Pub Date : 2024-12-01Epub Date: 2024-07-01DOI: 10.1080/08916934.2024.2364686
Wenjuan Xu, Yuanyuan Zhang, Lijuan Li, Liyan Pan, Li Lu, Shenshen Zhi, Wei Li
Background: Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic agents for OA.
Objective: This study aimed to investigate the role of exosomes derived from osteocytes in OA, particularly focusing on their effects on cartilage repair and molecular mechanisms.
Methods: An injury cell model was established by treating chondrocytes with IL-1β. Cartilage repair was evaluated using cell counting kit-8, flow cytometry, scratch test, and Western Blot. Molecular mechanisms were analyzed using quantitative real-time PCR, bioinformatic analysis, and Western Blot. An OA mouse model was established to explore the role of exosomal DLX2 in vivo.
Results: Osteocyte-released exosomes promoted cell viability and migration, and inhibited apoptosis and extracellular matrix (ECM) deposition. Moreover, exosomes upregulated DLX2 expression, and knockdown of DLX2 activated the Wnt pathway. Additionally, exosomes attenuated OA in mice by transmitting DLX2.
Conclusion: Osteocyte-derived exosomal DLX2 alleviated IL-1β-induced cartilage repair and inactivated the Wnt pathway, thereby alleviating OA progression. The findings suggested that osteocyte-derived exosomes may hold promise as a treatment for OA.
背景:软骨细胞的活力、凋亡和迁移与骨关节炎(OA)关节软骨损伤密切相关。外泌体被认为是治疗 OA 的潜在药物:本研究旨在探讨从骨细胞中提取的外泌体在 OA 中的作用,特别是其对软骨修复的影响和分子机制:方法:用 IL-1β 处理软骨细胞,建立损伤细胞模型。方法:用 IL-1β 处理软骨细胞,建立损伤细胞模型,使用细胞计数试剂盒-8、流式细胞术、划痕试验和 Western Blot 评估软骨修复情况。使用定量实时 PCR、生物信息分析和 Western 印迹分析了分子机制。建立了OA小鼠模型,以探索外泌体DLX2在体内的作用:结果:骨细胞释放的外泌体促进了细胞活力和迁移,抑制了细胞凋亡和细胞外基质(ECM)沉积。此外,外泌体可上调 DLX2 的表达,敲除 DLX2 可激活 Wnt 通路。此外,外泌体通过传递 DLX2 减轻了小鼠的 OA:结论:骨细胞衍生的外泌体DLX2可缓解IL-1β诱导的软骨修复,并使Wnt通路失活,从而缓解OA进展。研究结果表明,骨细胞衍生的外泌体有望成为治疗OA的一种方法。
{"title":"Osteocyte-derived exosomes regulate the DLX2/wnt pathway to alleviate osteoarthritis by mediating cartilage repair.","authors":"Wenjuan Xu, Yuanyuan Zhang, Lijuan Li, Liyan Pan, Li Lu, Shenshen Zhi, Wei Li","doi":"10.1080/08916934.2024.2364686","DOIUrl":"10.1080/08916934.2024.2364686","url":null,"abstract":"<p><strong>Background: </strong>Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic agents for OA.</p><p><strong>Objective: </strong>This study aimed to investigate the role of exosomes derived from osteocytes in OA, particularly focusing on their effects on cartilage repair and molecular mechanisms.</p><p><strong>Methods: </strong>An injury cell model was established by treating chondrocytes with IL-1β. Cartilage repair was evaluated using cell counting kit-8, flow cytometry, scratch test, and Western Blot. Molecular mechanisms were analyzed using quantitative real-time PCR, bioinformatic analysis, and Western Blot. An OA mouse model was established to explore the role of exosomal DLX2 <i>in vivo</i>.</p><p><strong>Results: </strong>Osteocyte-released exosomes promoted cell viability and migration, and inhibited apoptosis and extracellular matrix (ECM) deposition. Moreover, exosomes upregulated DLX2 expression, and knockdown of DLX2 activated the Wnt pathway. Additionally, exosomes attenuated OA in mice by transmitting DLX2.</p><p><strong>Conclusion: </strong>Osteocyte-derived exosomal DLX2 alleviated IL-1β-induced cartilage repair and inactivated the Wnt pathway, thereby alleviating OA progression. The findings suggested that osteocyte-derived exosomes may hold promise as a treatment for OA.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-02-07DOI: 10.1080/08916934.2024.2312927
Yeke Wu, Bin Li, Disi Deng, Hongling Zhou, Min Liu, Huangping Ai, Yilin Xin, Weihan Hua, Lixing Zhao, Li Li
