Antitumor activity of RUNX3: Upregulation of E-cadherin and downregulation of the epithelial-mesenchymal transition in clear-cell renal cell carcinoma.

RUNX3 is a transcription factor and tumor suppressor that is silenced or inactivated in diverse tumors. The effect of RUNX3 on the epithelial-mesenchymal transition in clear-cell renal cell carcinoma (CCRCC) remains unclear. We determined the expression of RUNX3 and E-cadherin in tumor tissues and adjacent normal tissues of 30 CCRCC patients; established cultured CCRCC cells with the overexpression of RUNX3; and examined the in vivo tumorigenic function of RUNX3 in a nude mouse xenograft model of CCRCC. RUNX3 and E-cadherin were downregulated in human CCRCC samples. Cell lines with RUNX3 overexpression had reduced cell proliferation, invasion, and migration, a prolonged cell cycle, increased apoptosis, and increased expression of E-cadherin. In the nude mouse xenograft model of CCRCC, tumors with the overexpression of RUNX3 had smaller volumes and weights and had increased expression of E-cadherin. In conclusion, RUNX3 overexpression increased the level of E-cadherin and inhibited the proliferation, invasion, and migration of CCRCC in vitro and in vivo. RUNX3 has potential use as a biomarker for prognostic monitoring of CCRCC and as a therapeutic target for the treatment of this cancer.

The Role and Mechanism of SIRT6 in Regulating Phenotype Transformation of Vascular Smooth Muscle Cells in Abdominal Aortic Aneurysm.

BACKGROUND: Data mining of current gene expression databases has not been previously performed to determine whether sirtuin 6 (SIRT6) expression participates in the pathological process of abdominal aortic aneurysm (AAA). The present study was aimed at investigating the role and mechanism of SIRT6 in regulating phenotype transformation of vascular smooth muscle cells (VSMC) in AAA. METHODS: Three gene expression microarray datasets of AAA patients in the Gene Expression Omnibus (GEO) database and one dataset of SIRT6-knockout (KO) mice were selected, and the differentially expressed genes (DEGs) were identified using GEO2R. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of both the AAA-related DEGs and the SIRT6-related DEGs were conducted. RESULTS: GEO2R analysis showed that the expression of SIRT6 was downregulated for three groups and upregulated for one group in the three datasets, and none of them satisfied statistical significance. There were top 5 DEGs (KYNU, NPTX2, SCRG1, GRK5, and RGS5) in both of the human AAA group and SIRT6-KO mouse group. Top 25 ontology of the SIRT6-KO-related DEGs showed that several pathways including tryptophan catabolic process to kynurenine and negative regulation of cell growth were enriched in the tissues of thickness aortic wall biopsies of AAA patients. CONCLUSIONS: Although SIRT6 mRNA level itself did not change among AAA patients, SIRT6 may play an important role in regulating several signaling pathways with significant association with AAA, suggesting that SIRT6 mRNA upregulation is a protective factor for VSMC against AAA.

Efficacy of Low-Dose Trimethoprim/Sulfamethoxazole for the Treatment of Pneumocystis jirovecii Pneumonia in Deceased Donor Kidney Recipients.

BACKGROUND: Trimethoprim/sulfamethoxazole (TMP-SMX) is considered the first-choice treatment for Pneumocystis jirovecii pneumonia (PJP) in recipients of solid organ transplantation. However, this treatment is associated with various severe adverse events that might not be tolerable for some renal transplant recipients, and the optimal dose remains elusive. The present study assessed the efficacy of low-dose TMP-SMX in recipients of a deceased donor kidney. METHODS: A total of 37 adult deceased donor kidney recipients who suffered PJP between January 2015 and June 2020 were included. The survival rates of the patients and grafts, the rate of invasive ventilation, and adverse events, including gastrointestinal discomfort, hematologic side effects, hyperkalemia, and renal function impairments, were assessed. RESULTS: The patient and graft survival rates were both 100%. Two patients (5.4%) required invasive ventilation. Eight patients (21.6%) reported gastrointestinal discomfort, but none required dose reduction or discontinued treatment. The frequencies of hematologic side effects, hyperkalemia and impaired kidney function were 5.4% (2/37), 2.7% (1/37), and 2.7% (1/37), respectively. CONCLUSION: Optimization of TMP-SMX dose may reduce the risk of adverse events without compromising efficacy for the treatment of PJP in deceased donor kidney recipients.

