Background Glioma is one of the most malignant tumors, which leads to high mortality in cancer patients. At present, there is no effective therapy for glioma. Therefore, it is urgent and necessary to find new molecular targets for anti-glioma therapy. Objective The present study aimed to investigate the role of signal transducer and activator of transcription 1 (STAT1) in the development and progression of human glioma and related mechanisms. Methods According to the instructions of Lipofectamine TM 2000 transfection reagent, we transiently transfected the plasmid pcDNA3.1-STAT1 into glioma U251 cells. Then STAT1 expression in glioma U251 and LN382 cells was detected by Western blot. MTT was performed to assay the proliferative activity of U251 cells after STAT1 transduction, flow cytometry was used to detect cell cycle and apoptosis indicators, cell migration indicator was determined by Wound healing, and Western blot was used for detecting the expression level and change trend of p53, p21, bcl-2, Caspase-8, Cyclin A and Cyclin E in transfected cells. Results Overexpressed STAT1 significantly inhibited U251 cell proliferation and promoted U251 cell apoptosis. Meanwhile, high expression of STAT1 can increase the expression of p53, p21, and Caspase-8 while inhibiting the expression of bcl-2, Cyclin A, and Cyclin E. Conclusion Highly expressed STAT1 inhibits the proliferative activity of human glioma U251 cells and can promote tumor cell apoptosis and block cell cycle progression while regulating the expression of various signal transduction molecules. Thus, STAT1 has a critical function in the development and progression of glioma and is a novel target for glioma therapy.
{"title":"STAT1 negatively regulates human glioma U251 cell proliferation Huang et al: Role of STAT1 in glioma","authors":"Ping Huang, Qiang Huang, Hongwei Wang, Changwu Dou, Haitao Ju, Rui Xiao, Lixia Zhang, Hailong Li","doi":"10.1177/1721727x231214924","DOIUrl":"https://doi.org/10.1177/1721727x231214924","url":null,"abstract":"Background Glioma is one of the most malignant tumors, which leads to high mortality in cancer patients. At present, there is no effective therapy for glioma. Therefore, it is urgent and necessary to find new molecular targets for anti-glioma therapy. Objective The present study aimed to investigate the role of signal transducer and activator of transcription 1 (STAT1) in the development and progression of human glioma and related mechanisms. Methods According to the instructions of Lipofectamine TM 2000 transfection reagent, we transiently transfected the plasmid pcDNA3.1-STAT1 into glioma U251 cells. Then STAT1 expression in glioma U251 and LN382 cells was detected by Western blot. MTT was performed to assay the proliferative activity of U251 cells after STAT1 transduction, flow cytometry was used to detect cell cycle and apoptosis indicators, cell migration indicator was determined by Wound healing, and Western blot was used for detecting the expression level and change trend of p53, p21, bcl-2, Caspase-8, Cyclin A and Cyclin E in transfected cells. Results Overexpressed STAT1 significantly inhibited U251 cell proliferation and promoted U251 cell apoptosis. Meanwhile, high expression of STAT1 can increase the expression of p53, p21, and Caspase-8 while inhibiting the expression of bcl-2, Cyclin A, and Cyclin E. Conclusion Highly expressed STAT1 inhibits the proliferative activity of human glioma U251 cells and can promote tumor cell apoptosis and block cell cycle progression while regulating the expression of various signal transduction molecules. Thus, STAT1 has a critical function in the development and progression of glioma and is a novel target for glioma therapy.","PeriodicalId":11913,"journal":{"name":"European Journal of Inflammation","volume":"16 5","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134957726","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 : 2023-11-13DOI: 10.1177/1721727x231210425
Waleed Hakami, Gasim Dobie, Abdullah A Mobarki, Aymen M Madkhali, Mohmmad S. Akhter, Abdulrahim R Hakami, Mohammed H Nahari, Yahya H Matari, Khaled Essawi, Ali Hakamy, Mohammad Algahtani, Denise E Jackson, Hassan A Hamali
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still a global concern with high morbidity and mortality rates. The role of endothelial cells in the progress of COVID-19 is well established. Therefore, the current study aimed to measure the endothelial markers and their correlation with the hematological parameters in intensive care unit-admitted COVID-19 patients. This study involved 111 adult participants, including 55 ICU-admitted patients with COVID-19 and 56 healthy controls. Levels of E-selectin, ICAM-1, and VCAM-1 in the plasma of the study participants were measured and correlated with hematological parameters. The study demonstrates that COVID-19 patients admitted to the ICU have higher levels of E-selectin, ICAM-1, and VCAM-1 compared to healthy controls ( p < .05). These elevated levels can serve as reliable indicators of endothelial dysfunction and early markers for the detection and prediction of endothelial cell involvement in COVID-19 complications. The findings of this study suggest that increased levels of E-selectin, VCAM-1, and ICAM-1 in patients with COVID-19 are indicative of the participation of endothelial cells in the pathogenesis of COVID-19 complications. Consequently, these endothelial markers are proposed as potential early indicators for predicting the severity of COVID-19.
