Cell division cycle 42 effector protein 4 inhibits prostate cancer progression by suppressing ERK signaling pathway.

Prostate cancer (PCa) is the most common malignancy among men worldwide. The cell division cycle 42 effector protein 4 (CDC42EP4) functions downstream of CDC42, yet its role and molecular mechanisms in PCa remain unexplored. This study aimed to elucidate the role of CDC42EP4 in the progression of PCa and its underlying mechanisms. Bioinformatical analysis indicated that CDC42EP4 expression was significantly lower in PCa tissue compared to normal prostate tissue. Cellular phenotyping analysis suggested that CDC42EP4 markedly inhibited the proliferation, migration, and invasion of PCa cells. Xenograft tumor assays further demonstrated that CDC42EP4 suppressed the growth of PCa cells in vivo. Mechanistically, the study established that CDC42EP4 inhibited the ERK pathway in PCa cells. Additionally, the ERK pathway inhibitor PD0325901 was employed, revealing that PD0325901 significantly nullified the effects of CDC42EP4 on PCa cell proliferation, migration, and invasion. Collectively, our findings demonstrate that CDC42EP4 acts as a critical tumor suppressor gene, inhibiting PCa cell proliferation, migration, and invasion through the ERK pathway, thereby presenting potential targets for PCa therapy.

Ribosomal protein L22-like1 promotes prostate cancer progression by activating PI3K/Akt/mTOR signalling pathway.

Prostate cancer (PCa) is one of the most common malignancies in men. Ribosomal protein L22-like1 (RPL22L1), a component of the ribosomal 60 S subunit, is associated with cancer progression, but the role and potential mechanism of RPL22L1 in PCa remain unclear. The aim of this study was to investigate the role of RPL22L1 in PCa progression and the mechanisms involved. Bioinformatics and immunohistochemistry analysis showed that the expression of RPL22L1 was significantly higher in PCa tissues than in normal prostate tissues. The cell function analysis revealed that RPL22L1 significantly promoted the proliferation, migration and invasion of PCa cells. The data of xenograft tumour assay suggested that the low expression of RPL22L1 inhibited the growth and invasion of PCa cells in vivo. Mechanistically, the results of Western blot proved that RPL22L1 activated PI3K/Akt/mTOR pathway in PCa cells. Additionally, LY294002, an inhibitor of PI3K/Akt pathway, was used to block this pathway. The results showed that LY294002 remarkably abrogated the oncogenic effect of RPL22L1 on PCa cell proliferation and invasion. Taken together, our study demonstrated that RPL22L1 is a key gene in PCa progression and promotes PCa cell proliferation and invasion via PI3K/Akt/mTOR pathway, thus potentially providing a new target for PCa therapy.

Blockage of MDM2-mediated p53 ubiquitination by yuanhuacine restrains the carcinogenesis of prostate carcinoma cells by suppressing LncRNA LINC00665.

Prostate cancer (PCa) is a challenging issue for men's health worldwide due to its uncontrolled proliferation and high metastatic potential. Increasing evidence has supported plant extracts and natural plant derivatives as promising antitumor therapy with less toxic side effects. Yuanhuacine is an active component isolated from Daphne genkwa and can effectively suppress the tumorigenesis of several cancers. However, its role in PCa remains unclear. In this study, yuanhuacine dose-dependently inhibited the proliferation and induced apoptosis of PCa cells. Moreover, yuanhuacine also restrained the invasion and migration of PCa cells. Mechanically, yuanhuacine decreased the ubiquitination and degradation of p53 protein, and ultimately increased p53 levels, which was regulated by inhibiting the phosphorylation and total protein levels of mouse double minute 2 (MDM2). Moreover, elevation of MDM2 reversed the suppressive efficacy of yuanhuacine in PCa cell viability, invasion, and migration. The network pharmacologic and bioinformatics analysis confirmed that MDM2 might be a common target of D. genkwa and LINC00665. Furthermore, yuanhuacine inhibited LINC00665 expression. Upregulation of LINC00665 reversed yuanhuacine-mediated inhibition in MDM2 protein expression and suppressed p53 levels by enhancing its ubiquitination in yuanhuacine-treated cells. Importantly, the inhibitory effects of yuanhuacine on cell viability and metastatic potential were offset after LINC00665 elevation. Together, the current findings highlight that yuanhuacine may possess tumor-suppressive efficacy by inhibiting LINC00665-mediated MDM2/p53 ubiquitination signaling. Therefore, this study indicates that yuanhuacine may be a promising candidate for the treatment of PCa.

