68Ga-PSMA PET/CT targeted biopsy for the diagnosis of clinically significant prostate cancer compared with transrectal ultrasound guided biopsy: a prospective randomized single-centre study.

PURPOSE: 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is valuable for detecting primary and recurrent prostatic lesions. This study aimed to evaluate the efficacy of 68Ga-PSMA-11 PET/CT as a triage tool for prostate biopsy (PSMA-TB) and compare with transrectal ultrasound-guided biopsy (TRUS-GB) for the diagnosis of clinically significant prostate cancer (csPCa). METHODS: This single-centre study randomly allocated 120 patients with elevated serum prostate-specific antigen (PSA) levels (> 4 ng/ml) to PSMA-PET or TRUS group. Patients with PSMA-avid lesions (SUVmax ≥ 8.0) underwent PSMA-TB via a single-puncture percutaneous transgluteal approach (n = 25), whilst patients with negative PSMA-PET underwent systematic TRUS-GB (n = 35). All patients in the TRUS group underwent TRUS-GB directly (n = 60). RESULTS: PCa and csPCa were detected in 26/60 (43.3%) and 24/60 (40.0%) patients in the PSMA-PET group and 19/60 (31.6%) and 15/60 (25.0%) in the TRUS group, respectively. In the PSMA-PET group, the detection rate of PCa and csPCa were significantly higher in PSMA-PET-positive than negative patients (PCa, 23/25 (92.0%) vs 3/35 (8.6%), P < 0.01; csPCa, 22/25 (88.0%) vs 2/35 (5.7%), P < 0.01). PSMA-TB detected significantly more PCa and csPCa than TRUS-GB in the TRUS controls (PCa, 21/25 (84.0%) vs 19/60 (31.6%), P < 0.01; csPCa, 20/25 (80.0%) vs 15/60 (25.0%), P < 0.01). PSMA-PET detected significantly more cases of csPCa amongst patients with PSA 4.0-20.0 ng/ml than TRUS (27.02% vs 8.82%, P < 0.05). No haematuria, urinary retention or pelvic infection was observed after PSMA-TB compare with TRUS-GB. CONCLUSIONS: 68Ga-PSMA-11 PET/CT is a feasible imaging technique that may serve as a triage tool for prostate biopsy, and may improve the detection rate of csPCa compared with TRUS-GB, especially in patients with serum PSA 4.0-20.0 ng/ml.

A Molecular Signature of Two Long Non-Coding RNAs in Peripheral Blood Predicts Acute Renal Allograft Rejection.

BACKGROUND/AIMS: Acute rejection (AR) is a major complication post renal transplantation, with no widely-accepted non-invasive biomarker. This study aimed to explore the expression profiles of long non-coding RNAs (lncRNAs) in the peripheral blood (PB) of renal transplant recipients and their potential diagnostic values. METHODS: The genome-wide lncRNA expression profiles were analyzed in 150 PB samples from pediatric and adult renal transplant (PRTx and ARTx) cohorts. The diagnostic performance of differentially expressed lncRNA was determined using receiver operator characteristic curve, with area under the curve (AUC) and 95% confidential interval (CI). Finally, a risk score was constructed with logistical regression model. RESULTS: A total of 162 lncRNAs were found differentially expressed in PRTx cohort, while 163 in ARTx cohort. Among these identified lncRNAs, 23 deregulated accordingly in both cohorts, and could distinguish AR recipients from those without AR. Finally, a risk score with two most significant lncRNAs (AF264622 and AB209021) was generated and exhibited excellent diagnostic performance in both PRTx (AUC:0.829, 95% CI:0.735-0.922) and ARTx cohorts (AUC: 0.889, 95% CI: 0.817-0.960). CONCLUSION: A molecular signature of two lncRNAs in PB could serve as a novel non-invasive biomarker for the diagnosis of AR in both pediatric and adult renal transplant recipients.

Applications of genome editing tools in precision medicine research.

