Recent studies suggest that cuproptosis, a novel mode of cell death, may be associated with the development of cancer. However, no studies are showing its role in tumorigenesis, progression, and prognosis. In the present study, we comprehensively analyzed the expression difference, gene variation and methylation modification of cuproptosis-related genes (CRGs) in pan-cancer. Then, Single sample gene set enrichment analysis (ssGSEA) was used to calculate individual cuproptosis scores (CS). The association of CS with copy number variation, clinical features, immune-related genes, TMB, MSI, and tumor immune dysfunction and exclusion (TIDE) was comprehensively assessed. Single-cell transcriptome sequencing (scRNA-seq) to analyze the activation of cuproptosis in the tumor microenvironment. Immunohistochemistry (IHC) were used to validate the expression of cuproptosis hub-gene. Our study shows that CRGs were significantly expressed in a variety of tumors, and CDKN2A had the highest mutation frequency (49%) in all tumors. A significant increase in the CS was observed in most cancers and were associated with poor prognosis in the majority of tumors. CS was significantly negatively correlated with tumor microenvironment scores in more than 10 tumors and positively correlated with PD-L1 in 11 tumors, suggesting involvement in tumor immune escape. scRNA-seq suggests that CRG scores significantly increased in the cancer cells. This study opens avenues for further research on the role of cuproptosis in the occurrence and development of cancer and the development of targeted therapies based on cuproptosis.
5 April 2022 in European Journal of Psychotraumatology
Pre-hospitalisation, hospitalisation and post-hospitalisation factors may significantly affect depression, anxiety and post-traumatic growth (PTG) among COVID-19 survivors.Our study investigated de... Antecedentes: Los factores pre-hospitalización, durante la hospitalización y post-hospitalización pueden afectar significativamente la depresión, la ansiedad y el crecimiento postraumático (CPT) en... 背景: 住院前、住院和住院后因素可能会显著影响 COVID-19 幸存者的抑郁、焦虑和创伤后成长 (PTG)。目的: 我们的研究考查了 COVID-19 幸存者的抑郁、焦虑和 PTG 及其相关性。方法: 在中国五个城市(即武汉、深圳、珠海、东莞和南宁)进行的一项横断面电话调查招募了出院后六个月随访中的199 名 COVID-19 患者(平均年龄 = 42.7;53.3% 女性)。对其人口统计...
Manganese ions (Mn2+) combined with adjuvants capable of damaging and lysing tumor cells form an antitumor nano-modulator that enhances the immune efficacy of cancer therapy through the cascade activation of the cyclic GMP-AMP interferon gene synthase-stimulator (cGAS-STING) pathway, which underscores the importance of developing antitumor nano-modulators, which induce DNA damage and augment cGAS-STING activity, as a critical future research direction. We have successfully synthesized an antitumor nano-modulator, which exhibits good dispersibility and biosafety. This nano-modulator is engineered by loading manganese dioxide nanosheets (M-NS) with zebularine (Zeb), known for its immunogenicity-enhancing effects, and conducting targeted surface modification using hyaluronic acid (HA). After systemic circulation to the tumor site, Mn2+, Zeb, and reactive oxygen species (ROS) are catalytically released in the tumor microenvironment by H+ and H2O2. These components can directly or indirectly damage the DNA or mitochondria of tumor cells, thereby inducing programmed cell death. Furthermore, they promote the accumulation of double-stranded DNA (dsDNA) in the cytoplasm, enhancing the activation of the cGAS-STING signalling pathway and boosting the production of type I interferon and the secretion of pro-inflammatory cytokines. Additionally, Zeb@MH-NS enhances the maturation of dendritic cells, the infiltration of cytotoxic T lymphocytes, and the recruitment of natural killer cells at the tumor site. This HA-modified manganese-based hybrid nano-regulator can enhance antitumor therapy by boosting innate immune activity and may provide new directions for immunotherapy and clinical translation in cancer.
