Pub Date : 2024-01-01DOI: 10.1615/critrevimmunol.2024051292
Qiang Shao, Lin Sun
C1q/tumor necrosis factor-related protein 3 (CTRP3) has been demonstrated to play a protective role in mice with severe acute pancreatitis (SAP). However, its clinical significance in SAP remains unknown. This study was conducted to explore the clinical values of serum C1q/tumor necrosis factor-related protein 3 (CTRP3) level in the diagnosis of cardiac dysfunction (CD) and intestinal mucosal barrier dysfunction (IMBD) in SAP. Through RT-qPCR, we observed decreased CTRP3 level in the serum of SAP patients. Serum CTRP3 level was correlated with C-reactive protein, procalcitonin, creatine, modified computed tomography severity index score, and Acute Physiology and Chronic Health Evaluation II score. The receiver-operating characteristic curve revealed that CTRP3 serum level < 1.005 was conducive to SAP diagnosis with 72.55% sensitivity and 60.00% specificity, CTRP3 < 0.8400 was conducive to CD diagnosis with 80.49% sensitivity and specificity 65.57%, CTRP3 < 0.8900 was conducive to IMBD diagnosis with 94.87% sensitivity and 63.49% specificity, and CTRP3 < 0.6250 was conducive to the diagnosis of CD and IMBD co-existence with 65.22% sensitivity and 89.87% specificity. Generally, CTRP3 was downregulated in the serum of SAP patients and served as a candidate biomarker for the diagnosis of SAP and SAP-induced CD and IMBD.
C1q/ 肿瘤坏死因子相关蛋白 3（CTRP3）已被证实在重症急性胰腺炎（SAP）小鼠体内发挥保护作用。然而，其在 SAP 中的临床意义仍然未知。本研究旨在探讨血清 C1q/肿瘤坏死因子相关蛋白 3（CTRP3）水平在诊断 SAP 中心脏功能障碍（CD）和肠粘膜屏障功能障碍（IMBD）中的临床价值。通过 RT-qPCR，我们观察到 SAP 患者血清中 CTRP3 水平下降。血清 CTRP3 水平与 C 反应蛋白、降钙素原、肌酸、改良计算机断层扫描严重程度指数评分以及急性生理学和慢性健康评估 II 评分相关。接受者工作特征曲线显示，CTRP3 血清水平 < 1.005 有利于 SAP 诊断，灵敏度为 72.55%，特异度为 60.00%；CTRP3 < 0.8400 有利于 CD 诊断，灵敏度为 80.49%，特异度为 65.57%，CTRP3 <0.8900有利于IMBD诊断，灵敏度为94.87%，特异度为63.49%，CTRP3 <0.6250有利于CD和IMBD并存的诊断，灵敏度为65.22%，特异度为89.87%。总体而言，CTRP3在SAP患者血清中下调，可作为诊断SAP和SAP诱发的CD和IMBD的候选生物标志物。
{"title":"Clinical significance of serum CTRP3 level in the prediction of cardiac dysfunction and intestinal mucosal barrier dysfunction in patients with severe acute pancreatitis","authors":"Qiang Shao, Lin Sun","doi":"10.1615/critrevimmunol.2024051292","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051292","url":null,"abstract":"C1q/tumor necrosis factor-related protein 3 (CTRP3) has been demonstrated to play a protective role in mice with severe acute pancreatitis (SAP). However, its clinical significance in SAP remains unknown. This study was conducted to explore the clinical values of serum C1q/tumor necrosis factor-related protein 3 (CTRP3) level in the diagnosis of cardiac dysfunction (CD) and intestinal mucosal barrier dysfunction (IMBD) in SAP. Through RT-qPCR, we observed decreased CTRP3 level in the serum of SAP patients. Serum CTRP3 level was correlated with C-reactive protein, procalcitonin, creatine, modified computed tomography severity index score, and Acute Physiology and Chronic Health Evaluation II score. The receiver-operating characteristic curve revealed that CTRP3 serum level < 1.005 was conducive to SAP diagnosis with 72.55% sensitivity and 60.00% specificity, CTRP3 < 0.8400 was conducive to CD diagnosis with 80.49% sensitivity and specificity 65.57%, CTRP3 < 0.8900 was conducive to IMBD diagnosis with 94.87% sensitivity and 63.49% specificity, and CTRP3 < 0.6250 was conducive to the diagnosis of CD and IMBD co-existence with 65.22% sensitivity and 89.87% specificity. Generally, CTRP3 was downregulated in the serum of SAP patients and served as a candidate biomarker for the diagnosis of SAP and SAP-induced CD and IMBD.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"9 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139586345","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}
Objective: To explore the protective effect and mechanism of mild hypothermia on lung tissue damage after cardiopulmonary resuscitation in pigs. Methods: In this experiment, we electrically stimulated 16 pigs (30±2kg) for 10 minutes to cause ventricular fibrillation. The successfully resuscitated animals were randomly divided into two groups, a mild hypothermia group and a control group. We took arterial blood 0.5h, 1h, 3h and 6h after ROSC recovery in the two groups of animals for blood gas analysis. We observed the structural changes of lung tissue under an electron microscope and calculate the wet weight/dry weight (W/D) ratio. We quantitatively analyzed the expression differences of representative inflammatory factors (IL-6 and TNF-α) through the Elisa test. We detected the expression levels of Bax, Bcl-2 and Caspase-3 proteins in lung tissues by Western blot. Results: The 3 h and 6 h after spontaneous circulation was restored, compared with the control group, PaO2/FiO2 decreased significantly (P <0.05). In addition, the pathological changes, lung W/D and lung MDA of the mild hypothermia group were better than those of the control group. The levels of IL-6 and TNF-α in the lung tissue of the mild hypothermia group were significantly lower than those of the control group (P <0.05). The content of Caspase-3 and Bax in the mild hypothermia group was significantly lower than that of the control group. Conclusion: Our experiments have shown that mild hypothermia can reduce lung tissue damage after cardiopulmonary resuscitation.