{"title":"Correlation of circulating endothelial markers in COVID-19 patients admitted to the intensive care unit with laboratory data","authors":"Waleed Hakami, Gasim Dobie, Abdullah A Mobarki, Aymen M Madkhali, Mohmmad S. Akhter, Abdulrahim R Hakami, Mohammed H Nahari, Yahya H Matari, Khaled Essawi, Ali Hakamy, Mohammad Algahtani, Denise E Jackson, Hassan A Hamali","doi":"10.1177/1721727x231210425","DOIUrl":"https://doi.org/10.1177/1721727x231210425","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still a global concern with high morbidity and mortality rates. The role of endothelial cells in the progress of COVID-19 is well established. Therefore, the current study aimed to measure the endothelial markers and their correlation with the hematological parameters in intensive care unit-admitted COVID-19 patients. This study involved 111 adult participants, including 55 ICU-admitted patients with COVID-19 and 56 healthy controls. Levels of E-selectin, ICAM-1, and VCAM-1 in the plasma of the study participants were measured and correlated with hematological parameters. The study demonstrates that COVID-19 patients admitted to the ICU have higher levels of E-selectin, ICAM-1, and VCAM-1 compared to healthy controls ( p < .05). These elevated levels can serve as reliable indicators of endothelial dysfunction and early markers for the detection and prediction of endothelial cell involvement in COVID-19 complications. The findings of this study suggest that increased levels of E-selectin, VCAM-1, and ICAM-1 in patients with COVID-19 are indicative of the participation of endothelial cells in the pathogenesis of COVID-19 complications. Consequently, these endothelial markers are proposed as potential early indicators for predicting the severity of COVID-19.","PeriodicalId":11913,"journal":{"name":"European Journal of Inflammation","volume":"1 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136347867","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}
Following infection with SARS-CoV-2, cellular components of the adaptive immune system play a crucial role in eliminating the virus. Specifically, virus-specific CD4+ and CD8+ T cells generate effector cytokines and display cytotoxic activity. A number of studies carried out during the COVID-19 pandemic highlighted the importance of CD4+ T cells, CD8+ T cells, and memory cells in this process. T-cell responses emerge early and contribute to protection, but are comparatively impaired in severe cases, often accompanied by intense activation or lymphopenia. Since December 2020, SARS-CoV-2 vaccines have been licensed and administered worldwide. These vaccines induce a targeted T-cell response against SARS-CoV-2. The cellular response after the third dose was strong and superior to that obtained with the second dose. COVID-19 multiple vaccines elicit a robust CD4+ and CD8+ T cell response after the short-term booster. While, the T-cell response induced by COVID-19 vaccines has been shown to decline within 6-12 months of vaccination. In addition, the long-term persistence of cellular immunity may protect against the development of severe disease. In addition, adoptive T-cell therapies have shown considerable potential in the development of COVID-19 traitement. These therapies involve the transfer of T cells with specific antiviral properties into patients to boost their immune response against SARS-CoV-2.