Antibiotic Resistance and Virulence Genes of Escherichia coli Isolated from Patients with Urinary Tract Infections After Kidney Transplantation from Deceased Donors.

OBJECTIVE: This study aimed to determine the prevalence of antibiotic resistance and virulence genes of Escherichia coli strains among patients with urinary tract infections (UTIs) after kidney transplantation from deceased donors. METHODS: Between January 2014 and June 2018, 64 patients who received kidney transplants from deceased donors at our institution developed a UTI due to E. coli. Polymerase chain reaction was used to detect virulence genes in E. coli strains. The Kirby-Bauer method was used to evaluate the antibiotic susceptibility pattern of the isolates. RESULTS: Among the study cohort, 46 (71.9%) UTIs were community-acquired (CA), and 18 (28.1%) were hospital-acquired (HA). The percentages of isolated E. coli strains that showed antibiotic resistance were as follows: 92.2% to ampicillin, 76.6% to cefalotin, 81.3% to carbenicillin, 29.7% to ciprofloxacin, 62.5% to cotrimoxazole, 35.9% to gentamicin, 34.4% to levofloxacin, 28.1% to norfloxacin, 68.8% to pefloxacin, 57.8% to trimethoprim/sulfamethoxazole, and 20.3% to amikacin. HA E. coli showed higher resistance to ciprofloxacin, cotrimoxazole, trimethoprim/sulfamethoxazole and amikacin, compared with CA E. coli (P<0.05). The most prevalent virulence genes among the E. coli strains were fim (64.1%), followed by irp2 (56.3%), iroN (46.9%), pap GII (45.3%), sfa (31.3%), pap (25%), iuc (23.4%), pap GI (15.6%), pap GIII (14.1%), hly (9.4%), and cnf (4.7%). The irp2 and iroN genes were found more frequently in the HA E. coli than in the CA E. coli (P<0.05). CONCLUSION: The E. coli strains, especially HA E. coli, isolated from UTI patients after kidney transplantation from deceased donors showed resistance to multiple antibiotics and harbored numerous virulence genes. These findings provide insight for genetic characterizations and epidemiological studies of E. coli strains causing UTIs in patients after kidney transplantation from deceased donors.

Circular RNA YAP1 acts as the sponge of microRNA-21-5p to secure HK-2 cells from ischaemia/reperfusion-induced injury.

Circular RNA YAP1 (circYAP1) was reported to participate in progression of gastric cancer. However, the role of circYAP1 in acute kidney injury (AKI) remains obscure. We attempted to examine the effects of circYAP1 on ischaemia/reperfusion-stimulated renal injury. AKI model was established by treating HK-2 cells in ischaemia/reperfusion (I/R) environment. CircYAP1 expression in blood of AKI patients and I/R-treated HK-2 cells was evaluated via RT-qPCR. CCK-8, flow cytometry, ELISA and ROS assay were executed to test the impact of circYAP1 on cell viability, apoptosis, inflammatory cytokines and ROS generation. Bioinformatic analysis was executed to explore miRNA targets. The relativity between circYAP1 and miR-21-5p was verified by RT-qPCR and luciferase assay. The functions of miR-21-5p in I/R-triggered injury were reassessed. PI3K/AKT/mTOR pathway was detected by Western blot. Down-regulated circYAP1 was observed in AKI blood samples and I/R-treated HK-2 cells. CircYAP1 overexpression expedited cell growth and weakened secretion of inflammatory factors and ROS generation in I/R-disposed cells. Besides, we found circYAP1 could sponge to miR-21-5p. Interestingly, miR-21-5p overexpression overturned the repressive effects of circYAP1 on cell injury. Moreover, PI3K/AKT/mTOR pathway was activated by circYAP1 via inhibiting miR-21-5p. We demonstrated that circYAP1 activated PI3K/AKT/mTOR pathway and secured HK-2 cells from I/R injury via sponging miR-21-5p.

