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Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 368
Xuechun Sun ◽  
Xiaodan Sun ◽  
Huali Meng ◽  
Junduo Wu ◽  
Xin Guo ◽  

Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus (DM), resulting in high mortality. Myocardial fibrosis, cardiomyocyte apoptosis and inflammatory cell infiltration are hallmarks of DCM, leading to cardiac dysfunction. To date, few effective approaches have been developed for the intervention of DCM. In the present study, we investigate the effect of krill oil (KO) on the prevention of DCM using a mouse model of DM induced by streptozotocin and a high-fat diet. The diabetic mice developed pathological features, including cardiac fibrosis, apoptosis and inflammatory cell infiltration, the effects of which were remarkably prevented by KO. Mechanistically, KO reversed the DM-induced cardiac expression of profibrotic and proinflammatory genes and attenuated DM-enhanced cardiac oxidative stress. Notably, KO exhibited a potent inhibitory effect on NLR family pyrin domain containing 3 (NLRP3) inflammasome that plays an important role in DCM. Further investigation showed that KO significantly upregulated the expression of Sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), which are negative regulators of NLRP3. The present study reports for the first time the preventive effect of KO on the pathological injuries of DCM, providing SIRT3, PGC-1α and NLRP3 as molecular targets of KO. This work suggests that KO supplementation may be a viable approach in clinical prevention of DCM.

2022 ◽  
Vol 12 ◽  
Zhixiao Xu ◽  
Chengshui Chen

Background: Interstitial lung disease in systemic sclerosis (SSc-ILD) is one of the most severe complications of systemic sclerosis (SSc) and is the main cause of mortality. In this study, we aimed to explore the key genes in SSc-ILD and analyze the relationship between key genes and immune cell infiltration as well as the key genes relevant to the hallmarks of cancer.Methods: Weighted gene co-expression network analysis (WGCNA) algorithm was implemented to explore hub genes in SSc-ILD samples from the Gene Expression Omnibus (GEO) database. Logistic regression analysis was performed to screen and verify the key gene related to SSc-ILD. CIBERSORT algorithms were utilized to analyze immune cell infiltration. Moreover, the correlation between the key genes and genes relevant to cancer was also evaluated. Furthermore, non-coding RNAs (ncRNAs) linking to PTGS2 were also explored.Results: In this study, we first performed WGCNA analysis for three GEO databases to find the potential hub genes in SSc-ILD. Subsequently, we determined PTGS2 was the key gene in SSC-ILD. Furthermore, in CIBERSORT analyses, PTGS2 were tightly correlated with immune cells such as regulatory T cells (Tregs) and was negatively correlated with CD20 expression. Moreover, PTGS2 was associated with tumor growth. Then, MALAT1, NEAT1, NORAD, XIST identified might be the most potential upstream lncRNAs, and LIMS1 and RANBP2 might be the two most potential upstream circRNAs.Conclusion: Collectively, our findings elucidated that ncRNAs-mediated downregulation of PTGS2, as a key gene in SSc-ILD, was positively related to the occurrence of SSc-ILD and abnormal immunocyte infiltration. It could be a promising factor for SSc-ILD progression to malignancy.

2022 ◽  
Vol 8 ◽  
Hui Zhang ◽  
Xu Zhang ◽  
Weiguo Xu ◽  
Jian Wang

Background: The oncological role of TMC5 in human cancers has only been revealed partially. We performed integrated bioinformatics analysis to provide a thorough and detailed insight of associations between TMC5 and tumorigenesis, cancer progression, and prognosis.Methods: With reference to the accessible online databases, the TMC5 expressions in tumor tissues and corresponding normal tissues, different pathological stages, and various cancer cells were analyzed, while the protein levels of TMC5 in different cancers were also inspected. Meanwhile, the prognostic value of TMC5 expression in multiple cancers as well as in advanced-stage patients was investigated. Furthermore, the mutational data of TMC5 and its correlation with cancer prognosis were assessed. Moreover, the association between the TMC5 level and immune cell infiltration was evaluated. Next, TMC5-related pathway alterations and drug responses were summarized. Finally, the TMC5 based protein network was generated, and relevant enrichment was performed.Results: In our study, the expression level of TMC5 was significantly higher in the tumor tissue than that of the normal tissues in most cancer types. Fluctuations of TMC5 levels were also observed among different pathological stages. In the meantime, the protein level elevated in the tumor tissue in the cancers enrolled. Moreover, the expression of TMC5 was not only prognostic for overall survival (OS) or recurrence free survival (RFS) in various types of cancers but also correlated to OS in patients with more advanced cancers. Additionally, the mutational status of TMC5 is also associated with prognosis in cancer patients. It is worth noting that the TMC5 level was closely related to immune cell infiltrations, especially in ESCA, TGCT, and USC. The TMC5 expression was also identified as an activator for pathways including PI3K/AKT, RAS/MAPK, and TSC/mTOR, proved to be associated with multiple drug responses and assessed to be interactive with the TMEM family.Conclusion: TMC5 might function as a potential marker for cancer survival and immune responses.

