Prostate cancer (PCa) now remains the 2nd most frequently diagnosed cancer. In recent years, chemoprevention for PCa becomes a possible concept. Especially, many phytochemicals rich foods are suggested to lower the risk of cancer. Among these foods, green tea is considered as effective prevention for various cancers. However, clinical trials and previous meta-analyses on the relationship between green tea consumption and the risk of PCa have produced inconsistent outcomes. This study aims to determine the dose–response association of green tea intake with PCa risk and the preventive effect of green tea catechins on PCa risk. Seven observational studies and 3 randomized controlled trials were retrieved from Cochrane Library, PubMed, Sciencedirect Online, and hand searching. The STATA (version 12.0) was applied to analyze the data. The relative risks (RRs) and 95% confidence intervals were pooled by fixed or random effect modeling. Dose–response relations were evaluated with categories of green tea intake. Although there was no statistical significance in the comparison of the highest versus lowest category, there was a trend of reduced incidence of PCa with each 1 cup/day increase of green tea (P = 0.08). Our dose–response meta-analysis further demonstrated that higher green tea consumption was linearly associated with a reduced risk of PCa with more than 7 cups/day. In addition, green tea catechins were effective for preventing PCa with an RR of 0.38 (P = 0.02). In conclusion, our dose–response meta-analysis evaluated the association of green tea intake with PCa risk systematically and quantitatively. And this is the first meta-analysis of green tea catechins consumption and PCa incidence. Our novel data demonstrated that higher green tea consumption was linearly reduced PCa risk with more than 7 cups/day and green tea catechins were effective for preventing PCa. However, further studies are required to substantiate these conclusions.

Background: Benign prostatic hyperplasia (BPH) is a common disease in elderly men, mainly resulted from an imbalance between cell proliferation and death. Glutathione peroxidase 3 (GPX3) was one of the differentially expressed genes in BPH identified by transcriptome sequencing of 5 hyperplastic and 3 normal prostate specimens, which had not been elucidated in the prostate. This study aimed to ascertain the mechanism of GPX3 involved in cell proliferation, apoptosis, autophagy and ferroptosis in BPH. Methods: Human prostate tissues, GPX3 silencing and overexpression prostate cell (BPH-1 and WPMY-1) models and testosterone-induced rat BPH (T-BPH) model were utilized. The qRT-PCR, CCK8 assay, flow cytometry, Western blotting, immunofluorescence, hematoxylin and eosin, masson’s trichrome, immunohistochemical staining and transmission electron microscopy analysis were performed during in vivo and in vitro experiments. Results: Our study indicated that GPX3 was localized both in the stroma and epithelium of prostate, and down-regulated in BPH samples. Overexpression of GPX3 inhibited AMPK and activated ERK1/2 pathway, thereby inducing mitochondria-dependent apoptosis and G0/G1 phase arrest, which could be significantly reversed by MEK1/2 inhibitor U0126 preconditioning. Moreover, overexpression of GPX3 further exerted anti-autophagy by inhibiting AMPK/m-TOR and up-regulated nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4, mitochondrial GPX4 and cytoplasmic GPX4) to antagonize autophagy-related ferroptosis. Consistently, GPX3 deficiency generated opposite changes in both cell lines. Finally, T-BPH rat model was treated with GPX3 indirect agonist troglitazone (TRO) or GPX4 inhibitor RAS-selective lethal 3 (RSL3) or TRO plus RSL3. These treatments produced significant atrophy of the prostate and related molecular changes were similar to our in vitro observations. Conclusions: Our novel data manifested that GPX3, which was capable of inducing apoptosis via AMPK/ERK1/2 pathway and antagonizing autophagy-related ferroptosis through AMPK/m-TOR signalling, was a promising therapeutic target for BPH in the future.

Lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) is common in adult men and can impair erectile function (EF). It was believed surgical treatments for this illness can improve EF due to the relief of LUTS while they were also reported harmed EF as heating or injury effect. Current network meta-analysis aimed to elucidate this discrepancy. Randomized controlled trials (RCTs) were identified. Direct comparisons were conducted by STATA and network meta-analysis was conducted by Generate Mixed Treatment Comparison. Random-effects models were used to calculate pooled standard mean difference and 95% confidence intervals and to incorporate variation between studies. Eighteen RCTs with 2433 participants were analyzed. Nine approaches were studied as transurethral resection of the prostate (TURP), plasmakinetic resection of the prostate (PKRP), plasmakinetic enucleation of the prostate (PKEP), Holmium laser enucleation of the prostate (HoLEP), Holmium laser resection of the prostate (HoLRP), photoselective vaporization of the prostate (PVP), Thulium laser, open prostatectomy (OP), and laparoscopic simple prostatectomy (LSP). In direct comparisons, all surgical treatments did not decrease postoperative International Index of Erectile Function (IIEF)-5 score except PVP. Moreover, patients who underwent HoLEP, PKEP, Thulium laser, and TURP had their postoperative EF significantly increased. Network analysis including direct and indirect comparisons ranked LSP at the highest position on the variation of postoperative IIEF-5 score, followed by PKRP, HoLEP, TURP, Thulium laser, PKEP, PVP, HoLRP, and OP. In subgroup analysis, only PVP was found lower postoperative EF in the short term and decreased baseline group, whereas TURP increased postoperative IIEF-5 score only for patients with normal baseline EF. However, HoLEP and PKEP showed pro-erectile effect even for patients with decreased baseline EF and short-term follow-up. Our novel data demonstrating surgical treatments for LUTS/BPH showed no negative impact on postoperative EF except PVP. Moreover, HoLEP and PKEP were found pro-erectile effect for all subgroups. New technologies, such as LSP, PKRP, and Thulium laser, were ranked at top positions in the network analysis, although they had no pro-erectile effect in direct comparison due to limited original studies or poor baseline EF. Therefore, further studies and longer follow-up are required to substantiate our findings.

Background: Adrenocortical carcinoma (ACC) is a limited endocrine fatality with a minor diagnosis and rare remedial options. The progressive and predictive meaning of message RNA (mRNA) expression oddity in ACC has been studied extensively in recent years. However, differences in measurement platforms and lab protocols as well as small sample sizes can render gene expression levels incomparable.

Benign prostatic hyperplasia (BPH) is a quite common illness but its etiology and mechanism remain unclear. Neural epidermal growth factor-like like 2 (NELL2) plays multifunctional roles in neural cell growth and is strongly linked to the urinary tract disease. Current study aims to determine the expression, functional activities and underlying mechanism of NELL2 in BPH. Human prostate cell lines and tissues from normal human and BPH patients were utilized. Immunohistochemical staining, immunofluorescent staining, RT-polymerase chain reaction (PCR) and Western blotting were performed. We further generated cell models with NELL2 silenced or overexpressed. Subsequently, proliferation, cycle, and apoptosis of prostate cells were determined by cell counting kit-8 (CCK-8) assay and flow cytometry analysis. The epithelial–mesenchymal transition (EMT) and fibrosis process were also analyzed. Our study revealed that NELL2 was up-regulated in BPH samples and localized in the stroma and the epithelium compartments of human prostate tissues. NELL2 deficiency induced a mitochondria-dependent cell apoptosis, and inhibited cell proliferation via phosphorylating extracellular signal-regulated kinase 1/2 (ERK1/2) activation. Additionally, suppression of ERK1/2 with U0126 incubation could significantly reverse NELL2 deficiency triggered cell apoptosis. Consistently, overexpression of NELL2 promoted cell proliferation and inhibited cell apoptosis. However, NELL2 interference was observed no effect on EMT and fibrosis process. Our novel data demonstrated that up-regulation of NELL2 in the enlarged prostate could contribute to the development of BPH through enhancing cell proliferation and inhibited a mitochondria-dependent cell apoptosis via the ERK pathway. The NELL2–ERK system might represent an important target to facilitate the development of future therapeutic approaches in BPH.

Benign prostatic hyperplasia (BPH) is a common condition in aging males. The current study aims to identify differentially expressed genes (DEGs) associated with BPH and to elucidate the role of matrix-remodeling associated 5 (MXRA5) protein and mitogen-activated protein kinase (MAPK) signaling pathways in BPH. A total of 198 DEGs and a number of related pathways were identified with MXRA5 being one of the most significantly altered DEGs. MXRA5 was upregulated in BPH samples and localized mostly in stroma. Knockdown of MXRA5 induced stromal cell cycle arrest instead of inhibiting apoptosis. Consistently, MXRA5 overexpression enhanced epithelial cell proliferation. In addition, phosphorylated ERK1/2 and p38, key members of the MAPK family, were strongly decreased with knockdown but increased with overexpression. Our novel data demonstrates that upregulation of MXRA5 in the enlarged prostate could contribute to the development of BPH through increasing cell proliferation via the MAPK pathway. Thus, the MXRA5-MAPK system could be rediscovered as a new therapeutic target for treating BPH. Microarray analysis and integrated bioinformatics were conducted. The expression and biologic functions of MXRA5 was investigated via RT-PCR, western-blot, immunofluorescence, flow cytometry and MTT assay. Finally, genes involved in regulation of the MAPK pathway were investigated.