Efficacy of anti-T-lymphocyte globulin-Fresenius as an induction agent in deceased-donor renal transplantation: A cohort study.

Anti-T-lymphocyte globulin (ATG) is frequently used in the induction regimen of renal transplantation, but its dose has not been standardized. In the present study, the efficacy of different ATG-Fresenius (ATG-F) doses was assessed in recipients of renal transplantation. A total of 131 adult recipients of renal transplantation who received ATG-F induction between August 2015 and July 2018 were included. The incidence of biopsy-confirmed acute rejection, graft function, as well as graft and patient survival within 12 months post-transplant, was assessed, and adverse events, including hematologic and infection-associated side effects, were compared between patients receiving a cumulative ATG-F dose of <7 or ≥7 mg/kg. The incidence of biopsy-confirmed acute rejection was similar between patients receiving cumulative doses of <7 and ≥7 mg/kg (7.5 vs. 4.7%, P=0.766). The incidence of infection within 12 months was lower in the ATG-F <7 mg/kg group compared with that in the ≥7 mg/kg group (26.9 vs. 50.0%, P=0.006), but the incidence of pneumonia did not differ between the ATG-F <7 and ≥7 mg/kg groups (10.4 vs. 20.3%, P=0.117). The incidence of urinary infection was higher in the ≥7 mg/kg group than in the <7 mg/kg group (20.4 vs. 7.46%, P=0.033), while the extent and duration of anemia and lymphopenia was similar between groups. There was no difference in graft function, delayed graft function, as well as overall and graft survival between the groups. In conclusion, a moderate reduction in the cumulative ATG-F dose was not associated with an increased risk of acute rejection, while the risk of infection was reduced. Optimization of the ATG-F dose for induction may facilitate the reduction of the risk of infection without compromising the induction efficacy in renal transplant recipients.

The circular RNA-NRIP1 plays oncogenic roles by targeting microRNA-505 in the renal carcinoma cell lines.

We explored the roles and regulatory mechanisms of the circular RNA (circRNA) nuclear receptor-interacting protein 1 (NRIP1; circNRIP1) in ACHN and CAKI-1 cells. ACHN and CAKI-1 cells were transfected with small-interfering-circNRIP1 (si-circNRIP1) and microRNA-505 (miR-505) inhibitor or the corresponding controls. Cell viability was detected with the Cell Counting Kit-8. The protein expression levels of Bcl-2, Bax, cleaved-caspase-3, matrix metalloproteinase (MMP)-2, MMP-9, adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), protein kinase B (AKT), phosphatidylinositol 3-kinase (PI3K), and mammalian target of rapamycin (mTOR) were individually determined via Western blot. Quantitative reverse transcription polymerase chain reaction was used to examine the expressions of circNRIP1 and miR-505 both in tumor cells and tissues. The apoptotic rate, the colony numbers, and the migration rate were separately determined by the Annexin V-fluorescein isothiocyanate/propidium iodide and flow cytometer, colony formation assay, and migration assay. We found that circNRIP1 was overexpressed in tumor tissue but miR-505 was overproduced. Silencing circZNF292 induced inhibition of cell viability, colony formation, and migration, as well as the activity of AMPK and PI3K/AKT/mTOR cascades but enhancement of apoptosis. si-circNRIP1 stimulated the upregulation of miR-505, whose silence abolished the effects of si-circNRIP1 on these elements mentioned above. In conclusion, the circNRIP1 played oncogenic roles in the ACHN and the CAKI-1 cell lines by targeting miR-505 via stimulating AMPK and PI3K/AKT/mTOR cascades.

Prognostic utility of the combination of pretreatment monocyte-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with NMIBC after transurethral resection.

