{"title":"Identification of key chondrocyte apoptosis-related genes in osteoarthritis based on weighted gene co-expression network analysis and experimental verification","authors":"Wei Wang, Junyi Hong, Tianyi Cao, Fusheng Ye, Junwei Gao, Shumei Qin","doi":"10.1615/critrevimmunol.2024051935","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051935","url":null,"abstract":"Objective: Osteoarthritis (OA) is the primary cause of disability worldwide. Chondrocyte apoptosis has important implications for OA onset and progression. This work was designed to explore the mechanisms of chondrocyte apoptosis in OA and identify key chondrocyte apoptosis-related genes (CARGs).\u0000Methods: GSE32317 and GSE55235 datasets were acquired from the Gene Expression Omnibus (GEO) database. OA-associated module genes were determined via weighted gene co-expression network analysis (WGCNA) in GSE32317. CARGs were acquired from public databases. ClusterProfiler was employed for GO and KEGG analyses. Protein-protein interaction (PPI) network establishment was realized via STRING database and Cytoscape, and the hub genes were screened by MCC, MNC, and DMNC algorithms of cytoHubba. The diagnostic values of the hub CARGs in OA in GSE55235 was verified via receiver operating characteristic (ROC) curve analysis. C28/I2 cells were stimulated with IL-1β to establish the in vitro OA model.\u0000Results: WGCNA identified 9,141 OA-related genes and 248 CARGs, resulting in 75 CARGs in OA. GO and KEGG analyses demonstrated that the 75 CARGs were primarily enriched in response to lipopolysaccharide, transcription regulator complex, DNA-binding transcription factor binding, along with NF-kappa B and TNF signaling pathways. NFKB1 and ICAM1 were identified as the hub CARGs in OA through the three algorithms, which showed favorable prognostic values for OA. Notably, both bioinformatics analysis and in vitro assays revealed upregulated NFKB1 and ICAM1 expression in OA.\u0000Conclusions: NFKB1 and ICAM1 were the hub CARGs in OA, which might serve as the diagnostic signatures and therapeutic","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"28 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140569998","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":"Advances in Vaccines, Checkpoint Blockade and Chimeric Antigen Receptor based Cancer Immunotherapeutics","authors":"Disha Agarwal, Gaurav Sharma, Alka Khadwal, Devinder Toor, Pankaj Malhotra","doi":"10.1615/critrevimmunol.2024053025","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024053025","url":null,"abstract":"Increase in cancer cases -numerically and etiologically encouraged research aiming development of novel treatment strategies, amongst which few are even implemented but with varying degrees of success along with specific limitations. For example, conventional treatment strategies viz. chemotherapy and radiotherapy have limited potential owing to their nonspecific cytotoxic nature thereby shifting focus towards immunotherapy. Recently, target specific immunotherapeutic regimens have been evaluated for their efficacy including 1) vaccines harnessing tumor specific/associated antigens, 2) checkpoint blockade therapy using monoclonal antibodies against PD1, CTLA-4 and others, 3) adoptive cell transfer approaches viz. CAR-cell-based therapies. Here we review recent advancements on these target specific translational immunotherapeutic strategies against cancer/s and concerned limitations.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"57 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140833301","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}
Jiawang Lang, Jianchang Luo, Luodan Wang, Wenbin Xu, Jie Jia, Zhipeng Zhao, Boxu Lang
{"title":"Electroacupuncture Alleviates Ischemic Stroke by Activating the mTOR/SREBP1 Pathway","authors":"Jiawang Lang, Jianchang Luo, Luodan Wang, Wenbin Xu, Jie Jia, Zhipeng Zhao, Boxu Lang","doi":"10.1615/critrevimmunol.2024051934","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051934","url":null,"abstract":"Objective: Ischemic stroke (IS) is one of the leading causes of death and disability worldwide. Electroacupuncture (EA) has been shown to exert a neuroprotective effect in IS. However, the specific anti-IS mechanisms of EA remain to be further elucidated. Thus, we aimed to investigate the anti-IS role of EA and its mechanism.