The emergence of genome editing tools, such as the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system, has enabled researchers to achieve somatic and germline genomic manipulations in cell lines and model organisms. Within a couple of years, genome editing is now being rapidly developed for multiple applications and widely used in biomedical researches, including creation of disease models with desired genetic mutations, screening in a high-throughput manner for drug resistance genes, and making appropriate editions to genes in vivo for disease treatment. All these applications have been facilitating the development of precision medicine research. In this review, we describe the use of genome editing technologies for a variety of research and translational applications in the precision medicine field. We also highlight some of the existing limitations or challenges as well as future directions.

MicroRNA expression profiles in muscle-invasive bladder cancer: identification of a four-microRNA signature associated with patient survival.

Bladder cancer ranks the second most common genitourinary tract cancer, and muscle-invasive bladder cancer (MIBC) accounts for approximately 25 % of all bladder cancer cases with high mortality. In the current study, with a total of 202 treatment-naïve primary MIBC patients identified from The Cancer Genome Atlas dataset, we comprehensively analyzed the genome-wide microRNA (miRNA) expression profiles in MIBC, with the aim to investigate the relationship of miRNA expression with the progression and prognosis of MIBC, and generate a miRNA signature of prognostic capabilities. In the progression-related miRNA profiles, a total of 47, 16, 3, and 84 miRNAs were selected for pathologic T, N, M, and histologic grade, respectively. Of the eight most important progression-related miRNAs, four (let-7c, mir-125b-1, mir-193a, and mir-99a) were significantly associated with survival of patients with MIBC. Finally, a four-miRNA signature was generated and proven as a promising prognostic parameter. In summary, this study identified the specific miRNAs associated with the progression and aggressiveness of MIBC and a four-miRNA signature as a promising prognostic parameter of MIBC.

The association between RASSF1A promoter methylation and prostate cancer: evidence from 19 published studies.

Ras-associated domain family 1A (RASSF1A) is a putative tumor suppressor gene located at 3p21.3, and the epigenetic inactivation of RASSF1A by hypermethylation of CpG islands within the promoter region has been observed in various cancer types, including prostate cancer (PCa). However, results from published studies on the association between RASSF1A promoter methylation and PCa risk are conflicting and inconclusive. Hence, we conducted a meta-analysis of 19 eligible studies with odds ratio (OR) and its corresponding 95% confidence intervals (95% CI) in order to investigate the strength of relationship of RASSF1A promoter methylation with PCa risk and its clinicopathological variables. Overall, the RASSF1A promoter methylation was significantly associated with PCa risk (OR = 9.58, 95% CI 5.64-16.88, P heterogeneity <0.001) and Gleason score (GS) (OR = 2.58, 95% CI 1.64-4.04, P(heterogeneity) = 0.019). In addition, subgroup analysis by testing material demonstrated the significant association between RASSF1A methylation and GS (OR = 3.09, 95% CI 1.92-4.97, P heterogeneity =0.042), PSA level (OR = 2.75, 95% CI 1.67-4.52, P(heterogeneity) = 0.639), and tumor stage (OR = 1.74, 95% CI 1.05-2.87, P(heterogeneity) = 0.026) in tissue rather than urine samples. In conclusion, this meta-analysis suggested that RASSF1A promoter methylation was significantly associated with an increased risk for PCa; furthermore, the RASSF1A methylation status in tissue rather than urine was positively correlated with GS, serum PSA level, and tumor stage, which can be utilized for the early detection and prognosis prediction of PCa.

Lack of association between interferon gamma +874 T/A polymorphism and cancer risk: an updated meta-analysis.