MicroRNA (miRNA) plays a regulatory role in periodontitis. This study aimed to explore whether miR-29a could affect lipopolysaccharides (LPSs)-induced injury in human gingival fibroblasts (HGFs) through the competitive endogenous RNAs (ceRNA) mechanism. Periodontal ligament (PDL) tissues and HGFs were derived from patients with periodontitis and healthy volunteers. Periodontitis cell model was established by treating HGFs with LPS. Expression levels of circ_0036490, miR-29a, and DKK1 were evaluated by the reverse transcription quantitative real-time PCR (RT-qPCR) method. Western blotting assay was performed to assess protein expression levels of pyroptosis-related proteins and Wnt signalling related proteins. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Concentration of lactate dehydrogenase (LDH), interleukin (IL)-1β, and IL-18 were determined by Enzyme-linked immunosorbent assay (ELISA). Pyroptosis rate were determined by flow cytometry assay to evaluate pyroptosis. The interaction between miR-29a and circ_0036490 or DKK1 was verified by dual-luciferase reporter and RNA pull-down assays. MiR-29a expression was lower in PDL tissues of patients with periodontitis than that in healthy group; likewise, miR-29a was also downregulated in LPS-treated HGFs. Overexpression of miR-29a increased cell viability and decreased pyroptosis of HGFs induced by LPS while inhibition of miR-29a exerted the opposite role. MiR-29a binds to circ_0036490 and elevation of circ_0036490 contributed to dysfuntion of LPS-treated HGFs and reversed the protection function of elevated miR-29a. In addition, miR-29a targets DKK1. Overexpression of DKK1 abrogated the effects of overexpressed miR-29a on cell vaibility, pyroptosis, and protein levels of Wnt signalling pathway of LPS-treated HGFs. Circ_0036490 and DKK1 competitively bind miR-29a to promote LPS-induced HGF injury in vitro. Wnt pathway inactivated by LPS was activated by miR-29a. Thence, miR-29a may be a promising target for periodontitis.
{"title":"Circ_0036490 and DKK1 competitively bind miR-29a to promote lipopolysaccharides-induced human gingival fibroblasts injury.","authors":"Yeke Wu, Bin Li, Disi Deng, Hongling Zhou, Min Liu, Huangping Ai, Yilin Xin, Weihan Hua, Lixing Zhao, Li Li","doi":"10.1080/08916934.2024.2312927","DOIUrl":"10.1080/08916934.2024.2312927","url":null,"abstract":"<p><p>MicroRNA (miRNA) plays a regulatory role in periodontitis. This study aimed to explore whether miR-29a could affect lipopolysaccharides (LPSs)-induced injury in human gingival fibroblasts (HGFs) through the competitive endogenous RNAs (ceRNA) mechanism. Periodontal ligament (PDL) tissues and HGFs were derived from patients with periodontitis and healthy volunteers. Periodontitis cell model was established by treating HGFs with LPS. Expression levels of circ_0036490, miR-29a, and DKK1 were evaluated by the reverse transcription quantitative real-time PCR (RT-qPCR) method. Western blotting assay was performed to assess protein expression levels of pyroptosis-related proteins and Wnt signalling related proteins. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Concentration of lactate dehydrogenase (LDH), interleukin (IL)-1β, and IL-18 were determined by Enzyme-linked immunosorbent assay (ELISA). Pyroptosis rate were determined by flow cytometry assay to evaluate pyroptosis. The interaction between miR-29a and circ_0036490 or DKK1 was verified by dual-luciferase reporter and RNA pull-down assays. MiR-29a expression was lower in PDL tissues of patients with periodontitis than that in healthy group; likewise, miR-29a was also downregulated in LPS-treated HGFs. Overexpression of miR-29a increased cell viability and decreased pyroptosis of HGFs induced by LPS while inhibition of miR-29a exerted the opposite role. MiR-29a binds to circ_0036490 and elevation of circ_0036490 contributed to dysfuntion of LPS-treated HGFs and reversed the protection function of elevated miR-29a. In addition, miR-29a targets DKK1. Overexpression of DKK1 abrogated the effects of overexpressed miR-29a on cell vaibility, pyroptosis, and protein levels of Wnt signalling pathway of LPS-treated HGFs. Circ_0036490 and DKK1 competitively bind miR-29a to promote LPS-induced HGF injury <i>in vitro</i>. Wnt pathway inactivated by LPS was activated by miR-29a. Thence, miR-29a may be a promising target for periodontitis.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139696870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-03-28DOI: 10.1080/08916934.2024.2332340
Yang Xue, Pengqi Yin, Hongping Chen, Guozhong Li, Di Zhong
Interferon-beta (IFN-) is one of the classical drugs for immunomodulatory therapy in relapsing-remitting multiple sclerosis (RRMS) patients, but the drug responsiveness of different patients varies. Currently, there is no valid model to predict IFN- responsiveness. This research attempted to develop an IFN- responsiveness prediction model based on mRNA expression in RRMS patient peripheral blood mononuclear cells. Peripheral blood mononuclear cell mRNA expression datasets including 50 RRMS patients receiving IFN- treatment were obtained from GEO. Among the datasets, 24 cases from GSE24427 were included in a training set, and 18 and 9 cases from GSE19285 and GSE33464, respectively, were adopted as two independent test sets. In the training set, blood samples were collected immediately before first, second, month 1, 12, and 24 IFN- injection, and the mRNA expression data at four time points, namely, two days, one month, one year and two years after the onset of IFN- treatment, were compared with pre-treatment data to identify IFN-stimulated genes (ISGs). The ISGs at the one-month time point were used to construct the drug responsiveness prediction model. Next, the drug responsiveness model was verified in the two independent test sets to examine the performance of the model in predicting drug responsiveness. Finally, we used CIBERSORTx to estimate the content of cell subtypes in samples and evaluated whether differences in the proportions of cell subtypes were related to differences in IFN- responsiveness. Among the four time points, one month was the time point when the training set GSE24427 and test set GSE33464 had the highest number of ISGs. Functional analysis showed that these one-month ISGs were enriched in biological functions such as the innate immune response, type-I interferon signalling pathway, and other IFN--associated functions. Based on these ISGs, we obtained a four-factor prediction model for IFN- responsiveness including MX1, MX2, XAF1, and LAMP3. In addition, the model demonstrated favourable predictive performance within the training set and two external test sets. A higher proportion of activated NK cells and lower naive CD4/total CD4 ratio might indicate better drug responsiveness. This research developed a polygene-based biomarker model that could predict RRMS patient IFN- responsiveness in the early treatment period. This model could probably help doctors screen out patients who would not benefit from IFN- treatment early and determine whether a current treatment plan should be continued.