{"title":"The protective effect and mechanism of mild hypothermia on pig lung injury after cardiopulmonary resuscitation","authors":"Jinlin Ren, Fangfang Zhu, Dongdong Sang, Mulin Cong, Shujuan Jiang","doi":"10.1615/critrevimmunol.2024052420","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024052420","url":null,"abstract":"Objective: To explore the protective effect and mechanism of mild hypothermia on lung tissue damage after cardiopulmonary resuscitation in pigs. Methods: In this experiment, we electrically stimulated 16 pigs (30±2kg) for 10 minutes to cause ventricular fibrillation. The successfully resuscitated animals were randomly divided into two groups, a mild hypothermia group and a control group. We took arterial blood 0.5h, 1h, 3h and 6h after ROSC recovery in the two groups of animals for blood gas analysis. We observed the structural changes of lung tissue under an electron microscope and calculate the wet weight/dry weight (W/D) ratio. We quantitatively analyzed the expression differences of representative inflammatory factors (IL-6 and TNF-α) through the Elisa test. We detected the expression levels of Bax, Bcl-2 and Caspase-3 proteins in lung tissues by Western blot. Results: The 3 h and 6 h after spontaneous circulation was restored, compared with the control group, PaO2/FiO2 decreased significantly (P <0.05). In addition, the pathological changes, lung W/D and lung MDA of the mild hypothermia group were better than those of the control group. The levels of IL-6 and TNF-α in the lung tissue of the mild hypothermia group were significantly lower than those of the control group (P <0.05). The content of Caspase-3 and Bax in the mild hypothermia group was significantly lower than that of the control group. Conclusion: Our experiments have shown that mild hypothermia can reduce lung tissue damage after cardiopulmonary resuscitation.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"172 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139585635","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 : 2024-01-01DOI: 10.1615/critrevimmunol.2024051316
Kang Zhang, Xiaoqun Chen
Objective: Zilongjin (ZLJ) is a common Traditional Chinese medicine for lung adenocarcinoma (LUAD) treatment. However, its mechanisms of action remain to be elucidated. Network pharmacology was used to explore underlying mechanisms of ZLJ on LUAD. Methods: The disease-related targets were found out from the GeneCards and DisGeNET databases. Active compounds and targets of ZLJ were obtained from the HIT, TCMSP, and TCMID databases. Then, the protein-protein interaction (PPI) network was built by STRING database to identify core-hub targets of ZLJ in LUAD. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to analyze the enriched regulatory pathways of targets. Molecular docking analysis were used to evaluate interactions between potential targets and active compounds. Finally, qRT-PCR method was further to verify the results of network pharmacology. Results: A total of 124 LUAD-related targets of ZLJ and 5 active compounds of ZLJ from the relevant databases were screened out. Among these target proteins, JUN, CDH1, PPARG, and FOS were core-hub genes in PPI network. GO and KEGG pathway enrichment analysis indicated that these targets might regulate the PPAR signaling pathway in LUAD. JUN, PPARG, and FOS levels were upregulated, while CDH1 level was downregulated in LUAD cells. Conclusion: This study discerned that ZLJ may target genes such as JUN, FOS, PPARG, and CDH1 via the PPAR signaling pathway in LUAD, offering foundational insights for further exploration of ZLJ in clinical applications.