Interferon gamma (IFN-γ) is a potent proinflammatory cytokine which plays a pivotal role in the antiviral, antiproliferative, and antitumor activities. A T-to-A transition at the position +874 of human IFN-γ gene (IFNG) has been reported to influence the secretion of IFN-γ and affect cancer susceptibility. However, results from published studies on the association between IFNG +874 T/A polymorphism and cancer risk are inconclusive or even controversial. In order to derive a more precise estimation of the association, a meta-analysis of 38 eligible studies including 5,630 cases and 6,096 controls was conducted with odds ratio (OR) and its corresponding 95 % confidence interval (95 % CI). Overall, no significant association was detected in allelic model (A allele vs. T allele-OR = 0.96, 95 % CI, 0.86-1.08), homozygote comparison (AA vs. TT-OR = 0.97, 95 % CI, 0.79-1.21), heterozygote comparison (AT vs. TT-OR = 1.03, 95 % CI, 0.87-1.23), dominant model (AA + AT vs. TT-OR = 1.00, 95 % CI, 0.87-1.15), nor recessive model (AA vs. AT + TT-OR = 0.93, 95 % CI, 0.78-1.12). Further subgroup analyses based on ethnicity, cancer types, and Hardy-Weinberg equilibrium status failed to demonstrate any significant relationship except in African population under recessive model (AA vs. AT + TT-OR = 0.68, 95 % CI, 0.47-0.97). In conclusion, the current meta-analysis suggested that IFNG +874 T/A polymorphism may not contribute to cancer susceptibility, and further well-designed studies with large sample size are warranted to validate our conclusion.

Association of polymorphisms in estrogen receptors (ESR1 and ESR2) with male infertility: a meta-analysis and systematic review.

PURPOSE: Estrogens play an important role in male reproduction via interacting with estrogen receptors (ERs), whose expression can be regulated by the polymorphisms in different regions of ESR1 and ESR2 genes. However, results from published studies on the association between four well-characterized polymorphisms (PvuII, XbaI, RsaI, and AluI) in the gene of ERs (ESR1 and ESR2) and male infertility risk are inconclusive. METHODS: To investigate the strength of relationship of PvuII and XbaI in ESR1 and RsaI and AluI in ESR2 with male infertility, we conducted a meta-analysis of 12 eligible studies with odds ratio (OR) and its corresponding 95 % confidence intervals (95 % CI). RESULTS: Overall, ESR1 PvuII and ESR2 RsaI polymorphisms were significantly associated with male infertility risk. The subgroup analyses by ethnicities demonstrated that in Asians, ESR1 PvuII, XbaI and ESR2 RsaI polymorphisms were significantly associated with a decreased infertility risk, while in Caucasians both ESR1 PvuII and ESR2 RsaI polymorphisms increased the susceptibility to male infertility. As for ESR2 AluI polymorphism, no significant association was detected in either overall analysis or subgroup analyses by ethnicities/genotyping methods. CONCLUSIONS: This meta-analysis suggested that polymorphisms in the genes of ERs (ESR1 and ESR2) may have differential roles in the predisposition to male infertility according to the different ethnic backgrounds. Further well-designed and unbiased studies with larger sample size and diverse ethnic backgrounds should be conducted to verify our findings.

Turning waste into treasure: A new direction for low-cost production of lipid chemicals from Thraustochytrids.

Thraustochytrids are marine microorganisms known for their fast growth and ability to store lipids, making them useful for producing polyunsaturated fatty acids (PUFAs), biodiesel, squalene, and carotenoids. However, the high cost of production, mainly due to expensive fermentation components, limits their wider use. A significant challenge in this context is the need to balance production costs with the value of the end products. This review focuses on integrating the efficient utilization of waste with Thraustochytrids fermentation, including the economic substitution of carbon sources, nitrogen sources, and fermentation water. This approach aligns with the 3Rs principles (reduction, recycling, and reuse). Furthermore, it emphasizes the role of Thraustochytrids in converting waste into lipid chemicals and promoting sustainable circular production models. The aim of this review is to emphasize the value of Thraustochytrids in converting waste into treasure, providing precise cost reduction strategies for future commercial production.

