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To detect and analyze the changes of microorganisms in expressed prostatic secretion (EPS) of patients with IIIB prostatitis before and after low-intensity pulsed ultrasound (LIPUS) treatment, and to explore the mechanism of LIPUS in the treatment of chronic prostatitis (CP). 25 patients (study power was estimated using a Dirichlet-multinomial approach and reached 96.5% at α = 0.05 using a sample size of 25) with IIIB prostatitis who were effective in LIPUS treatment were divided into two groups before and after LIPUS treatment. High throughput second-generation sequencing technique was used to detect and analyze the relative abundance of bacterial 16 s ribosomal variable regions in EPS before and after treatment. The data were analyzed by bioinformatics software and database, and differences with P < 0.05 were considered statistically significant. Beta diversity analysis showed that there was a significant difference between groups (P = 0.046). LEfSe detected four kinds of characteristic microorganisms in the EPS of patients with IIIB prostatitis before and after LIPUS treatment. After multiple comparisons among groups by DESeq2 method, six different microorganisms were found. LIPUS may improve patients' clinical symptoms by changing the flora structure of EPS, stabilizing and affecting resident bacteria or opportunistic pathogens.
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Próstata , Prostatite , Ondas Ultrassônicas , Humanos , Masculino , Prostatite/terapia , Prostatite/microbiologia , Prostatite/metabolismo , Próstata/microbiologia , Próstata/metabolismo , Próstata/patologia , Adulto , Bactérias/metabolismo , Bactérias/genética , Pessoa de Meia-Idade , Terapia por Ultrassom/métodos , Microbiota , RNA Ribossômico 16S/genéticaRESUMO
Erectile dysfunction (ED) is one of the most common sexual disorders in males, which seriously affects the health of the patient and well-being of the family. The therapeutic strategy of ED is an individualized comprehensive treatment based on phosphodiesterase inhibitors. At present, as a new option for the treatment of ED, micro-energy medicine has attracted more and more attention in its therapeutic effects and advantages. This article presents an overview of the progress in the studies of micro-energy medicine in the treatment of ED.
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Disfunção Erétil , Disfunção Erétil/terapia , Humanos , Masculino , Tratamento por Ondas de Choque Extracorpóreas/métodos , Inibidores de Fosfodiesterase/uso terapêuticoRESUMO
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common pelvic pain syndrome in males, seriously affecting patients' quality of life. For a long time, CP/CPPS has been considered a complex and variable disease, and its pathogenesis remains incompletely understood. Currently, CP/CPPS is believed to be a group of diseases characterized by pelvic pain or discomfort, urinary abnormalities, and other symptoms, each with its unique etiology, clinical characteristics, and outcomes, likely resulting from the action of pathogens or (and) certain non-infectious factors. Traditionally, CP/CPPS was thought to be unrelated to bacterial infections. However, in recent years, with the development of microbiology and the advancement of high-throughput sequencing technology, an increasing number of studies have suggested that microorganisms in the reproductive system may play an important role in the pathogenesis of CP/CPPS. The unique characteristics of CP/CPPS, such as its refractory nature and tendency to recur, may be closely related to the microbiota and their biological functions in the reproductive system. The relationship between CP/CPPS and reproductive system microorganisms is one of the current hot topics in microbiology and urology, receiving considerable attention from scholars in recent years and making a series of new advances. Through this review, we will comprehensively explore the relationship between CP/CPPS and reproductive system microorganisms, and look forward to future research directions, aiming to provide new ideas and methods for clinical diagnosis and treatment, thereby improving the treatment outcomes and quality of life of CP/CPPS patients.
