RESUMO
Renal clear cell carcinoma (KIRC) is one malignancy whose development and prognosis have been associated with aberrant DHRS7 expression. However, the catalytic activity and pathophysiology of KIRC are poorly understood, and no sensitive tumor biomarkers have yet been discovered. In our study, we examined the significant influence of DHRS7 on the tumor microenvironment (TME) and tumor progression using an overall predictable and prognostic evaluation approach. We found novel cancer staging, particularly in KIRC, as well as potential therapeutic drugs out of 27 drug sensitivity tests. Using Perl scripts, it was possible to determine the number of somatic mutations present in 33 tumors, as well as the relative scores of 22 immune cells using CIBERSORT, the relationship between immune infiltration and differential expression using TCGA data, and the immune microenvironment score using the estimate technique. Our results show that DHRS7 is abnormally expressed in pan-cancer patients, which influences their survival. Low DHRS7 expression was associated with late clinical stages and a low survival rate in KIRC patients, suggesting a poor prognosis and course of treatment, in HNSG, MESO, and KIRC patients. We also found that DHRS7 was associated with TMB and MSI in certain tumors. Using KIRC as an example, we discovered a negative correlation between DHRS7 expression and immunological assessments, suggesting that this substance might be used as a tumor biomarker.
RESUMO
Rheumatoid arthritis (RA) is a chronic, heterogeneous autoimmune disease with a high disability rate that seriously affects society and individuals. However, there is a lack of effective and reliable diagnostic markers and therapeutic targets. In this study, we identified diagnostic markers of RA based on RNA modification and explored its role as well as degree of immune cell infiltration. We used the gene expression profile data of three synovial tissues (GSE55235, GSE55457, GSE77298) from the Gene Expression Omnibus (GEO) database and the gene of 5 RNA modification genes (including m6A, m1A, m5C, APA, A-1), combined with cluster analysis, identified four RNA modifiers closely related to RA (YTHDC1, LRPPRC, NOP2, and CLP1) and five immune cells namely T cell CD8, CD4 memory resting, T cells regulatory (Tregs) Macrophages M0, and Neutrophils. Based on the LASSO regression algorithm, hub genes and immune cell prediction models were established respectively in RA and a nomogram based on the immune cell model was built. Around 4 key RNA modification regulator genes, miRNA-mRNA, mRNA-TF networks have been established, and GSEA-GO, KEGG-GSEA enrichment analysis has been carried out. Finally, CLP1 was established as an effective RA diagnostic marker, and was highly positively correlated with T cells follicular helper (Tfh) infiltration. On the other hand, highly negatively correlated with the expression of mast cells. In short, CLP1 may play a non-negligible role in the onset and development of RA by altering immune cell infiltration, and it is predicted to represent a novel target for RA clinical diagnosis and therapy.
RESUMO
BACKGROUND: Mesenchymal stem cells (MSCs) exert positive effects in chronic wounds. However, critical parameters, such as the most effective administration routes, remain unclear. Accordingly, the purpose of this study was to compare the effects of topical and systemic transplantation MSCs on diabetic ischemic wound healing and explored the underlying mechanisms. METHOD: A diabetic ischemic wound model was created on the dorsal foot of type 2 diabetes mellitus (T2DM) rat. Bone marrow-derived mesenchymal stem cells (BM-MSCs) were administered via two routes: topical injection and intravenous (IV) infusion. Wound healing outcomes and blood glucose level were assessed dynamically. Meanwhile, blood flow recovery was evaluated in ischemic gastrocnemius muscles. The homing and transdifferentiation of mKate2-labeled BM-MSCs were assessed by fluorescence imaging and immunohistochemistry (IHC) analysis. RESULT: Both topical and systemic treatments had a positive effect on the diabetic ischemic wound showing a significant reduction in wound area at day 14. Histological results showed an increase in the length of epithelial edges, collagen content, microvessel density in the wound bed, and a higher expression of vascular endothelial growth factor (VEGF). Meanwhile, systemic administration can ameliorate hyperglycemia and improve the blood perfusion of the ischemic hindlimb. BM-MSCs administered systemically were found distributed in wounded tissue and transdifferentiated into endothelial cells. Furthermore, BM-MSCs stimulated angiogenesis at wound sites by downregulating phosphatase and tensin homolog (PTEN) and activation of AKT signaling pathway. CONCLUSIONS: The results demonstrated that both transplantation delivery method (topical and systemic) of BM-MSCs accelerated wound healing remarkably under pathological conditions. Nevertheless, systemic administration has the potential to ameliorate hyperglycemia and repair the damaged tissue.