{"title":"Novel peripheral blood mononuclear cell mRNA signature for IFN-beta therapy responsiveness prediction in multiple sclerosis.","authors":"Yang Xue, Pengqi Yin, Hongping Chen, Guozhong Li, Di Zhong","doi":"10.1080/08916934.2024.2332340","DOIUrl":"10.1080/08916934.2024.2332340","url":null,"abstract":"<p><p>Interferon-beta (IFN-<math><mrow><mi>β</mi></mrow></math>) is one of the classical drugs for immunomodulatory therapy in relapsing-remitting multiple sclerosis (RRMS) patients, but the drug responsiveness of different patients varies. Currently, there is no valid model to predict IFN-<math><mrow><mi>β</mi></mrow></math> responsiveness. This research attempted to develop an IFN-<math><mrow><mi>β</mi></mrow></math> responsiveness prediction model based on mRNA expression in RRMS patient peripheral blood mononuclear cells. Peripheral blood mononuclear cell mRNA expression datasets including 50 RRMS patients receiving IFN-<math><mrow><mi>β</mi></mrow></math> treatment were obtained from GEO. Among the datasets, 24 cases from GSE24427 were included in a training set, and 18 and 9 cases from GSE19285 and GSE33464, respectively, were adopted as two independent test sets. In the training set, blood samples were collected immediately before first, second, month 1, 12, and 24 IFN-<math><mrow><mi>β</mi></mrow></math> injection, and the mRNA expression data at four time points, namely, two days, one month, one year and two years after the onset of IFN-<math><mrow><mi>β</mi></mrow></math> treatment, were compared with pre-treatment data to identify IFN-stimulated genes (ISGs). The ISGs at the one-month time point were used to construct the drug responsiveness prediction model. Next, the drug responsiveness model was verified in the two independent test sets to examine the performance of the model in predicting drug responsiveness. Finally, we used CIBERSORTx to estimate the content of cell subtypes in samples and evaluated whether differences in the proportions of cell subtypes were related to differences in IFN-<math><mrow><mi>β</mi></mrow></math> responsiveness. Among the four time points, one month was the time point when the training set GSE24427 and test set GSE33464 had the highest number of ISGs. Functional analysis showed that these one-month ISGs were enriched in biological functions such as the innate immune response, type-I interferon signalling pathway, and other IFN-<math><mrow><mi>β</mi></mrow></math>-associated functions. Based on these ISGs, we obtained a four-factor prediction model for IFN-<math><mrow><mi>β</mi></mrow></math> responsiveness including MX1, MX2, XAF1, and LAMP3. In addition, the model demonstrated favourable predictive performance within the training set and two external test sets. A higher proportion of activated NK cells and lower naive CD4/total CD4 ratio might indicate better drug responsiveness. This research developed a polygene-based biomarker model that could predict RRMS patient IFN-<math><mrow><mi>β</mi></mrow></math> responsiveness in the early treatment period. This model could probably help doctors screen out patients who would not benefit from IFN-<math><mrow><mi>β</mi></mrow></math> treatment early and determine whether a current treatment plan should be continued.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140304557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-01-25DOI: 10.1080/08916934.2024.2304820
Xianzhao Cao, Hongyan Fang, Longshu Zhou
Circular RNA (circRNA) has been found to be differentially expressed and involved in regulating the processes of human diseases, including thoracic aortic dissection (TAD). However, the role and mechanism of circNRIP1 in the TAD process are still unclear. GEO database was used to screen the differentially expressed circRNA and mRNA in type A TAD patients and age-matched normal donors. Angiotensin II (Ang II)-induced human aortic vascular smooth muscle cells (HA-VSMCs) were used to construct TAD cell models. The expression levels of circNRIP1, NRIP1, CXC-motif chemokine 5 (CXCL5) and IGF2BP1 were detected by quantitative real-time PCR. Cell proliferation and migration were determined by EdU assay, transwell assay and wound healing assay. The protein levels of synthetic phenotype markers, contractile phenotype markers, CXCL5 and IGF2BP1 were tested by western blot analysis. The interaction between IGF2BP1 and circNRIP1/CXCL5 was confirmed by RIP assay, and CXCL5 mRNA stability was assessed by actinomycin D assay. CircNRIP1 was upregulated in TAD patients and Ang II-induced HA-VSMCs. Knockdown of circNRIP1 suppressed Ang II-induced proliferation, migration and phenotypic switch of HA-VSMCs. Also, high expression of CXCL5 was observed in TAD patients, and its knockdown could inhibit Ang II-induced HA-VSMCs proliferation, migration and phenotypic switch. Moreover, CXCL5 overexpression reversed the regulation of circNRIP1 knockdown on Ang II-induced HA-VSMCs functions. Mechanistically, circNRIP1 could competitively bind to IGF2BP1 and subsequently enhance CXCL5 mRNA stability. CircNRIP1 might contribute to TAD progression by promoting CXCL5 mRNA stability via recruiting IGF2BP1.
