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.

A novel three-dimensional Fe3SnC/C hybrid nanofiber absorber for lightweight and highly-efficient microwave absorption.

3D Fe3SnC/C hybrid nanofibers are proposed as a novel high-performance microwave absorber. At only 20 wt% filler loading, the optimal reflection loss reaches -119.2 dB at 17.1 GHz and the effective absorption bandwidth is 7.4 GHz with a thickness of 2.3 mm, outperforming most of the reported absorbers.

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.