Improvements in the physical coordination skills of gymnasts / Aprimoramentos na capacidade de coordenação física dos ginastas / Mejoras en las habilidades de coordinación física de los gimnastas

ABSTRACT Introduction In the specific sports of gymnastics, athletes' physical quality and professional ability are actively improved, and a special training plan is also actively designed. Objective Improve the physical coordination ability of gymnastic athletes. Methods 50 professional gymnasts were selected, 25 in the experimental group and 25 in the control group. The intervention took 2 hours of daily training in gymnastics class; the period was in a non-competitive season cycle. Results After the experiment, the average performance of the athletes in the experimental group was higher than those before the experiment in the four indicators of push-ups, extensions, supine, and high leg kicks; however, in the three indicators of push-ups, pull-ups, and high leg kicks, the standard deviation after the experiment presented higher than that before (the results after the experiment were not shown to be as stable as those before the experiment). Conclusion During exercise, especially in complex movements, abdominal core strength balances the distribution of physical force for athletes, reducing overall energy expenditure. Thus, athletes can coordinate lower limbs to move with greater speed and precision. Level of Evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução Nos esportes específicos da ginástica, a qualidade física e a capacidade profissional dos atletas são ativamente aperfeiçoadas, e o plano especial de treino é também ativamente delineado. Objetivo Aprimorar a capacidade de coordenação física nos atletas ginastas. Métodos Foram selecionados 50 ginastas profissionais, 25 no grupo experimental e 25 no grupo de controle. A intervenção deu-se por 2 horas de treinamento diário na aula de ginástica, o período foi em um ciclo de temporada não competitiva. Resultados Após o experimento, o desempenho médio dos atletas no grupo experimental foi maior do que aqueles antes do experimento, nos quatro indicadores de flexões, extensões, supino, chutes de perna alta, porém, nos três indicadores de flexões, flexões e chutes de perna alta, o desvio padrão após o experimento apresentou-se maior do que aquele anterior (os resultados após o experimento não se demonstraram tão estáveis quanto aqueles antes do experimento). Conclusão Durante os exercícios, especialmente em movimentos complexos, a força do core abdominal equilibra a distribuição da força física para os atletas, reduzindo o consumo energético geral. Assim, os atletas podem coordenar membros inferiores para moverem-se com maior rapidez e precisão. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción En los deportes específicos de la gimnasia, la calidad física y la capacidad profesional de los atletas se mejoran activamente, y el plan de entrenamiento especial también se perfila activamente. Objetivo Mejorar la capacidad de coordinación física en los atletas de gimnasia. Métodos Se seleccionaron 50 gimnastas profesionales, 25 en el grupo experimental y 25 en el grupo de control. La intervención se llevó a cabo mediante 2 horas diarias de entrenamiento en clase de gimnasia, el período fue en un ciclo de temporada no competitivo. Resultados Después del experimento, el rendimiento medio de los atletas del grupo experimental fue superior al de antes del experimento, en los cuatro indicadores de flexiones, extensiones, supinación y patadas altas, sin embargo, en los tres indicadores de flexiones, extensiones y patadas altas, la desviación estándar después del experimento se presentó más alta que antes (los resultados después del experimento no se mostraron tan estables como los de antes del experimento). Conclusión Durante los ejercicios, especialmente en los movimientos complejos, la fuerza del core abdominal equilibra la distribución de la fuerza física de los atletas, reduciendo el gasto energético total. Así, los atletas pueden coordinar los miembros inferiores para moverse con mayor velocidad y precisión. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Clinical analysis of transurethral holmium laser enucleation in the treatment of benign prostatic hyperplasia with prostatic inflammation: A prospective research study.