研究发现,环状 RNA(circRNA)存在差异表达,并参与调控包括胸主动脉夹层(TAD)在内的人类疾病的发生过程。然而,circNRIP1在TAD过程中的作用和机制仍不清楚。研究人员利用 GEO 数据库筛选了 A 型 TAD 患者和年龄匹配的正常供体中差异表达的 circRNA 和 mRNA。用血管紧张素 II(Ang II)诱导的人主动脉血管平滑肌细胞(HA-VSMCs)构建 TAD 细胞模型。通过实时定量 PCR 检测 circNRIP1、NRIP1、CXC-motif 趋化因子 5 (CXCL5) 和 IGF2BP1 的表达水平。细胞增殖和迁移通过 EdU 试验、Transwell 试验和伤口愈合试验进行测定。通过 Western 印迹分析检测了合成表型标记物、收缩表型标记物、CXCL5 和 IGF2BP1 的蛋白水平。RIP 试验证实了 IGF2BP1 与 circNRIP1/CXCL5 之间的相互作用,放线菌素 D 试验评估了 CXCL5 mRNA 的稳定性。circNRIP1 在 TAD 患者和 Ang II 诱导的 HA-VSMCs 中上调。敲除 circNRIP1 可抑制 Ang II 诱导的 HA-VSMCs 增殖、迁移和表型转换。同时,在 TAD 患者中观察到 CXCL5 的高表达,敲除 CXCL5 可抑制 Ang II 诱导的 HA-VSMCs 增殖、迁移和表型转换。此外,CXCL5 的过表达可逆转 circNRIP1 敲除对 Ang II 诱导的 HA-VSMCs 功能的调节。从机理上讲,circNRIP1可与IGF2BP1竞争性结合,从而增强CXCL5 mRNA的稳定性。CircNRIP1可能通过招募IGF2BP1促进CXCL5 mRNA的稳定性,从而促进TAD的进展。
{"title":"CircNRIP1 promotes proliferation, migration and phenotypic switch of Ang II-induced HA-VSMCs by increasing CXCL5 mRNA stability via recruiting IGF2BP1.","authors":"Xianzhao Cao, Hongyan Fang, Longshu Zhou","doi":"10.1080/08916934.2024.2304820","DOIUrl":"10.1080/08916934.2024.2304820","url":null,"abstract":"<p><p>Circular RNA (circRNA) has been found to be differentially expressed and involved in regulating the processes of human diseases, including thoracic aortic dissection (TAD). However, the role and mechanism of circNRIP1 in the TAD process are still unclear. GEO database was used to screen the differentially expressed circRNA and mRNA in type A TAD patients and age-matched normal donors. Angiotensin II (Ang II)-induced human aortic vascular smooth muscle cells (HA-VSMCs) were used to construct TAD cell models. The expression levels of circNRIP1, NRIP1, CXC-motif chemokine 5 (CXCL5) and IGF2BP1 were detected by quantitative real-time PCR. Cell proliferation and migration were determined by EdU assay, transwell assay and wound healing assay. The protein levels of synthetic phenotype markers, contractile phenotype markers, CXCL5 and IGF2BP1 were tested by western blot analysis. The interaction between IGF2BP1 and circNRIP1/CXCL5 was confirmed by RIP assay, and CXCL5 mRNA stability was assessed by actinomycin D assay. CircNRIP1 was upregulated in TAD patients and Ang II-induced HA-VSMCs. Knockdown of circNRIP1 suppressed Ang II-induced proliferation, migration and phenotypic switch of HA-VSMCs. Also, high expression of CXCL5 was observed in TAD patients, and its knockdown could inhibit Ang II-induced HA-VSMCs proliferation, migration and phenotypic switch. Moreover, CXCL5 overexpression reversed the regulation of circNRIP1 knockdown on Ang II-induced HA-VSMCs functions. Mechanistically, circNRIP1 could competitively bind to IGF2BP1 and subsequently enhance CXCL5 mRNA stability. CircNRIP1 might contribute to TAD progression by promoting CXCL5 mRNA stability <i>via</i> recruiting IGF2BP1.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139544636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-03-11DOI: 10.1080/08916934.2024.2321908
Qi Liu, Li Liao
Macrophages play a crucial role in tumor initiation and progression, while macrophage-associated gene signature in colorectal cancer (CRC) patients has not been investigated. Our study aimed to identify macrophage-related molecular subgroups and develop a macrophage-related risk model to predict CRC prognosis. The mRNA expression profile and clinical information of CRC patients were obtained from TCGA and GEO databases. CRC patients from TCGA were divided into high and low macrophage subgroups based on the median macrophage score. The ESTIMATE and CIBERSORT algorithms were used to assess immune cell infiltration between subgroups. GSVA and GSEA analyses were performed to investigate differences in enriched pathways between subgroups. Univariate and LASSO Cox regression were used to build a prognostic risk model, which was further validated in the GSE39582 dataset. A high macrophage score subgroup was associated with