{"title":"Exploring mechanism of Zilongjin in treating lung adenocarcinoma based on network pharmacology combined with experimental verification","authors":"Kang Zhang, Xiaoqun Chen","doi":"10.1615/critrevimmunol.2024051316","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051316","url":null,"abstract":"Objective: Zilongjin (ZLJ) is a common Traditional Chinese medicine for lung adenocarcinoma (LUAD) treatment. However, its mechanisms of action remain to be elucidated. Network pharmacology was used to explore underlying mechanisms of ZLJ on LUAD.\u0000Methods: The disease-related targets were found out from the GeneCards and DisGeNET databases. Active compounds and targets of ZLJ were obtained from the HIT, TCMSP, and TCMID databases. Then, the protein-protein interaction (PPI) network was built by STRING database to identify core-hub targets of ZLJ in LUAD. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to analyze the enriched regulatory pathways of targets. Molecular docking analysis were used to evaluate interactions between potential targets and active compounds. Finally, qRT-PCR method was further to verify the results of network pharmacology.\u0000Results: A total of 124 LUAD-related targets of ZLJ and 5 active compounds of ZLJ from the relevant databases were screened out. Among these target proteins, JUN, CDH1, PPARG, and FOS were core-hub genes in PPI network. GO and KEGG pathway enrichment analysis indicated that these targets might regulate the PPAR signaling pathway in LUAD. JUN, PPARG, and FOS levels were upregulated, while CDH1 level was downregulated in LUAD cells.\u0000Conclusion: This study discerned that ZLJ may target genes such as JUN, FOS, PPARG, and CDH1 via the PPAR signaling pathway in LUAD, offering foundational insights for further exploration of ZLJ in clinical applications.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"59 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139551724","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 : 2023-12-01DOI: 10.1615/critrevimmunol.2023050325
Nisar Shaikh, Xiao-Bing Zhang, Maisa Abdalla, David Baylink, Xiaolei Tang
Regulatory T (Treg) cells hold promise for the ultimate cure of immune-mediated diseases. However, how to effectively restore Treg function in patients remains unknown. Previous reports suggest that activated dendritic cells (DCs) de novo synthesize locally high concentrations of 1,25-dihydroxy vitamin D, i.e., the active vitamin D or 1,25(OH)2D by upregulating the expression of 25-hydroxy vitamin D 1α-hydroxylase. Although 1,25(OH)2D has been shown to induce Treg cells, DC-derived 1,25(OH)2D only serves as a checkpoint to ensure well-balanced immune responses. Our animal studies have shown that 1,25(OH)2D requires high concentrations to generate Treg cells, which can cause severe side effects. In addition, our animal studies have also demonstrated that dendritic cells (DCs) overexpressing the 1α-hydroxylase de novo synthesize the effective Treg-inducing 1,25(OH)2D concentrations without causing the primary side effect of hypercalcemia (i.e., high blood calcium levels). This study furthers our previous animal studies and explores the efficacy of the 1α-hydroxylase-overexpressing DCs in inducing human CD4+FOXP3+ regulatory T (Treg) cells. We discovered that the Treg-inducing doses of 1,25(OH)2D were within a range, not the higher, the better. Additionally, our data corroborated that the 1α-hydroxylase-overexpressing DCs synthesized 1,25(OH)2D within this concentration range in vivo, thus facilitating effective Treg cell induction. Moreover, this study demonstrated that α-hydroxylase expression levels were pivotal for DCs to induce Treg cells because physiological 25(OH)D levels were sufficient for the engineered but not parental DCs to enhance Treg cell induction. Int
调节性 T（Treg）细胞有望最终治愈免疫介导疾病。然而，如何有效恢复患者的 Treg 功能仍是未知数。以前的报告表明，活化的树突状细胞（DC）通过上调 25- 羟基维生素 D 1α- 羟化酶的表达，在局部从头合成高浓度的 1,25-二羟基维生素 D，即活性维生素 D 或 1,25(OH)2D。虽然 1,25（OH）2D 已被证明能诱导 Treg 细胞，但 DC 衍生的 1,25（OH）2D 只是确保免疫反应平衡的一个检查点。我们的动物实验表明，1,25(OH)2D 需要高浓度才能生成 Treg 细胞，而高浓度会导致严重的副作用。此外，我们的动物实验还证明，过表达 1α- 羟化酶的树突状细胞（DCs）能从头合成有效的 Treg 诱导浓度的 1,25（OH）2D，而不会引起高钙血症（即高血钙）这一主要副作用。这项研究进一步推进了我们之前的动物实验，并探索了1α-羟化酶外表达的DC在诱导人类CD4+FOXP3+调节性T（Treg）细胞方面的功效。我们发现，1,25(OH)2D的Treg诱导剂量在一定范围内，并非越高越好。此外，我们的数据还证实，1α-羟化酶脱表达的DC在体内合成的1,25（OH）2D也在这个浓度范围内，从而促进了Treg细胞的有效诱导。此外，这项研究还证明了α-羟化酶的表达水平是DC诱导Treg细胞的关键，因为生理25(OH)D水平足以使工程DC而非亲代DC增强Treg细胞诱导。中
