Circular RNAs (circRNAs), which are single-stranded closed-loop RNA molecules lacking terminal 5' caps and 3' poly(A) tails, are attracting increasing scientific attention for their crucial ...regulatory roles in the occurrence and development of various diseases. With the rapid development of high-throughput sequencing technologies, increasing numbers of differentially expressed circRNAs have been identified in bladder cancer (BCa) via exploration of the expression profiles of BCa and normal tissues and cell lines. CircRNAs are critically involved in BCa biological behaviours, including cell proliferation, tumour growth suppression, cell cycle arrest, apoptosis, invasion, migration, metastasis, angiogenesis, and cisplatin chemoresistance. Most of the studied circRNAs in BCa regulate cancer biological behaviours via miRNA sponging regulatory mechanisms. CircRNAs have been reported to be significantly associated with many clinicopathologic characteristics of BCa, including tumour size, grade, differentiation, and stage; lymph node metastasis; tumour numbers; distant metastasis; invasion; and recurrence. Moreover, circRNA expression levels can be used to predict BCa patients' survival parameters, such as overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). The abundance, conservation, stability, specificity and detectability of circRNAs render them potential diagnostic and prognostic biomarkers for BCa. Additionally, circRNAs play crucial regulatory roles upstream of various signalling pathways related to BCa carcinogenesis and progression, reflecting their potential as therapeutic targets for BCa. Herein, we briefly summarize the expression profiles, biological functions and mechanisms of circRNAs and the potential clinical applications of these molecules for BCa diagnosis, prognosis, and targeted therapy.
Deregulation or mutation of the
gene causes various tumors, including clear cell renal cell carcinoma (ccRCC). Although several splice variants of EZH2 have been identified, little is known about how ...EZH2 splicing is regulated or the contribution of alternative splicing to its protumorigenic functions.
We conducted RT-PCR, Western blot analysis, and IHC techniques to examine EZH2 and its alternative splicing transcript expression in renal cancer tissue and renal cancer cell lines. Proliferation, migration, clonogenicity, and tumorigenicity of renal cancer cells either exhibiting knockdown of EZH2 or its splicing factor SF3B3 were assessed by CCK8, Transwell assay, and murine xenograft experiments.
We found that the inclusion of alternative EZH2 exon 14 was significantly increased in ccRCC samples and renal cancer cell lines. In ccRCC lines, enforced expression of EZH2Δ14 inhibited, and EZH2 promoted, cell growth, migration, proliferation, and tumorigenicity in a xenograft model. Mechanistic studies demonstrated that EZH2Δ14 isoform functions as a dominant-negative inhibitor of full-length EZH2. Coexpression of EZH2Δ14 variant with full-length EZH2 not only abrogated DAB2IP and HOXA9 suppression but also inhibited EZH2-driven tumorigenesis. Strikingly, the splicing factor SF3B3 stimulates inclusion of exon14 and has pro-proliferative activity. Importantly, the upregulation of SF3B3 expression observed in clinical ccRCC samples parallels the increased inclusion of EZH2 exon14, and the SF3B3 level is associated with higher tumor stage and poor overall survival.
These results suggest SF3B3 as a key regulator of EZH2 pre-mRNA splicing and SF3B3 may represent a novel prognostic factor and potential therapeutic target in ccRCC.
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Objectives
To investigate the prevalence and associated factors of kidney stones among adults in China.
Subjects and Methods
A nationwide cross‐sectional survey was conducted among individuals aged ...≥18 years across China, from May 2013 to July 2014. Participants underwent urinary tract ultrasonographic examinations, completed pre‐designed and standardised questionnaires, and provided blood and urine samples for analysis. Kidney stones were defined as particles of ≥4 mm. Prevalence was defined as the proportion of participants with kidney stones and binary logistic regression was used to estimate the associated factors.
Results
A total of 12 570 individuals (45.2% men) with a mean (sd, range) age of 48.8 (15.3, 18–96) years were selected and invited to participate in the study. In all, 9310 (40.7% men) participants completed the investigation, with a response rate of 74.1%. The prevalence of kidney stones was 6.4% 95% confidence interval (CI) 5.9, 6.9, and the age‐ and sex‐adjusted prevalence was 5.8% (95% CI 5.3, 6.3; 6.5% in men and 5.1% in women). Binary logistic regression analysis showed that male gender, rural residency, age, family history of urinary stones, concurrent diabetes mellitus and hyperuricaemia, increased consumption of meat, and excessive sweating were all statistically significantly associated with a greater risk of kidney stones. By contrast, consumption of more tea, legumes, and fermented vinegar was statistically significantly associated with a lesser risk of kidney stone formation.
Conclusion
Kidney stones are common among Chinese adults, with about one in 17 adults affected currently. Some Chinese dietary habits may lower the risk of kidney stone formation.