{"title":"Insights into the T-cell response to SARS-CoV-2","authors":"Chaimae Kadi, Nouhaila Najimi, Menanne Zakaria, Bakri Youssef, Elmtili Noureddine, Seghrouchni Fouad","doi":"10.1177/1721727x231211458","DOIUrl":"https://doi.org/10.1177/1721727x231211458","url":null,"abstract":"Following infection with SARS-CoV-2, cellular components of the adaptive immune system play a crucial role in eliminating the virus. Specifically, virus-specific CD4+ and CD8+ T cells generate effector cytokines and display cytotoxic activity. A number of studies carried out during the COVID-19 pandemic highlighted the importance of CD4+ T cells, CD8+ T cells, and memory cells in this process. T-cell responses emerge early and contribute to protection, but are comparatively impaired in severe cases, often accompanied by intense activation or lymphopenia. Since December 2020, SARS-CoV-2 vaccines have been licensed and administered worldwide. These vaccines induce a targeted T-cell response against SARS-CoV-2. The cellular response after the third dose was strong and superior to that obtained with the second dose. COVID-19 multiple vaccines elicit a robust CD4+ and CD8+ T cell response after the short-term booster. While, the T-cell response induced by COVID-19 vaccines has been shown to decline within 6-12 months of vaccination. In addition, the long-term persistence of cellular immunity may protect against the development of severe disease. In addition, adoptive T-cell therapies have shown considerable potential in the development of COVID-19 traitement. These therapies involve the transfer of T cells with specific antiviral properties into patients to boost their immune response against SARS-CoV-2.","PeriodicalId":11913,"journal":{"name":"European Journal of Inflammation","volume":"12 7","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135868074","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 : 2023-11-02DOI: 10.1177/1721727x231207720
Tena Djuartina, Iskandar Rahardjo Budianto, Andreas Steven, Maria Stefani, Melani Kawilarang, Melisa Kawilarang
Objective: To conduct a systematic review and meta-analysis of all available published data related to rats about spermatogenesis to provide a comprehensive overview of the effects of cigarette smoke exposure on the parameters of spermatogenesis.Methods: A comprehensive search of electronic databases including PubMed, EBSCO, ProQuest, Science Direct, Taylor & Francis, Springer Link, GARUDA, and Google Scholar, spanning from their inception until January 29th, 2021, was conducted to retrieve relevant studies and full-text articles evaluating the effect of cigarette smoke exposure on the parameters of spermatogenesis in rats. Data were taken from eligible studies. We use SYRCLE’s Risk of Bias tool for this animal studies. The overall size effect was measured, and forest plots and funnel plots were generated using the statistical software JASP.Results: The present study comprised 23 studies involving 527 rats. The findings of this meta-analysis revealed that parameters of spermatogenesis, such as sperm count, morphology, and viability, were substantially impaired in response to conventional cigarette smoke exposure, exhibiting and aggregate correlation coefficient of 0,70 (95% CI:0.61-0.79, p < .001).Conclusion: Exposure to conventional cigarette smoke has a significant negative effect on spermatogenic parameters in rats, particularly in terms of sperm count, morphology, and viability.
{"title":"The effect of cigarette smoke exposure on rat’s spermatogenesis: A systematic literature review and meta-analysis","authors":"Tena Djuartina, Iskandar Rahardjo Budianto, Andreas Steven, Maria Stefani, Melani Kawilarang, Melisa Kawilarang","doi":"10.1177/1721727x231207720","DOIUrl":"https://doi.org/10.1177/1721727x231207720","url":null,"abstract":"Objective: To conduct a systematic review and meta-analysis of all available published data related to rats about spermatogenesis to provide a comprehensive overview of the effects of cigarette smoke exposure on the parameters of spermatogenesis.Methods: A comprehensive search of electronic databases including PubMed, EBSCO, ProQuest, Science Direct, Taylor & Francis, Springer Link, GARUDA, and Google Scholar, spanning from their inception until January 29th, 2021, was conducted to retrieve relevant studies and full-text articles evaluating the effect of cigarette smoke exposure on the parameters of spermatogenesis in rats. Data were taken from eligible studies. We use SYRCLE’s Risk of Bias tool for this animal studies. The overall size effect was measured, and forest plots and funnel plots were generated using the statistical software JASP.Results: The present study comprised 23 studies involving 527 rats. The findings of this meta-analysis revealed that parameters of spermatogenesis, such as sperm count, morphology, and viability, were substantially impaired in response to conventional cigarette smoke exposure, exhibiting and aggregate correlation coefficient of 0,70 (95% CI:0.61-0.79, p < .001).Conclusion: Exposure to conventional cigarette smoke has a significant negative effect on spermatogenic parameters in rats, particularly in terms of sperm count, morphology, and viability.","PeriodicalId":11913,"journal":{"name":"European Journal of Inflammation","volume":"25 S3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135875565","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 : 2023-10-20DOI: 10.1177/1721727x231209827
Mengdi Feng, Jinfang Zhang, Guoqiang Zhang
A 64-year-old man presented with painful rash on the trunk and extremities for more than half a month. Nephrotic syndrome had been diagnosed 2 years ago and had been regularly treated with glucocorticoids and immunosuppressants. He developed herpes zoster 1 year ago. Laboratory investigation demonstrated varicella-zoster virus DNA (VZV-DNA), varicella-zoster virus IgM (VZV-IgM), and varicella-zoster virus antibody IgG (VZV-IgG) were all positive. After the clinical diagnosis of relapsed disseminated cutaneous herpes zoster had been confirmed, systemic therapy with brivudine 125 mg everyday was started.