Objective: To investigate the clinical efficacy of holmium laser enucleation of the prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH) with prostatic inflammation (PI). Methods: We prospectively collected and followed up data on patients with BPH who underwent HoLEP at the Affiliated Hospital of Weifang Medical University between July 2021 and July 2022. According to the postoperative pathological results, the patients were divided into two groups: BPH without PI group (BPH group) and BPH with PI group. Statistical analysis was performed on clinical data, including age and body mass index (BMI), prostate volume (PV), postoperative residual urine volume (PVR), preoperative serum total prostate-specific antigen (tPSA), serum-free prostate-specific antigen (fPSA), preoperative and postoperative maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS) before and 3 months after surgery, quality of life index (QoL) before and 3 months after surgery, and postoperative complications. Results: A total of 41 patients were included in this study, including 16 in the BPH group and 25 in the BPH with PI group. There were no significant differences in preoperative age, BMI, PV, PVR, tPSA, fPSA, and f/tPSA between the BPH and BPH with PI groups (P > 0.05). The preoperative mean Qmax of the BPH and BPH with PI groups were 9.44 ± 2.449 and 7.52 ± 2.946 [mean ± standard deviation (SD)] ml/s, mean IPSS were 17.75 ± 5.335 and 24.24 ± 5.861 (mean ± SD), and mean QoL were 4.13 ± 0.806 and 4.48 ± 0.8 (mean ± SD), respectively. The postoperative mean Qmax of the BPH and BPH with PI groups were 20.38 ± 4.787 and 14.32 ± 3.827 (mean ± SD) ml/s, mean IPSS were 2.69 ± 1.25 and 5.84 ± 3.579 (mean ± SD), and mean QoL were 0.13 ± 0.342 and 0.92 ± 0.759 (mean ± SD), respectively. In both groups, Qmax significantly increased (P < 0.05) and IPSS and QoL significantly decreased after HoLEP (P < 0.05). Before and after surgery, the Qmax in the BPH with PI group was lower than that in the BPH group, and the IPSS and QoL levels in the BPH with PI group were higher than those in the BPH group (P < 0.05). Compared with the BPH group, the increase in Qmax in the BPH with PI group was smaller and the decrease in IPSS was larger (P < 0.05), but the variation in QoL was not statistically significant (P > 0.05). Conclusion: Improvements in Qmax, IPSS, and QoL in BPH patients with PI after HoLEP surgery were lower than those in BPH patients alone. PI may be a predictor of a worse response to surgical treatment. However, more multicenter randomized controlled trials with larger samples and long-term follow-up are needed to verify this.

Construction of a survival prediction model for high-and low -grade UTUC after tumor resection based on "SEER database": a multicenter study.

BACKGROUND: There are differences in survival between high-and low-grade Upper Tract Urothelial Carcinoma (UTUC). Our study aimed to develop a nomogram to predict overall survival (OS) of patients with high- and low-grade UTUC after tumor resection, and to explore the difference between high- and low-grade patients. METHODS: Patients confirmed to have UTUC between 2004 and 2015 were selected from the Surveillance, Epidemiology and End Results (SEER) database. The UTUCs were identified and classified as high- and low-grade, and 1-, 3- and 5-year nomograms were established. The nomogram was then validated using the Chinese multicenter dataset (patients diagnosed in Shandong, China between January 2010 and October 2020). RESULTS: In the high-grade UTUC patients, nine important factors related to survival after tumor resection were identified to construct nomogram. The C index of training dataset was 0.740 (95% confidence interval [CI]: 0.727-0.754), showing good calibration. The C index of internal validation dataset was 0.729(95% CI:0.707-0.750). On the other hand, Two independent predictors were identified to construct nomogram of low-grade UTUC. The C index was 0.714 (95% CI: 0.671-0.758) for the training set,0.731(95% CI:0.670-0.791) for the internal validation dataset. Encouragingly, the nomogram was clinically useful and had a good discriminative ability to identify patients at high risk. CONCLUSION: We constructed a nomogram and a corresponding risk classification system predicting the OS of patients with an initial diagnosis of high-and low-grade UTUC.

EGCG Promotes Neurite Outgrowth through the Integrin ß1/FAK/p38 Signaling Pathway after Subarachnoid Hemorrhage.