Alternative splicing represents a critical posttranscriptional regulation of gene expression, which contributes to the protein complexity and mRNA processing. Defects of alternative splicing ...including genetic alteration and/or altered expression of both pre-mRNA and trans-acting factors give rise to many cancers. By integrally analyzing clinical data and splicing data from TCGA and SpliceSeq databases, a number of splicing events were found clinically relevant in tumor samples. Alternative splicing of KLK2 (KLK2_51239) was found as a potential inducement of nonsense-mediated mRNA decay and associated with poor survival in prostate cancer. Consensus K-means clustering analysis indicated that alternative splicing events could be potentially used for molecular subtype classification of cancers. By random forest survival algorithm, prognostic prediction signatures with well performances were constructed for 31 cancers by using survival-associated alternative splicing events. Furthermore, an online tool for visualization of Kaplan-Meier plots of splicing events in 31 cancers was explored. Briefly, alternative splicing was found of significant clinical relevance with cancers.
Background:
Non-coding RNA-activated by DNA damage (NORAD), a novel identified lncRNA, was found to be aberrantly expressed in various types of cancer. This meta-analysis was performed to evaluate ...the value of lncRNA NORAD as a prognostic biomarker in human cancers.
Methods:
We searched PubMed, Web of Science, PMC, and Embase databases thoroughly for eligible literatures. Studies which explored the relationship of lncRNA NORAD expression with clinical outcomes in human cancers were included in our meta-analysis. Review Manager version 5.3 and Stata SE 12.0 were used to perform the data analyses.
Results:
Our meta-analysis results indicated that cancer patients with high lncRNA NORAD expression tended to have unfavorable overall survival (OS) (HR = 1.67; 95% CI, 1.44-1.95; P < 0.00001). Moreover, elevated lncRNA NORAD expression showed a significant relationship with poor tumor grade (OR = 1.61; 95% CI, 1.01-2.56; P = 0.05) and more lymph node metastasis (LNM) (OR = 2.66; 95% CI, 1.60-4.43; P = 0.0002).
Conclusions:
LncRNA NORAD could serve as a valuable biomarker to predict poor prognosis and LNM in various human tumors.
More recently laparoscopic radical cystectomy (LRC) has increasingly been an attractive alternative to open radical cystectomy (ORC) and many centers have reported their early experiences in the ...treatment of bladder cancer. Evaluate the safety and efficacy of LRC compared with ORC in the treatment of bladder cancer.
A systematic search of Medline, Scopus, and the Cochrane Library was performed up to Mar 1, 2013. Outcomes of interest assessing the two techniques included demographic and clinical baseline characteristics, perioperative, pathologic and oncological variables, and post-op neobladder function and complications.
Sixteen eligible trials evaluating LRC vs ORC were identified including seven prospective and nine retrospective studies. Although LRC was associated with longer operative time (p<0.001), patients might benefit from significantly fewer overall complications (p<0.001), less blood loss (p<0.001), shorter length of hospital stay (p<0.001), less need of blood transfusion (p<0.001), less narcotic analgesic requirement (p<0.001), shorter time to ambulation (p = 0.03), shorter time to regular diet (p<0.001), fewer positive surgical margins (p = 0.006), fewer positive lymph node (p = 0.05), lower distant metastasis rate (p = 0.05) and fewer death (p = 0.004). There was no significant difference in other demographic parameters except for a lower ASA score (p = 0.01) in LRC while post-op neobladder function were similar between the two groups.
Our data suggest that LRC appears to be a safe, feasible and minimally invasive alternative to ORC with reliable perioperative safety, pathologic & oncologic efficacy, comparable post-op neobladder function and fewer complications. Because of the inherent limitations of the included studies, further large sample prospective, multi-centric, long-term follow-up studies and randomized control trials should be undertaken to confirm our findings.
Renal tubular cell injury induced by calcium oxalate (CaOx) is a critical initial stage of kidney stone formation. Theaflavin (TF) has been known for its strong antioxidative capacity; however, the ...effect and molecular mechanism of TF against oxidative stress and injury caused by CaOx crystal exposure in kidneys remains unknown. To explore the potential function of TF on renal crystal deposition and its underlying mechanisms, experiments were conducted using a CaOx nephrocalcinosis mouse model established by glyoxylate intraperitoneal injection, and HK-2 cells were subjected to calcium oxalate monohydrate (COM) crystals, with or without the treatment of TF. We discovered that TF treatment remarkably protected against CaOx-induced kidney oxidative stress injury and reduced crystal deposition. Additionally, miR-128-3p expression was decreased and negatively correlated with SIRT1 level in mouse CaOx nephrocalcinosis model following TF treatment. Moreover, TF suppressed miR-128-3p expression and further abolished its inhibition on SIRT1 to attenuate oxidative stress
. Mechanistically, TF interacted with miR-128-3p and suppressed its expression. In addition, miR-128-3p inhibited SIRT1 expression by directly binding its 3'-untranslated region (UTR). Furthermore, miR-128-3p activation partially reversed the acceerative effect of TF on SIRT1 expression. Taken together, TF exhibits a strong nephroprotective ability to suppress CaOx-induced kidney damage through the recovery of the antioxidant defense system regulated by miR-128-3p/SIRT1 axis. These findings provide novel insights for the prevention and treatment of renal calculus.
