Critical Reviews in Immunology最新文献

{"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}

{"title":"Human Oropharyngeal Candidiasis: From Etiology to Current Treatment.","authors":"Muhammad Imran Qadir,&nbsp;Hina Bashir,&nbsp;Muhammad Hammad Ahmad","doi":"10.1615/CritRevImmunol.2023049730","DOIUrl":"10.1615/CritRevImmunol.2023049730","url":null,"abstract":"<p><p>Oral candidiasis is a common but most harmful oral cavity infection caused by yeast-like fungus, this condition is called Oropharyngeal candidiasis. There are various species of candida that are responsible for oral cavity fungal infection including mostly Candida albicans. Different candida infections may be acute and chronic. Cell-mediated immunity, humoral immunity, and granulocytes are the immune factors for the cause of this infection. Different antifungal drugs like nystatin, fluconazole, and amphotericin are used to treat oral cavity fungal infections.</p>","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41220743","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}

{"title":"Losartan-Induced Angioedema with Acute Hypoxemic Respiratory Failure (Anaphylaxis): A Case Report.","authors":"Yusuf Kagzi,&nbsp;David Bradley Money,&nbsp;Asa Zoe Oxner,&nbsp;Alifiya Kagzi","doi":"10.1615/CritRevImmunol.2023050290","DOIUrl":"10.1615/CritRevImmunol.2023050290","url":null,"abstract":"<p><p>Angioedema is a condition characterized by swelling of the skin or mucosa resulting from loss of vascular integrity that leads to swelling of mucosal tissues and can lead to life-threatening respiratory compromise. Drug-induced angioedema is not a frequent side effect seen with angiotensin receptor blockers (ARBs), particularly when there are no other contributing risk factors like a prior episode. Few studies reported subsequent angioedema episodes after ARB use in patients who had a prior episode with angiotensin converting enzyme inhibitors; however, there are very few cases that documented non-fatal angioedema after ARB as the only therapy. We report a rare case of life-threatening anaphylaxis after losartan use. We hope that our case will bring awareness to this rare but fatal side effect in order to quickly recognize it and encourage further research.</p>","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41220749","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}

{"title":"The Potential Role of Cytotoxic Immune Effectors in Amyotrophic Lateral Sclerosis (ALS); A Longitudinal Case Study Comparing Patients with Genetically Identical Healthy Twin.","authors":"Kawaljit Kaur,&nbsp;Po-Chun Chen,&nbsp;Meng-Wei Ko,&nbsp;Sara Huerta-Yepez,&nbsp;Dipnarine Maharaj,&nbsp;Anahid Jewett","doi":"10.1615/CritRevImmunol.2023047233","DOIUrl":"https://doi.org/10.1615/CritRevImmunol.2023047233","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is an auto-immune neurodegenerative disorder affecting the motor-neurons. The causes of ALS are heterogeneous, and are only partially understood to date. We studied percentage and function of immune cell subsets in particular natural killer (NK) and CD8+ T cells in an ALS patient and compared the results to those obtained from his genetically identical healthy twin in a longitudinal study. We found several basic mechanisms which were potentially involved in the disease induction and progression. Our findings demonstrate that ALS patient's peripheral blood contained higher NK and B cells and, lower T cell percentages compared with the healthy twin brother's peripheral blood. Significantly increased interferon-gamma secretion by anti-CD3/28 monoclonal antibody-treated peripheral blood mononuclear cells, and sorted CD8+ T cells were observed in the ALS patient, suggesting that hyper-responsiveness of T cell compartment could be a potential mechanism of ALS progression. Significant increase in NK cell function due to genetic mutations in ALS associated genes may partly be responsible for the increase expansion and function of CD8+ T cells with effector/memory phenotype, in addition to direct activation and expansion of antigen specific T cells by such mutations. Weekly N-acetyl cysteine infusion to block cell death in patient in addition to a number of other therapies listed in this paper were not effective, and even though the treatments might have extended the patient's life, it was not curative. Therefore, activated CD8+ T and NK cells are likely cells targeting motor neurons in the patient, and strategies should be designed to decrease the aggressive nature of these cells to achieve longer lasting therapeutic benefits.</p>","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9889280","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}