{"title":"Case report: Relapsed disseminated cutaneous herpes zoster successfully treated with brivudine","authors":"Mengdi Feng, Jinfang Zhang, Guoqiang Zhang","doi":"10.1177/1721727x231209827","DOIUrl":"https://doi.org/10.1177/1721727x231209827","url":null,"abstract":"A 64-year-old man presented with painful rash on the trunk and extremities for more than half a month. Nephrotic syndrome had been diagnosed 2 years ago and had been regularly treated with glucocorticoids and immunosuppressants. He developed herpes zoster 1 year ago. Laboratory investigation demonstrated varicella-zoster virus DNA (VZV-DNA), varicella-zoster virus IgM (VZV-IgM), and varicella-zoster virus antibody IgG (VZV-IgG) were all positive. After the clinical diagnosis of relapsed disseminated cutaneous herpes zoster had been confirmed, systemic therapy with brivudine 125 mg everyday was started.","PeriodicalId":11913,"journal":{"name":"European Journal of Inflammation","volume":"158 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135570180","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}
Objectives: The Notch signaling pathway serves as the key regulator of the biological functions of macrophages and may affect the role of macrophages in the development of pigeon breeder’s lung (PBL). This study investigated the possible association of the Notch signaling pathway with the development of fibrotic PBL based on regulation of the polarization of macrophages. Methods: Normal Sprague‒Dawley rats and rats with pigeon exfoliation-induced fibrotic hypersensitivity pneumonitis were selected. DAPT was used to inhibit the Notch signaling pathway in rats, and pulmonary fibrosis, the Notch signaling pathway, macrophage polarization, and dynamic changes in the Th1/Th2 ratio were observed. Results: The levels of key proteins in the Notch signaling pathway were higher in the lung tissues of rats with fibrotic hypersensitivity pneumonitis than in those of normal controls ( p < 0.05). The mRNA expression levels of the M1 marker genes tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) were lower in the lung macrophages of rats with fibrotic hypersensitivity pneumonitis than in those of normal controls. In contrast, the mRNA expression levels of the M2 marker genes Mrc2 and Arg-1 in macrophages were higher in the rats with pneumonitis than in normal controls ( p < 0.05). The bronchoalveolar lavage fluid Th1/Th2 ratio was lower in the fibrotic hypersensitivity pneumonitis group than in the control group, but this trend was reversed DAPT application ( p < 0.05). Conclusion: Notch pathway receptors and ligands activate the inflammatory response of macrophages and participate in the polarization of macrophages to the M1 type. Inhibition of the Notch signaling pathway plays a role in Th1/Th2 imbalance.
