Elevated histone deacetylase 10 expression promotes the progression of clear cell renal cell carcinoma by Notch-1-PTEN signaling axis.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC), the most common pathological subtype of kidney cancer, accounts for approximately 70% to 80% of all cases. Histone deacetylase 10 (HDAC10) belongs to the HDAC class IIb subgroup, one of the histone deacetylases (HDAC) family. Previous studies suggest that HDAC10 may regulate the development of multiple tumor types. The specific molecular mechanisms employed by HDAC10 in the etiology of ccRCC still need to be discovered. METHODS: The analysis included examining HDAC10 expression levels and their clinical importance within a cohort of inpatients and ccRCC patients documented in the Tumor Genome Atlas (TCGA). Moreover, the biological functions and underlying molecular mechanisms of HDAC10 were investigated. RESULTS: HDAC10 showed increased expression in ccRCC tumor tissues. Subsequent analysis revealed overexpression of HDAC10 was associated with advanced clinical phenotype and unfavorable prognosis. The absence of HDAC10 significantly decreased ccRCC cell proliferation and migration capabilities. Mechanistic research suggests that HDAC10 may promote RCC development by activating the Notch-1 pathway and downregulating PTEN expression levels. CONCLUSION: In summary, HDAC10 can modulate critical biological processes in ccRCC, including proliferation, migration, and apoptosis. Notably, the Notch-1 pathway and PTEN serve as crucial signaling pathways and target genes through which HDAC10 regulates the progression of ccRCC. These findings offer a novel outlook for ccRCC treatment.

Type 2 diabetes mellitus and the risk of male infertility: a Mendelian randomization study.

Objective: To assess the causal effect of type 2 diabetes mellitus (T2DM) on male infertility (MI) and erectile dysfunction (ED) by Mendelian randomization (MR) analysis. Methods: Data for T2DM, MI, and ED were obtained from genome-wide association studies (GWAS) involving 298, 957, 73, 479, and 223, 805 Europeans, respectively. We performed univariate MR analysis using MR Egger, Weighted median (WM) and Inverse variance weighted (IVW) methods to assess causal effects among the three. Through the Genotype Tissue Expression (GTEx) database, single-nucleotide polymorphisms (SNPs) that affect the expression levels of T2DM-related genes were located using expression quantitative trait loci (eQTL). Results: MR analysis showed a significant causal relationship between T2DM and ED (WM, OR: 1.180, 95%CI: 1.010-1.378, P = 0.037; IVW, OR: 1.190, 95%CI: 1.084-1.300, P < 0.001). There is also a significant causal relationship between T2DM and MI (MR Egger, OR: 0.549, 95%CI: 0.317-0.952, P = 0.037; WM, OR: 0.593, 95%CI: 0.400, P = 0.010; IVW, OR: 0.767, 95%CI: 0.600-0.980, P = 0.034). ED may not cause MI (P > 0.05). We also found that rs6585827 corresponding to the PLEKHA1 gene associated with T2DM is an eQTL variant affecting the expression of this gene. Conclusion: T2DM has a direct causal effect on ED and MI. The level of PLEKHA1 expression suppressed by rs6585827 is potentially associated with a lower risk of T2DM.

A novel technique for avoidance of sternotomy, diaphragmic incision and cardiopulmonary bypass during cavoatrial tumor thrombectomy for renal cell carcinoma with intraatrial tumor thrombus: a case series at a single center.

BACKGROUND: Radical nephrectomy with thrombectomy in patients with renal cell carcinoma (RCC) and level IV thrombus extending to the right atrium (RA) offers improved survival. However, this procedure is associated with significant perioperative morbidity and mortality. In this report, we describe a novel milking technique for patients with RA tumor thrombus using abdominal access, which does not require diaphragmic incision, sternotomy, right atriotomy, or cardiopulmonary bypass (CPB). METHODS: Between January 2019 and January 2022, four patients underwent resection of renal cell carcinoma extending into RA by a milking technique developed to avoid diaphragmic incision, sternotomy, or CPB. Patient characteristics, perioperative data, pathological features, and survival were evaluated. RESULTS: Complete resection was successful through pure transabdominal access without diaphragmic incision, sternotomy, or CPB in all patients. CONCLUSION: We conclude that radical nephrectomy and thrombectomy in optimized cases with renal cell carcinoma extending into RA can be safely and effectively performed without diaphragmic incision, sternotomy, or CPB, avoiding serious perioperative complications while providing acceptable oncological outcomes.