The abnormal neurites have long been regarded as the main player contributing to the poor outcome of patients with subarachnoid hemorrhage (SAH). (-)-Eigallocatechin-3-gallate (EGCG), the major biological component of tea catechin, exhibited strong neuroprotective effects against central nervous system diseases; however, the role of EGCG-mediated neurite outgrowth after SAH has not been delineated. Here, the effect of reactive oxygen species (ROS)/integrin ß1/FAK/p38 pathway on neurite outgrowth was investigated. As expected, oxyhemoglobin- (OxyHb-) induced excessive ROS level was significantly reduced by EGCG as well as antioxidant N-acetyl-l-cysteine (NAC). Consequently, the expression of integrin ß1 was significantly inhibited by EGCG and NAC. Meanwhile, EGCG significantly inhibited the overexpression of phosphorylated FAK and p38 to basal level after SAH. As a result, the abnormal neurites and cell injury were rescued by EGCG, which eventually increased energy generation and neurological score after SAH. These results suggested that EGCG promoted neurite outgrowth after SAH by inhibition of ROS/integrin ß1/FAK/p38 signaling pathway. Therefore, EGCG might be a new pharmacological agent that targets neurite outgrowth in SAH therapy.

Oncological Outcome of Combining Cytoreductive Prostatectomy and Metastasis-Directed Radiotherapy in Patients with Prostate Cancer and Bone Oligometastases: A Retrospective Cohort Study.

BACKGROUND: The current standard of care for metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT) with or without anti-androgen and chemotherapy. The aim of this study was to evaluate the efficacy and safety of a multimodal approach including local primary tumor therapy, metastasis-directed therapy (MDT), and hormonal therapy in patients with oligometastatic prostate cancer (PCa). METHODS: We reviewed data of patients with PCa and bone oligometastases at diagnosis treated in three institutions with ADT followed by cytoreductive surgery with or without metastases-directed radiotherapy. Oligometastases were defined as the presence of five or fewer metastatic lesions with the absence of visceral metastases. In this retrospective cohort study, 58 patients underwent cytoreductive radical prostatectomy and ADT. Of these, 26 patients (45%) received stereotactic body radiation therapy (SBRT) to all metastatic sites as a MDT. Oncological outcomes were analyzed using the Kaplan-Meier method. RESULTS: The median follow-up period was 46.2 months. Of the 58 patients, the 3-year castration-resistant prostate cancer (CRPC)-free survival and cancer-specific survival was 75.9% and 91.4%, respectively. Pre- or post-treatment predictive factors for progression to CRPC, including prostate-specific antigen (PSA) level at diagnosis ≥20 ng/mL, Gleason grade groups 5, clinical T stage cT3b-4, PSA nadir level of ≥0.05 ng/mL, and no MDT with SBRT, were significantly associated with progression to CRPC. Subgroup analysis showed that the MDT group had significantly better CRPC-free survival than the non-MDT group with Gleason grade groups 1-4 (HR=0.228; 95% CI= 0.056-0.926). A total of 3.4% of the patients had grade 2 acute genitourinary toxicities and 5.2% had grade 2 acute gastrointestinal toxicities. No late grade >2 adverse events were observed. CONCLUSION: This multi-center, retrospective cohort study revealed the feasibility of combining cytoreductive prostatectomy and metastasis-directed radiotherapy for newly-diagnosed oligometastatic PCa. This treatment strategy has the potential to delay the progression to CRPC.

Coagulation factor 2 thrombin receptor promotes malignancy in glioma under SOX2 regulation.

Glioma is the most common human primary brain cancer with high mortality and unfavorable clinical outcome. Coagulation factor 2 thrombin receptor (F2R), is a key component in the thrombosis process and has been demonstrated upregulated in various cancers. However, the effect and molecular mechanisms of F2R in glioma remains unclear. In our study, we confirmed that the expression of F2R was upregulated in glioma and predicted poor prognosis. Gene Set Enrichment Analysis (GSEA) and function assays demonstrated that F2R overexpression promoted glioma cell proliferation, metastasis and epithelial-mesenchymal transition (EMT) in vitro and tumor growth in vivo. Then, we identified and validated F2R was the target gene of SRY-box 2 (SOX2) by dual luciferase reporter assay and chromatin immunoprecipitation assay. Besides, High expression of F2R in malignant glioma was associated with ß-catenint signaling pathway activation. Our findings conclude that F2R promotes glioma cell proliferation and metastasis under SOX2 and actives WNT/ß-catenin Signaling pathway, which provides novel insight to the therapeutic regimen in glioma.