The safety and feasibility of robotic-assisted radical prostatectomy (RARP) compared with retropubic radical prostatectomy(RRP) is debated. Recently, a number of large-scale and high-quality studies ...have been conducted.
To obtain a more valid assessment, we update the meta-analysis of RARP compared with RRP to assessed its safety and feasibility in treatment of prostate cancer.
A systematic search of Medline, Embase, Pubmed, and the Cochrane Library was performed to identify studies that compared RARP with RRP. Outcomes of interest included perioperative, pathologic variables and complications.
78 studies assessing RARP vs. RRP were included for meta-analysis. Although patients underwent RRP have shorter operative time than RARP (WMD: 39.85 minutes; P < 0.001), patients underwent RARP have less intraoperative blood loss (WMD = -507.67ml; P < 0.001), lower blood transfusion rates (OR = 0.13; P < 0.001), shorter time to remove catheter (WMD = -3.04day; P < 0.001), shorter hospital stay (WMD = -1.62day; P < 0.001), lower PSM rates (OR:0.88; P = 0.04), fewer positive lymph nodes (OR:0.45;P < 0.001), fewer overall complications (OR:0.43; P < 0.001), higher 3- and 12-mo potent recovery rate (OR:3.19;P = 0.02; OR:2.37; P = 0.005, respectively), and lower readmission rate (OR:0.70, P = 0.03). The biochemical recurrence free survival of RARP is better than RRP (OR:1.33, P = 0.04). All the other calculated results are similar between the two groups.
Our results indicate that RARP appears to be safe and effective to its counterpart RRP in selected patients.
Calcium oxalate (CaOx) crystal can trigger kidney injury, which contributes to the pathogenesis of nephrocalcinosis. The phenotypes of infiltrating macrophage may impact CaOx-mediated kidney ...inflammatory injury as well as crystal deposition. How aryl hydrocarbon receptor (AhR) regulates inflammation and macrophage polarization is well understood; however, how it modulates CaOx nephrocalcinosis remains unclear. Methods: Mice were intraperitoneally injected with glyoxylate to establish CaOx nephrocalcinosis model with or without the treatment of AhR activator 6-formylindolo(3,2-b)carbazole (FICZ). Positron emission tomography computed tomography (PET-CT) imaging, Periodic acid-Schiff (PAS) staining, and polarized light optical microscopy were used to evaluate kidney injury and crystal deposition in mice kidney. Western blotting, immunofluorescence, chromatin immunoprecipitation, microRNA-fluorescence in situ hybridization, and luciferase reporter assays were applied to analyze polarization state and regulation mechanism of macrophage. Results: AhR expression was significantly upregulated and negatively correlated with interferon-regulatory factor 1 (IRF1) and hypoxia inducible factor 1-alpha (HIF-1α) levels in a murine CaOx nephrocalcinosis model following administration of FICZ. Moreover, AhR activation suppressed IRF1 and HIF-1α levels and decreased M1 macrophage polarization in vitro. In terms of the mechanism, bioinformatics analysis and chromatin immunoprecipitation assay confirmed that AhR could bind to miR-142a promoter to transcriptionally activate miR-142a. In addition, luciferase reporter assays validated that miR-142a inhibited IRF1 and HIF-1α expression by directly targeting their 3'-untranslated regions. Conclusions: Our results indicated that AhR activation could diminish M1 macrophage polarization and promote M2 macrophage polarization to suppress CaOx nephrocalcinosis via the AhR-miR-142a-IRF1/HIF-1α pathway.
Nanotechnology-enhanced photodynamic therapy (PDT) and immunotherapy are emerging as exciting cancer therapeutic methods with significant potential for improving patient outcomes. By combining these ...approaches, synergistic effects have been observed in preclinical studies, resulting in enhanced immune responses to cancer and the capacity to conquer the immunosuppressive tumor microenvironment (TME). Despite challenges such as addressing treatment limitations and developing personalized cancer treatment strategies, the integration of nanotechnology-enabled PDT and immunotherapy, along with advanced photosensitizers (PSs), represents an exciting new avenue in cancer treatment. Continued research, development, and collaboration among researchers, clinicians, and regulatory agencies are crucial for further advancements and the successful implementation of these promising therapies, ultimately benefiting cancer patients worldwide.
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