{"title":"Enhancing Human Treg Cell Induction through Engineered Dendritic Cells and Zinc Supplementation","authors":"Nisar Shaikh, Xiao-Bing Zhang, Maisa Abdalla, David Baylink, Xiaolei Tang","doi":"10.1615/critrevimmunol.2023050325","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2023050325","url":null,"abstract":"Regulatory T (Treg) cells hold promise for the ultimate cure of immune-mediated diseases. However, how to effectively restore Treg function in patients remains unknown. Previous reports suggest that activated dendritic cells (DCs) de novo synthesize locally high concentrations of 1,25-dihydroxy vitamin D, i.e., the active vitamin D or 1,25(OH)2D by upregulating the expression of 25-hydroxy vitamin D 1α-hydroxylase. Although 1,25(OH)2D has been shown to induce Treg cells, DC-derived 1,25(OH)2D only serves as a checkpoint to ensure well-balanced immune responses. Our animal studies have shown that 1,25(OH)2D requires high concentrations to generate Treg cells, which can cause severe side effects. In addition, our animal studies have also demonstrated that dendritic cells (DCs) overexpressing the 1α-hydroxylase de novo synthesize the effective Treg-inducing 1,25(OH)2D concentrations without causing the primary side effect of hypercalcemia (i.e., high blood calcium levels). This study furthers our previous animal studies and explores the efficacy of the 1α-hydroxylase-overexpressing DCs in inducing human CD4+FOXP3+ regulatory T (Treg) cells. We discovered that the Treg-inducing doses of 1,25(OH)2D were within a range, not the higher, the better. Additionally, our data corroborated that the 1α-hydroxylase-overexpressing DCs synthesized 1,25(OH)2D within this concentration range in vivo, thus facilitating effective Treg cell induction. Moreover, this study demonstrated that α-hydroxylase expression levels were pivotal for DCs to induce Treg cells because physiological 25(OH)D levels were sufficient for the engineered but not parental DCs to enhance Treg cell induction. Int","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138548199","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 : 2023-12-01DOI: 10.1615/critrevimmunol.2023051651
Peng Wan, Xiang Tan, Mengting Sheng, Yan Xiang, Peng Wang, Min Yu
Background The present study investigated that the roles and mechanisms of platelet-derived exosomes in sepsis-induced acute renal injury. Methods The blood samples of septic patients and healthy controls were collected for clinical examination. The plasma level of miR-223-3p and NLRP3 mRNA were analyzed by qRT-PCR and the serum IL-1β and creatinine levels were quantified by ELISA(Enzyme-linked immunosorbent assay). C57BL/6 mice injected with LPS(lipopolysaccharide) were employed as the animal model for sepsis-induced acute renal injury. Human coronary artery endothelial cells(HCAECs) were treated with TNF-α as a cellular model for sepsis-induced endothelial damages. Results The number of PMP(platelet-derived microparticles) in patients with sepsis was increased. The level of miR-223-3p in the platelet exosomes isolated from the serum sample in patients with sepsis was significantly lower than that of the healthy controls. The level of miR-223-3p was also decreased in the platelet exosomes of mouse model with sepsis-induced acute renal injury. Downregulating miR-223-3p promoted sepsis-induced acute renal injury in mice model, while the administration of miR-223-3p reduced the inflammation in endothelial cells of sepsis-induced acute renal injury. NLRP3 (NLR Family Pyrin Domain Containing 3) was identified as one target of miR-223-3p in the platelet exosomes of sepsis-induced acute kidney injury. MiR-223-3p attenuated NLRP3-induced pyroptosis in endothelial cell model of sepsis-induced acute kidney injury. Conclusion In summary, platelet exosome-derived miR-223-3p regulates NLRP3 inflammasome and pyroptosis of endothelial cells in model of sepsis-induced acute renal
{"title":"Platelet exosome-derived miR-223-3p regulates pyroptosis in the cell model of sepsis-induced acute renal injury by targeting mediates NLRP3","authors":"Peng Wan, Xiang Tan, Mengting Sheng, Yan Xiang, Peng Wang, Min Yu","doi":"10.1615/critrevimmunol.2023051651","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2023051651","url":null,"abstract":"Background The present study investigated that the roles and mechanisms of platelet-derived exosomes in sepsis-induced acute renal injury.\u0000Methods The blood samples of septic patients and healthy controls were collected for clinical examination. The plasma level of miR-223-3p and NLRP3 mRNA were analyzed by qRT-PCR and the serum IL-1β and creatinine levels were quantified by ELISA(Enzyme-linked immunosorbent assay). C57BL/6 mice injected with LPS(lipopolysaccharide) were employed as the animal model for sepsis-induced acute renal injury. Human coronary artery endothelial cells(HCAECs) were treated with TNF-α as a cellular model for sepsis-induced endothelial damages.