Identification of potential diagnostic and prognostic biomarkers for prostate cancer.

Prostate cancer (PCa) is one of the most common malignant tumors worldwide. The aim of the present study was to determine potential diagnostic and prognostic biomarkers for PCa. The GSE103512 dataset was downloaded, and the differentially expressed genes (DEGs) were screened. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) analyses of DEGs were performed. The result of GO analysis suggested that the DEGs were mostly enriched in 'carboxylic acid catabolic process', 'cell apoptosis', 'cell proliferation' and 'cell migration'. KEGG analysis results indicated that the DEGs were mostly concentrated in 'metabolic pathways', 'ECM-receptor interaction', the 'PI3K-Akt pathway' and 'focal adhesion'. The PPI analysis results showed that Golgi membrane protein 1 (GOLM1), melanoma inhibitory activity member 3 (MIA3), ATP citrate lyase (ACLY) and G protein subunit ß2 (GNB2) were the key genes in PCa, and the Module analysis revealed that they were associated with 'ECM-receptor interaction', 'focal adhesion', the 'PI3K-Akt pathway' and the 'metabolic pathway'. Subsequently, the gene expression was confirmed using Gene Expression Profiling Interactive Analysis and the Human Protein Atlas. The results demonstrated that GOLM1 and ACLY expression was significantly upregulated (P<0.05) in PCa compared with that in normal tissues. Receiver operating characteristic and survival analyses were performed. The results showed that area under the curve values of these genes all exceeded 0.85, and high expression of these genes was associated with poor survival in patients with PCa. In conclusion, this study identified GOLM1 and ACLY in PCa, which may be potential diagnostic and prognostic biomarker of PCa.

Identification of candidate diagnostic and prognostic biomarkers for human prostate cancer: RPL22L1 and RPS21.

Prostate cancer (PCa) is one of the most common malignancies in men worldwide. This study was designed to investigate the potential of Ribosomal Protein L22-like1 (RPL22L1) and Ribosomal Protein S21 (RPS21) as diagnostic and prognostic biomarkers for PCa. First, RPL22L1 and RPS21 were screened as the key molecular of PCa by bioinformatics analysis. Subsequently, the prostate tissue samples were stained for antibodies against RPL22L1 and RPS21. The unbiased signal quantification was performed by ImageJ software, and the results showed that the expression of RPL22L1 and RPS21 exhibited significant differences between the PCa tissues and the normal prostate tissues. Receiver-operating characteristics (ROC) curves were prepared, and then the area under the curve (AUC) values of RPL22L1 and RPS21 were calculated as 0.798 and 0.768, and the likelihood ratio (LR) values of RPL22L1 and RPS21 were calculated as 2.86 and 2.53. These data implied that the over-expression of RPL22L1 and RPS21 is associated with the presence of PCa. The further analysis suggested that the expression of RPL22L1 and RPS21 were significantly higher in high Gleason grade than they were in low Gleason grade. In addition, in vitro studies were undertaken to evaluate the roles of RPL22L1 and RPS21 in PCa. The results revealed that these genes promote PCa cell proliferation, migration and invasion, and inhibit PCa cell apoptosis. Taken together, these data showed that RPL22L1 and RPS21 exhibited higher expression in human prostate cancer tissue, and involved in PCa cell proliferation and invasion. This research provided a novel insight into diagnostic and prognostic biomarkers for PCa.

Long noncoding RNA FOXD2-AS1 promotes glioma malignancy and tumorigenesis via targeting miR-185-5p/CCND2 axis.