Genomic Characterization and gE/gI-Deleted Strain Construction of Novel PRV Variants Isolated in Central China.

Pseudorabies virus (PRV) variants have caused substantial economic losses in the swine industry in China since 2011. To surveil the genetic variation in PRV field strains, here, two novel variant strains of PRV were isolated from Shanxi Province in central China and were designated SX1910 and SX1911. To identify the genetic characteristics of the two isolates, their complete genomes were sequenced, and phylogenetic analysis and sequence alignment revealed that field PRV variants have undergone genetic variations; notably, the protein-coding sequences UL5, UL36, US1 and IE180 exhibited extensive variation and contained one or more hypervariable regions. Furthermore, we also found that the glycoproteins gB and gD of the two isolates had some novel amino acid (aa) mutations. Importantly, most of these mutations were located on the surface of the protein molecule, according to protein structure model analysis. We constructed a mutant virus of SX1911 with deletion of the gE and gI genes via CRISPR/Cas9. When tested in mice, SX1911-ΔgE/gI-vaccinated mice were protected within a comparable range to Bartha-K61-vaccinated mice. Additionally, a higher dose of inactivated Bartha-K61 protected the mice from lethal SX1911 challenge, while a lower neutralization titer, higher viral load and more severe microscopic lesions were displayed in Bartha-K61-vaccinated mice. These findings highlight the need for continuous monitoring of PRV and novel vaccine development or vaccination program design for PRV control in China.

Uterine cytokine profiles after low-molecular-weight heparin administration are associated with pregnancy outcomes of patients with repeated implantation failure.

Introduction: Low molecular-weight heparin (LMWH) plays a role in repeated implantation failure (RIF), but outcomes are controversial. LMWH can potentially modulate local immune responses associated with the establishment and maintenance of pregnancy. The study aimed to explore the effects of LWMH in uterine inflammatory cytokine profiles and pregnancy outcomes of patients with repeated implantation failure (RIF) but without thrombophilia. Methods: We compared clinical characteristics and reproductive outcomes among 326 patients with RIF, but not thrombophilia, undergoing frozen embryo transfer (FET) cycle with or without LMWH treatment. Endometrium secretions were aspirated from both groups after 3 days of progesterone administration before and after LMWH treatment. Cytokine mRNA expression was analyzed in primary endometrial cells in vitro. Results: The clinical and ongoing pregnancy rates did not significantly differ between the groups (31.5% vs. 24.4%, p = 0.15; 29.6% vs. 20.7%, p = 0.06). Concentrations of IL-6 and granulocyte-colony stimulating factor (G-CSF) in uterine secretions were significantly increased in the LWMH group, regardless of pregnancy outcomes (P < 0.05). And, in all patients treated with LWMH, those of secreted IL-6, IL-15 and G-CSF were significantly increased in pregnant group (P < 0.05). The expression of mRNA for G-CSF and IL-6 was significantly increased in human endometrial stromal cells in vitro (P < 0.05) after stimulation with LWMH (10 IU/mL). Conclusions: Uterine cytokine profiles after LMWH administration are associated with pregnancy outcomes and LMWH may be beneficial for patients with three implantation failures who do not have coagulation disorders.

Ectopic pregnancy and failed oocyte retrieval during in vitro fertilization stimulation: Two case reports.