\u0000Results The number of PMP(platelet-derived microparticles) in patients with sepsis was increased. The level of miR-223-3p in the platelet exosomes isolated from the serum sample in patients with sepsis was significantly lower than that of the healthy controls. The level of miR-223-3p was also decreased in the platelet exosomes of mouse model with sepsis-induced acute renal injury. Downregulating miR-223-3p promoted sepsis-induced acute renal injury in mice model, while the administration of miR-223-3p reduced the inflammation in endothelial cells of sepsis-induced acute renal injury. NLRP3 (NLR Family Pyrin Domain Containing 3) was identified as one target of miR-223-3p in the platelet exosomes of sepsis-induced acute kidney injury. MiR-223-3p attenuated NLRP3-induced pyroptosis in endothelial cell model of sepsis-induced acute kidney injury.\u0000Conclusion In summary, platelet exosome-derived miR-223-3p regulates NLRP3 inflammasome and pyroptosis of endothelial cells in model of sepsis-induced acute renal","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"65 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138537044","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 : 2023-12-01DOI: 10.1615/critrevimmunol.2023050473
Jianye Yang, Wenbin Hu, Jiaming Zhao
Objective. Homeobox A1 (HOXA1) is a protein coding gene involved in regulating immunity signaling. This study aims to explore the function and mechanism of HOXA1 in asthma. Methods. An asthma mouse model was established via ovalbumin (OVA) induction. Airway hyperresponsiveness was evaluated by the value of pause enhancement (Penh). Inflammatory cells in bronchoalveolar lavage fluid (BALF) were detected by Trypan blue and Wright staining. The pathological morphology of lung tissues was assessed by H&E staining. The IgE and inflammatory biomarkers (IL-1β, IL-6, IL-17, and TNF-α) in BALF and lung tissues were measured by ELISA. Western blot was performed to detect the expression of NF-κB pathway-related proteins. Results. HOXA1 was down-regulated in OVA-induced asthmatic mice. Overexpression of HOXA1 decreased Penh and relieved pathological injury of lung tissues in OVA-induced mice. Overexpression of HOXA1 also reduced the numbers of total cells, leukocytes, eosinophils, neutrophils, macrophages, and lymphocytes, as well as the levels of IgE, IL-1β, IL-6, IL-17, and TNF-α in BALF of OVA-induced mice. The inflammatory biomarkers were also decreased in lung tissues by HOXA1 overexpression. In addition, HOXA1 overexpression blocked the NF-κB signaling pathway in OVA-induced mice. Conclusion. Overexpression of HOXA1 relieved OVA-induced asthma in female mice by blocking the NF-κB signaling pathway.
{"title":"Overexpression Of Homeobox A1 Relieves Ovalbumin-Induced Asthma In Mice By Inhibiting The Nf-Κb Signaling Pathway","authors":"Jianye Yang, Wenbin Hu, Jiaming Zhao","doi":"10.1615/critrevimmunol.2023050473","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2023050473","url":null,"abstract":"Objective. Homeobox A1 (HOXA1) is a protein coding gene involved in regulating immunity signaling. This study aims to explore the function and mechanism of HOXA1 in asthma.\u0000Methods. An asthma mouse model was established via ovalbumin (OVA) induction. Airway hyperresponsiveness was evaluated by the value of pause enhancement (Penh). Inflammatory cells in bronchoalveolar lavage fluid (BALF) were detected by Trypan blue and Wright staining. The pathological morphology of lung tissues was assessed by H&E staining. The IgE and inflammatory biomarkers (IL-1β, IL-6, IL-17, and TNF-α) in BALF and lung tissues were measured by ELISA. Western blot was performed to detect the expression of NF-κB pathway-related proteins.\u0000Results. HOXA1 was down-regulated in OVA-induced asthmatic mice. Overexpression of HOXA1 decreased Penh and relieved pathological injury of lung tissues in OVA-induced mice. Overexpression of HOXA1 also reduced the numbers of total cells, leukocytes, eosinophils, neutrophils, macrophages, and lymphocytes, as well as the levels of IgE, IL-1β, IL-6, IL-17, and TNF-α in BALF of OVA-induced mice. The inflammatory biomarkers were also decreased in lung tissues by HOXA1 overexpression. In addition, HOXA1 overexpression blocked the NF-κB signaling pathway in OVA-induced mice.\u0000Conclusion. Overexpression of HOXA1 relieved OVA-induced asthma in female mice by blocking the NF-κB signaling pathway.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"47 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138629136","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 : 2023-12-01DOI: 10.1615/critrevimmunol.2023051702
jing Guo, Yi-Zhi Yan, jinglou chen, Yang Duan, Peng Zeng