Glioma is the most aggressive malignant tumor in the adult central nervous system. Abnormal long noncoding RNA (lncRNA) FOXD2-AS1 expression was associated with tumor development. However, the possible role of FOXD2-AS1 in the progression of glioma is not known. In the present study, we used in vitro and in vivo assays to investigate the effect of abnormal expression of FOXD2-AS1 on glioma progression and to explore the mechanisms. FOXD2-AS1 was upregulated in glioma tissue, cells, and sphere subpopulation. Upregulation of FOXD2-AS1 was correlated with poor prognosis of glioma. Downregulation of FOXD2-AS1 decreased cell proliferation, migration, invasion, stemness, and epithelial-mesenchymal transition (EMT) in glioma cells and inhibited tumor growth in transplanted tumor. We also revealed that FOXD2-AS1 was mainly located in cytoplasm and microRNA (miR)-185-5p both targeted FOXD2-AS1 and CCND2 messenger RNA (mRNA) 3'-untranslated region (3'-UTR). miR-185-5p was downregulated in glioma tissue, cells, and sphere subpopulation. Downregulation of miR-185-5p was closely correlated with poor prognosis of glioma patients. In addition, miR-185-5p mimics decreased cell proliferation, migration, invasion, stemness, and EMT in glioma cells. CCND2 was upregulated in glioma tissue, cells, and sphere subpopulation. Upregulation of CCND2 was closely correlated with poor prognosis of glioma patients. CCND2 knockdown decreased cell proliferation, migration, invasion, and EMT in glioma cells. In glioma tissues, CCND2 expression was negatively associated with miR-185-5p, but positively correlated with FOXD2-AS1. FOXD2-AS1 knockdown and miR-185-5p mimics decreased CCND2 expression. Inhibition of miR-185-5p suppressed FOXD2-AS1 knockdown-induced decrease of CCND2 expression. Overexpression of CCND2 suppressed FOXD2-AS1 knockdown-induced inhibition of glioma malignancy. Taken together, our findings highlight the FOXD2-AS1/miR-185-5p/CCND2 axis in the glioma development.

Randomized study of percutaneous ureteroscopic plasma column electrode decortication and laparoscopic decortication in managing simple renal cyst.

BACKGROUND: To assess the safety and efficacy of a novel technology referred to as percutaneous ureteroscopic plasma column electrode (PCE) by comparing laparoscopic decortication in the management of simple renal cyst (SRC). METHODS: Between March 2016 and June 2017, 53 patients with SRCs were randomized to divided into two groups, the PCE group (24 patients), or laparoscope group (29 patients). The operative time, blood loss, days of drainage, catheter, and hospital stay and complications were compared with the two groups. All patients were followed- up to 6 months after treatment. RESULTS: No patients had intraoperative complications such as hemopneumothorax, adjacent organ injury, infection or hemorrhage shock. In the PCE group and laparoscope group: the mean operation time was 34.1±8.2 vs. 58.4±16.7 min (P<0.05). The mean blood loss was 2.0±1.16 vs. 9.7±4.09 mL (P<0.05). The mean postoperative indwelling drainage tube time was 2.5±1.5 vs. 2.9±1.09 d (P>0.05). The mean intra-urethral indwelling catheter time was 2.1±0.88 vs. 2.0±1.15 d (P>0.05). The mean postoperative hospital stay was 3.0±1.7 vs. 3.7±1.53 (P>0.05). One patient in electrode group was suffered from rupture of the collecting system during the operation, and was treated by indwelling D-J stent. During follow up, no cysts recurrence was found. CONCLUSIONS: Percutaneous ureteroscopic PCE decortication is a safe, minimally invasive and effective therapy to treat SRCs, with equal efficacy and advantages in shortening the operation time and reducing the amount of intraoperative bleeding compared with laparoscopic decortication.

LncRNA DANCR functions as a competing endogenous RNA to regulate RAB1A expression by sponging miR-634 in glioma.

Long noncoding RNA (lncRNA) differentiation antagonizing nonprotein coding RNA (DANCR) plays important regulatory roles in many solid tumors. However, the effect of DANCR in glioma progression and underlying molecular mechanisms were not entirely explored. In the present study, we determined the expression of DANCR in glioma tissues and cell lines using qRT-PCR and further defined the biological functions. Furthermore, we used luciferase reporter assay, Western blot, and RNA immunoprecipitation (RIP) to explore the underlying mechanism. Our results showed that DANCR was significantly up-regulated in glioma tissues and cell lines (U251, U118, LN229, and U87MG). High DANCR expression was correlated with advanced tumor grade. Inhibition of DANCR suppressed the glioma cells proliferation and induced cells arrested in the G0/G1 phase. In addition, we verified that DANCR could directly interact with miR-634 in glioma cells and this interaction resulted in the inhibition of downstream of RAB1A expression. The present study demonstrated that DANCR/miR-634/RAB1A axis plays crucial roles in the progression of glioma, and DANCR might potentially serve as a therapeutic target for the treatment of glioma patients.

