>Lcn2</em> following HS, providing a theoretical basis for the clinical application of taurine in preventing or treating HS-induced cognitive impairment.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142437963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1016/j.intimp.2024.113377
Background
Cardiac lymphatic vessels are important channels for cardiac fluid circulation and immune regulation. In myocardial infarction and chronic heart failure, promoting cardiac lymphangiogenesis is beneficial in reducing cardiac edema and inflammation. However, the specific involvement of cardiac lymphangiogenesis in viral myocarditis (VMC) has not been studied. Despite the recognized participation of macrophages in lymphangiogenesis, the contribution of macrophages to cardiac lymphangiogenesis in VMC is still unclear.
Methods
The male Balb/c mice with VMC were grouped according to the time to explore changes in inflammation, cardiac function and lymphangiogenesis. Adeno-associated virus (AAV) was used to determine the effect of cardiac lymphangiogenesis in VMC. Macrophage depletion and VEGF-CC156S treatment were used to investigate the connection between macrophages and cardiac lymphangiogenesis.
Results
Cardiac inflammation and lymphatic vessel density were both upregulated, peaking on day 7 following CVB3 infection. After treatment with AAV-sVEGFR3, lymphangiogenesis was inhibited, leading to worsened cardiac dysfunction and aggravated inflammation. However, these effects were reversed by AAV-VEGF-C treatment. Furthermore, macrophages infiltrated the inflamed myocardium and secreted VEGF-C. In vitro, VEGF-C was upregulated when RAW264.7 cells were co-cultured with CVB3. Macrophage depletion in mice with VMC inhibited lymphangiogenesis, while supplementation with VEGF-CC156S depressed it.
Conclusion
Collectively, these results indicate that activation of the VEGF-C/VEGFR3 axis exerts a protective effect in CVB3-induced VMC by resolving inflammation and alleviating cardiac dysfunction through increased lymphatic vasculature density, with macrophage-derived VEGF-C partially contributing to this effect.
{"title":"Macrophage-derived VEGF-C reduces cardiac inflammation and prevents heart dysfunction in CVB3-induced viral myocarditis via remodeling cardiac lymphatic vessels","authors":"","doi":"10.1016/j.intimp.2024.113377","DOIUrl":"10.1016/j.intimp.2024.113377","url":null,"abstract":"<div><h3>Background</h3><div>Cardiac lymphatic vessels are important channels for cardiac fluid circulation and immune regulation. In myocardial infarction and chronic heart failure, promoting cardiac lymphangiogenesis is beneficial in reducing cardiac edema and inflammation. However, the specific involvement of cardiac lymphangiogenesis in viral myocarditis (VMC) has not been studied. Despite the recognized participation of macrophages in lymphangiogenesis, the contribution of macrophages to cardiac lymphangiogenesis in VMC is still unclear.</div></div><div><h3>Methods</h3><div>The male Balb/c mice with VMC were grouped according to the time to explore changes in inflammation, cardiac function and lymphangiogenesis. Adeno-associated virus (AAV) was used to determine the effect of cardiac lymphangiogenesis in VMC. Macrophage depletion and VEGF-C<sub>C156S</sub> treatment were used to investigate the connection between macrophages and cardiac lymphangiogenesis.</div></div><div><h3>Results</h3><div>Cardiac inflammation and lymphatic vessel density were both upregulated, peaking on day 7 following CVB3 infection. After treatment with AAV-sVEGFR3, lymphangiogenesis was inhibited, leading to worsened cardiac dysfunction and aggravated inflammation. However, these effects were reversed by AAV-VEGF-C treatment. Furthermore, macrophages infiltrated the inflamed myocardium and secreted VEGF-C. In vitro, VEGF-C was upregulated when RAW264.7 cells were co-cultured with CVB3. Macrophage depletion in mice with VMC inhibited lymphangiogenesis, while supplementation with VEGF-C<sub>C156S</sub> depressed it.</div></div><div><h3>Conclusion</h3><div>Collectively, these results indicate that activation of the VEGF-C/VEGFR3 axis exerts a protective effect in CVB3-induced VMC by resolving inflammation and alleviating cardiac dysfunction through increased lymphatic vasculature density, with macrophage-derived VEGF-C partially contributing to this effect.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142437966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号