Stroke remained the leading cause of disability in the world, and the most important non-modifiable risk factor was age. The treatment of stroke for elder patients faced multiple difficulties due to its complicated pathogenesis and mechanism. Therefore, we aimed to identify the potential differentially expressed genes (DEGs) and singnalling pathways for aged people of stroke. To compare the DEGs in the aged rats with or without middle cerebral artery occlusion (MCAO) and to analyse the important genes and the key signalling pathways involved in the development of cerebral ischaemia in aged rats. The Gene Expression Omnibus (GEO) analysis tool was used to analyse the DEGs in the GSE166162 dataset of aged MCAO rats compared with aged sham rats. Differential expression analysis was performed in aged MCAO rats and sham rats using limma. In addition, the 74 DEGs (such as Fam111a, Lcn2, Spp1, Lgals3 and Gpnmb were up-regulated; Egr2, Nr4a3, Arc, Klf4 and Nr4a1 were down-regulated) and potential compounds corresponding to the top 20 core genes in the Protein-Protein Interaction (PPI) network was constructed using the STRING database (version 12.0). Among these 30 compounds, resveratrol, cannabidiol, honokiol, fucoxanthin, oleandrin and tyrosol were significantly enriched. These DEGs were subjected to Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to determine the most significantly enriched pathway in aged MCAO rats. Moreover, innate immune response, the complement and coagulation cascades signalling pathway, the IL-17 and other signalling pathways were significantly correlated with the aged MCAO rats. Our stu
{"title":"Identification of hub genes and pathways of middle cerebral artery occlusion in aged rats via the Gene Expression Omnibus database","authors":"jing Guo, Yi-Zhi Yan, jinglou chen, Yang Duan, Peng Zeng","doi":"10.1615/critrevimmunol.2023051702","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2023051702","url":null,"abstract":"Stroke remained the leading cause of disability in the world, and the most important non-modifiable risk factor was age. The treatment of stroke for elder patients faced multiple difficulties due to its complicated pathogenesis and mechanism. Therefore, we aimed to identify the potential differentially expressed genes (DEGs) and singnalling pathways for aged people of stroke. To compare the DEGs in the aged rats with or without middle cerebral artery occlusion (MCAO) and to analyse the important genes and the key signalling pathways involved in the development of cerebral ischaemia in aged rats. The Gene Expression Omnibus (GEO) analysis tool was used to analyse the DEGs in the GSE166162 dataset of aged MCAO rats compared with aged sham rats. Differential expression analysis was performed in aged MCAO rats and sham rats using limma. In addition, the 74 DEGs (such as Fam111a, Lcn2, Spp1, Lgals3 and Gpnmb were up-regulated; Egr2, Nr4a3, Arc, Klf4 and Nr4a1 were down-regulated) and potential compounds corresponding to the top 20 core genes in the Protein-Protein Interaction (PPI) network was constructed using the STRING database (version 12.0). Among these 30 compounds, resveratrol, cannabidiol, honokiol, fucoxanthin, oleandrin and tyrosol were significantly enriched. These DEGs were subjected to Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to determine the most significantly enriched pathway in aged MCAO rats. Moreover, innate immune response, the complement and coagulation cascades signalling pathway, the IL-17 and other signalling pathways were significantly correlated with the aged MCAO rats. Our stu","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"125 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139065063","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 : 2023-12-01DOI: 10.1615/critrevimmunol.2023052059
Jing Chen, Bo Zeng
Background: The methyltransferase 14, N6-adenosine-methyltransferase subunit (METTL14) and Cyclin-dependent kinase inhibitor 2A (CDKN2A) have been identified as involved in the regulation of various cancer progression, while their mechanism and regulatory effect in retinoblastoma (RB) is still unclear. Methods: Cell colony formation, CCK-8 as well as western blotting were used to evaluate the proliferation, apoptosis as well as p53 protein level of RB cell line. The METTL14 and CDKN2A levels were detected by qRT-PCR or western blotting when METTL14 was up-regulated or CDKN2A was down-regulated. MeRIP and Pearson analysis were performed to confirm the regulatory relationship between METTL14 among CDKN2A. Results: We found that the levels of CDKN2A and METTL14 were abundant in RB samples, as well as RB cells. METTL14 enhances N6-methyladenosine (m6A) modification of CDKN2A to upregulate its mRNA and protein levels. The proliferation of RB cells can be inhibited by silencing CDKN2A, which promotes apoptosis and p53 protein level. Furthermore, high-expression of METTL14 eliminated the anti-tumor effect of CDKN2A silencing in RB progression in vitro. Conclusion: CDKN2A is mediated by METTL14-m6A modified and restrains p53 pathway activation to accelerate the malignancy of RB. This points to the METTL14-m6A-CDKN2A-p53 pathway axis as a possible prospective target for the future RB treatment.
