Don't wait any longer, conceive in time: a systematic review and meta-analysis based on semen parameters after varicocelectomy.

BACKGROUND: Varicocelectomy was considered to be beneficial to patients with varicocele-related infertility. However, there are only a few researchers who have explored the relationship between better timing and postoperative semen improvement in patients. METHODS: We conducted this meta-analysis by enrolling published prospective studies to find out the best waiting time after varicocelectomy to wait for better improvement of semen quality. An extensive search was conducted in PubMed, Web of Science, and Cochrane Library to identify eligible studies. The included studies were then analyzed comprehensively using STATA software and standardized mean differences (SMDs) and their corresponding 95% confidence intervals were calculated. RESULTS: Our comprehensive analysis showed that after varicocelectomy, follow-up results within 3 months or longer showed a significant improvement in semen parameters compared to the preoperative period. Notably, no further improvement in semen parameters was observed when the follow-up period reached six months or longer (semen volume: WMD: - 0.07 (- 0.29, 0.16); sperm concentration: WMD: - 1.33 (- 2.33, - 4.99); sperm motility: WMD: 2.31 (- 0.55, 5.18); sperm morphology: WMD: 1.29 (- 0.66, 3.24); sperm total motile count: WMD: 3.95 (- 6.28, 14.19)). CONCLUSIONS: Three months after varicocelectomy may be the optimal time for semen parameters compared to six months or even longer, which means it is also the preferable time for conception. However, more well-designed prospective studies are needed in the future to validate our conclusion.

Causal effects of gut microbiota on erectile dysfunction: a two-sample Mendelian randomization study.

Background: Several observational studies have reported the correlation between gut microbiota and the risk of erectile dysfunction (ED). However, the causal association between them remained unestablished owing to intrinsic limitations, confounding factors, and reverse causality. Therefore, the two-sample Mendelian randomization (MR) study was performed to determine the causal effect of gut microbiota on the risk of ED. Methods: The MR analysis utilized the publicly available genome-wide association study (GWAS) summary-level data to explore the causal associations between gut microbiota and ED. The gut microbiota data were extracted from the MiBioGen study (N = 18,340), and the ED data were extracted from the IEU Open GWAS (6,175 ED cases and 217,630 controls). The single nucleotide polymorphisms (SNPs) served as instrumental variables (IVs) by two thresholds of P-values, the first P-value setting as <1e-05 (locus-wide significance level) and the second P-value setting as <5e-08 (genome-wide significance level). The inverse variance weighted approach was used as the primary approach for MR analysis, supplemented with the other methods. In addition, sensitivity analyses were performed to evaluate the robustness of the MR results, including Cochran's Q test for heterogeneity, the MR-Egger intercept test for horizontal pleiotropy, the Mendelian randomization pleiotropy residual sum, and outlier (MR-PRESSO) global test for outliers, and the forest test and leave-one-out test for strong influence SNPs. Results: Our results presented that the increased abundance of Lachnospiraceae at family level (OR: 1.265, 95% CI: 1.054-1.519), Senegalimassilia (OR: 1.320, 95% CI: 1.064-1.638), Lachnospiraceae NC2004 group (OR: 1.197, 95% CI: 1.018-1.407), Tyzzerella3 (OR: 1.138, 95% CI: 1.017-1.273), and Oscillibacter (OR: 1.201, 95% CI: 1.035-1.393) at genus level may be risk factors for ED, while the increased abundance of Ruminococcaceae UCG013 (OR: 0.770, 95% CI: 0.615-0.965) at genus level may have a protective effect on ED. No heterogeneity or pleiotropy was found based on the previously described set of sensitivity analyses. Conclusion: Our MR analysis demonstrated that the gut microbiota had inducing and protective effects on the risk of ED. The results provide clinicians with novel insights into the treatment and prevention of ED in the future. Furthermore, our study also displays novel insights into the pathogenesis of microbiota-mediated ED.

Serum folic acid: an effective indicator for arteriogenic erectile dysfunction.