\u0000Methods: By constructing a rat IS (middle cerebral artery occlusion, MCAO) model and performing EA treatment, the neurological deficit score, brain water content, and cerebral infarction were evaluated. ELISA was used to measure the levels of oxidative stress (OS)-related molecules (MDA, SOD, GSH, and CAT). Ferroptosis-related proteins (GPX4, SLC7A11, TfR1, L-ferritin, and hepcidin), neurological damage-related proteins (GFAP, Iba-1, and Nestin), α7nAChR, and mTOR pathway-related proteins (mTOR, p-mTOR, and SREBP1) in rat brain penumbra were assessed using western blotting.\u0000Results: Following EA treatment, the neurological deficit score, brain water content, cerebral infarction, and GFAP, Iba-1, and Nestin expression were reduced in the brain penumbra of MCAO rats. Additionally, EA treatment decreased MDA level and increased SOD, GSH, and CAT levels in the brain penumbra of MCAO rats. Moreover, MCAO rats showed elevated GPX4 and SLC7A11 expression and reduced TfR1, L-ferritin, and hepcidin in the brain penumbra following EA treatment. After EA treatment, α7nAChR, mTOR, p-mTOR, and SREBP1 expression were upregulated in the brain penumbra of MCAO rats.\u0000Conclusions: EA treatment inhibited OS and ferroptosis to exert a neuroprotective effect in IS, which might be realized via the activation of mTOR/SREBP1 signaling.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"32 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140035956","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":"Function of steroid receptor coactivators (SRCs) in T cells and cancers: Implications for cancer immunotherapy","authors":"Wencan Zhang, Xu Cao, Hongmin Wu, Xiancai Zhong, Yun Shi, Zuoming Sun","doi":"10.1615/critrevimmunol.2024051613","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051613","url":null,"abstract":"Steroid receptor coactivator (SRC) family members (SRC1, SRC2 and SRC3) are transcriptional co-regulators. SRCs orchestrate gene transcription by inducing transactivation of nuclear receptors and other transcription factors. Overexpression of SRCs is widely implicated in a range of cancers, especially hormone-related cancers. As coactivators, SRCs regulate multiple metabolic pathways involved in tumor growth, invasion, metastasis, and chemo-resistance. Emerging evidence in recent years suggest that SRCs also regulate maturation, differentiation, and cytotoxicity of T cells by controlling metabolic activities. In this review, we summarize the current understanding of the function of SRCs in T cells as well as cancer cells. Importantly, the controversies of targeting SRCs for cancer immunotherapy as well as possible reconciliation strategies are also discussed.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"12 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140069872","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":"KIAA1429 induces the m6A modification of LINC01106 to enhance the malignancy of lung adenocarcinoma cell via JAK/STAT3 pathway","authors":"Di Xu, Ziming Wang, Fajiu Li","doi":"10.1615/critrevimmunol.2024052728","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024052728","url":null,"abstract":"Background: Sustained expression of LINC01106 in tumors is crucial for malignant phenotype of tumor cells; Nevertheless, LINC01106’s mechanisms and clinical effects in lung adenocarcinoma (LUAD) is confined. This report focus on reveal the effect of vir-like m6A methyltransferase associated (KIAA1429)-mediated N6-methyladenosine (m6A) modification to steady LINC01106 expression on LUAD progression.\u0000Methods: qRT-PCR was conducted to clarify the LINC01106 and KIAA1429 levels in LUAD tissues. LINC01106’s and KIAA1429’s functional roles were analyzed utilizing Transwell, EdU as well as CCK-8 assays. Xenograft was cconducted to verify the function of silencing LINC01106 in tumor growth. The regulatory role between LINC01106 was investigated using MeRIP, qRT-PCR as well as Actinomycin D assay. Key proteins of JAK/STAT3 (JAK2, STAT3) pathway were revealed via western blotting.\u0000Results: LINC01106 and KIAA1429 were high-expressed in LUAD, and LINC01106 were interconnected with high tumor grade, stage, and poor prognosis. Data revealed LINC01106 inhibition reduced LUAD cell proliferation, invasion as well as migration, and restrained LUAD cell tumorigenicity. Additionally, phosphorylated JAK2, STAT3 levels were reduced by LINC01106 silencing. LINC01106 was mediated by KIAA1429 to enhance its m6A modification and expression in LUAD cells. Moreover, KIAA1429 promotion abolished the malignant phenotypic suppression induced by LINC01106 lowexpression in LUAD cells.