No abstract

In this study, a double-modified bacterial cellulose/ soybean protein isolate (DMBC/SPI), a new type of urethral tissue engineering scaffold with good biocompatibility, biodegradability, and cell-oriented growth, was prepared. Bacterial cellulose (BC) was physically and chemically modified by laser hole forming and selective oxidation to obtain the double-modified bacterial cellulose (DMBC). The soybean protein isolate (SPI) was compounded on DMBC to obtain DMBC/SPI with better biocompatibility. DMBC/SPI was used to repair the damaged urethra in rabbits. The results showed that DMBC/SPI was beneficial to heal the damaged urethra and did not cause a milder inflammatory response. The repaired urethra was smooth and continuous. DMBC/SPI has a good urethral repair effect and is expected to be used as a new urethral reconstruction material in clinical applications. In addition, FT-IR spectroscopy, SEM, static contact angle measurements, mechanical property investigation, and cell experiments were also performed to characterize the properties of DMBC/SPI composites.

Early detection and accurate evaluation were both critical to improving the prognosis of clear cell Renal Cell Carcinoma (ccRCC) patients. More importantly, RNA Binding Proteins (RBPs) play a vital role in the tumorigenesis and progression of numerous cancers. However, the relationship between RBPs and ccRCC is still unclear. Exploring the potential biological functions of RBPs in ccRCC and establishing a prognostic signature to predict the survival probability remains meaningful. In this study, transcriptome profiling and the corresponding clinical information were obtained from the TCGA database, GEO database, and ICGC database. By using the "edgeR" R package, 200 DERBPs were found, including 128 up-regulated and 72 down-regulated RBPs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DERBPs were mainly involved in regulating transcriptional processes and metabolism. Furthermore, there were 4 hub genes (RPS2, RPS14, RPS20, and RPLP0) were found in the PPI network, which may play vital biological roles among those DERBPs. Then we used LASSO regression to construct a prognostic signature and validated the signature in the GEO and ICGC cohort. The time-dependent receiver operating characteristic (ROC) curve showed that the signature could accurately predict the prognosis of ccRCC patients. Then we established a nomogram, and the calibration curve and ROC curve showed that the nomogram could accurately predict 1-year, 3-year, and 5-year overall survival (OS) of ccRCC patients (The AUC value: 0.871, 0.829, and 0.816). In conclusion, we constructed a 10-RBPs-based prognostic signature integrating clinical parameters to predict the prognosis of ccRCC patients. The prognostic signature based on the differentially expressed RBPs (DERBPs) might serve as promising diagnostic and prognostic biomarkers in ccRCC.

Purpose: Clear cell renal cell carcinoma (ccRCC) is among the most common malignant tumors worldwide, with a high incidence rate and poor prognosis. Currently, there are no biomarkers that can accurately guide prognostic evaluation and therapeutic strategy for ccRCC. The prognostic value and potential biological function of claudin-8 (CLDN8), a critical component of tight junctions in ccRCC, remain unclear. Methods: Sequencing data were obtained from The Cancer Genome Atlas, International Cancer Genome Consortium, and Gene Expression Omnibus databases. R packages were used to explore CLDN8 mRNA expression levels and analyze differentially expressed genes. Results were validated in clinical specimens and cell lines, and bioinformatics analyses were conducted to explore the potential biological functions of CLDN8. Finally, functional analyses were carried out using 786-O ccRCC cell line. Results: Both CLDN8 mRNA and protein expression levels were significantly lower in ccRCC compared with the normal control tissues. Kaplan-Meier analyses showed that low CLDN8 expression levels were associated with the poor overall survival, while univariate and multivariate Cox regression indicated that CLDN8 could serve as an independent prognostic factor in patient with ccRCC. Bioinformatic and Western blot analyses showed that CLDN8 suppressed proliferation, migration, and invasion of 786-O ccRCC cells through the epithelial-mesenchymal transition and AKT pathways. Conclusion: CLDN8 could serve as an independent prognostic factor in ccRCC, in which it suppresses 786-O proliferation, migration, and invasion through EMT and AKT pathways.

Background: Early detection and precise prognostic evaluation of clear cell renal cell carcinoma (ccRCC) are crucial for patient life expectancy. Ion channel-related genes (ICRGs) are of great diagnostic and prognostic value as components that maintain the normal structure of the kidney. Therefore, we systematically explored the diagnostic, prognostic, and therapeutic value of ICRGs in ccRCC using the multi-database.Methods: RNA transcriptome profiles and clinical data of ccRCC patients were extracted and integrated from public databases including The Cancer Genome Atlas, ICGC, GEO, and E-MTAB databases. Ion channel-related genes were obtained from the literature collection. The diagnostic signature was performed using the LASSO and SVM-REF analyses. Meanwhile, the prognostic signature was conducted using the LASSO analyses. Molecular subtyping was performed using the ConsensusClusterPlus and the corresponding therapeutic targets were evaluated using the pRRophetic package. In addition, a prognostic nomogram was constructed based on the results of cox regression analyses.Results: We successfully constructed diagnostic signatures for five ICRGs and prognostic signatures for 10 ICRGs with AUC values greater than 0.7, showing good predictive performance. Based on the median risk score, we found that high-risk patients had a significantly worse prognosis. We also divided ccRCC patients into two clusters according to prognostic ICRGs, and there was a significant survival outcome between the two clusters and different sensitivity to diverse clinical therapeutic strategies. Meanwhile, we constructed a nomogram based on clinical molecules and signatures, and its predictive efficacy was better than the signature or the present tumor-node-metastasis staging system.Conclusion: In this study, we established useful signatures for early detection, prognosis evaluation, and individualized treatment for ccRCC. Moreover, KCNJ16 deserves to be explored comprehensively in the future.