Does combination therapy with tamsulosin and trospium chloride improve lower urinary tract symptoms after SEEDS brachytherapy for prostate cancer compared with tamsulosin alone? : A prospective, randomized, controlled trial.

OBJECTIVE: To compare the efficacy of combination therapy with an alpha-blocker and an anticholinergic to monotherapy with an alpha blocker on lower urinary tract symptoms (LUTS) following brachytherapy in prostate cancer patients. MATERIAL AND METHODS: A total of 124 patients that had been clinically diagnosed with localized prostate cancer and underwent prostate brachytherapy were enrolled in the present study. Patients were randomized and allocated to two groups, including 60 to the combination group (tamsulosin 0.2 mg/day and trospium chloride 20 mg twice daily) and 64 to the monotherapy group (tamsulosin 0.2 mg/day). Treatment began 1 day after brachytherapy and continued for 6 months. LUTS were compared between the two groups using the total International Prostate Symptom Score (IPSS), storage and voiding IPSS subscores, quality of life (QoL) scores, maximum flow rate (Qmax), and postvoid residual (PVR) urine volume at 1, 3, 6, and 12 months after implantation. RESULTS: In all, 111 patients were ultimately analyzed in the study. Compared with pretreatment scores, a significant increase in total IPSS was found at 1, 3, and 6 months in both groups, but no statistically significant differences were observed between the two groups. The combination therapy group showed a greater decrease in the IPSS storage score compared with the monotherapy group at 1, 3, and 6 months (p = 0.031, 0.030 and 0.042, respectively). Patients receiving tamsulosin plus trospium chloride also showed significant improvements in QoL at 1 and 3 months compared with tamsulosin alone (P = 0.039, P = 0.047). Between the two groups, there was no significant difference in IPSS voiding score, Qmax, and PVR from baseline to each point of the study period. CONCLUSIONS: Combination therapy with tamsulosin and trospium chloride helped to improve IPSS storage symptoms and Qol scores in prostate brachytherapy patients with LUTS compared with tamsulosin monotherapy.

Microsecond molecular dynamics simulations provide insight into the ATP-competitive inhibitor-induced allosteric protection of Akt kinase phosphorylation.

Akt is a serine/threonine protein kinase, a critical mediator of growth factor-induced survival in key cellular pathways. Allosteric signaling between protein intramolecular domains requires long-range communication mediated by hotspot residues, often triggered by ligand binding. Here, based on extensive 3 µs explicit solvent molecular dynamics (MD) simulations of Akt1 kinase domain in the unbound (apo) and ATP-competitive inhibitor, GDC-0068-bound states, we propose a molecular mechanism for allosteric regulation of Akt1 kinase phosphorylation by GDC-0068 binding to the ATP-binding site. MD simulations revealed that the apo Akt1 is flexible with two disengaged N- and C-lobes, equilibrated between the open and closed conformations. GDC-0068 occupancy of the ATP-binding site shifts the conformational equilibrium of Akt1 from the open conformation toward the closed conformation and stabilizes the closed state. This effect enables allosteric signal propagation from the GDC-0068 to the phosphorylated T308 (pT308) in the activation loop and restrains phosphatase access to pT308, thereby protecting the pT308 in the GDC-0068-bound Akt1. Importantly, functional hotspots involved in the allosteric communication from the GDC-0068 to the pT308 are identified. Our analysis of GDC-0068-induced allosteric protection of Akt kinase phosphorylation yields important new insights into the molecular mechanism of allosteric regulation of Akt kinase activity.

miRNA-133b and miRNA-135a induce apoptosis via the JAK2/STAT3 signaling pathway in human renal carcinoma cells.