poor prognosis, highly activated immune-related pathways and an immune-active microenvironment. A total of 547 differentially expressed macrophage-related genes (DEMRGs) were identified, among which seven genes (including RIMKLB, UST, PCOLCE2, ZNF829, TMEM59L, CILP2, DTNA) were identified by COX regression analyses and used to build a risk score model. The risk model shows good predictive and diagnostic values for CRC patients in both TCGA and GSE39852 datasets. Furthermore, multivariate Cox regression analysis showed that the risk score was an independent risk factor for overall survival in CRC patients. Our findings provided a novel insight into macrophage heterogeneity and its immunological role in CRC. This risk score model may serve as an effective prognostic tool and contribute to personalised clinical management of CRC patients.
{"title":"Identification of macrophage-related molecular subgroups and risk signature in colorectal cancer based on a bioinformatics analysis.","authors":"Qi Liu, Li Liao","doi":"10.1080/08916934.2024.2321908","DOIUrl":"10.1080/08916934.2024.2321908","url":null,"abstract":"<p><p>Macrophages play a crucial role in tumor initiation and progression, while macrophage-associated gene signature in colorectal cancer (CRC) patients has not been investigated. Our study aimed to identify macrophage-related molecular subgroups and develop a macrophage-related risk model to predict CRC prognosis. The mRNA expression profile and clinical information of CRC patients were obtained from TCGA and GEO databases. CRC patients from TCGA were divided into high and low macrophage subgroups based on the median macrophage score. The ESTIMATE and CIBERSORT algorithms were used to assess immune cell infiltration between subgroups. GSVA and GSEA analyses were performed to investigate differences in enriched pathways between subgroups. Univariate and LASSO Cox regression were used to build a prognostic risk model, which was further validated in the GSE39582 dataset. A high macrophage score subgroup was associated with poor prognosis, highly activated immune-related pathways and an immune-active microenvironment. A total of 547 differentially expressed macrophage-related genes (DEMRGs) were identified, among which seven genes (including RIMKLB, UST, PCOLCE2, ZNF829, TMEM59L, CILP2, DTNA) were identified by COX regression analyses and used to build a risk score model. The risk model shows good predictive and diagnostic values for CRC patients in both TCGA and GSE39852 datasets. Furthermore, multivariate Cox regression analysis showed that the risk score was an independent risk factor for overall survival in CRC patients. Our findings provided a novel insight into macrophage heterogeneity and its immunological role in CRC. This risk score model may serve as an effective prognostic tool and contribute to personalised clinical management of CRC patients.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Soil-transmitted helminth (STH) among children aged 24-59 months is one cause of chronic infection that could lead to stunting. The association of 25(OH)D and immune responses during chronic infection in stunted populations has not yet been well established. An association study of case-control data was conducted in Bandung district from October 2019 to January 2023. Sociodemographic factors, stool samples, and serum levels of 25(OH)D, interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13) were assessed. Statistical analysis was performed to evaluate the prevalence and association of 25(OH)D, IL-4, IL-5, and IL-13 with the burden of STH infection in stunted children. In total, 401 stunted children were recruited. A higher burden of STH infection was found for lower levels of IL-5 (r = -0.477; p = 0.004) and IL-13 (r = -0.433; p = 0.028). Thus, 25(OH)D, IL-4, IL-5, and IL-13 play a role in the burden of STH infection.