Background: The present study is the first to explore the correlation between serum folic acid (FA) level and penile arterial peak systolic velocity (PSV) as measured via penile color Doppler ultrasonography (PDU), which directly reflects endothelial function in the penile artery. Materials and methods: A total of 244 consecutive erectile dysfunction (ED) patients and 72 healthy controls, recruited from the Andrology department and the Healthy Physical Examination Center of our hospital, respectively, from June 2020 to April 2022, were included in the study. Serum FA was measured in ED patients and healthy controls, and PDU examinations were conducted for all eligible ED patients. The Pearson method was used to evaluate the correlation between FA levels and PDU parameters in ED patients. A receiver operating characteristic (ROC) curve analysis was also performed to calculate the sensitivity and specificity of these parameters for prediction of arteriogenic ED. Results: After the PDU test, the average serum FA level among patients diagnosed with arteriogenic ED was 8.08 ± 2.64 ng/ml, lower than the average of 10.78 ± 2.87 ng/ml among healthy controls. There were no statistically significant inter-group differences on any basic parameters, including age, body mass index, fasting blood glucose, total cholesterol, and triglyceride. For further analysis, we divided the arteriogenic ED group into three subgroups by PSV range to compare serum FA levels among these subgroups. The mean FA levels in each of these groups were 5.97 ± 1.51ng/ml, and 8.21 ± 2.37ng/ml, and 10.55 ± 2.56ng/ml, while the corresponding PSV values were 15.75 ± 2.39cm/s, 23.53 ± 2.19cm/s, and 32.72 ± 1.64cm/s. Overall, a positive correlation between PSV and FA level was found among patients with arteriogenic ED (r=0.605, P<0.001). Furthermore, when FA level was used, with a cut-off value of 10.045 ng/ml, as a criterion to distinguish patients with arteriogenic ED from healthy controls, the area under the curve (AUC) was 0.772 (95% confidential interval: [0.696, 0.848]), for a sensitivity of 0.611 and specificity of 0.824. Conclusion: Serum FA level is positively correlated with PSV in ED patients, and has the ability to distinguish patients with arteriogenic ED from healthy controls. Taking these findings together, FA deficiency should be regarded as an independent risk factor for arteriogenic ED.

Association between neutrophil to lymphocyte ratio and erectile dysfunction among US males: a population-based cross-sectional study.

Objective: The purpose of the study was to investigate the relationship between neutrophil-to-lymphocyte ratio (NLR) and erectile dysfunction (ED) in adult American males using a large database. Methods: We adopted a series of statistical analyses of the relationship between NLR indices and ED prevalence among participants in the 2001-2004 National Health and Nutrition Examination Survey (NHANES) database using the R software. Results: The study included a total of 3012 participants, of whom 570 (18.9%) presented with ED. NLR levels were 2.13 (95% CI: 2.08,2.17) in those without ED and 2.36 (95% CI: 2.27,2.45) in those with ED. After adjusting for confounding variables, NLR levels were higher in patients with ED, (ß, 1.21, 95% CI, 1.09-1.34, P < 0.001). In addition, a U-shaped relationship between NLR and ED was observed after controlling for all confounders. A more significant correlation (ß, 1.35, 95% CI, 1.19 to 1.53, P < 0.001) existed to the right of the inflection point (1.52). Conclusion: The results of the large cross-sectional study showed a statistically significant association between the occurrence of ED and NLR, a simple, inexpensive, and readily available parameter of inflammation, in US adults. Further studies are still needed in the future to validate and replicate our findings and to investigate the specific mechanisms involved.

Preoperative low-density lipoprotein cholesterol as a predictor of favorable prognosis in patients with clear cell renal cell carcinoma.

