miR-190 promotes malignant transformation and progression of human urothelial cells through CDKN1B/p27 inhibition.

BACKGROUND: Although miR-190 has been reported to be related to human diseases, especially in the development and progression of cancer, its expression in human bladder cancer (BC) and potential contribution to BC remain unexplored. METHODS: RT-qPCR was used to verify the expression level of miR-190 and CDKN1B. Flow cytometry (FCM) assays were performed to detect cell cycle. Soft agar assay was used to measure anchorage-independent growth ability. Methylation-Specific PCR, Dual-luciferase reporter assay and Western blotting were used to elucidate the potential mechanisms involved. RESULTS: Our studies revealed that downregulation of the p27 (encoded by CDKN1B gene) protein is an important event related to miR-190, promoting the malignant transformation of bladder epithelial cells. miR-190 binds directly to CDKN1B 3'-UTR and destabilizes CDKN1B mRNA. Moreover, miR-190 downregulates TET1 by binding to the TET1 CDS region, which mediates hypermethylation of the CDKN1B promoter, thereby resulting in the downregulation of CDKN1B mRNA. These two aspects led to miR-190 inhibition of p27 protein expression in human BC cells. A more in-depth mechanistic study showed that c-Jun promotes the transcription of Talin2, the host gene of miR-190, thus upregulating the expression of miR-190 in human BC cells. CONCLUSIONS: In this study, we found that miR-190 plays an important role in the development of BC. Taken together, these findings indicate that miR-190 may promote the malignant transformation of human urothelial cells by downregulating CDKN1B, which strengthens our understanding of miR-190 in regulating BC cell transformation.

Expression of Serum Cytokines Profile in Neonatal Sepsis.

Objective: Sepsis remains a major cause of neonatal death. To better characterize the inflammatory response during neonatal sepsis, we compared the differences in serum cytokines and chemokines between full-term neonates with sepsis and without infection. Methods: We enrolled 40 full-term neonates with sepsis and 26 full-term neonates without infection as controls between October 2016 and June 2018. Forty cytokines /chemokines in serum were analyzed using the Luminex Bead Immunoassay System. Results: Our results showed that serum IL-6, IL-8, TNF-α, IL-1ß, MIF, CXCL13, CXCL1, CXCL2, CXCL5, CXCL6, CXCL16, CCL27, CCL2, CCL8, CCL3, CCL20, CCL23, and CX3CL1 levels were significantly increased in neonates with sepsis compared to those in the control group (all p<0.05). The levels of serum CCL20, and IL-17 were higher in late-onset sepsis (LOS) than those in early-onset sepsis (EOS) (all p<0.05). Conversely, serum CXCL16 was lower in LOS than that in EOS (p<0.05). Conclusion: Our findings revealed that excessive pro-inflammatory cytokines might be involved in neonatal sepsis. In addition, chemokines significantly increased the recruitment of immune cells after infection to participate in the anti-infection defense of neonates, but this could lead to damage.

High LARGE1 Expression May Predict Benefit from Adjuvant Chemotherapy in Resected Non-Small-Cell Lung Cancer.

BACKGROUND: LARGE1 plays a pivotal role in glycosylation of alpha-Dystroglycan (α-DG) and is aberrantly downregulated in cell lines originating from epithelium-derived cancers including lung cancer. However, the expression of LARGE1 and its clinical significance in NSCLC are not clear. MATERIALS AND METHODS: The data were collected from the TCGA database to investigate LARGE1 expression in stage I-III NSCLC and explore its associations with clinicopathological parameters and overall survival of patients. The prognostic role of LARGE1 was examined in subgroups according to clinical features and treatments. The results were validated in external cohorts from the NCBI GEO database. Gene Set Enrichment Analysis (GSEA) was performed to investigate the potential molecular mechanisms during LARGE1 alteration in NSCLC. RESULTS: LARGE1 was aberrantly downregulated in NSCLC compared with adjacent tissues and normal lung tissues and in tumors with advanced stage compared with early stage. There was only a trend of association between high LARGE1 with OS in multivariate analysis. Surprisingly, high LARGE1 was significantly associated with improved OS in a subgroup of the patients with adjuvant chemotherapy (ACT) and a significant interaction between LARGE1 expression and ACT was found. Improved OS after ACT was also found in patients with high LARGE1 compared to those with low LARGE1. When combining LARGE1 expression and ACT, compared with patients with non-ACT, HR of low LARGE1/ACT was 0.592 (95% CI=0.432-0.813, P=0.0012), and HR of high LARGE1/ACT was 0.124 (95% CI=0.031-0.505, P=0.0036). The results were verified in two external cohorts from the GEO database. GSEA indicated that LARGE1 might downregulate cell cycle pathway to improve ACT sensitivity and subsequently the prognosis in NSCLC. CONCLUSION: High LARGE1 can be used to identify the patients with resected stage I-III NSCLC most likely to benefit from adjuvant chemotherapy.

Epidemiological Characteristics and Drug Resistance Analysis of Cerebrospinal Fluid Microbial Infections in Wenzhou Area.

OBJECTIVE: Central nervous system infections (CNSI) are serious diseases that endanger human health. Identifying pathogens and their susceptibility to antibiotics, and promptly using antibiotics under this guidance is essential for treatment. The purpose of this study is to investigate the pathogen characteristics of CNSI patients, which can help clinicians choose appropriate empiric antibiotic . METHODS: We retrospectively collected data on CNSI patients with cerebrospinal fluid (CSF) culture positive from 2012 to 2020, including demographic characteristics, laboratory data, pathogenic bacteria, and antimicrobial susceptibility test results. RESULTS: A total of 166 patients with 168 isolates out of 8188 patients were available for data analysis. Among the isolates, Gram-positive bacteria, Gram-negative bacteria and fungi accounted for 59.5%, 36.3%, and 4.2%, respectively. Among newborns, children under 12, and patients over 12, the most isolated strains were Streptococcus agalactiae (24/46, 52.2%), Streptococcus pneumoniae (21/68, 30.9%) and Staphylococcus epidermidis (10/54, 18.5%), respectively. Streptococcus agalactiae is more sensitive to linezolid and vancomycin. Streptococcus pneumoniae is more sensitive to vancomycin. Staphylococcus epidermidis is more sensitive to clindamycin and rifampicin. The sugar content in the CSF of Gram-negative bacteria of children ≤12 years old was significantly lower than that of Gram-positive bacteria (P<0.05). CONCLUSION: We comprehensively studied the etiological characteristics and antimicrobial resistance patterns of positive cerebrospinal fluid cultures in Wenzhou City, Zhejiang Province from 2012 to 2020, which can provide valuable strategies for preventing pathogens and improving evidence-based treatment.