BACKGROUND: Due to a slight rise in beta-human chorionic (ß-hCG) levels that are undetectable, and vaginal bleeding that is similar to regular menstruation, ectopic pregnancy (EP) that occurs during the expected menstrual cycle prior to ovulation induction as part of in vitro fertilization (IVF) is likely to be undiagnosed. We present two cases of unexpected EP and emphasize the importance of the ß-hCG assay when an unexplained increase in progesterone is present prior to the triggering of ovulation during controlled ovarian stimulation (COS). CASE SUMMARY: A 26-year-old woman with primary infertility and a 31-year-old woman with secondary infertility. Both patients sought IVF treatment due to fallopian tube obstruction and underwent COS using the gonadotropin-releasing-hormone (GnRH)-antagonist protocol. In the late stage of COS, progesterone levels in both patients significantly increased, and luteinizing hormone levels decreased, followed by oocyte retrieval failure. A right salpingectomy was performed and tubal ectopic pregnancy was diagnosed by pathology in the first patient, and the second patients was diagnosed with a suspected EP abortion because her ß-hCG levels declined to 12.5 mIU/mL. After full recovery for 2 mo, the first patient entered a new IVF treatment cycle with a GnRH-antagonist regimen and successfully achieved eight oocytes and three viable embryos. After 6 mo, the second patient received another COS treatment with a progestin-primed ovarian stimulation protocol and successfully achieved nine oocytes and five viable embryos. CONCLUSION: ß-hCG levels in the initial and midterm phases of COS must be considered in patients with unusual hormone dynamics.

The feasibility and safety of adopting the left lumbar vein to localize the renal artery location during left transperitoneal laparoscopic partial nephrectomy.

Background: Laparoscopic partial nephrectomy (LPN) is the standard of care for localized small renal cancer. The most critical step in this form of surgery is to localize the renal artery. In the present study, we describe a novel technique that uses the left lumbar vein (LV) to access the left renal artery during LPN. Materials and methods: This was a retrospective review of 130 cases of transperitoneal laparoscopic partial nephrectomies (TLPNs) performed on patients with renal cancer in our center between January 2018 and December 2021. Either the LV or non-lumbar vein (N-LV) technique was used to locate and manage the left renal artery. We recorded relevant clinical data from all patients, including patient characteristics, tumor data, and perioperative outcomes (artery mobilization time, operative time, estimated blood loss, and complications). Comparative analysis was then carried out between the cases using LV or N-LV vein techniques. Results: All TLPNs were successfully accomplished without conversion to open approaches. There were no complications involving the renal vessels during the entire study. The LV technique resulted in a significantly shorter time to mobilize the renal and significantly less estimated blood loss (p < 0.05). There was no significant difference between the two techniques with regard to perioperative complications. Conclusion: The left LV represents an anatomical landmark for locating the left renal artery in TLPN. This approach has numerous advantages over the transperitoneal approach including facilitating access to the left renal artery and reducing the duration of surgery.

Pitfalls in the diagnosis and treatment of fat-poor angiomyolipoma of the renal pelvis mimicking urothelial carcinoma: report of three rare cases.

Angiomyolipoma (AML) represents the most frequent benign neoplasm of the kidney. It arises mostly in the cortex and protrudes into the perirenal space. It is extremely rare for a fat-poor AML to originate from the renal sinus, invade the pelvis, and present with hematuria. Because of the rarity of this lesion, differentiating it from a urothelial carcinoma is difficult, thereby making a preoperative diagnosis and management complex and challenging. We report three cases of fat-poor AML centered within the renal pelvis mimicking a urothelial carcinoma that underwent radical nephroureterectomy. The clinical characteristics, surgical management, and prognosis are discussed to achieve better preoperative evaluation of these entities. This is the first report of fat-poor AMLs involving the renal pelvis and presenting with hematuria. Nephron-sparing treatment is crucial for patients with these entities. Accurate diagnosis may allow partial resection or kidney-preserving treatment.

Alternative polarization of resident macrophages improves hyperglycemia-associated male infertility.