Background: Studies have shown that dyslipidemia is closely tied to a variety of cancers, and the level of low-density-lipoprotein-cholesterol (LDL-C) is related to the prognosis of cancer patients. However, what remains unclear is the predictive meaning of LDL-C among patients who suffer from renal cell carcinoma, especially clear cell renal cell carcinoma (CCRCC). The aim of this study was to investigate the correlation between the preoperative levels of serum LDL-C and the prognosis of surgical patients who suffer from clear cell renal cell carcinoma. Methods: A total of 308 CCRCC patients that received radical or partial nephrectomy were retrospectively included in this study. The clinical data of each included patient were collected. Overall survival (OS) and cancer-specific survival (CSS) were calculated using Kaplan-Meier method and Cox proportional hazards regression model. Results: Univariate analysis showed that a higher LDL-C level indicated a better OS and CSS in CCRCC patients (P=0.002 and P=0.001, respectively). The same was shown in the Multivariate analysis that a higher LDL-C level indicated a better OS and CSS in CCRCC patients (P<0.001 and P<0.001, respectively). Following propensity score matching (PSM) analysis, a higher LDL-C level still existed as an ideal indicator for both OS and CSS. Conclusions: The study indicated that a higher serum level of LDL-C showed clinical significance for predicting better OS and CSS in patients with CCRCC.

BAFF signaling drives interstitial transformation of mouse renal tubular epithelial cells in a Pin1-dependent manner.

Aberrant expression of B cell-activating factor belonging to TNF superfamily (BAFF) and its receptors results in abnormal biological activities in hematopoietic and non-hematopoietic cells and is closely associated with the occurrence and development of various diseases. However, the biological significance and potential mechanisms underlying BAFF signaling in renal tubular epithelial cells (RTECs) remain unknown. This study aimed to investigate the biological role of BAFF signaling in RTECs. Mice primary RTECs were applied. The proliferation status and apoptotic rates were examined by MTS assay and flow cytometry, respectively. The expression of BAFF and its receptors was analyzed via flow cytometry and sodium ion transport function, and cytokeratin-18 expression was detected through immunofluorescence staining. In addition, Pin1 was knocked down via siRNA and its expression was assessed through reverse transcription PCR. Lastly, western blotting was performed to analyze E-cadherin, ɑ-SMA, and Pin1 expression. Results suggested that BAFF-R was significantly upregulated upon IFN-γ stimulation, and enhancement of BAFF signaling promoted cell survival and reduced their apoptotic rate, while simultaneously reducing the epithelial phenotype and promoting the interstitial transformation of cells. Furthermore, Pin1 was significantly increased, along with the upregulation of BAFF signaling in the RTECs, and participated in interstitial transformation induced by BAFF signaling. Collectively, the present results elucidate the potential mechanism of loss of normal function of RTECs under long-term high dose of BAFF stimulation provides a potential therapeutic target for renal interstitial fibrosis, and underlining mechanisms of shortening of long-term outcomes of kidney allografts via augmenting of BAFF signaling.

Cyclin-dependent kinase 1 shows to be a potential genetic target for chemical cystitis.

BACKGROUND: In the present study, we aimed to explore whether common genetic targets or signaling pathways existed in chemical cystitis. METHODS: Gene Expression Omnibus (GEO) database was used to search the related gene expression profiles. The differentially expressed genes (DEGs) were identified by using GEO2R. The DAVID 6.8 Beta and R software were used to perform Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology function analysis of DEGs. The protein-protein interaction network was constructed by STRING 11.0 to reveal the potential gene interactions. The expression of cyclin-dependent kinase 1 (Cdk1) at the messnger RNA (mRNA) and protein levels was examined by real-time polymerase chain reaction (PCR) and Western blot analysis analysis, respectively. RESULTS: The GEO database was searched, and the gene expression profiles of GSE55986 and GSE68539 were downloaded. A total of 262 DEGs and 356 DEGs were identified from GSE55986 and GSE68539, respectively. We found that the p53 signaling pathway might play a key role in the development of chemical cystitis, and Cdk1 acted as a crucial gene in the p53 signaling pathway. Moreover, the experimental results of real-time PCR and Western blot analysis analysis demonstrated that the expression of Cdk1 at the mRNA and protein levels in cystitis tissues was significantly increased in different animal models of chemical cystitis compared with the control group. CONCLUSION: Cdk1 might be a potential pathogenic genetic target for chemical cystitis.