The high incidence and vulnerability to recurrence of bladder urothelial carcinoma (BLCA) is a challenge in the clinical. Recent studies have revealed that NFE2L3 plays a vital role in the carcinogenesis and progression of different human tumors. However, the role of NFE2L3 in bladder cancer has not been elucidated. In this study, NFE2L3 expression was significantly increased in bladder cancer samples. Its high expression was associated with advanced clinicopathological characteristics and was an independent prognostic factor for overall survival (OS) and metastasis-free survival (MFS) in 106 patients with BLCA. In vitro and in vivo experiments demonstrated that NFE2L3 knockdown inhibited bladder cancer cells proliferation by inducing the cell cycle arrest and cell apoptosis. Meanwhile, NFE2L3 overexpression promotes BLCA cell migration and invasion in vitro cell lines and in vivo xenografts. Moreover, we identified many genes and pathway alterations associated with tumor progression and metastasis by performing RNA-Seq analysis and functional enrichment of NFE2L3 overexpressing BLCA cells. Mechanistic investigation reveals that overexpression of NFE2L3 promoted epithelial-mesenchymal transition (EMT) in bladder cancer cells with decreased expression of gap junction-associated protein ZO-1 and epithelial marker E-cadherin with the elevation of transcription factors Snail1 and Snail2. Finally, we performed a comprehensive proteomics analysis to explore more potential molecular mechanisms. Our findings revealed that NFE2L3 might serve as a valuable clinical prognostic biomarker and therapeutic target in BLCA.

Background Urethral stricture and reconstruction are one of the thorny difficult problems in the field of urology. The continuous development of tissue engineering and biomaterials has given new therapeutic thinking to this problem. Bacterial cellulose (BC) is an excellent biomaterial due to its accessibility and strong plasticity. Moreover, adipose-derived stem cells (ADSCs) could enhance their wound healing ability through directional modification. Methods First, we used physical drilling and sulfonation in this study to make BC more conducive to cell attachment and degradation. We tested the relevant mechanical properties of these materials. After that, we attached Fibroblast Growth Factor Receptor 2 (FGFR2)-modified ADSCs to the material to construct a urethra for tissue engineering. Afterward, we verified this finding in the male New Zealand rabbit model and carried out immunohistochemical and imaging examinations 1 and 3 months after the operation. At the same time, we detected the potential biological function of FGFR2 by bioinformatics and a cytokine chip. Results The results show that the composite has excellent repairability and that this ability is correlated with angiogenesis. The new composite in this study provides new insight and therapeutic methods for urethral reconstruction. The preliminary mechanism showed that FGFR2 could promote angiogenesis and tissue repair by promoting the secretion of Vascular Endothelial Growth Factor A (VEGFA) from ADSCs. Conclusions Double-modified sulfonated bacterial cellulose scaffolds combined with FGFR2-modified ADSCs provide new sight and treatments for patients with urethral strictures.

Clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignant tumors and early detection contributes to a better prognosis. Finding new biomarkers for the diagnosis or treatment remains meaningful. DEF6 guanine nucleotide exchange factor (DEF6) is upregulated in ccRCC compared to normal controls, but the relationship between DEF6 expression and prognosis in ccRCC is unclear. Moreover, the potential biological functions of DEF6 in ccRCC remains unclear. In the present study, the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), TISIDB and the clinical database of the Peking University First Hospital were used to analyze DEF6 expression in ccRCC. Immunohistochemistry (IHC), western blotting and reverse transcription-quantitative PCR were used to examine the DEF6 protein and mRNA expression levels in cell lines and clinical samples. Subsequently, the Kaplan-Meier method and Cox regression analyses were used to determine the impact of DEF6 expression on the overall survival of patients alongside other clinical variables in both the TCGA database and the present clinical database. The results showed that both DEF6 mRNA and protein expression levels were upregulated in ccRCC compared to normal controls. The Kaplan-Meier survival analysis showed that patients with high DEF6 expression had poor prognoses from both the TCGA database and the present clinical database. Univariate survival analysis and multivariate survival analysis revealed that DEF6 could be an independent prognostic factor for ccRCC. Additionally, bioinformatics analysis indicated that differentially expressed genes related to DEF6 expression influenced ccRCC by regulating the tumor immune microenvironment. In conclusion, overexpression of DEF6 is significantly correlated with a poor prognosis for patients with ccRCC and DEF6 may influence the biological processes involved with ccRCC by regulating the immune microenvironment.