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Microbiota , Dor Pélvica , Prostatite , Prostatite/microbiologia , Humanos , Masculino , Dor Pélvica/microbiologia , Dor Pélvica/etiologia , Animais , Qualidade de Vida , Dor Crônica/microbiologia , Dor Crônica/etiologia , Genitália/microbiologia , Doença CrônicaRESUMO
Due to the non-targeted release and low solubility of anti-gastric cancer agent, apatinib (Apa), a first-line drug with long-term usage in a high dosage often induces multi-drug resistance and causes serious side effects. In order to avoid these drawbacks, lipid-film-coated Prussian blue nanoparticles (PB NPs) with hyaluronan (HA) modification was used for Apa loading to improve its solubility and targeting ability. Furthermore, anti-tumor compound of gamabufotalin (CS-6) was selected as a partner of Apa with reducing dosage for combinational gastric therapy. Thus, HA-Apa-Lip@PB-CS-6 NPs were constructed to synchronously transport the two drugs into tumor tissue. In vitro assay indicated that HA-Apa-Lip@PB-CS-6 NPs can synergistically inhibit proliferation and invasion/metastasis of BGC-823 cells via downregulating vascular endothelial growth factor receptor (VEGFR) and matrix metalloproteinase-9 (MMP-9). In vivo assay demonstrated strongest anti-tumor growth and liver metastasis of HA-Apa-Lip@PB-CS-6 NPs administration in BGC-823 cells-bearing mice compared with other groups due to the excellent penetration in tumor tissues and outstanding synergistic effects. In summary, we have successfully developed a new nanocomplexes for synchronous Apa/CS-6 delivery and synergistic gastric cancer (GC) therapy.
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Spermatogonial stem cells (SSCs) are capable of transmitting genetic information to the next generations and they are the initial cells for spermatogenesis. Nevertheless, it remains largely unknown about key genes and signaling pathways that regulate fate determinations of human SSCs and male infertility. In this study, we explored the expression, function, and mechanism of USP11 in controlling the proliferation and apoptosis of human SSCs as well as the association between its abnormality and azoospermia. We found that USP11 was predominantly expressed in human SSCs as shown by database analysis and immunohistochemistry. USP11 silencing led to decreases in proliferation and DNA synthesis and an enhancement in apoptosis of human SSCs. RNA-sequencing identified HOXC5 as a target of USP11 in human SSCs. Double immunofluorescence, Co-immunoprecipitation (Co-IP), and molecular docking demonstrated an interaction between USP11 and HOXC5 in human SSCs. HOXC5 knockdown suppressed the growth of human SSCs and increased apoptosis via the classical WNT/ß-catenin pathway. In contrast, HOXC5 overexpression reversed the effect of proliferation and apoptosis induced by USP11 silencing. Significantly, lower levels of USP11 expression were observed in the testicular tissues of patients with spermatogenic disorders. Collectively, these results implicate that USP11 regulates the fate decisions of human SSCs through the HOXC5/WNT/ß-catenin pathway. This study thus provides novel insights into understanding molecular mechanisms underlying human spermatogenesis and the etiology of azoospermia and it offers new targets for gene therapy of male infertility.
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Apoptose , Proliferação de Células , Espermatogênese , Tioléster Hidrolases , Via de Sinalização Wnt , Humanos , Masculino , Células-Tronco Germinativas Adultas/metabolismo , Apoptose/genética , Azoospermia/metabolismo , Azoospermia/genética , Azoospermia/patologia , beta Catenina/metabolismo , beta Catenina/genética , Proliferação de Células/genética , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Espermatogênese/genética , Espermatogônias/metabolismo , Espermatogônias/citologia , Testículo/metabolismo , Testículo/citologia , Tioléster Hidrolases/genética , Tioléster Hidrolases/metabolismo , Via de Sinalização Wnt/genéticaRESUMO
This study aimed to investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on erectile function in Chinese patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). A retrospective study was conducted on 657 CP/CPPS patients who visited The Third Xiangya Hospital of Central South University (Changsha, China) from November 2018 to November 2022. Patients were divided into two groups based on the timeline before and after the COVID-19 outbreak in China. The severity of CP/CPPS, penile erection status, anxiety, and depression was evaluated using the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), International Index of Erectile Function-5 (IIEF-5), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) scales, respectively. Compared with patients before the COVID-19 outbreak, more CP/CPPS patients developed severe erectile dysfunction (ED) due to depression and anxiety caused by the pandemic. After developing moderate-to-severe ED, mild and moderate-to-severe CP/CPPS patients exhibited more apparent symptoms of anxiety and depression ( P < 0.001 and P = 0.001, respectively), forming a vicious cycle. The COVID-19 pandemic has adversely affected the psychological status of CP/CPPS patients, exacerbating their clinical symptoms and complicating ED. The exacerbation of clinical symptoms further worsens the anxiety and depression status of patients, forming a vicious cycle. During the COVID-19 pandemic, paying more attention to the mental health of CP/CPPS patients, strengthening psychological interventions, and achieving better treatment outcomes are necessary.