{"title":"Role of the Notch signaling pathway in regulating macrophage polarization in a rat model of fibrotic pigeon breeder’s lung","authors":"Wenyi Wang, Yaoyuan Shen, Qiuping Leng, Wei Ding, Zhen Peng, Yuan Zhou, Xiaohong Yang, Chao Wu","doi":"10.1177/1721727x231202431","DOIUrl":"https://doi.org/10.1177/1721727x231202431","url":null,"abstract":"Objectives: The Notch signaling pathway serves as the key regulator of the biological functions of macrophages and may affect the role of macrophages in the development of pigeon breeder’s lung (PBL). This study investigated the possible association of the Notch signaling pathway with the development of fibrotic PBL based on regulation of the polarization of macrophages. Methods: Normal Sprague‒Dawley rats and rats with pigeon exfoliation-induced fibrotic hypersensitivity pneumonitis were selected. DAPT was used to inhibit the Notch signaling pathway in rats, and pulmonary fibrosis, the Notch signaling pathway, macrophage polarization, and dynamic changes in the Th1/Th2 ratio were observed. Results: The levels of key proteins in the Notch signaling pathway were higher in the lung tissues of rats with fibrotic hypersensitivity pneumonitis than in those of normal controls ( p < 0.05). The mRNA expression levels of the M1 marker genes tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) were lower in the lung macrophages of rats with fibrotic hypersensitivity pneumonitis than in those of normal controls. In contrast, the mRNA expression levels of the M2 marker genes Mrc2 and Arg-1 in macrophages were higher in the rats with pneumonitis than in normal controls ( p < 0.05). The bronchoalveolar lavage fluid Th1/Th2 ratio was lower in the fibrotic hypersensitivity pneumonitis group than in the control group, but this trend was reversed DAPT application ( p < 0.05). Conclusion: Notch pathway receptors and ligands activate the inflammatory response of macrophages and participate in the polarization of macrophages to the M1 type. Inhibition of the Notch signaling pathway plays a role in Th1/Th2 imbalance.","PeriodicalId":11913,"journal":{"name":"European Journal of Inflammation","volume":"17 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135344422","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}
Subsequent to trauma and systemic inflammatory response syndrome, the typical reaction is an enhancement of the total white blood cell count. Neutrophils are abundant circulating leukocytes in humans that play a crucial role in initial immune response against invading microbes through phagocytosis and exerting inflammatory mediators. However, lymphocytes are the main cellular compartments of the immune system that are negatively affected in the setting of trauma. The neutrophil to lymphocyte ratio (NLR), which can be easily measured in daily clinical practices, is an alternative marker of inflammation before any clinical findings can be observed. Therefore, in this mini-review study, we briefly discussed recent evidence on NLR variations at the time of hospitalization and its prognostic values in trauma patients. Most investigations declared high values of NLR potentially have a poor prognosis in traumatically ill patients on admission and contribute to coagulopathy, increased hospitalization and mortality. Moreover, given that various cut-off points have been considered for the NLR value, receiving a unique one and linking with subsequent outcomes of the disease should be in ongoing researches.