Recent studies have demonstrated that hyperglycemia induces inflammation in male reproductive system to cause sperm damages and infertility, which may be associated with re-polarization of tissue macrophages from an anti-inflammation M2-like subtype to a pro-inflammation M1-like subtype. However, the underlying mechanisms are not fully determined and a practical approach to interfere with the progression of infertility is lacking. Here, we transduced the testicular macrophages back to the M2-like phenotype with adeno-associated viruses carrying an M2-trigger, Jumonji domain-containing protein D3 (JMJD3), under a macrophage-specific CD68 promoter (CD68p-JMJD3), in streptozotocin-induced diabetic mice. We found that JMJD3-induced M2-polarization of testicular macrophages significantly improved the mating capability of diabetic male mice. The diabetes-induced impairment of the motility of spermatozoa and the decreases in the serum and testicular testosterone levels were both significantly alleviated in CD68p-JMJD3-treated diabetic mice. Thus, our study proposes a practical strategy to treat hyperglycemia-associated infertility.

Laparoscopic ureteral reimplantation with a Boari flap for long-segment ureteric avulsion or ureteric strictures: our experience.

BACKGROUND: This study was designed to evaluate the feasibility of laparoscopic ureteral reimplantation with a Boari flap for long-segment ureteric avulsion or ureteric strictures of the middle and lower ureters. By observing its curative effect and prognosis, we can provide a safer and reliable treatment option for patients with middle and lower ureteral injury. METHODS: In this study, of the eight cases under study, five were diagnosed with long-segment ureteric strictures, one had long-segment ureteric avulsion, one was diagnosed with ureteral rupture caused by surgical injury of appendicitis, and the remaining one underwent ureterostomy after ureteral injury. The location of ureteral injury was in the middle lower segment. All eight patients underwent laparoscopic ureteral reimplantation with a Boari flap from January 2018 to October 2021. In this study, two patients were treated with a Boari bladder flap with psoas hitching. All procedures were performed by the same surgeon with over 20 years of experience in urological surgery. RESULTS: The mean length of ureteric avulsion or ureteric strictures was 7.94 cm (range, 4-15 cm). Laparoscopic ureteral reimplantation with a Boari flap was performed successfully between 120 and 240 min. The mean duration of postoperative hospital stay was 6 days, and no major complications related to the procedure in the perioperative period occurred. Postoperative follow-up showed no obvious hydronephrosis on computed tomography urography or urinary ultrasound in all eight patients. Postoperative reexamination did not reveal any significant hydronephrosis, urinary tract infection, or ureteral reflux, and none of the postoperative renal functions were abnormal. CONCLUSIONS: Laparoscopic ureteral reimplantation with a Boari flap is safe and feasible for experienced physicians. In our case, the length/width ratio of bladder flap is more than 4:1, with good blood supply and no obvious complications, it provides a longer alternative length.

Surgical Management of a Giant Desmoid Fibromatosis of Abdominal Wall With Vessels Invasion in a Young Man: A Case Report and Review of the Literature.

Background: Desmoid fibromatosis (DF) is a rare clonal proliferation of fibroblasts and myofibroblasts. It develops in the connective tissues and does not metastasize but may infiltrate adjacent structures. Because of the rarity of these tumors and the unpredictable natural history of the disease, well-defined and precise guidelines of the optimal treatment for DF have not been formulated. Case Presentation: Here, we present a giant abdominal DF that invaded the right spermatic cord and iliac vessels. The lesion was excised with external iliac artery dissection; however, the vein was sacrificed. The abdominal wall defect was then repaired with a polypropylene mesh. The lesional cells are positive for ß-catenin. Conclusions: In the past decades, there has been a change in the treatment of DF. The "wait and see" policy has been considered initially in most cases. Surgical intervention remains a valid option for symptomatic lesions. The optimal regimes of the tumor should not take the risk of making the patient more symptomatic than the lesion itself.