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COVID-19 , Disfunção Erétil , Prostatite , Masculino , Humanos , Disfunção Erétil/etiologia , Pandemias , Ereção Peniana , Prostatite/complicações , Estudos Retrospectivos , População do Leste Asiático , COVID-19/complicações , Doença Crônica , Dor Pélvica/complicaçõesRESUMO
Objective: To explore whether type III prostatitis is related to bacterial infection by detecting the composition and function of microorganisms in expressed prostatic secretion (EPS) of patients with chronic prostatitis (CP) and healthy people. Methods: According to the inclusion and exclusion criteria, 57 subjects were included in our study, divided into the healthy group, type II prostatitis group, and type III prostatitis group. 16s rRNA sequencing technique was used to detect and analyze the microbial composition of EPS in each group. Additionally, the metagenomics sequencing technique was used to further explore the function of different bacteria in the type III prostatitis group. Data analysis was performed by bioinformatics software, and the results were statistically significant when P<0.05. Results: Many microorganisms exist in EPS in both CP patients and healthy populations. However, the relative abundance of Pseudomonas, Haemophilus, Sneathia, Allobaculum, and Enterococcus in CP patients (including type II and III) were significantly different. Still, the relative abundance of different bacteria in type II prostatitis patients was much higher than in type III. The metagenomics sequencing results for the type III prostatitis group showed that the different bacteria had certain biological functions. Conclusion: Based on our sequencing results and previous studies, we suggest that type III prostatitis may also be caused by bacterial infection.
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Infecções Bacterianas , Prostatite , Masculino , Humanos , Prostatite/complicações , Prostatite/diagnóstico , RNA Ribossômico 16S/genética , Doença Crônica , Infecções Bacterianas/complicações , Infecções Bacterianas/microbiologia , Bactérias/genéticaRESUMO
Adrenocortical carcinoma (ACC) has a low incidence but a poor prognosis. And ACC has complex clinical manifestations and limited treatment. Pyroptosis has a dual character and has both positive and negative effects on cancer. However, the role of pyroptosis-related genes (PRGs) in ACC and the impact on ACC progression remains unelucidated. This study performed systematic bioinformatics analysis and basic experimental validation to enable the establishment of prognostic models and demonstrate levels of immune infiltration. Pearson's correlation analysis was used to assess the association of PRGs with tumor immune infiltration, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoints. There 4 PRGs were upregulated, and 25 PRGs were downregulated in ACC. At the same time, we analyzed and reviewed the genetic mutation variation landscape of PRGs. Functional enrichment analysis was also performed to clarify the function of PRGs. Pyroptosis, the inflammatory response, the Toll-like receptor signaling pathway, and the NOD-like receptor signaling pathway are the functions and pathways mainly involved and exerted effects by these 33 PRGs. The results of the prognosis analysis revealed high expression of CASP3, CASP9, GSDMB, GSDMD, NLRC4, PRKACA, and SCAF11 caused a poor survival rate for ACC patients. The above seven PRGs were screened by the optimal λ value of LASSO Cox analysis, and the five selected genes (CASP3, CASP9, GSDMB, GSDMD, NLRC4) were involved in constructing a prognostic PRGs model which enables the overall survival in ACC patients can be predicted with moderate to high accuracy. Prognostic PRGs, especially CASP9, which is the independent factor of ACC prognosis, may be closely correlated with immune-cell infiltration, tumor mutation burden, microsatellite instability, and immune checkpoints. Quantitative Real-Time PCR (qRT-PCR), Western blot and immunohistochemical were performed to validate the mRNA expression levels of CASP9 in adjacent normal tissues and ACC tissues. According to the result of immune checkpoints analysis, NLRC4 and GSDMB may be identified as potential therapeutic targets. In conclusion, we established a prognostic model of PRG characteristics in ACC and analyzed the relationship between PRGs and immune infiltration. Through our study, it may be helpful to find the mechanism of pyroptosis in ACC.