Upregulation of miR-18a-5p promotes the proliferation of prostate cancer via inhibiting the expression of SLC40A1.

Prostate cancer (PCa) is the most commonly diagnosed cancer in males and the fifth most common cause of cancer death worldwide. Previous studies indicated that miR-18a-5p modulated epithelial-mesenchymal transition in breast cancer via targeting SREBP1 forming a co-repressor complex with Snail and HDAC1/2. However, the function of miR-18a-5p in prostate cancer remains largely unknown. In this study, we identified miR-18a-5p as a tumor promoter in prostate cancer. miR-18a-5p expression was found upregulated in human prostate cancer tissues while SLC40A1 was down-regulated. Cell proliferation assay demonstrated that miR-18a-5p promoted prostate cancer cell proliferation. We also found SLC40A1 was downregulated by miR-18a-5p in prostate cancer cell lines. Restoration of SLC40A1 reversed the effects of miR-18a-5p in prostate cancer cells. Taken together, our results suggest that miR-18a-5p might function as a tumor-promoting factor in PCa and might contribute to its proliferation.

Overexpression of Capns1 Predicts Poor Prognosis and Correlates with Tumor Progression in Renal Cell Carcinoma.

INTRODUCTION: Calpain small subunit 1 (Capns1) has shown its correlation with the metastasis and invasion of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. However, the expression and function of Capns1 in human renal cell carcinoma (RCC) have not been clarified. This study aimed to examine the expression of Capns1 in RCC tissues and cell lines and to assess its role performed in RCC. METHODS: Capns1 expression was evaluated in 75 pairs of RCC and matched adjacent non-tumor tissues by immunohistochemistry. The prognostic value of Capns1 in RCC was assessed by Kaplan-Meier and Cox regression analyses. The action of Capns1 in the proliferation, adhesion, migration, and invasion of RCC cells and the effects on matrix metalloproteinase (MMP) 2 and 9 expression were evaluated after Capns1 silence. RESULTS: Capns1 expression was significantly higher in RCC tissues compared with the adjacent non-tumor tissues. Multivariate analysis showed that Capns1 overexpression was an independent poor prognostic marker in RCC. The silencing of Capns1 prohibited cell adhesion and impaired the migration and invasion ability of 786-O cells in vitro. Furthermore, Capns1 silence reduced MMP2 and MMP9 expression. CONCLUSION: Capns1 overexpression predicts poor prognosis and correlates with tumor progression in RCC. Capns1 expression might serve a prognostic marker and therapeutic target for RCC.

Alleviation of TGF-ß1 induced tubular epithelial-mesenchymal transition via the δ-opioid receptor.

Renal fibrosis is a common pathological feature of progressive chronic kidney disease (CKD). It is indicated that transforming growth factor-ß1 (TGF-ß1) plays as a central mediator in renal fibrosis. The present study aimed to investigate the role of δ-opioid receptor (DOR) on renal fibrosis of the rat renal proximal tubular epithelial cell line (NRK-52E) induced by TGF-ß1 and to elucidate its underlying mechanism, as well as its involvement in signaling pathways. Cells were treated with TGF-ß1 (10 ng·mL-1 ), along with a specific DOR agonist (UFP-512) or naltrindole (a DOR antagonist). Cell viability and morphology, as well as cell migration, were measured after drug administration. Western blotting was employed to examine the extracellular matrix (ECM) protein Fibronectin, and the tubular epithelial-mesenchymal transition (EMT) markers (E-cadherin and α-smooth muscle actin (α-SMA)), signal transducer (p-Smad3), and EMT-regulatory gene (Snail). The expression level of phosphorylated Akt and p38 was also examined. Our results showed that TGF-ß1 induced fibroblastic appearance and increased the expression of Fibronectin, α-SMA, P-Smad3, and Snail, while it decreased the expression of E-cadherin in NRK-52E cells. Moreover, TGF-ß1 induced the activation of Akt and p38 MAPK signaling pathways. DOR activation was found to efficiently block morphological changes and cell migration, as long as the expression changes of Fibronectin, E-cadherin, α-SMA, P-Smad3, Snail, P-Akt, and P-p38 were induced by TGF-ß1. These findings suggest that DOR may serve as an antifibrotic factor for renal proximal tubule cells by inhibiting the fibrosis process via TGF-ß/Smad, Akt, and p38 MAPK signaling pathways.