Aberrantly expressed microRNAs (miRNAs) are involved in many diseases including cancer. In clear cell renal cell carcinoma (ccRCCs) expression of miR-133b and miR-135a is reduced compared to control tissue and other sarcomas but the functional effects of this downregulation are not fully understood. This study aimed at evaluating the miR-133b and miR-135a expression profiles in different RCC subtypes and the functional role of these miRNAs. Viability and apoptosis were examined in three different ccRCC cell lines (786-O, A498 and SN12-PM6) after over-expression of these miRNAs. The modulation of JAK2 and the JAK2/STAT3 pathways was determined by Western blot. Transient transfection of miR-133b and miR-135a reduced viability and induced apoptosis by inhibition of JAK2 expression and its phosphorylation and activation of caspase 3 and 7 in all three ccRCC cell lines. p-STAT3 and Bcl-2 expression was reduced after miRNA transfection whereas only slight influence on Bcl-2 L11 (BIM) was detected. Our results demonstrate that miR-133b and miR-135a which are down-regulated in wildtype and mutated ccRCCs, induce apoptosis in vitro by a signaling cascade involving JAK2, STAT3 and Bcl-2. Therefore, over-expression of these miRNAs seems to functionally counteract oncogenic signalling pathways in ccRCCs.

MicroRNA-383 expression regulates proliferation, migration, invasion, and apoptosis in human glioma cells.

This study aims to evaluate microRNA-383 (miR-383) expression level in glioma cells and its influences on proliferation, migration, invasion, apoptosis, and cell cycle in glioma cells. miR-383 expression levels were determined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Thirty BALB/c-nu mice were randomly assigned into three groups: U87-miR-383 group, vector-control group, and blank group. Tumorigenicity experiment was conducted to confirm the function of miR-383. U251 and U87 glioma cells were divided into three groups: non-transfected control cells (NT group), glioma cells transfected with miR-383 (miR-383 group), and glioma cells transfected with negative sequence (NC group). Transfection efficiency was measured by qRT-PCR. Cell counting kit-8 (CCK-8) assay was used to detect cell proliferation. Cell migration and invasion were examined by utilizing a Transwell chamber. Cell cycle and apoptosis were analyzed by flow cytometry. The qRT-PCR results revealed that miR-383 expression was down-regulated in human glioma cells, and was negatively related to the pathological grading of glioma. The rates of tumor growth in vector-control group and blank group were significantly faster than that in U87-miR-383 group, and the average tumor volume and weight in vector-control group and blank group were increased as compared with U87-miR-383 group. Additionally, miR-383 levels in miR-383 group were higher than those in NT group and NC group. CCK-8 assay indicated lower cell viability in miR-383 group as compared with NT group and NC group. Flow cytometry implied that the percentages of cells in miR-383 group reduced, while the cell apoptosis rate enhanced compared with NT group and NC group. In conclusion, our findings suggest that miR-383 expression is down-regulated in glioma cells, inhibiting cell proliferation, migration, and invasion, affecting the cell cycle, and inducing cell apoptosis.

Short-term therapeutic effects of low-dose cytarabine plus surgical resection on elderly patients with trigeminal nerve tumor and safety observation.

OBJECTIVE: To evaluate the short-term therapeutic effects of low-dose cytarabine plus surgical resection on elderly patients with trigeminal nerve tumor and to observe the safety. METHODS: A total of 120 elderly patients with trigeminal nerve tumor were divided into a treatment group and a control group by random draw (n=60), and both groups were subjected to resection by stereotactic image-guided endoscopic nasal surgery. Afterwards, the control group was administered with high-dose cytarabine while the treatment group was given low-dose cytarabine for 14 days. RESULTS: Both groups completed treatment, but the effective rate of the treatment group (96.7%) was significantly higher than that of the control group (83.3%) (P < 0.05). The pain scores of the two groups were similar at T0, T1 and T2, but the score of the treatment group at T2 was significantly different from those at T0 and T1 (P < 0.05). During treatment, the treatment group was significantly less prone to complications such as headache, vomiting, vision impairment, nausea and local swelling than the control group (P < 0.05). During three months of follow-up, the appetite, sleep and daily living scores were significantly higher than those of the control group (P < 0.05). CONCLUSION: Stereotactic image-guided surgery was able to treat trigeminal nerve tumor well, and the effect was enhanced by low-dose cytarabine that improved postoperative outcomes and quality of life by dramatically decreasing complications.