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Objective: To assess the value of using the prognostic nutritional index (PNI) and serum albumin/globulin ratio (AGR) in predicting the overall survival (OS) of patients with penile cancer (PC) undergoing penectomy. Materials and methods: A retrospective analysis of 123 patients who were admitted to our hospital due to PC from April 2010 to September 2021 and who underwent penectomy were included in the study. The optimal cut-off value of the PNI and AGR was determined by receiver operating characteristic curve analysis. Kaplan-Meier analysis and the Cox proportional hazard model were used to evaluate the correlation between the PNI, AGR, and OS in patients with PC. Results: A total of 16 of the 123 patients died during the follow-up period, and the median follow-up time was 58.0 months. The best cut-off values of the PNI and AGR were set to 49.03 (95% confidence interval 0.705-0.888, Youden index = 0.517, sensitivity = 57.9%, specificity = 93.7%, p < 0.001) and 1.28 (95% confidence interval 0.610-0.860, Youden index = 0.404, sensitivity = 84.1%, specificity = 56.2%, p = 0.003). The Kaplan-Meier analysis showed that the OS of the patients in the high PNI group and the high AGR group was significantly higher than that of the patients in the low PNI group and the low AGR group (p < 0.001). The univariable analysis showed that the aCCI, the clinical N stage, the pathological stage, and the PNI, AGR, SII, and PLR are all predictors of OS in patients with PC (p < 0.05). The multivariable analysis showed that the PNI (risk rate [HR] = 0.091; 95% CI: 0.010-0.853; p = 0.036) and the AGR (risk rate [HR] = 0.171; 95% CI: 0.043-0.680; p = 0.012) are independent prognostic factors for predicting OS in patients with PC undergoing penectomy. Conclusions: Both the PNI score and the serum AGR are independent prognostic factors for predicting OS in patients with PC undergoing penectomy.
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Globulinas , Neoplasias Penianas , Masculino , Humanos , Avaliação Nutricional , Prognóstico , Neoplasias Penianas/cirurgia , Estudos Retrospectivos , Albumina Sérica/análise , Globulinas/análiseRESUMO
[This retracts the article DOI: 10.3892/etm.2018.6537.].
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Gastric cancer (GC) is a serious affliction worldwide and remains to be the fourth most common cancer with poor prognosis, especially in advanced stage. Chemotherapy is one of the main therapeutic means. The purpose of this study was to investigate the antitumor effects of Schisandrin B (Sch B) on GC cells both in vitro and in vivo, as well as the synergistic effect with 5-fluorouracil (5-FU), and to preliminarily explore the relevant mechanism of action. Our results showed that Sch B inhibited the growth, migration and invasion of GC cells. Besides, Sch B could effectively inhibit the phosphorylation of STAT3 (signal transducer and activator of transcription 3), induce autophagy, and enhance the efficacy of chemotherapy drug 5-FU in vitro and in vivo. Taken together, the findings indicate that Sch B displays potent antitumor activities. The co-administration of Sch B and 5-FU might be a promising way for future therapy of GC.