Enhanced fatty acid storage combined with the multi-factor optimization of fermentation for high-level production of docosahexaenoic acid in Schizochytrium sp.

Schizochytrium sp. hasreceived much attention for itsability to synthesize and accumulate high-level docosahexaenoic acid (DHA), which can reach nearly 40 % of total fatty acids. In this study, the titer of DHA in Schizochytrium sp. was successfully improved by enhancing DHA storage through overexpressing the diacylglycerol acyltransferase (ScDGAT2C) gene, as well as optimizing the supply of precursors and cofactors required for DHA synthesis by response surface methodology. Notably, malic acid, citric acid, and biotin showed synergistic and time-dependent effects on DHA accumulation. The maximum lipid and DHA titers of the engineered Schizochytrium sp. strain reached 84.28 ± 1.02 g/L and 42.23 ± 0.69 g/L, respectively, with the optimal concentration combination (1.62 g/L malic acid + 0.37 g/L citric acid + 8.28 mg/L biotin) were added 48 h after inoculation. This study provides an effective strategy for improving lipid and DHA production in Schizochytrium sp.

Integration of genetic engineering and multi-factor fermentation optimization for co-production of carotenoid and DHA in Schizochytrium sp.

Schizochytrium sp., a microalga with high lipid content, holds the potential for co-producing docosahexaenoic acid (DHA) and carotenoids. In this study, the ability of Schizochytrium sp. to naturally produce carotenoids was systematically explored. Further, by enhancing the precursor supply of geranylgeranyl diphosphate, regulating carbon source through sugar limitation fermentation and employing a combination of response surface methodology and artificial neural networks to precisely optimize nitrogen sources, a new record of 43-fold increase in ß-carotene titer was achieved in the 5L bioreactor (653.2 mg/L). Meanwhile, a high DHA content was maintained (13.4 g/L). Furthermore, the use of corn stover hydrolysate has effectively lowered the production costs of carotenoid and DHA while sustaining elevated production levels (with total carotenoid titer and DHA titer reached 502.0 mg/L and 13.2 g/L, respectively). This study offers an efficient and cost-effective method for the co-production of carotenoid and DHA in Schizochytrium sp..

The performance of 18F-PSMA PET/CT in the detection of prostate cancer: a systematic review and meta-analysis.

This paper presents a meta-analysis regarding the detection rate (DR) of fluorine-18 (18F)-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 18F-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 18F-PSMA PET/CT in managing PCa patients, while the secondary outcome was the DR of 18F-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 18F-PSMA PET/CT was 0.83 (95% CI: 0.78-0.88), in the random-effects model. Subsequently, the analysis of DR of 18F-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 18F-PSMA PET/CT. The DR of 18F-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 18F-PSMA PET/CT in managing PCa patients and was associated with Gleason score and serum PSA level.

[Effects of endothelial progenitor cells on spermatogenic functions in testicular detorsion in rats].

OBJECTIVE: To investigate the effects of transplanted endothelial progenitor cells (EPCs) on the spermatogenic functions in testicular detorsion. METHODS: Bone-marrow-derived EPCs were obtained from rats and transfected by enhanced green fluorescent protein adenovirus (Ad-eGFP). The rats were divided into 3 groups (n = 6 each). In the sham group, left testis was not twisted. In the ischemia reperfusion injury (IRI) group, 1 ml saline was injected into the femoral vein of each rat after testicular detorsion. In the EPCs group, 1 ml EPCs suspension (1.0 × 10(6) EPCs) was injected into each rat after testicular detorsion. The Ad-eGFP transfected EPCs were injected into the 3 additional rats of testicular torsion-detorsion. At Day 5 post-transplantation, the characteristics of transplanted EPCs homing were detected. And the pathological changes and apoptotic cells/seminiferous tubules in left testis were examined. RESULTS: When the value of multiplication of infection (MOI) was at 50, the transfection rate of EPCs by Ad-eGFP exceeded 73.7%. At Day 5 post-treatment, the cells exhibiting green fluorescence were detected in left testis. The germ cells in rats of the sham group were normal. And the ratio of apoptotic cells to seminiferous tubules was 0.09 ± 0.02. The germ cells in rats of the IRI group were much fewer. And the ratio of apoptotic cells to seminiferous tubules was 2.82 ± 0.81. As compared with the IRI group, seminiferous epithelium was thicker in the EPCs group. And the ratio of apoptotic cells to seminiferous tubules was 0.32 ± 0.09 in the EPCs group. It was much smaller than that in the IRI group. There was significant difference (P < 0.01). CONCLUSION: The transplantation of EPCs is effective for treating the spermatogenic dysfunctions caused by testicular torsion so as to greatly enhance the spermatogenic functions.