{"title":"METTL14-mediated m6a modification of CDKN2A promoted the development of retinoblastoma by inhibiting p53 pathway","authors":"Jing Chen, Bo Zeng","doi":"10.1615/critrevimmunol.2023052059","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2023052059","url":null,"abstract":"Background: The methyltransferase 14, N6-adenosine-methyltransferase subunit (METTL14) and Cyclin-dependent kinase inhibitor 2A (CDKN2A) have been identified as involved in the regulation of various cancer progression, while their mechanism and regulatory effect in retinoblastoma (RB) is still unclear.\u0000Methods: Cell colony formation, CCK-8 as well as western blotting were used to evaluate the proliferation, apoptosis as well as p53 protein level of RB cell line. The METTL14 and CDKN2A levels were detected by qRT-PCR or western blotting when METTL14 was up-regulated or CDKN2A was down-regulated. MeRIP and Pearson analysis were performed to confirm the regulatory relationship between METTL14 among CDKN2A.\u0000Results: We found that the levels of CDKN2A and METTL14 were abundant in RB samples, as well as RB cells. METTL14 enhances N6-methyladenosine (m6A) modification of CDKN2A to upregulate its mRNA and protein levels. The proliferation of RB cells can be inhibited by silencing CDKN2A, which promotes apoptosis and p53 protein level. Furthermore, high-expression of METTL14 eliminated the anti-tumor effect of CDKN2A silencing in RB progression in vitro.\u0000Conclusion: CDKN2A is mediated by METTL14-m6A modified and restrains p53 pathway activation to accelerate the malignancy of RB. This points to the METTL14-m6A-CDKN2A-p53 pathway axis as a possible prospective target for the future RB treatment.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"4 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139065172","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 : 2023-11-01DOI: 10.1615/critrevimmunol.2023050922
Libin Jiang, Liying Xu, Huazuo Liu, Hanwen Chen, Weiyi Wang
Objectives: Rhizoma Dioscoreae Nipponicae (RDN) is a traditional Chinese medicine that widely applied in the treatment of human diseases. This study aims to explore the therapeutic potential of RDN in asthma and the underlying mechanisms. Methods: A mouse model of asthma was established by the stimulation of ovalbumin (OVA). HE staining was performed to detect the pathological injuries of tracheal tissues. The protein expression of collagen Ⅰ, FN1, α-SMA (airway remodeling markers), and p-p38 (a marker of the p38 MAPK pathway) were detected by Western blot. Eosinophils were then isolated from the model mice. Cell viability and ROS level were measured by CCK-8 and Flow cytometry, respectively. The mRNA expression of GPX4 and ACSL4 (ferroptosis markers) in eosinophils were measured by qRT-PCR. Results: RDN significantly reduced the numbers of total cells and eosnophils in BALF, inhibited inflammatory cell infiltration, and down-regulated remodeling markers (Collagen Ⅰ, FN1, and α-SMA) in OVA-induced mice. The p38 MAPK pathway was blocked by the intervention of RDN in the model mice, and its blocking weakens the poor manifestations of OVA-induced asthma. In addition, RDN induced the ferroptosis of eosnophils both in vitro and in vivo. Blocking of the p38 MAPK pathway also enhanced the ferroptosis of eosnophils in vitro, evidenced by the decreased cell viability and GPX4 expression, and increased ROS level and ACSL4 expression. Conclusion: RDN induced the ferroptosis of eosinophils through inhibiting the p38 MAPK pathway, contributing to the remission of asthma.