Identification of New m6A Methylation Modification Patterns and Tumor Microenvironment Infiltration Landscape that Predict Clinical Outcomes for Papillary Renal Cell Carcinoma Patients.

N6-methyladenosine (m6A) is the product of the most prevalent mRNA modification in eukaryotic cells. Accumulating evidence shows that tumor microenvironment (TME) plays a pivotal role in tumor development. However, the underlying relationship between m6A modification and the TME of a papillary renal cell carcinoma (PRCC) is still unclear. To investigate the relationship between m6A modification and prognosis and immunotherapeutic efficacy for PRCC, we looked for distinct m6A modification patterns based on 23 m6A-related genes. Next, the correlation between m6A modification patterns and TME-related characteristics was investigated. Then, the intersected differentially expressed genes were selected and the scoring system, denoted as m6A score, was established to evaluate m6A modification, prognosis, and immunotherapeutic efficacy. In this study, three distinct m6A expression clusters were identified. Based on the results of immune cell infiltration analysis and functional analysis, carcinogenic pathways, TME-related immune cells, and pathways were identified as well. More importantly, the established m6A score showed good value in predicting clinical outcomes according to results using external cohorts. Specifically, PRCC patients with low m6A score value showed better survival, immunotherapeutic response, and higher tumor mutation burden. Furthermore, immunohistochemistry using PRCC clinical samples from our medical center was carried out and verified our results. In conclusion, this study highlights the underlying correlation between m6A modification and the immune landscape and, hence, enhances our understanding of the TME and improved the therapeutic outlook for PRCC patients.

Influence of ambient air pollution on successful pregnancy with frozen embryo transfer: A machine learning prediction model.

Numerous air pollutants have been reported to influence the outcomes of in vitro fertilization (IVF). However, whether air pollution affects implantation in frozen embryo transfer (FET) process is under debate. We aimed to find the association between ambient air pollution and implantation potential of FET and test the value of adding air pollution data to a random forest model (RFM) predicting intrauterine pregnancy. Using a retrospective study of a 4-year single-center design，we analyzed 3698 cycles of women living in Shanghai who underwent FET between 2015 and 2018. To estimate patients' individual exposure to air pollution, we computed averages of daily concentrations of six air pollutants including PM2.5, PM10, SO2, CO, NO2, and O3 measured at 9 monitoring stations in Shanghai for the exposure period (one month before FET). Moreover, A predictive model of 15 variables was established using RFM. Air pollutants levels of patients with or without intrauterine pregnancy were compared. Our results indicated that for exposure periods before FET, NO2 were negatively associated with intrauterine pregnancy (OR: 0.906, CI: 0.816-0.989). AUROC increased from 0.712 to 0.771 as air pollutants features were added. Overall, our findings demonstrate that exposure to NO2 before transfer has an adverse effect on clinical pregnancy. The performance to predict intrauterine pregnancy will improve with the use of air pollution data in RFM.

Association between transferred embryos and multiple pregnancy/live birth rate in frozen embryo transfer cycles: A retrospective study.

Background: Physicians need an appropriate embryo transfer strategy to address the challenge of reducing multiple birth rates, while maintaining the couples' live birth rate during assisted reproductive technology. Methods: We included 10,060 frozen embryo transfer cycles from January 2015 to March 2020 in reproductive medical center of Ruijin hospital, Shanghai, China. Patients were grouped according to the number and grade of cleavage-stage embryo or blastocysts transferred. Live birth rate and multiple live birth rate were compared among groups of women of different ages. Multivariable logistic regression models were used to estimate the risk of multiple live birth using different combinations of transferred embryos. Results: The transfer of double good-quality embryos was an independent predictor for multiple birth in women aged <30 years and those aged 36-39 years [<30 years: aOR =1.54 (95% CI: 1.14-2.06, P < 0.01); 36-39 years: aOR =1.84 (95% CI: 1.0-3.4, P < 0.01)]. Further, for women aged <36 years, the transfer of good-quality + poor-quality blastocysts was an independent predictor for multiple birth rate [<30 years: aOR=2.46 (95% CI: 1.45-4.18, P < 0.01); 31-35 years: aOR =4.45 (95% CI: 1.97-10.06, P < 0.01)]. Conclusions: Single-good-quality blastocyst transfer is recommended for women of all ages. When good-quality cleavage embryos are available, the choice of single or double embryo transfer with good- or average-quality embryo should depend on the age of women. Double embryo transfer with the highest possible grade of embryos is recommended for women aged ≥40 years.

