: Ischemia/reperfusion (IR)-induced acute kidney injury (AKI) is a common clinical syndrome. Stem/progenitor cell therapy is a promising option to foster the intrinsic capacity for kidney regeneration. However, there are still several challenges to be resolved, including the potential risks during cell culture, low retention rate after transplantation, and unclear effect on the progression of chronic kidney disease (CKD). Recently, nonexpanded adipose stromal vascular fraction (SVF) has been regarded as an attractive cell source for cell-based therapy. Preconditioning with ischemia has been suggested as a useful method to promote the retention and survival of transplanted cells in vivo. In this study, freshly isolated autologous SVF was transplanted to the kidney of rats before ischemia, and then an IR-induced AKI model was established. Postischemic administration of SVF to the kidney was performed after renal IR injury was induced. A higher cell retention rate was detected in the preischemic group. Preischemic administration of SVF showed stronger functional and morphologic protection from renal IR injury than postischemic administration, through enhancing tubular cell proliferation and reducing apoptosis. Progression of kidney fibrosis was also significantly delayed by preischemic administration of SVF, which exhibited stronger inhibition of transforming growth factor-β1-induced epithelia-mesenchymal transition and microvascular rarefaction. In addition, in vitro study showed that prehypoxic administration of SVF could significantly promote the proliferation, migration, and survival of hypoxic renal tubular epithelial cells. In conclusion, our study demonstrated that preischemic administration of nonexpanded adipose SVF protected the kidney from both acute IR injury and long-term risk of developing CKD.Renal ischemia/reperfusion (IR) injury is a common clinical syndrome. Cell-based therapy provides a promising option to promote renal repair after IR injury. However, several challenges still remain because of the potential risks during cell culture, low retention rate after transplantation, and unclear effect on the progression of chronic kidney disease. Stromal vascular fraction (SVF) is considered as an attractive cell source. This study demonstrated that preischemic administration of uncultured SVF could increase cell retention and then improve renal function and structure at both early and long-term stage after IR, which may provide a novel therapeutic approach for IR injury.
Benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS) is a common disease among elderly men, for which safe and effective treatment strategies remain limited. The aim of the present study was to explore the potential effects of phosphodiesterase 5A3 (PDE5A3) silencing on human prostate smooth muscle cells (HPSMCs). HPSMCs were initially obtained from patients with BPH/LUTS. Short hairpin RNA (shRNA) targeting the PDE5A3 gene was subsequently transfected into cultured HPSMCs. The expression of PDE5A3 was measured using reverse transcription‑quantitative PCR and western blotting. cGMP levels were then measured using western blotting and immunocytochemical staining and intracellular Ca2+ concentration was measured using rhod2‑AM in HPSMCs after transfection. HPSMC proliferation was also observed within 4 days. Cells transfected with PDE5A3‑shRNA2 exhibited the most notable decline in PDE5A3 expression compared with that in the Control or NC groups. cGMP levels in HPSMCs transfected with PDE5A3‑shRNA2 was significantly increased compared with those in the Control or NC groups, whereas intracellular Ca2+ concentrations in cells in the PDE5A3‑shRNA2 group were decreased compared with that in the Control or NC groups. The proliferation of HPSMCs in the PDE5A3‑shRNA2 group was also inhibited compared with that in the Control or NC groups after 72 h of culture. In conclusion, shRNA‑mediated silencing of PDE5A3 was able to increase the levels of cGMP whilst reducing the concentration of Ca2+ in HPSMCs, in turn suppressing their proliferation. These findings may potentially provide a novel therapeutic target for treating BPH/LUTS.
Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent histologic subtype of kidney cancers in adults, which could be divided into two distinct subgroups according to the BRCA1 associated protein-1 (BAP1) mutation status. In the current study, we comprehensively analyzed the genome-wide microRNA (miRNA) expression profiles in ccRCC, with the aim to identify the differentially expressed miRNAs between BAP1 mutant and wild-type tumors, and generate a BAP1 mutation-specific miRNA signature for ccRCC patients with wild-type BAP1. Methods: The BAP1 mutation status and miRNA profiles in BAP1 mutant and wild-type tumors were analyzed. Subsequently, the association of the differentially expressed miRNAs with patient survival was examined, and a BAP1 mutation-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate and multivariate Cox regression analyses. Finally, the bioinformatics methods were adopted for the target prediction of selected miRNAs and functional annotation analyses. Results: A total of 350 treatment-naïve primary ccRCC patients were selected from The Cancer Genome Atlas project, among which 35 (10.0%) subjects carried mutant BAP1 and had a shorter overall survival (OS) time. Furthermore, 33 miRNAs were found to be differentially expressed between BAP1 mutant and wild-type tumors, among which 11 (miR-149, miR-29b-2, miR-182, miR-183, miR-21, miR-365-2, miR-671, miR-365-1, miR-10b, miR-139, and miR-181a-2) were significantly associated with OS in ccRCC patients with wild-type BAP1. Finally, a BAP1 mutation-specific miRNA signature consisting of 11 miRNAs was generated and validated as an independent prognostic parameter. Conclusions: In summary, our study identified a total of 33 miRNAs differentially expressed between BAP1 mutant and wild-type tumors, and generated a BAP1 mutation-specific miRNA signature including eleven miRNAs, which could serve as a novel prognostic biomarker for ccRCC patients with wild-type BAP1.
This paper presents a meta-analysis regarding the detection rate (DR) of fluorine-18 ( 18 F)-labeled prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) in the management of patients with prostate cancer (PCa). Relevant studies regarding 18 F-PSMA PET/CT in the management of PCa published until June 1, 2021, were electronically searched in online databases including EMBASE, PubMed, and Web of Science. The primary outcome was the DR of 18 F-PSMA PET/CT in managing PCa patients, while the secondary outcome was the DR of 18 F-PSMA PET/CT according to Gleason scores and serum prostate-specific antigen (PSA) level. The pooled DR was calculated on a per-patient basis, with pooled odd ratios and 95% confidence intervals (CIs). In total, 17 observational studies evaluating 1019 patients with PCa met the inclusion criteria. The DR of 18 F-PSMA PET/CT was 0.83 (95% CI: 0.78–0.88), in the random-effects model. Subsequently, the analysis of DR of 18 F-PSMA PET/CT in PCa patients using Gleason score (≤7 vs ≥8), showed a significant difference in PCa patients. Based on the above results, the higher Gleason score of PCa patients, the higher DR of 18 F-PSMA PET/CT. The DR of 18 F-PSMA PET/CT in PCa was 0.57 for PSA <0.5 ng ml −1 ; 0.75 for PSA ≥0.5 ng ml -1 and <1.0 ng ml -1 ; 0.93 for PSA ≥1.0 ng ml -1 and <2.0 ng ml -1 ; and 0.95 for PSA ≥2.0 ng ml −1 . Therefore, the significant diagnostic value was found in terms of the DR of 18 F-PSMA PET/CT in managing PCa patients and was associated with Gleason score and serum PSA level.
BACKGROUND:The present study was conducted to explore the influence of remote ischemic preconditioning (RIPC) on the adjustment of renal fibrosis after ischemia-reperfusion injury (IRI). MATERIAL AND METHODS:Male Sprague-Dawley rats were randomly assigned to 3 groups following right-side nephrectomy: the Sham group (without renal artery clamping), the IRI group (45 min left renal artery clamping), and the RIPC group (rats were treated daily with 3 cycles of 5 min of limb ischemia and 5 min of reperfusion on 3 consecutive days before left renal artery occlusion). After 3 months of reperfusion, the renal function and the extent of tubular injury and renal fibrosis were assessed. The expressions of transforming growth factor beta1 (TGF-β1), p-Smad2, Smad2, p-Smad3, and Smad3 were also evaluated. RESULTS:There was no significant difference in renal function and tubular damage among the 3 groups after 45 min of kidney ischemia followed by 3 months of reperfusion. However, an obvious increase of extracellular matrix components and α-SMA could be observed in the kidney tissues of the IRI group, and the changes were significantly ameliorated in rats treated with enhanced RIPC. Compared with the IRI group, the expression of TGF-β1 and the level of p-Smad2 and p-Smad3 were decreased after the intervention of enhanced RIPC. CONCLUSIONS:Enhanced RIPC ameliorated renal fibrosis after IRI in rats, which appears to be associated with inhibition of the TGF-β1/p-Smad2/3 signalling pathway.
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