{"title":"The prognostic values of neutrophil to lymphocyte ratio in traumatically injured patients upon admission: A mini-Review","authors":"Maryam Hosseini, Pooria Fazeli, Mahsa Hajivalili, Shahram Paydar","doi":"10.1177/1721727x231197494","DOIUrl":"https://doi.org/10.1177/1721727x231197494","url":null,"abstract":"Subsequent to trauma and systemic inflammatory response syndrome, the typical reaction is an enhancement of the total white blood cell count. Neutrophils are abundant circulating leukocytes in humans that play a crucial role in initial immune response against invading microbes through phagocytosis and exerting inflammatory mediators. However, lymphocytes are the main cellular compartments of the immune system that are negatively affected in the setting of trauma. The neutrophil to lymphocyte ratio (NLR), which can be easily measured in daily clinical practices, is an alternative marker of inflammation before any clinical findings can be observed. Therefore, in this mini-review study, we briefly discussed recent evidence on NLR variations at the time of hospitalization and its prognostic values in trauma patients. Most investigations declared high values of NLR potentially have a poor prognosis in traumatically ill patients on admission and contribute to coagulopathy, increased hospitalization and mortality. Moreover, given that various cut-off points have been considered for the NLR value, receiving a unique one and linking with subsequent outcomes of the disease should be in ongoing researches.","PeriodicalId":11913,"journal":{"name":"European Journal of Inflammation","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135536827","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}
Background: The mechanism of sepsis especially non-survivors has not yet been identified. Objective: To identify the key genes concerned with non-survivor sepsis (NSS) and analyze its molecular mechanism. Methods: The original data were obtained from the GEO database to screen deferentially expressed genes (DEGs). GO and KEGG analysis were performed to analyze the functional annotation of DEGs. The protein-protein interaction (PPI) network and related analysis of hub genes were carried out. Further, hub genes were confirmed in the lipopolysaccharide (LPS)-induced septic mice by western blotting and immunohistochemistry. Results: We obtained 188 DEGs and 32 hub genes between NSS patients and healthy volunteers. Among of them, the top 10 hub genes including STAT1, ISG15, HERC1, EIF2AK2, RPL27, LY6E, IFI44L, XAF1, RSAD2 and HERC6 were studied, which predict sepsis based on receiver operator characteristic curve analysis. These hub genes were enriched in positive regulation of biomedical process including translation, response to virus and suppression of mitochondrial depolarization, etc.; cell component including mitochondrial inner membrane; molecular function containing ligase activity, etc. These hub genes are also enriched in influenza A infection and leukocyte trans-endothelial migration. The expression of these hub genes is better involved in a diagnosis of NSS, such as HERC6 (AUC = 0.9753, p = .0007), RPL27 (AUC = 0.9691, p = .0008), ISG15 (AUC = 0.9630, p = .0009), STAT1 (AUC = 0.9383, p = .0017), HERC1 (AUC = 0.9259, p = .0023), and XAF1 (AUC = 0.9259, p = .0023). Furthermore, 20 mg/kg of LPS injection up-regulated the expression of ISG15, RPL27, LY6E and HERC6 in the lung tissues compared with control mice. Conclusion: These identified 188 DEGs and 10 hub genes were associated with NSS, especially ISG15, RPL27, LY6E and HERC6 genes expressed in the lung as the most vulnerable organ.
背景:脓毒症的机制，特别是非幸存者尚未确定。目的:鉴定与非幸存者脓毒症(NSS)相关的关键基因并分析其分子机制。方法:从GEO数据库中获取原始数据，筛选恭顺表达基因(DEGs)。使用GO和KEGG分析分析DEGs的功能注释。对枢纽基因进行了蛋白-蛋白相互作用(PPI)网络和相关分析。此外，通过免疫组织化学和免疫印迹技术，在脂多糖(LPS)诱导的脓毒症小鼠中证实了hub基因。结果:在NSS患者和健康志愿者之间获得了188个deg和32个hub基因。其中，研究了STAT1、ISG15、HERC1、EIF2AK2、RPL27、LY6E、IFI44L、XAF1、RSAD2、HERC6等前10位枢纽基因，通过受体操作者特征曲线分析预测败血症。这些中心基因在翻译、病毒应答和抑制线粒体去极化等生物医学过程中具有丰富的正向调控作用;包括线粒体内膜在内的细胞成分;含连接酶活性等的分子功能。这些中心基因也在甲型流感感染和白细胞跨内皮迁移中富集。这些枢纽基因的表达与NSS的诊断有较好的相关性，如HERC6 (AUC = 0.9753, p = 0.0007)、RPL27 (AUC = 0.9691, p = 0.0008)、ISG15 (AUC = 0.9630, p = 0.0009)、STAT1 (AUC = 0.9383, p = 0.0017)、HERC1 (AUC = 0.9259, p = 0.0023)和XAF1 (AUC = 0.9259, p = 0.0023)。此外，与对照组相比，20 mg/kg LPS可上调肺组织中ISG15、RPL27、LY6E和HERC6的表达。结论:共鉴定出188个DEGs和10个hub基因与NSS相关，其中以肺中表达的ISG15、RPL27、LY6E和HERC6基因最为易感。
