A retrospective study of mineral and bone disorder in kidney transplant recipients: Single-center experience.

BACKGROUND: The status of mineral and bone disorder (MBD) after kidney transplantation is not fully understood, and the assessment of abnormal mineral and bone metabolism in kidney transplant recipients (KTRs) has not been standardized. MATERIALS AND METHODS: We performed a retrospective analysis of 292 KTRs in our center. The levels of biochemical markers of bone metabolism and bone mineral density (BMD) were assessed. We evaluated the influencing factors of BMD using linear regression analysis. And correlation test was used for the correlation analysis between bone metabolism indicators and other indicators. RESULTS: Postoperative MBD mainly manifested as hypercalcemia (8.9%), hypophosphatemia (27.1%), low levels of 25-hydroxyvitamin D(25(OH)vitD) (67.0%), hyperparathyroidism (50.6%), and high levels of bone turnover markers (BTMs). The prevalence of osteopenia/osteoporosis in the femoral neck (FN) and lumbar spine (LS) was 20.1%/2.8% and 26.1%/3.6%, respectively. Multivariate analysis indicated that FN BMD was positively associated with body mass index (BMI) and negatively associated with acute rejection history (p < 0.05); while LS BMD was positively associated with BMI, and negatively associated with intact parathyroid hormone (iPTH) (p < 0.05). Biochemical markers of bone metabolism were affected by age, sex, preoperative dialysis mode and time, postoperative time, transplanted kidney function, and iPTH levels. LS BMD was negatively correlated with iPTH and BTMs (p < 0.05). CONCLUSION: MBD persisted after kidney transplantation. Decreased bone mass was associated with persistent hyperparathyroidism, acute rejection history, low BMI, advanced age, and menopause. Dynamic monitoring of bone metabolism index and BMD helps to assess MBD after kidney transplantation.

LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer.

Epigenetic alteration is a key feature that contributes to the progression of bladder cancer (BC) and long non-coding RNAs serve crucial role in the epigenetic modulation. This study was designed to explore the epigenetic regulation of LINC00592 in BC. LINC00592 expression in BC was examined. Then, LINC00592 was silenced in BC cell followed by cell behavior analyses using CCK-8, transwell, western blot, or flow cytometry. Potential downstream target of LINC00592 was explored using RNA pull-down assay and methylation of WIF1 was determined using methylated-specific PCR. In addition, WIF1 or/and LINC00592 were silenced in BC cells followed by cell behavior analyses to explore the regulation between them. Upregulation of LINC00592 was significantly detected in BC tissues and cells. In BC cells silencing LINC00592 suppressed the proliferation, migration, and epithelial-mesenchymal transitions (EMT), but enhanced apoptosis. Moreover, LINC00592 recruited DNMT1, DNMT3A, and DNMT3B to enhance WIF1 promoter methylation. In addition, WIF1 overexpression suppressed the proliferation, migration, as well as EMT, but enhanced apoptosis. Silencing WIF1 significantly attenuated the role of silencing LINC00592 in suppressing the proliferative, migratory, and EMT ability of BC cells, and increasing the apoptosis. LINC00592 promoted the growth and metastasis of BC via enhancing the promoter methylation of WIF1 and decreasing WIF1 transcription.

Cyclophilin A/CD147 signaling induces the epithelial-to-mesenchymal transition and renal fibrosis in chronic allograft dysfunction by regulating p38 MAPK signaling.