Mucinous tubular and spindle cell carcinoma of the kidney: Five case reports and review of the literature.

Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a rare and polymorphic tumor, which has been previously considered to be a low-grade malignancy, predominantly occurring in women. To the best of our knowledge, MTSCC with bladder metastasis has never been reported. The current study presents five adult cases of MTSCC that included three male and two female patients. Among the male cases, two were of advanced stage, one with MTSCC and renal chromophobe cell carcinoma with bladder metastasis and the other with MTSCC with invasion of the renal vein. The other three cases with small masses were at an early stage. All five cases had a good prognosis and were without recurrence after several years of follow-up. A 70-year-old male with intermittent gross hematuria, intermittent renal colic, and groin radiation pain for a year (case 1), was incidentally detected to have a left renal density mass by total abdominal enhanced computed tomography scans. In the other four cases, renal masses were found by B-ultrasound. The patient in case 1 underwent a retroperitoneal laparoscopic radical nephroureterectomy with bladder cuff resection and transurethral resection of the bladder tumor, and received gemcitabine hydrochloride via intravesical instillation therapy plus cisplatin chemotherapy every 3 months. The patient in case 2 underwent an open left radical nephrectomy and renal pedicle lymph node dissection. The other three patients underwent a laparoscopic radical nephrectomy. All five patients had no recurrence or new metastasis in other organs after follow-up. In conclusion, the incidence of MTSCC in men and women is not as disparate as reported in previous publications. The characteristics of the images of the five adult cases in the present study showed a considerable consistency, with only minor differences. The malignancy and prognosis of MTSCC are still controversial, and thus inclusion and review of more cases is required to reach a definite final conclusion. Sunitinib and gemcitabine chemotherapy in combination with cisplatin may be effective for the therapy of MTSCC patients with metastasis, but a larger range of treatments needs to be identified.

ACTH4-10 protects the ADR-injured podocytes by stimulating B lymphocytes to secrete interleukin-10.

OBJECTIVES: In the present study, we aimed to assess whether adrenocorticotropic hormone (ACTH) could protect the podocytes from adriamycin (ADR)-induced injury by stimulating B lymphocytes to secrete the associated cytokines. METHODS: Proliferation assay was used to assess the proliferation and activity of podocytes. Enzyme-linked immunosorbent assay was used to examine the secretion of IL-10 and IL-4. TUNEL apoptosis detection kit was used to detect the apoptosis of podocytes. Real-time PCR and Western blotting analysis were used to examine the expressions of nephrin and podocin at the mRNA and protein levels. RESULTS: Compared with the normal control group, the podocyte proliferation of ADR group was significantly inhibited. However, compared with the ADR group, the podocyte proliferation of the supernatant (1 µg/L, 10 µg/L or 100 µg/L ACTH4-10) + ADR groups was generally increased, and the pro-proliferative effect of the supernatant containing 10 µg/L ACTH4-10 was the highest. Moreover, we found that after B lymphocytes were intervened by 10 µg/L ACTH4-10, the IL-10 level in the cell supernatant was significantly elevated (p < 0.05). When anti-IL-10R was added, the podocyte proliferation of the supernatant (10 µg/L ACTH4-10) + ADR group was significantly inhibited. Furthermore, the supernatant of B cells stimulated with 10 µg/L ACTH4-10 could better decrease the apoptosis rate of injured podocytes and increase the expressions of nephrin and podocin at the mRNA and protein levels by elevating the secretion of IL-10. CONCLUSION: Compared with ACTH4-10, the supernatant of B cells stimulated with ACTH4-10 could better protect the podocytes from ADR-induced injury by elevating the secretion of IL-10.