Integrative Analysis of Immune-Related Genes in the Tumor Microenvironment of Renal Clear Cell Carcinoma and Renal Papillary Cell Carcinoma.

Kidney cancer encompasses a range of primary cancers, such as clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC). Our knowledge about the tumor microenvironment (TME) of kidney cancer is still limited. Therefore, we comprehensively assessed the TME of kidney cancers (including ccRCC and pRCC) using the ESTIAMTE, and CIBERSORT algorithms, and conducted distinct functional and correlation analyses with data from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Gene Expression Omnibus (GEO), Connectivity map and CellMiner database. Next, we identified two immune-related hub genes, IGLL5 and IL2RA, which play essential roles in the TME as well as on survival in ccRCC and pRCC. Furthermore, ccRCC and pRCC samples from our medical center were collected to verify the clinical application value of these two immune-related genes. A specific enrichment analysis of immune cells related to IGLL5 and IL2RA was also conducted in two types of renal cell cancer. Based on selected genes, we predicted the drug response and uncovered novel drug candidate for RCC treatment. Considering the unfavorable outcomes of kidney cancer and emerging interest in TME-targeted treatments, our results may offer insights into immune-related molecular mechanisms and possible targets to control the kidney cancer.

TRIB3 regulates FSHR expression in human granulosa cells under high levels of free fatty acids.

BACKGROUND: Granulosa cells (GCs) in cumulus oophorus highly express follicle stimulating hormone receptor (FSHR), which is the most important mediator of both estradiol synthesis and oocyte maturation. Obese women have elevated free fatty acids (FFAs) levels in their follicular fluids and decreased FSHR expression in GCs, which is related to an altered protein kinase B/glycogen synthase kinase 3ß (Akt/GSK3ß) signaling pathway. Such FFA increases accompany 3-fold rises in pseudokinase 3 (TRIB3) expression and reduce the Akt phosphorylation status in both the human liver and in insulinoma cell lines. Therefore, in a high FFA environment, we determined if TRIB3 mediates regulation of FSHR via the Akt/GSK3ß signaling pathway in human GCs. METHODS: GCs from women undergoing in vitro fertilization were collected and designated as high and low FFAs cohorts based on their follicular fluid FFA content. GCs with low FFA levels and a human granulosa-like tumor (KGN) cell line were exposed to palmitic acid (PA), which is a dominate FFA follicular fluid constituent. The effects were assessed of this substitution on the Akt/GSK3ß signaling pathway activity as well as the expressions of TRIB3 and FSHR at both the gene and protein levels by qPCR, Western blot and immunofluorescence staining analyses. Meanwhile, the individual effects of TRIB3 knockdown in KGN cells and p-AKT inhibitors were compared to determine the mechanisms of FFA-induced FSHR downregulation. RESULTS: The average FSH dose consuming per oocyte (FSH dose/oocyte) was elevated and Top embryo quality ratio was decreased in women with high levels of FFAs in their follicular fluid. In these women, the GC TRIB3 and ATF4 protein expression levels were upregulated which was accompanied by FSHR downregulation. Such upregulation was confirmed based on corresponding increases in their gene expression levels. On the other hand, the levels of p-Akt decreased while p-GSK3ß increased in the GCs. Moreover, TRIB3 knockdown reversed declines in FSHR expression and estradiol (E2) production in KGN cells treated with PA, which also resulted in increased p-Akt levels and declines in the p-GSK3ß level. In contrast, treatment of TRIB3-knockdown cells with an inhibitor of p-Akt (Ser473) resulted in rises in the levels of both p-GSK3ß as well as FSHR expression whereas E2 synthesis fell. CONCLUSIONS: During exposure to a high FFA content, TRIB3 can reduce FSHR expression through stimulation of the Akt/GSK3ß pathway in human GCs. This response may contribute to inducing oocyte maturation.