OBJECTIVE: Our study was designed to explore the role of Cyclophilin A (CyPA)/CD147 signaling in renal allograft fibrosis and chronic allograft dysfunction (CAD). MATERIALS AND METHODS: A rat renal transplant model with significant CAD was successfully achieved. Renal allograft tissues and blood samples were collected. Hematoxylin and eosin, Masson's, and immunohistochemistry staining were performed. Since CD147 is mainly expressed in the renal tubular epithelial cells, human HK-2 cells were used and intervened by specific concentrations of CyPA, and the total protein and mRNA were extracted. Western blot assay and polymerase chain reaction were performed to explore the protein and mRNA expression of CyPA, CD147, and epithelial-to-mesenchymal transition (EMT)-related biomarkers. SiRNA-CD147 and specific inhibitors of p38 MAPK were used to explore the cellular mechanisms involved in the process. RESULTS: We have successfully established and validated a 20-week renal transplant CAD model. We observed significant distributed and expressed CyPA and CD147 in the renal allograft fibrotic tissues. We also found a significant expression of CD147 and EMT-related markers in the HK-2 cells stimulated by CyPA. The CD147 siRNA confirmed the previous in vitro results. The selective inhibition of MAPK suggested the notable role of p38 MAPK signaling pathway in the CyP/CD147 signaling involved in renal allograft fibrosis. CONCLUSIONS: Our study reported the positive relationship of CyPA-CD147 signaling with renal allograft dysfunction. The in vitro study suggested that CyPA-CD147 signaling induce the development of the EMT process by p38 MAPK signaling, thus contributing to renal allograft fibrosis and CAD.

Construction of an individualized clinical prognostic index based on ubiquitination-associated lncRNA in clear cell renal cell carcinoma patients.

BACKGROUND: ccRCC is considered as the main subtype of RCC, which accounted for sixth deadliest cancer worldwide. Recently, ubiquitination has been reported to be closely involved in the progression of tumore. The purpose of this study was to identify the ubiquitination-associated genes and co-expressed lncRNAs on the prognosis of clear cell renal cell carcinoma (ccRCC) patients. METHODS AND PATIENTS: We downloaded 530 cases and the corresponding transcriptome profiling from The Cancer Genome Atlas (TCGA) database. We distinguished mRNA and lncRNA expression data from the transcriptome profiling and then extracted the expression of mRNAs that regulate protein ubiquitination. We obtained lncRNAs associated with protein ubiquitination regulation from the lncRNA data by gene co-expression analysis. Cox regression analysis of survival time, survival status, and lncRNA expression level was carried out, and a prognostic index (PI) was constructed. RESULTS: The PI was established based on 8 prognostic lncRNAs that regulate protein ubiquitination and distinguish the high-risk group patients from all patients. Multivariate analysis indicated that this PI was an individualized clinical prognostic factor for patients with ccRCC. Regarding clinical characteristics, a ubiquitination-associated clinical-prognostic index (UCPI), containing 8 ubiquitination-related lncRNAs and age, was established and tested with AUC of 0.80. CONCLUSION: We established a UCPI containing 8 lncRNAs related to protein ubiquitination. This UCPI may become an appropriate model to predict the prognosis in ccRCC patients and guide clinicians to adjust the follow-up regimen.

miR­589­5p is downregulated in prostate cancer and regulates tumor cell viability and metastasis by targeting CCL­5.

Prostate cancer is one of the most common human malignancies, which represents a serious threat to health, and microRNAs (miRNAs/miRs) have been reported to be closely associated with the progression and development of prostate cancer. The present study aimed to investigate the expression patterns, functions and underlying mechanisms of miR­589­5p in prostate cancer. The results demonstrated that the expression levels of miR­589­5p were downregulated in prostate cancer tissues and cell lines. Overexpression of miR­589­5p inhibited cell viability, migration and invasion in prostate cancer cells. Subsequently, chemokine (C­C motif) ligand 5 (CCL­5) was identified as a direct target gene of miR­589­5p, which was highly expressed at the mRNA and protein levels in prostate cancer tissues and cells. Furthermore, CCL­5 mRNA was negatively correlated with miR­589­5p expression in prostate cancer tissues. Silencing CCL­5 promoted the apoptosis, and inhibited the migration and invasion of prostate cancer cells. Taken together, these results indicated that miR­589­5p may act as a tumor suppressor in prostate cancer by targeting CCL­5, thus suggesting that miR­589­5p may be a novel and reliable molecular marker for the diagnosis and prognosis of prostate cancer.