{"title":"TLR9 knockdown alleviates sepsis via disruption of the MyD88/NF-κB pathway activation","authors":"Lili Li, Lili Jiang, Shuzhu Mao, Jiajian Ye","doi":"10.1615/critrevimmunol.2023050273","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2023050273","url":null,"abstract":"Sepsis is a life-threatening organ dysfunction due to dysregulated host response to infection, accompanied by a high rate of mortality worldwide. During sepsis progression, toll-like receptors (TLRs) play essential roles in the aberrant inflammatory response that contributes to sepsis-related mortality. Here, we demonstrated a critical role of TLR9 in the progression of sepsis. A septic mouse model was established by cecal ligation and puncture (CLP), then administered with lentivirus encoding si-TLR9/LY294002. TLR9 protein expression and p65 nuclear translocation level/TLR9 protein positive expression/interaction between TLR9 and MyD88 in the intestinal tissues were examined by Western blot/immunohistochemistry/Co-IP assays. Serum levels of pro-inflammatory factors (IL-6, TNF-α) as well as bacterial contents in the liver/spleen/mesenteric lymph nodes (MLN) were measured by ELISA and bacterial mobility assay. TLR9 expression was augmented in the intestinal tissues, TLR9 and MyD88 interaction was enhanced, nuclear p65 protein level was increased, cytoplasmic p65 protein level was decreased, and the MyD88/NF-κB pathway was activated in CLP-induced septic mice, while TLR9 knockout protected against CLP-induced sepsis via the MyD88/NF-κB pathway inactivation. Briefly, TLR9 inhibition-mediated protection against CLP-induced sepsis was associated with a reduction in pro-inflammatory cytokine release and a promotion of bacterial clearance via a mechanism involving the MyD88/NF-κB pathway inactivation.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136053037","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}

{"title":"Successes and Challenges in Taming the Beast: Cytotoxic Immune Effectors in Amyotrophic Lateral Sclerosis.","authors":"Kawaljit Kaur,&nbsp;Po-Chun Chen,&nbsp;Meng-Wei Ko,&nbsp;Ao Mei,&nbsp;Sara Huerta-Yepez,&nbsp;Dipnarine Maharaj,&nbsp;Subramaniam Malarkannan,&nbsp;Anahid Jewett","doi":"10.1615/CritRevImmunol.2023047235","DOIUrl":"https://doi.org/10.1615/CritRevImmunol.2023047235","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a neurological disease characterized by the progressive loss of motor neurons in the brain and spinal cord. No effective therapeutic strategies have been established thus far, and therefore there is a significant unmet need for effective therapeutics to arrest the disease and reverse the pathologies induced by it. Although the cause of ALS is not well-defined, it appears to be heterogenous. Currently over 20 genes have been found to be associated with ALS. Family history can only be found in 10% of ALS patients, but in the remaining 90% no association with family history is found. The most common genetic causes are expansion in the C9orf72 gene and mutations in superoxide dismutase 1, TDP-43, and FUS. In our recent study, we also found mutations in TDP43 and FUS in ALS patients. To understand the pathogenesis of the disease, we set ourselves the task of analyzing the phenotype and function of all key immune effectors in ALS patients, comparing them with either a genetically healthy twin or healthy individuals. Our study demonstrated a significant increase in functional activation of NK and CD8+ T cytotoxic immune effectors and release of significant IFN-γ not only by the effector cells but also in the serum of ALS patients. Longitudinal analysis of CD8+ T cell-mediated IFN-γ secretion from ALS patients demonstrated continued and sustained increase in IFN-γ secretion with periods of decrease which coincided with certain treatments; however, the effects were largely short-lived. N-acetyl cysteine (NAC), one of the treatments used, is known to block cell death; however, even though such treatment was able to block most of the proinflammatory cytokines, chemokines, and growth factor release, it was not able to block IFN-γ and TNF-α, the two cytokines we had demonstrated previously to induce differentiation of the cells. In this review, we discuss the contribution of cytotoxic effector cells, especially primary NK cells, supercharged NK cells (sNK), and the contribution of sNK cells in expansion and functional activation of CD8+ T cells to memory/effector T cells in the pathogenesis of ALS. Potential new targeted therapeutic strategies are also discussed.</p>","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9971719","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}