{"title":"Identification of potential biomarkers for nonsurvivor sepsis patients via microarray technology: A study based on GEO datasets","authors":"Yan Ma, Shichao Shan, Cheng Luo, Jianlan Mo, Zhaokun Hu, Ren Jing","doi":"10.1177/1721727x231202661","DOIUrl":"https://doi.org/10.1177/1721727x231202661","url":null,"abstract":"Background: The mechanism of sepsis especially non-survivors has not yet been identified. Objective: To identify the key genes concerned with non-survivor sepsis (NSS) and analyze its molecular mechanism. Methods: The original data were obtained from the GEO database to screen deferentially expressed genes (DEGs). GO and KEGG analysis were performed to analyze the functional annotation of DEGs. The protein-protein interaction (PPI) network and related analysis of hub genes were carried out. Further, hub genes were confirmed in the lipopolysaccharide (LPS)-induced septic mice by western blotting and immunohistochemistry. Results: We obtained 188 DEGs and 32 hub genes between NSS patients and healthy volunteers. Among of them, the top 10 hub genes including STAT1, ISG15, HERC1, EIF2AK2, RPL27, LY6E, IFI44L, XAF1, RSAD2 and HERC6 were studied, which predict sepsis based on receiver operator characteristic curve analysis. These hub genes were enriched in positive regulation of biomedical process including translation, response to virus and suppression of mitochondrial depolarization, etc.; cell component including mitochondrial inner membrane; molecular function containing ligase activity, etc. These hub genes are also enriched in influenza A infection and leukocyte trans-endothelial migration. The expression of these hub genes is better involved in a diagnosis of NSS, such as HERC6 (AUC = 0.9753, p = .0007), RPL27 (AUC = 0.9691, p = .0008), ISG15 (AUC = 0.9630, p = .0009), STAT1 (AUC = 0.9383, p = .0017), HERC1 (AUC = 0.9259, p = .0023), and XAF1 (AUC = 0.9259, p = .0023). Furthermore, 20 mg/kg of LPS injection up-regulated the expression of ISG15, RPL27, LY6E and HERC6 in the lung tissues compared with control mice. Conclusion: These identified 188 DEGs and 10 hub genes were associated with NSS, especially ISG15, RPL27, LY6E and HERC6 genes expressed in the lung as the most vulnerable organ.","PeriodicalId":11913,"journal":{"name":"European Journal of Inflammation","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135965247","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 : 2023-09-14DOI: 10.1177/1721727x231202662
Fahidah Alenzi, Shirish R Sangle, David P D’Cruz
Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an uncommon condition with heterogeneous multisystem organ involvement and significant morbidity and mortality. This study aimed to characterize the clinical features and laboratory characteristics, including B cell depletion, the ability to reduce corticosteroid dosage, and outcomes, of patients with AAV following rituximab treatment. Methods: Retrospective clinical and laboratory data were collected from patients with AAV who visited our lupus unit, including 50 treated with rituximab. Numeric response variables (median and range) were collected, including age, follow-up duration, disease duration, and Birmingham Vasculitis Activity Score (version 3). Statistical analyses were conducted using the SPSS 25.0 software. Statistical significance was considered a p-value <.05. Results: Of the 50 patients, 40 (80%) had granulomatosis with polyangiitis, 30 (75%) achieved remission, and 10 (25%) had active disease. Fifteen patients (30%) had positive ANCA levels at their last ANCA level assessment follow-up. Thirty-seven patients (74%) had B cell depletion, and 30 (81.1%) were in remission. Their median immunoglobulin levels were 7.6 (2.7–21.2) g/L for IgG, 0.5 (0.07–1.71) g/L for IgM, and 1.83 (0.14–4.87) g/L for IgA. Forty-two patients (84%) were able to lower their steroid dose to <7.5 mg, with 36 (85.7%) in remission and six (14.3%) having active disease ( p = .003). Conclusion: Our data suggests that most patients experience clinical remission after rituximab maintenance treatment. Half the patients were in remission, with normal creatinine levels and inflammatory markers. In addition, our patients could reduce steroid use.