[Tadalafil for ED after transurethral resection of the prostate: a report of 113 cases].

OBJECTIVE: To evaluate the efficacy of tadalafil in the treatment of ED after transurethral resection of the prostate (TURP). METHODS: A total of 113 patients with ED after TURP received 3 months of tadalafil treatment and were followed up for 6 months. The IIEF-5 scores of the patients and the number of successful penile intromissions and sustained penile erections in the patients' sexual life diary were compared before and after the treatment. RESULTS: The IIEF-5 scores were 9.83 +/- 3.96 before the medication, 20.23 +/- 3.25 after it, and 17.28 +/- 3.03 at 6 months after drug withdrawal, with statistically significant differences between pre- and post-treatment (P < 0.05). The patients' success rates of penile intromission and sexual intercourse were increased from 44.8% and 7.5% before the medication to 81.7% and 63.2% after it. CONCLUSION: Tadalafil can be used as a first-line drug for the treatment of ED after TURP.

[Diabetes mellitus reduces the expression of SK3 in rat cavernous tissues].

OBJECTIVE: SK3, one of the small conductance calcium-activated potassium channels, is the key substance of the endothelium-derived hyperpolarizing factor (EDHF) passway. This study aimed to investigate the expression of SK3 in the cavernous tissue of rats with diabetes mellitus (DM). METHODS: Twenty-six DM models were made by injection of streptozocin (STZ) out of 50 male Sprague-Dawley rats, and another 15 that failed to be modeled were included in an STZ group. Ten healthy male rats were taken as blank controls. Eight weeks later, the penile erectile function of the rats was detected by injection of apomorphine (APO) at 80 microg/kg, and the expression of SK3 in the cavernous tissue was determined by RT-PCR and Western blot. RESULTS: Penile erection was observed in 14 (54%) of the 26 DM rat models and in all the rats of the STZ and blank control groups. Both the mRNA and protein expressions of SK3 were significantly lower in the DM (0.50 +/- 0.09 and 0.65 +/- 0.06) than in the STZ (1.15 +/- 0.03 and 1.28 +/- 0.04) and blank control groups (1.21 +/- 0.04 and 1.34 +/- 0.05) (P < 0.05). There were no significant differences between the STZ and blank control groups in either penile erection or mRNA and protein expressions of SK3 (P > 0.05). CONCLUSION: Diabetes mellitus can significantly reduce erectile function in rats, which may be related to the decreased expression of SK3 in the corpus cavernosum.

[Implantation brachytherapy with 32P-chromic phosphate-poly (L-lactide) delayed-release particles for prostate cancer in nude mice].