\u0000Conclusion: This research revealed LINC01106 m6A modification was enhanced by KIAA1429 to play the promotive role in LUAD development. The results may conduce to the comprehending of the act of KIAA1429-m6A-LINC0110","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"18 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139977763","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":"Effect of p-estrogen receptor at serine on its function and breast growth","authors":"Yuan Liang, Junhui Qin, Tiancheng Ma, Tong Yang, Zhenyu Ke, Ruian Wang","doi":"10.1615/critrevimmunol.2024052499","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024052499","url":null,"abstract":"Background: Estrogen receptor (ER) signaling plays an important role in the development and functional differentiation of breast and participates in the process of breast cancer. Activated ER can affect various aspects of the cell’s behavior, including proliferation, via modulating the expression of many downstream target genes. Phosphorylation is one of the activation pathways of ER. However, the relationship between estrogen receptor phosphorylation sites and breast development and carcinogenesis is not clear.\u0000Methods: Using Crisper-Cas9 gene editing technology, we constructed ER S309A mutant mice. Using carmine staining of mammary gland of mice at different developmental stages, we examined breast development of ER S309Amice. Using HE staining of vaginal smears of mice at the same time for 5 consecutive days, we measured the vaginal epithelial keratinocytes.\u0000Results: We established ER S309A mutant mice and observed breast defects in ER S309A mice. In addition, we observed decreased reproductive ability, estrous cycle disorder in ER S309A mice. And number of vaginal epithelial keratinocytes in the estrous cycle of ER S309A mice was decreased.\u0000Conclusion: These results suggest that phosphorylation site of ER at serine 309 is important for ER function and breast development.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"6 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139918547","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":"Oral Cancer: Past, present and future of NK cell-based cancer immunotherapy","authors":"Kawaljit Kaur, Anahid Jewett","doi":"10.1615/critrevimmunol.2024052389","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024052389","url":null,"abstract":"Despite advancements in the field of cancer therapeutics the five-year survival rate remains low in oral cancer patients. There, the effective therapeutics are needed to control the disease. Also, several studies including ours have shown severely suppressed function and number of NK cells in oral cancer patients. In this review, we discuss the approach to inhibit the tumor growth and metastasis by direct killing or NK cell-mediated tumor differentiation. This review also provides the overview on supercharging NK cells using osteoclasts and probiotic bacteria, and their efficacy as cancer immunotherapeutic in humanized-BLT mice.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"12 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139754824","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 value of systemic immune-inflammation index and T cell subsets in the severity and prognosis of sepsis","authors":"Hao Zhou","doi":"10.1615/critrevimmunol.2024051413","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051413","url":null,"abstract":"Systemic immune-inflammation index (SII) and T cell subsets show involvement in mortality risk in septic patients, and we explored their predictive value in sepsis. Subjects were categorized into the Sepsis (SP)/Septic Shock (SSP)/Septic Shock (SPS) groups. T cell subsets [T-helper (Th)1, Th2, regulatory T cells (Treg), Th17]/platelets (PLT)/neutrophils (NEU)/lymphocytes (LYM)/C-reactive protein (CRP)/procalcitonin (PCT)/interleukin (IL)-4/IL-10/fibrinogen (FIB) were measured by an automatic blood biochemical analyzer/flow cytometry/Countess II FL automatic blood cell analyzer, with SII calculated. The correlations between SII/T cell subsets with Acute Physiology and Chronic Health Evaluation (APACH) II/Sequential Organ Failure Assessment (SOFA) scores and the predictive value of SII/Th1/Th2 for septic diagnosis/prognosis were analyzed using Spearman/ROC curve/Kaplan-Meier. The