{"title":"The association of 25(OH)D, interleukin-4, interleukin-5, and interleukin-13 levels with the burden of soil-transmitted helminth infection in stunted children aged 24-59 months.","authors":"Riyadi Adrizain, Monika Verena Nagari, Djatnika Setiabudi, Afiat Berbudi, Budi Setiabudiawan","doi":"10.1080/08916934.2024.2330394","DOIUrl":"10.1080/08916934.2024.2330394","url":null,"abstract":"<p><p>Soil-transmitted helminth (STH) among children aged 24-59 months is one cause of chronic infection that could lead to stunting. The association of 25(OH)D and immune responses during chronic infection in stunted populations has not yet been well established. An association study of case-control data was conducted in Bandung district from October 2019 to January 2023. Sociodemographic factors, stool samples, and serum levels of 25(OH)D, interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13) were assessed. Statistical analysis was performed to evaluate the prevalence and association of 25(OH)D, IL-4, IL-5, and IL-13 with the burden of STH infection in stunted children. In total, 401 stunted children were recruited. A higher burden of STH infection was found for lower levels of IL-5 (<i>r</i> = -0.477; <i>p</i> = 0.004) and IL-13 (<i>r</i> = -0.433; <i>p</i> = 0.028). Thus, 25(OH)D, IL-4, IL-5, and IL-13 play a role in the burden of STH infection.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140142657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-03-13DOI: 10.1080/08916934.2024.2319203
Divya Katikaneni, Laurence Morel, Yogesh Scindia
Lupus nephritis (LN) is the most severe end-organ pathology in Systemic Lupus Erythematosus (SLE). Research has enhanced our understanding of immune effectors and inflammatory pathways in LN. However, even with the best available therapy, the rate of complete remission for proliferative LN remains below 50%. A deeper understanding of the resistance or susceptibility of renal cells to injury during the progression of SLE is critical for identifying new targets and developing effective long-term therapies. The complex and heterogeneous nature of LN, combined with the limitations of clinical research, make it challenging to investigate the aetiology of this disease directly in patients. Hence, multiple murine models resembling SLE-driven nephritis are utilised to dissect LN's cellular and genetic mechanisms, identify therapeutic targets, and screen novel compounds. This review discusses commonly used spontaneous and inducible mouse models that have provided insights into pathogenic mechanisms and long-term maintenance therapies in LN.
{"title":"Animal models of lupus nephritis: the past, present and a future outlook.","authors":"Divya Katikaneni, Laurence Morel, Yogesh Scindia","doi":"10.1080/08916934.2024.2319203","DOIUrl":"10.1080/08916934.2024.2319203","url":null,"abstract":"<p><p>Lupus nephritis (LN) is the most severe end-organ pathology in Systemic Lupus Erythematosus (SLE). Research has enhanced our understanding of immune effectors and inflammatory pathways in LN. However, even with the best available therapy, the rate of complete remission for proliferative LN remains below 50%. A deeper understanding of the resistance or susceptibility of renal cells to injury during the progression of SLE is critical for identifying new targets and developing effective long-term therapies. The complex and heterogeneous nature of LN, combined with the limitations of clinical research, make it challenging to investigate the aetiology of this disease directly in patients. Hence, multiple murine models resembling SLE-driven nephritis are utilised to dissect LN's cellular and genetic mechanisms, identify therapeutic targets, and screen novel compounds. This review discusses commonly used spontaneous and inducible mouse models that have provided insights into pathogenic mechanisms and long-term maintenance therapies in LN.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10981450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140108985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-07-16DOI: 10.1080/08916934.2024.2378876
Ran Lu, Xin M Luo
Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by immune system dysfunction that can lead to serious health issues and mortality. Recent investigations highlight the role of gut microbiota alterations in modulating inflammation and disease severity in SLE. This review specifically summaries the variations in gut microbiota composition across various murine models of lupus. By focusing on these differences, we aim to elucidate the intricate relationship between gut microbiota dysbiosis and the development and progression of SLE in preclinical settings.