OBJECTIVE: To study the effects of implantation brachytherapy with delayed-release particles of 32P-chromic phosphate-poly (L-lactide) (32P-CP-PLLA) on prostate cancer (PCa) in nude mice. METHODS: We established a subcutaneous transplantable PCa model in nude mice, and randomly divided them into six groups, Groups A, B and C implanted intratumorally with 32P-CP-PLLA delayed-release particles at 3.7, 7.4 and 14.8 MBq, Groups D, E and F with 125I particles at the same doses as the former three, and another six nude mice were included in Group G as the blank control. Then we killed the mice at 21 days after the treatment, observed the effects of the particles on the morphology of the tumor and their inhibition of tumor growth, counted WBCs and platelets (PLTs) in the peripheral blood, and detected the toxic reaction of the blood. RESULTS: At 21 days after the treatment, the solid tumor tissues exhibited bleeding and necrotic changes, and the rates of tumor inhibition were positively correlated with the doses of administration. Groups A, B and C showed statistically significant differences from Groups D, E, F and G in the rate of tumor inhibition ([ 65.72 +/- 6.95]%, [77.58 +/- 4.32]% and [82.64 +/- 4.03]% versus [35.61 +/- 5.61]%, [43.30 +/- 6.94]% and [69.01 +/- 4.98]%), WBC count ([1.72 +/- 0.37] x 10(9)/L, [1.23 +/- 0.27] x 10(9)/L and [0.86 +/- 0.25] x 10(9)/L versus [1.45 +/- 0.40] x 10(9)/L, [0.51 +/- 0.24] x 10(9)/L, [0.37 +/- 0.26] x 10(9)/L and [3.96 +/- 0.26] x 10(9)/L), PLT count ([1.18 +/- 0.11] x 10(11)/L, [0.97 +/- 0.10] x 10(11)/L and [0.72 +/- 0.11] x 10(11)/L versus [0.97 +/- 0.15] x 10(11)/L, [0.76 +/- 0.16] x 10(11)/L, [0.64 +/- 0.12] x 10(11)/L and [2.89 +/- 0.21] x 10(11)/L) and body weight ([18.60 +/- 0.66] g, [17.60 +/- 0.39] g and [16.90 +/- 0.68] g versus [17.86 +/- 0.60] g, [15.56 +/- 0.39] g, [14.61 +/- 0.65] g and [19.95 +/- 0.73] g) (P < 0.01). CONCLUSION: Intratumoral implantation of 32P-CP-PL-LA is a safe, simple and effective radionuclide interventional therapy for prostate cancer.

Cyclooxygenase-2 expression is dependent upon epidermal growth factor receptor expression or activation in androgen independent prostate cancer.

AIM: To investigate the expression of cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) and the possible mechanism in the development in androgen independent prostate cancer (AIPC). METHODS: Immunohistochemistry was performed on paraffin-embedded sections with goat polyclonal against COX-2 and mouse monoclonal antibody against EGFR in 30 AIPC and 18 androgen dependent prostate cancer (ADPC) specimens. The effect of epidermal growth factor (EGF) treatments on the expression of COX-2 and signal pathway in PC-3 and DU-145 cells was studied using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. ELISA was used to measure prostaglandin E2 (PGE2) levels in the media of PC-3 and DU-145 incubated with EGF for 24 h. RESULTS: COX-2 was positively expressed in AIPC and ADPC, which were predominantly in endochylema of prostate cancer (PCa) cells. Intense staining was seen in AIPC (80%) and in ADPC (55.5%), but there was no significant association between the two groups. EGFR expression was also positive in the two groups (61.8% in ADPC and 90% in AIPC, P < 0.01). A significant association was found between EGFR expression and a higher Gleason score (P < 0.05) or tumor stage (P < 0.05). The expression of PGE2 was increased in PC-3 and DU-145 cells after being incubated with EGF. Both p38MAPK and PI-3K pathway were involved in the PC-3 cell COX-2 upregulation course. In DU-145, only p38MAPK pathway was associated with COX-2 upregulation. CONCLUSION: EGFR activation induces COX-2 expression through PI-3K and/or p38MAPK pathways. COX-2 and EGFR inhibitors might have a cooperative anti-tumor effect in PCa.

[Epidermal growth factor up-regulates the mRNA expression of endothelin-1 and its receptors in prostate cancer PC-3 cell lines].