three groups varied in PLT/NEU/LYM/CRP/PCT/IL-4/IL-10/FIB levels and APACH II/SOFA scores. Compared with the SP group, the other two groups showed elevated APACH II/SOFA scores and SII/Th1/Th2/Th17/Treg levels. SII/Th1/Th2 levels significantly positively correlated with APACH II/SOFA scores. SII/Th1/Th2 levels had high predictive value for septic diagnosis/prognosis, with their combination exhibiting higher predictive value. Septic patients with high SII/Th1/Th2 levels exhibited lower survival rates. Altogether, SII, Th1, and Th2 had good predictive value for the diagnosis and prognosis of patients with varying severity of sepsis, with their high levels increasing mortality in septic patients.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"2 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139663580","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}
Jianghui Wang, Shufang Ni, Kai Zheng, Yan Zhao, peihong zhang, Hong Chang
{"title":"Phillygenin alleviated arthritis through the inhibition of NLRP3 inflammasome and Ferroptosis by AMPK","authors":"Jianghui Wang, Shufang Ni, Kai Zheng, Yan Zhao, peihong zhang, Hong Chang","doi":"10.1615/critrevimmunol.2024051467","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051467","url":null,"abstract":"Background: We investigated the potential arthritis-inducing effects of Phillygenin and its underlying mechanisms.\u0000Methods: RAW264.7 cells were stimulated with lipopolysaccharide to induce inflammation.\u0000Results: Phillygenin was found to reduce arthritis score, histopathological changes, paw edema, spleen index, and ALP levels in a dose-dependent manner in a model of arthritis. Additionally, Phillygenin was able to decrease levels of inflammation markers in serum samples of mice with arthritis and also inhibited inflammation markers in the cell supernatant of an in vitro model of arthritis. Phillygenin increased cell viability and JC-1 disaggregation, enhanced calcien-AM/CoCl2, reduced LDH activity levels and IL-1α levels, and inhibited Calcein/PI levels and iron concentration in an in vitro model. Phillygenin was also found to reduce ROS-induced oxidative stress and Ferroptosis, and suppress the NLRP3 inflammasome in both in vivo and in vitro models through AMPK. In the in vivo model, Phillygenin was observed to interact with AMPK protein.Conclusions: These findings suggest that Phillygenin may be a potential therapeutic target for preventing arthritis by inhibiting NLRP3 inflammasome and Ferroptosis through AMPK. This indicates that Phillygenin could have disease-modifying effects on arthritis.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"16 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139754833","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}
Tu Nguyen, Po-Chun Chen, Janet Pham, Kawaljit Kaur, Steven Raman, Anahid Jewett, Jason Chiang
{"title":"The Current and Future States of Natural Killer Cell-Based Immunotherapy in Hepatocellular Carcinoma","authors":"Tu Nguyen, Po-Chun Chen, Janet Pham, Kawaljit Kaur, Steven Raman, Anahid Jewett, Jason Chiang","doi":"10.1615/critrevimmunol.2024052486","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024052486","url":null,"abstract":"Natural killer (NK) cells are innate lymphoid cells that exhibit high levels of cytotoxicity against NK-specific targets, produce various cytokines, and interact with T cells, B cells, and dendritic cells to effectively serve as frontliners of the innate immune system. Moreover, NK cells constitue the second most frequent immune cell in the liver. These properties have drawn significant attention towards leveraging NK cells in treating liver cancer, especially hepatocellular carcinoma (HCC), which accounts for 75% of all liver cancer and is the fourth leading cause of cancer-related death worldwide. Notable anti-cancer functions of NK cells against HCC include activating antibody-dependent cell cytotoxicity (ADCC), facilitating Gasdermin E-mediated pyroptosis of HCC cells, and initiating an antitumor response via the cGAS-STING signaling pathway. In this review, we describe how these mechanisms work in the context of HCC. We will then discuss the existing preclinical and clinical studies that leverage NK cell activity to create single and combined immunotherapies.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"25 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139754891","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}