1 February 2022 in Journal of Inflammation Research
Background: GIMAP, a GTP enzyme of immune-related proteins, plays a crucial role in immune mechanisms. Investigating GIMAP7 expression in pan-cancer can provide efficient guidance for predicting clinical prognosis and identifying novel immunotherapy targets. Methods: Gene expression in different tumour types and stages was analysed based on The Cancer Genome Atlas and the Genotype-Tissue Expression database. An immunohistochemical assay was used to explore the differences in GIMAP7 protein levels in different tumour types and stages. Further, the cBioPortal was used to obtain the genetic variation characteristics of GIMAP7. Kaplan–Meier analysis and multivariable Cox regression analysis were performed to assess the prognostic value of GIMAP7. The pathways affected by GIMAP7 were studied based on gene set enrichment analysis, and the correlation between GIMAP7 expression and immune infiltration was determined using the TIMER2 database and the CIBERSORT method. ESTIMATE was used to analyse the correlation between GIMAP7 expression and ESTIMATE, immune and stromal scores. In addition, the correlation between GIMAP7 and immunoregulators was analysed. Furthermore, tumour mutational burden and microsatellite instability were evaluated using Spearman correlation assay. Results: GIMAP7 expression was significantly low and predicted better survival status in most tumour types. GIMAP7 was positively correlated with the abundance of CD8 + and CD4 + T cells in the tumour microenvironment. However, the high expression of GIMAP7 was negatively correlated with tumour mutations in uveal melanoma and colon adenocarcinoma. A correlation between GIMAP7 and microsatellite instability was found in rectal adenocarcinoma. Additionally, GIMAP7 presented a robust correlation between immune modulators and immunotherapeutic markers. Moreover, high GIMAP7 expression was significantly related to immune-relevant pathways. Conclusion: This study suggests the potential role of GIMAP7 as a prognostic and immunotherapeutic marker in pan-cancer, laying the groundwork for prospective functional and mechanistic experiments and their impact in the clinical setting.
2 February 2023 in Diabetes Research and Clinical Practice
This study is to explore the relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and chronic kidney disease (CKD) among populations with type 2 diabetes through longitudinal cohort study. 3,627 subjects who had received at least three health examinations between 2008 and 2015 were included. CKD was stated as subjects with an eGFR < 60 mL/min per 1·73 m2 or the occurrence of 2 or more proteinuria during their follow-up. After median of 10·0 years follow up, 837 (23·1%) developed CKD (244·7 per 10,000 person-years; 95 % CI, 228.4 - 261·8). MAFLD ([HR] 1·46; 95 % CI 1·26-1·70, P < 0.001) acts as an important risk factor of developing CKD. After adjusting for confounding factors, this association was consistent (HR 1·30; 95 % CI 1·11-1·53, P < 0.001). In stratified analysis, subjects aged < 60 years were likely to have greater risk of MAFLD-related CKD (HR 1·58 and 1·03; 95 % CI 1·28-1·95 and 0·79-1·33, P < 0.001 in both cases, respectively). The risk of developing CKD in type 2 diabetes adults with MAFLD was higher, especially if they are below 60 years old. This study underscores the importance of early prevention strategies for MAFLD to reduce the occurrence of CKD in type 2 diabetes adults.
28 January 2022 in European Journal of Psychotraumatology
As a highly infectious disease with human-to-human transmission characteristics, COVID-19 has caused panic in the general public. Those who have recovered from COVID-19 may experience discriminatio... Internalized stigma fully mediated the effects of perceived discrimination and social support on social anxiety and partially mediated the effect of perceived affiliate stigma on social anxiety. Antecedentes: Como una enfermedad altamente infecciosa con características de transmisión de persona a persona, el COVID-19 ha causado pánico en el público en general. Aquellos que se han recuperad... 研究背景: 新型冠状病毒肺炎作为一种具有人传人特征的高传染性疾病, 在公众中一度引起了较大恐慌。感染过该疾病的康复者往往会被内在污名化, 甚至可能遭受歧视, 因而很可能会顾虑人际交往, 进而产生社交焦虑。研究目的: 本研究通过调查住院治疗经历, 人际社交因素, 个人因素与社交焦虑之间的关系, 揭示出新型冠状病毒肺炎幸存者在康复后的社交焦虑形成机制。研究方法: 本研究基于一项横断面调查, 以电...