2022 ◽  
Vol 9 (2) ◽  
pp. e1134
Jana Remlinger ◽  
Adrian Madarasz ◽  
Kirsten Guse ◽  
Robert Hoepner ◽  
Maud Bagnoud ◽  

Background and ObjectivesMyelin oligodendrocyte glycoprotein antibody–associated disorder (MOGAD) is a rare, autoimmune demyelinating CNS disorder, distinct from multiple sclerosis and neuromyelitis optica spectrum disorder. Characterized by pathogenic immunoglobulin G (IgG) antibodies against MOG, a potential treatment strategy for MOGAD is to reduce circulating IgG levels, e.g., by interference with the IgG recycling pathway mediated by the neonatal Fc receptor (FcRn). Although the optic nerve is often detrimentally involved in MOGAD, the effect of FcRn blockade on the visual pathway has not been assessed. Our objective was to investigate effects of a monoclonal anti-FcRn antibody in murine MOG-IgG–associated experimental autoimmune encephalomyelitis (EAE).MethodsWe induced active MOG35-55 EAE in C57Bl/6 mice followed by the application of a monoclonal MOG-IgG (8-18C5) 10 days postimmunization (dpi). Animals were treated with either a specific monoclonal antibody against FcRn (α-FcRn, 4470) or an isotype-matched control IgG on 7, 10, and 13 dpi. Neurologic disability was scored daily on a 10-point scale. Visual acuity was assessed by optomotor reflex. Histopathologic hallmarks of disease were assessed in the spinal cord, optic nerve, and retina. Immune cell infiltration was visualized by immunohistochemistry, demyelination by Luxol fast blue staining and complement deposition and number of retinal ganglion cells by immunofluorescence.ResultsIn MOG-IgG–augmented MOG35-55 EAE, anti-FcRn treatment significantly attenuated neurologic disability over the course of disease (mean area under the curve and 95% confidence intervals (CIs): α-FcRn [n = 27], 46.02 [37.89–54.15]; isotype IgG [n = 24], 66.75 [59.54–73.96], 3 independent experiments), correlating with reduced amounts of demyelination and macrophage infiltration into the spinal cord. T- and B-cell infiltration and complement deposition remained unchanged. Compared with isotype, anti-FcRn treatment prevented reduction of visual acuity over the course of disease (median cycles/degree and interquartile range: α-FcRn [n = 16], 0.50 [0.48–0.55] to 0.50 [0.48–0.58]; isotype IgG [n = 17], 0.50 [0.49–0.54] to 0.45 [0.39–0.51]).DiscussionWe show preserved optomotor response and ameliorated course of disease after anti-FcRn treatment in an experimental model using a monoclonal MOG-IgG to mimic MOGAD. Selectively targeting FcRn might represent a promising therapeutic approach in MOGAD.

BMC Genomics ◽  
2022 ◽  
Vol 23 (1) ◽  
Ping Liu ◽  
Ruoxu Chen ◽  
Xudong Zhang ◽  
Ruiting Fu ◽  
Lin Tao ◽  

Abstract Background High-grade serous ovarian carcinoma is highly heterogeneous, and although many studies have been conducted to identify high-grade serous ovarian carcinoma molecular subtypes that are sensitive to immunotherapy, no precise molecular subtype has been proposed to date. Immune cell infiltration and immune checkpoints are highly correlated with immunotherapy. Here, we investigated immune cell infiltration and immune checkpoint values for prognosis and precise immunotherapy for high-grade serous ovarian carcinoma based on molecular subtype classification. Results “High antigen-presenting cells infiltration molecular subtype of high-grade serous ovarian carcinoma” was identified in immune cell infiltration profiles. Each of the three immune cell infiltration clusters (A, B, and C) demonstrated distinct immune cell characterization, with immune cell infiltration cluster C exhibiting high antigen-presenting cell infiltration, improved prognosis, and higher sensitivity to immunotherapy. Programmed death-1/programmed death ligand 1 has a prognostic and predictive role that can help classify molecular subtypes. Conclusions Our findings redefined a unique molecular subtype of high-grade serous ovarian carcinoma, suggesting that high-grade serous ovarian carcinoma patients with higher antigen-presenting cell infiltration and programmed death-1/programmed death ligand 1 expression can benefit from precise immunotherapy.

2022 ◽  
Yang Bu ◽  
Kejun Liu ◽  
Yiming Niu ◽  
Ji Hao ◽  
Lei Cui ◽  

Abstract Background: Glucose-6-phosphate dehydrogenase (G6PD) plays an important role in the metabolic and immunological aspects of tumors. In hepatocellular carcinoma (HCC), the alteration of tumor microenvironment influences recurrence and metastasis. We extracted G6PD-related data from public databases of HCC tissues and used a bioinformatics approach to explore the correlation between G6PD expression and clinicopathological features and prognosis of immune cell infiltration in HCC.Methods: We extract G6PD expression information from TCGA and GEO databases in liver cancer tissues and normal tissues, validated by immunohistochemistry, and the correlation between G6PD expression and clinical features is analyzed, and the clinical significance of G6PD in liver cancer is assessed by Kaplan-Meier, Cox regression and prognostic line graph models. Functional enrichment analysis is performed by protein-protein interaction (PPI) network, GO/KEGG, GSEA and G6PD-associated differentially expressed genes (DEGs). TIMER and ssGSEA packages are used to assess the correlation between expression and the level of immune cell infiltration.Results: Our results show that G6PD expression is significantly upregulated in hepatocellular carcinoma tissues (P < 0.001). G6PD expression is associated with histological grade, pathological stage, T-stage, vascular infiltration and AFP level (P < 0.05); HCC patients in the low G6PD expression group had longer overall survival and better prognosis compared with the high G6PD expression group (P < 0.05). The level of G6PD expression also affects the levels of macrophages, unactivated dendritic cells, B cells, and follicular helper T cells in the tumor microenvironment.Conclusion: High expression of G6PD is a potential biomarker for poor prognosis of hepatocellular carcinoma, and G6PD may be a target for immunotherapy of HCC.

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