OBJECTIVE: To investigate the effects of the epidermal growth factor on the mRNA expression of endothelin-1 and its receptors (ET(A)R, ET(B)R) in hormone refractory prostate cancer (HRPC) PC-3 cell lines. METHODS: PC-3 cells were cultured in vitro. After the treatment with EGF, the mRNA expressions of endothelin-1, ET(A)R and ET(B)R were detected by RT-PCR in PC-3 cell lines. The levels of the mRNA expression of endothelin-1 and its receptors were examined at different time points by RT-PCR. RESULTS: The expressions of endothelin-1 and ET(A)R mRNA but not the mRNA expression of ET(B)R was observed in PC-3 cell lines. After 24 hours of treatment with EGF, the expressions of endothelin-1 and ET(A)R in PC-3 cell lines were both up-regulated and there was significant difference (P < 0.05) between the experimental and control groups. Different expression levels of endothelin-1 and ET(A)R mRNA were noted at different time points of EGF intervention, up-regulated with the increase of treatment time, and with significant difference (P < 0.05). CONCLUSION: EGF can up-regulate the mRNA expressions of endothelin-1 and ET(A)R in PC-3 cell lines and play a great role in prostate cancer progression, which may offer a substructure of molecular biology for the treatment of HRPC.

Identification of hub miRNA biomarkers for bladder cancer by weighted gene coexpression network analysis.

Bladder cancer (BC) is a common urinary system tumor with high aggressiveness, and it results in relatively high mortality due to a lack of precise and suitable biomarkers. In this study, we applied the weighted gene coexpression network analysis method to miRNA expression data from BC patients, and screened for network modules associated with BC progression. Hub miRNAs were selected, followed by functional enrichment analyses of their target genes for the most closely related module. These hub miRNAs were found to be involved in several functional pathways including pathway in cancer, regulation of actin cytoskeleton, PI3K-Akt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, Wnt signaling pathway, proteoglycans in cancer, focal adhesion and p53 signaling pathway via regulating target genes. Finally, their prognostic significance was tested using analyses of overall survival. A few novel prognostic miRNAs were identified based on expression profiles and related survival data. In conclusion, several miRNAs that were critical in BC initiation and progression have been identified in this study. These miRNAs, which may contribute to a comprehensive understanding of the pathogenesis of BC, could serve as potential biomarkers for BC prognosis or as new therapeutic targets.

A BAP1 Mutation-specific MicroRNA Signature Predicts Clinical Outcomes in Clear Cell Renal Cell Carcinoma Patients with Wild-type BAP1.

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.

Remote ischemic conditioning for the prevention of contrast-induced acute kidney injury in patients undergoing intravascular contrast administration: a meta-analysis and trial sequential analysis of 16 randomized controlled trials.

OBJECTIVE: We conducted this meta-analysis to examine the effect of remote ischemic conditioning (RIC) on contrast-induced acute kidney injury (CI-AKI) in patients undergoing intravascular contrast administrationon. METHODS: Pubmed, Embase, and Cochrane Library were comprehensively searched to identify all eligible studies by 15th March, 2017. Risk ratio (RR) and weighted mean difference with the corresponding 95% confidence intervals (CI) were used to examine the treatment effect. The heterogeneity and statistical significance were assessed with Q-test and Z-test, respectively. RESULTS: A total of 16 RCTs including 2175 patients were eventually analyzed. Compared with the control group, RIC could significantly decrease the incidence of CI-AKI (RR=0.58; 95% CI: 0.46, 0.74; P < 0.001), which was further confirmed by the trial sequential analysis. Subgroup analyses showed that remote ischemic preconditioning (RIPrC) and remote ischemic postconditioning (RIPoC) were both obviously effective, and perioperative hydration might enhance the efficiency of RIC. RIC also significantly reduced the major adverse cardiovascular events within six months. CONCLUSION: RIC, whether RIPrC or RIPoC, could effectively exert renoprotective role in intravascular contrast administration and reduce the incidence of relevant adverse events.