A novel circular RNA (hsa_circRNA_102336), a plausible biomarker, promotes the tumorigenesis by sponging miR-515-5p in human bladder cancer.

Bladder cancer (BC) ranks as the ninth common human tumor in the world with an increasing incidence. Circular RNAs (circRNAs) have been revealed to exhibit promotive or suppressive impacts on tumor progression of various human cancers, including BC. However, due to the variety of circRNAs, the whole circRNAs network in BC remains unclear. In our study, differentially expressed circRNAs between BC and normal samples in GSE92675 dataset was analyzed by microarray. Circ_102336 was identified to be sharply increased in both BC tissue samples and cell lines, and increased circ_102336 is correlated with a worse overall survival rate of BC patients. Overexpression of circ_102336 dramatically increased the cell proliferation viability of T24 and 5637 cells, while knockdown of circ_102336 exhibited opposite effects. Moreover, circ_102336 knockdown could increase the sensitivity of T24 and 5637 cells to CDDP. In mechanism, circ_102336 was demonstrated to directly bind to and negatively regulate miR-515-5p. Inhibition of miR-515-5p reversed the repressive effects of si-circ_102336 on BC cell proliferation viability. KEGG analysis showed that ATP-binding cassette (ABC) transporters and apoptosis were the major two pathways associated with circ_102336/miR-515-5p axis. therefore, we suggested that circ_102336 indirectly regulate apoptosis and ABC transport pathways through miR-515-5p to finally modulate BC cell proliferation and chemo-resistance.

Tumor-derived exosomes facilitate tumor cells escape from drug therapy in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent cancers in renal cancer patients. Currently, mTOR and vascular endothelial growth factor (VEGF) inhibitors are the main targets of clinical drugs used to treat ccRCC. However, the major clinical challenge with these treatments is drug resistance. So far, the mechanisms of drug resistance in cancer are not fully understood. METHODS: We applied tumor-derived exosomes to treat renal cells to detect the survival rate after co-treated with anti-tumor drugs-TNFα, mammalian target of rapamycin (mTOR) inhibitor or STAT3 inhibitor. Meanwhile, we also detected the expression change in the protein level related to the proliferation and exosome secretion. RESULTS: Exosomes derived from renal carcinoma cells facilitate resistance in tumors cells when given drug therapy via the mTOR-ERK-STAT-NF-κB signaling pathway. CONCLUSIONS: Our results provide new insights on tumor cells resistance to drug therapies in general, and that exosomes could be the potential targets in treatment of ccRCC in future clinical therapy.

Significance of examined lymph-node count in accurate staging and long-term survival in patients undergoing radical prostatectomy: a population-based study.

PURPOSE: The number of examined lymph node (ELN) is regarded as the critical quality index for cancer care. We scrutinize the relationship among ELN number, accurate staging, and long-term survival in prostate cancer (Pca). METHODS: Population-based data on Pca patients in 2004-2015 from the US SEER database were investigated. The connection among ELN number and stage migration, overall survival (OS), and prostate cancer-specific survival (CSS) were evaluated by performing multivariable-adjusted logistic, Cox proportional hazards, and fine-gray competing-risk regression models, respectively. LOWESS smoother was used to fit the series of ELN number, odds ratios (OR), and hazard ratios (HR), while the Chow test was used to resolve the structural breakpoints. Subgroup and interaction analyses were performed in different risk populations. RESULTS: Overall, 84,838 patients were analyzed. Serial improvements were seen in stage migration (OR, 1.072, P < 0.001), OS (HR, 0.991; P < 0.001), and CSS (HR, 0.983; P < 0.001) per additional ELN after adjusting for confounders. Subgroup analysis revealed that the ELN number gains the most staging and survival benefits in high-risk population (P for interaction < 0.001). Cut-point analyses suggested that an optimal number of 12 ELNs, which was verified by the cumulative incidence curve, had a strong capability to distinguish different probabilities of CSS. CONCLUSIONS: Higher quantities of ELNs are related to more-accurate nodal staging and long-term survival of Pca patients undergoing RP. We highlight that 12 ELNs are the optimal cut-point for the high-risk population to investigate the quality of LN detection and stratifying postoperative prognosis.