Aim: To investigate and validate predictive value of combination of pretreatment monocyte-to-lymphocyte ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) for disease free survival (DFS) and overall survival (OS) in nonmuscle invasive bladder cancer after transurethral resection. Materials & methods: Total 358 patients enrolled were assigned into three (MLR-NLR 0, 1 and 2) groups per the cut-off values of MLR and NLR. Results: Kaplan-Meier curves showed MLR, NLR and their combination were statistically associated with DFS (p < 0.001) and OS (p < 0.001). Univariate and multivariate COX regression analyses revealed that combination of MLR with NLR was an independent prognostic predictor for both DFS (HR: 3.080; 95% CI: 1.870-5.074; p < 0.001 for MLR-NLR 2 vs MLR-NLR 0) and OS (HR: 2.815; 95% CI: 1.778-4.456; p < 0.001 for MLR-NLR 2 vs MLR-NLR 0). Calibration plots and decision curve analysis exhibited combination of MLR and NLR had good calibration accuracy with potential clinical usefulness. Conclusion: Combined MLR and NLR is a prognostic predictive biomarker in nonmuscle invasive bladder cancer after transurethral resection.

Long Non-Coding RNA DUXAP8 Enhances Renal Cell Carcinoma Progression via Downregulating miR-126.

BACKGROUND Renal cell carcinoma (RCC) is one of the common malignant tumors in the urinary system, which endangers human health for a long time. The past decade, the molecular biology of renal cell carcinoma has made considerable progress, so that we have a more profound understanding of renal cell carcinoma. Molecular biological mechanism of renal cell carcinoma remains to be explored. Evidence indicates that long non-coding RNAs (lncRNAs) may be important players in human cancer progression, including RCC. In this study, we found that a newly discovered pseudogene-derived lncRNA named DUXAP8, a 2107-bp RNA, was remarkably upregulated in RCC. MATERIAL AND METHODS Expression of lncRNA DUXAP8 was determined by a qRT-PCR assay in RCC tissues. The proliferation and invasion of RCC cell were measured by a cell proliferation assay and a Transwell invasion assay. Expression of miR-126 was detected by real-time PCR. Interactions between lncRNA DUXAP8 and miR-126 were measured by a luciferase reporter assay and an RNA-pull down assay. In vivo experiments were used to detect tumor formation. RESULTS Together, our study not only identifies lncRNA DUXAP8 as a negative regulator of renal cancer with potential clinical value, but also reveals a regulatory mechanism by long non-coding RNAs to control tumor development. CONCLUSIONS Results from this study provide evidence that lncRNA DUXAP8 enhances renal cell carcinoma progression via downregulating of miR-126, which offers a new approach for the treatment of RCC.

[Significance of the R.E.N. A.L. nephrometry scoring system in renal tumour of T1 stage].

OBJECTIVE: To evaluate the application value of R.E.N. A.L. nephrometry score for surgery type decisions of T1 stage renal tumor. METHODS: Clinical data including image data, surgery type and prognosis etc were collected retrospectively for 122 cases from January 2010 to December 2012. There were 76 male and 46 female patients and they were 29-82 years (mean 51 years). The body mass index was (22.8 ± 3.9) kg/m(2). The patients were undergoing surgical excision with renal tumor of T1 stage. The R.E.N. A.L. nephrometry score was analyzed to evaluate their relationships to surgery type (RN or NSS) and the approach of NSS (ONSS or LNSS) using chi-square tests, Fisher's exact tests, and logistic regressions analysis. RESULTS: All surgery had been completed. The surgery included RN of 45 patients, LNSS of 45 patients and ONSS of 32 patients. The R.E.N. A.L. nephrometry score was significantly associated with the type of surgery (χ(2) = 27.89, P < 0.05), and the NSS approach (χ(2) = 12.87, P < 0.05). When the scores less than 7 points, it is majorly treated by nephron sparing surgery (92.9%), and when the scores more than 9 points, it is majorly treated by radical nephrectomy (69.4%). Individual component scores were analyzed to evaluate that they were all related to surgery type (χ(2) = 7.00-14.57, P < 0.05), and the individual component N associated the surgery type mostly. Furthermore, individual component R,E,N and L were statistically significant predictors of the NSS approach (χ(2) = 4.92-15.07, P < 0.05). CONCLUSION: The R.E.N. A.L. nephrometry scoring system provides a simple, useful, and stable system to character the salient renal anatomy of T1 stage, and can provide the best surgery approach.