{"title":"Anti-neutrophil cytoplasmic antibody associated vasculitis following rituximab: Outcomes of 50 patients in a tertiary single centre","authors":"Fahidah Alenzi, Shirish R Sangle, David P D’Cruz","doi":"10.1177/1721727x231202662","DOIUrl":"https://doi.org/10.1177/1721727x231202662","url":null,"abstract":"Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an uncommon condition with heterogeneous multisystem organ involvement and significant morbidity and mortality. This study aimed to characterize the clinical features and laboratory characteristics, including B cell depletion, the ability to reduce corticosteroid dosage, and outcomes, of patients with AAV following rituximab treatment. Methods: Retrospective clinical and laboratory data were collected from patients with AAV who visited our lupus unit, including 50 treated with rituximab. Numeric response variables (median and range) were collected, including age, follow-up duration, disease duration, and Birmingham Vasculitis Activity Score (version 3). Statistical analyses were conducted using the SPSS 25.0 software. Statistical significance was considered a p-value <.05. Results: Of the 50 patients, 40 (80%) had granulomatosis with polyangiitis, 30 (75%) achieved remission, and 10 (25%) had active disease. Fifteen patients (30%) had positive ANCA levels at their last ANCA level assessment follow-up. Thirty-seven patients (74%) had B cell depletion, and 30 (81.1%) were in remission. Their median immunoglobulin levels were 7.6 (2.7–21.2) g/L for IgG, 0.5 (0.07–1.71) g/L for IgM, and 1.83 (0.14–4.87) g/L for IgA. Forty-two patients (84%) were able to lower their steroid dose to <7.5 mg, with 36 (85.7%) in remission and six (14.3%) having active disease ( p = .003). Conclusion: Our data suggests that most patients experience clinical remission after rituximab maintenance treatment. Half the patients were in remission, with normal creatinine levels and inflammatory markers. In addition, our patients could reduce steroid use.","PeriodicalId":11913,"journal":{"name":"European Journal of Inflammation","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134911741","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 : 2023-09-11DOI: 10.1177/1721727x231199369
Yujie Sun, Yun Zhu, Andrzej Bartke, Lin Lin, Rong Yuan
Objective: Metformin is a widely used drug, with a good safety profile, for treatment of type 2 diabetes. Recently, it has been found to also exhibit immunomodulatory potential. We aim to preliminarily explore the potential role of metformin in regulating innate immunity using UM-HET3 mice. Methods: In this study, we treated juvenile UM-HET3 mice with metformin and investigated the alteration of the innate immune response. Peripheral blood of HET3 mice was treated with ex-vivo lipopolysaccharide (LPS) stimulation to induce a leukocyte inflammatory response, which was detected by analyzing the expression of LPS receptors TLR4 and CD14 on leukocytes with flow cytometry. Furthermore, cytokine release induced by LPS was measured in isolated cell culture supernatants with ELISA. Results: In this study LPS treatment triggered a downregulation of TLR4 as well as an upregulation of CD14 expressed on the cell surface. Besides, it enhanced the secretion of pro-inflammatory cytokines TNF-α, IL-1β and IL-6. The results showed that metformin treatment led to a significant ( p < .05) increase in the expression of CD14 and pro-inflammatory cytokines, including IL-1β and IL-6, as well as increased proportion of TLR4 downregulation on the cell surface in response to LPS, specifically in males. Conclusions: This study indicates that treating juvenile mice with metformin enhances the innate immune response to bacterial endotoxin in males, but not in females.
{"title":"Metformin treatment of juvenile mice potentiates innate immune response to bacterial lipopolysaccharide in males","authors":"Yujie Sun, Yun Zhu, Andrzej Bartke, Lin Lin, Rong Yuan","doi":"10.1177/1721727x231199369","DOIUrl":"https://doi.org/10.1177/1721727x231199369","url":null,"abstract":"Objective: Metformin is a widely used drug, with a good safety profile, for treatment of type 2 diabetes. Recently, it has been found to also exhibit immunomodulatory potential. We aim to preliminarily explore the potential role of metformin in regulating innate immunity using UM-HET3 mice. Methods: In this study, we treated juvenile UM-HET3 mice with metformin and investigated the alteration of the innate immune response. Peripheral blood of HET3 mice was treated with ex-vivo lipopolysaccharide (LPS) stimulation to induce a leukocyte inflammatory response, which was detected by analyzing the expression of LPS receptors TLR4 and CD14 on leukocytes with flow cytometry. Furthermore, cytokine release induced by LPS was measured in isolated cell culture supernatants with ELISA. Results: In this study LPS treatment triggered a downregulation of TLR4 as well as an upregulation of CD14 expressed on the cell surface. Besides, it enhanced the secretion of pro-inflammatory cytokines TNF-α, IL-1β and IL-6. The results showed that metformin treatment led to a significant ( p < .05) increase in the expression of CD14 and pro-inflammatory cytokines, including IL-1β and IL-6, as well as increased proportion of TLR4 downregulation on the cell surface in response to LPS, specifically in males. Conclusions: This study indicates that treating juvenile mice with metformin enhances the innate immune response to bacterial endotoxin in males, but not in females.","PeriodicalId":11913,"journal":{"name":"European Journal of Inflammation","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135937853","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}
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