{"title":"Rhizoma Dioscoreae Nipponicae relieves asthma through inducing the ferroptosis of eosinophils and inhibiting the p38 MAPK signaling pathway","authors":"Libin Jiang, Liying Xu, Huazuo Liu, Hanwen Chen, Weiyi Wang","doi":"10.1615/critrevimmunol.2023050922","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2023050922","url":null,"abstract":"Objectives: Rhizoma Dioscoreae Nipponicae (RDN) is a traditional Chinese medicine that widely applied in the treatment of human diseases. This study aims to explore the therapeutic potential of RDN in asthma and the underlying mechanisms.\u0000Methods: A mouse model of asthma was established by the stimulation of ovalbumin (OVA). HE staining was performed to detect the pathological injuries of tracheal tissues. The protein expression of collagen Ⅰ, FN1, α-SMA (airway remodeling markers), and p-p38 (a marker of the p38 MAPK pathway) were detected by Western blot. Eosinophils were then isolated from the model mice. Cell viability and ROS level were measured by CCK-8 and Flow cytometry, respectively. The mRNA expression of GPX4 and ACSL4 (ferroptosis markers) in eosinophils were measured by qRT-PCR.\u0000Results: RDN significantly reduced the numbers of total cells and eosnophils in BALF, inhibited inflammatory cell infiltration, and down-regulated remodeling markers (Collagen Ⅰ, FN1, and α-SMA) in OVA-induced mice. The p38 MAPK pathway was blocked by the intervention of RDN in the model mice, and its blocking weakens the poor manifestations of OVA-induced asthma. In addition, RDN induced the ferroptosis of eosnophils both in vitro and in vivo. Blocking of the p38 MAPK pathway also enhanced the ferroptosis of eosnophils in vitro, evidenced by the decreased cell viability and GPX4 expression, and increased ROS level and ACSL4 expression.\u0000Conclusion: RDN induced the ferroptosis of eosinophils through inhibiting the p38 MAPK pathway, contributing to the remission of asthma.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"289 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138537034","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}
Endothelial dysfunction is associated with the progression of sepsis. This study sought to probe the molecular route of sex-determining region on the Y chromosome-box transcription factor 18 (SOX18) in sepsis-associated endothelial injury. Human umbilical vein endothelial cells (HUVECs) were treated with lipopolysaccharide (LPS) to establish the sepsis cell model. Cell viability, lactate dehydrogenase (LDH) release, oxidative stress (reactive oxygen species/malondialdehyde/superoxide dismutase), and inflammation (interleukin-1β/tumor necrosis factor-α/interleukin-6) was evaluated by cell counting kit-8 assay and assay kits. The expression levels of SOX18, microRNA (miR)-204-5p, and cadherin-2 (CDH2) in cells were determined by real-time quantitative polymerase chain reaction and Western blot assay. The interaction of SOX18, miR-204-5p, and CDH2 were analyzed by chromatin immunoprecipitation and the dual-luciferase assay. LPS induced HUVECs injury and downregulation of SOX18. SOX18 overexpression increased cell viability, while decreased LDH activity, oxidative stress, and inflammation. SOX18 bound to the miR-204-5p promoter to promote miR-204-5p expression, and further repressed CDH2 expression. miR-204-5p knockdown and CDH2 overexpression abrogated the protective role of SOX18 in HUVECs injury. Overall, SOX18 alleviated LPS-induced injury of HUVECs by promoting miR-204-5p and repressing CDH2, suggesting it as a potential target for sepsis treatment.
{"title":"Molecular mechanism of SOX18 in lipopolysaccharide-induced injury of human umbilical vein endothelial cells","authors":"Jian Luo, Honglong Fang, Danqiong Wang, Jianhua Hu, Weiwen Zhang, Ronglin Jiang","doi":"10.1615/critrevimmunol.2023050792","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2023050792","url":null,"abstract":"Endothelial dysfunction is associated with the progression of sepsis. This study sought to probe the molecular route of sex-determining region on the Y chromosome-box transcription factor 18 (SOX18) in sepsis-associated endothelial injury. Human umbilical vein endothelial cells (HUVECs) were treated with lipopolysaccharide (LPS) to establish the sepsis cell model. Cell viability, lactate dehydrogenase (LDH) release, oxidative stress (reactive oxygen species/malondialdehyde/superoxide dismutase), and inflammation (interleukin-1β/tumor necrosis factor-α/interleukin-6) was evaluated by cell counting kit-8 assay and assay kits. The expression levels of SOX18, microRNA (miR)-204-5p, and cadherin-2 (CDH2) in cells were determined by real-time quantitative polymerase chain reaction and Western blot assay. The interaction of SOX18, miR-204-5p, and CDH2 were analyzed by chromatin immunoprecipitation and the dual-luciferase assay. LPS induced HUVECs injury and downregulation of SOX18. SOX18 overexpression increased cell viability, while decreased LDH activity, oxidative stress, and inflammation. SOX18 bound to the miR-204-5p promoter to promote miR-204-5p expression, and further repressed CDH2 expression. miR-204-5p knockdown and CDH2 overexpression abrogated the protective role of SOX18 in HUVECs injury. Overall, SOX18 alleviated LPS-induced injury of HUVECs by promoting miR-204-5p and repressing CDH2, suggesting it as a potential target for sepsis treatment.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"29 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138537042","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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