{"title":"The role of gut microbiota in different murine models of systemic lupus erythematosus.","authors":"Ran Lu, Xin M Luo","doi":"10.1080/08916934.2024.2378876","DOIUrl":"https://doi.org/10.1080/08916934.2024.2378876","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by immune system dysfunction that can lead to serious health issues and mortality. Recent investigations highlight the role of gut microbiota alterations in modulating inflammation and disease severity in SLE. This review specifically summaries the variations in gut microbiota composition across various murine models of lupus. By focusing on these differences, we aim to elucidate the intricate relationship between gut microbiota dysbiosis and the development and progression of SLE in preclinical settings.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-03-11DOI: 10.1080/08916934.2024.2323563
Hiromi Kubagawa, Pedram Mahmoudi Aliabadi, Khlowd Al-Qaisi, Peter K Jani, Kazuhito Honjo, Shozo Izui, Andreas Radbruch, Fritz Melchers
Unlike Fc receptors for switched immunoglobulin (Ig) isotypes, Fc receptor for IgM (FcµR) is selectively expressed by lymphocytes. The ablation of the FcµR gene in mice impairs B cell tolerance as evidenced by concomitant production of autoantibodies of IgM and IgG isotypes. In this essay, we reiterate the autoimmune phenotypes observed in mutant mice, ie IgM homeostasis, dysregulated humoral immune responses including autoantibodies, and Mott cell formation. We also propose the potential phenotypes in individuals with FCMR deficiency and the model for FcµR-mediated regulation of self-reactive B cells.
与切换免疫球蛋白(Ig)异型的 Fc 受体不同,IgM 的 Fc 受体(FcµR)由淋巴细胞选择性表达。小鼠 FcµR 基因的消减会损害 B 细胞耐受性,同时产生 IgM 和 IgG 同型的自身抗体就是证明。在这篇文章中,我们重申了在突变小鼠中观察到的自身免疫表型,即 IgM 稳态、包括自身抗体在内的体液免疫反应失调和莫特细胞形成。我们还提出了 FCMR 缺乏症患者的潜在表型以及 FcµR 介导的自我反应 B 细胞调控模型。
{"title":"Functions of IgM fc receptor (FcµR) related to autoimmunity.","authors":"Hiromi Kubagawa, Pedram Mahmoudi Aliabadi, Khlowd Al-Qaisi, Peter K Jani, Kazuhito Honjo, Shozo Izui, Andreas Radbruch, Fritz Melchers","doi":"10.1080/08916934.2024.2323563","DOIUrl":"10.1080/08916934.2024.2323563","url":null,"abstract":"<p><p>Unlike Fc receptors for switched immunoglobulin (Ig) isotypes, Fc receptor for IgM (FcµR) is selectively expressed by lymphocytes. The ablation of the FcµR gene in mice impairs B cell tolerance as evidenced by concomitant production of autoantibodies of IgM and IgG isotypes. In this essay, we reiterate the autoimmune phenotypes observed in mutant mice, ie IgM homeostasis, dysregulated humoral immune responses including autoantibodies, and Mott cell formation. We also propose the potential phenotypes in individuals with <i>FCMR</i> deficiency and the model for FcµR-mediated regulation of self-reactive B cells.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}