GATA3 suppresses human fibroblasts-induced metastasis of clear cell renal cell carcinoma via an anti-IL6/STAT3 mechanism.

Tumorigenesis and metastasis depend on intricate interactions between genetically altered tumor cells and their surrounding microenvironment. It is, however, unclear regarding the molecular mechanisms underlying the progress and metastasis of human clear-cell renal cell carcinoma in the microenvironment with fibroblasts. In this work, we investigated the effect of normal fibroblasts on the metastasis of renal cancer and the relevant signaling pathways. We isolated normal fibroblasts from normal renal tissues and used normal fibroblast-conditioned medium culture renal cancer cells. The CCK-8 and transwell assays showed that normal fibroblasts conditioned medium significantly enhanced ccRCC cell migration. IL6 mediated the cross talk between normal fibroblasts and the cancer cells, and promoted tumor cell migration through the STAT3 pathway. In contrast, GATA3 was downregulated at both mRNA and protein levels in the normal fibroblast-conditioned medium treated with renal cancer cells, but upregulated in adjacent normal tissues. GATA3 overexpression significantly reduced STAT3 phosphorylation and attenuated the migration in both renal cancer cell and IL6-stimulated renal cancer cell. Taken together, our findings suggest that the IL6/STAT3 pathway plays a crucial role in the normal fibroblast-enhanced clear-cell renal cell carcinoma metastasis, while GATA3 may mitigate this effect by inhibiting IL6/STAT3 signaling.

LncRNA MEG3 inhibits the progression of prostate cancer by facilitating H3K27 trimethylation of EN2 through binding to EZH2.

This study aims to study the effects of intra-nuclear lncRNA MEG3 on the progression of prostate cancer and the underlying mechanisms. Expressions of relative molecules were detected by Quantitative real time PCR (qRT-PCR) and western blot. Chromatin immunoprecipitation and RNA immunoprecipitation (RIP) assays were used to evaluate the interaction between intra-nuclear MEG3, histone methyltransferase EZH2 and Engrailed-2 (EN2). The impacts of MEG3 on the viability, proliferation and invasion of prostate cancer cells (PC3) were evaluated by methyl thiazolyl tetrazolium, colony formation and transwell assays, respectively. PC3 cells were transfected with MEG3 and transplanted into nude mice to analyse the effect of MEG3 on tumourigenesis of PC3 cells in vivo. EN2 expression was inversely proportional to MEG3 in the prostate cancer tissues and PC3 cells. RIP results showed that intra-nuclear MEG3 could bind to EZH2. Knockdown of MEG3 and/or EZH2 up-regulated EN2 expression and reduced the recruitment of EZH2 and H3K27me3 to EN2, while over-expressed MEG3 caused opposite effects. MEG3 over-expression suppressed cell viability, colony formation, cell invasion and migration of PC3 cells in vitro and inhibited tumourigenesis of PC3 cells in vivo, while EN2 over-expression diminished the effects. These findings indicated that MEG3 facilitated H3K27 trimethylation of EN2 via binding to EZH2, thus suppressed the development of prostate cancer.

Preservation Solutions for Kidney Transplantation: History, Advances and Mechanisms.

Solid organ transplantation was one of the greatest medical advances during the past few decades. Organ preservation solutions have been applied to diminish ischemic/hypoxic injury during cold storage and improve graft survival. In this article, we provide a general review of the history and advances of preservation solutions for kidney transplantation. Key components of commonly used solutions are listed, and effective supplementations for current available preservation solutions are discussed. At cellular and molecular levels, further insights were provided into the pathophysiological mechanisms of effective ingredients against ischemic/hypoxic renal injury during cold storage. We pay special attention to the cellular and molecular events during transplantation, including ATP depletion, acidosis, mitochondrial dysfunction, oxidative stress, inflammation, and other intracellular mechanisms.