Comprehensive analysis of new prognostic signature based on ferroptosis-related genes in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor and the most common subtype of RCC. Ferroptosis is a novel form of regulated cell death, and ferroptosis-related genes (FRGs) have been associated with the prognosis of patients with certain cancers. However, the detailed prognostic correlation between FRGs and ccRCC has not yet been elucidated. To address this, the current study used The Cancer Genome Atlas (TCGA) dataset to explore 64 FRGs and determine their prognostic value in ccRCC. Results showed that 52 out of the 64 genes displayed significantly different expression levels in tumor tissue, and 35 out of the 52 differentially expressed genes (DEGs) were associated with overall survival. Subsequently, a four-gene prognostic signature (CD44, DPP4, NCOA4 and SLC7A11) was constructed and could successfully distinguish ccRCC patients with different prognosis in TCGA train and test sets. Furthermore, clinical ccRCC samples from our medical center were used to verify the application value of the new prognostic signature through immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). Biological functional analysis implied that immune-related functions and pathways were enriched in the TCGA cohort and the immune status scores were significantly different between high- and low-risk sets. These results suggest that the four ferroptosis-related regulatory genes can act as reliable prognostic biomarkers of ccRCC, and might be exploited as potential targets of therapeutic strategies.

The Roles of CircRNAs in Bladder Cancer: Biomarkers, Tumorigenesis Drivers, and Therapeutic Targets.

Bladder cancer (BCa) is the most prevalent malignancy of the urinary system. Circular RNAs (circRNAs), a novel subtype of non-coding RNAs, play a crucial role in physiological and developmental processes. CircRNAs mainly function as regulators of splicing process and transcription, microRNA sponges, and protein brackets. Recent advances in understanding the pathogenesis of BCa have led to the identification of an abundance of dysregulated circRNAs associated with BCa. These aberrantly expressed circRNAs eventually lead to abnormalities in biological, genetic, and epigenetic information. In this review, we introduce the potential of circRNAs as biomarkers for BCa diagnosis and prognosis. Notably, diverse mechanisms have been proposed for circRNAs driving carcinogenesis, including increasing cell proliferation, promoting invasive and migratory capacity, enhancing endothelial-mesenchymal transition, sustaining stemness, and enabling resistance to chemotherapy. Importantly, a full understanding of circRNA mechanisms is needed to mine promising therapeutic approaches for targeting BCa. In this paper, we present the latest advances in circRNAs and systemically summarize the characteristics and mechanisms of circRNAs in BCa, providing potential perspectives for BCa treatment.

Comprehensive analysis of a new prognosis signature based on histone deacetylases in clear cell renal cell carcinoma.

Histone deacetylases (HDAC) family is vital for tumorigenesis and tumor progression. However, the exact role of the HDAC family in clear cell renal cell carcinoma (ccRCC) remains unclear. Based on The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and The Human Protein Atlas (HPA) database, we investigated and validated the expression profile, clinical significance and prognostic value of HDAC family members in ccRCC. Moreover, we further explored the correlation between HDACs and tumor microenvironment, tumor stemness, drug activity and immune subtype. The HDAC8, HDAC10, and HDAC11 manifested potential clinical value for prognosis, and the correlation analyses reveals underlying molecular mechanisms, which deserve further investigation for ccRCC. This Integrated bioinformatics analysis, based on transcriptomics and proteomics, implied that HDAC8, HDAC10, and HDAC11 may serve as potential molecular biomarkers and therapeutic targets for ccRCC, but some underlying molecular mechanisms still need to be elucidated.