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Neoplasias Gástricas , Apoptose , Linhagem Celular Tumoral , Ciclo-Octanos , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Lignanas , Compostos Policíclicos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologiaRESUMO
Postfinasteride syndrome (PFS) is a term coined to characterize a constellation of reported undesirable sexual, physical, and neuropsychiatric side effects. In the present study, we conducted the meta-analysis to demonstrate whether the use of 5α-reductase inhibitors (5ARIs) increases the risk of PFS-like adverse effects. A search of studies published until May 10, 2020, was performed using PubMed, EMBASE, and the Cochrane Library. We included randomized controlled trials with at least one comparison between male patients receiving 5ARIs versus placebo for the treatment of benign prostatic hyperplasia (BPH) or androgenetic alopecia (AGA), and identified 34 studies from 28 articles that met our eligibility criteria. In the random-effects model, the overall use of 5ARIs exhibited a 1.87-fold risk of PFS-like adverse effects during the trial (95% confidence interval [CI]: 1.64-2.14). Regarding specific types of adverse effects, the use of 5ARIs had a 1.89-fold risk of sexual adverse effects (95% CI: 1.74-2.05) and was associated with an increased risk of physical adverse effects (relative risk [RR]: 1.31, 95% CI: 0.80-2.15), albeit without statistical significance. This meta-analysis helped to better define the adverse effects caused by 5ARIs. We concluded that the overall use of 5ARIs significantly increased the risk of PFS-like adverse effects in men with AGA or BPH during treatment. Enhanced awareness of and education on the PFS-like adverse effects are necessary for clinicians.
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Inibidores de 5-alfa Redutase , Hiperplasia Prostática , Inibidores de 5-alfa Redutase/efeitos adversos , Humanos , Masculino , Oxirredutases/farmacologia , Oxirredutases/uso terapêutico , Hiperplasia Prostática/complicações , Hiperplasia Prostática/tratamento farmacológico , Comportamento SexualRESUMO
OBJECTIVE: To evaluate the prognostic nutritional index (PNI) in predicting the biochemical recurrence (BCR) of patients treated with robot-assisted laparoscopic radical prostatectomy (RALP). METHODS: The clinical data of 136 patients treated with RALP in the Department of Urology, The Third Xiangya Hospital of Central South University were retrospectively analyzed. The endpoint of observation was BCR. The area under the receiver operating characteristic (ROC) curve was evaluated to determine the optimal cutoff value of PNI. The correlation of the PNI with BCR was estimated using Kaplan-Meier analysis and Cox proportional hazards model. RESULTS: The optimal cutoff value of the PNI was 46.03 according to the ROC curve. (95% confidence interval: 0.604-0.805, Youden index = 0.401, sensitivity = 82.5%, specificity = 57.6%, p < 0.01). Multivariate Cox analysis showed that clinical staging, prostate-specific antigen, and PNI were independent prognostic factors for predicting BCR in patients treated with RALP. CONCLUSION: PNI is an independent prognostic factor for predicting BCR in patients treated with RALP. The incorporation of the PNI into risk assessments may provide additional prognostic information.
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Recidiva Local de Neoplasia , Avaliação Nutricional , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Idoso , Biomarcadores/sangue , China/epidemiologia , Humanos , Masculino , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/diagnóstico , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Medição de Risco/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To explore the mechanism of the action of the miR-576/ALK4 axis on the progression of prostate cancer (PCa). METHODS: PCa cells were transfected with miR-576 mimics/inhibitor, the proliferation and migration distance of the cells were detected by MTT and scratch wound healing assay, respectively. The targeted regulation effect of miR-576 on ALK4 was verified by dual-luciferase reporter assay. The effects of miR-576 on the mRNA and protein expressions and phosphorylation levels of the ALK4 and JAK/STAT signaling pathway factors JAK2 and STAT3 were determined by qPCR and Western blot, respectively. The C4-2 cells were co-treated with sh-ALK4 and Ruxolitinib for measurement of the proliferation and migration of the PCa cells. RESULTS: Bioinformatics analysis and binding site prediction showed that miR-576 was up-regulated in the PCa cells, and dual-luciferase reporter assay revealed its targeted regulation effect on ALK4 and its impact on the phosphorylation levels of JAK2 and STAT3. Overexpressed miR-576 promoted while knocked-down miR-576 inhibited the proliferation and migration of the PCa cells. sh-ALK4 increased the proliferation and migration of the cells, while Ruxolitinib suppressed the promoting effect of sh-ALK4. CONCLUSION: The expression of miR-576 is up-regulated in PCa, inhibits the expression of ALK4, regulates the activity of the JAK and STAT signaling pathways, and promotes the proliferation and migration of PCa cells.
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MicroRNAs , Neoplasias da Próstata , Masculino , Humanos , MicroRNAs/genética , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células , Transdução de Sinais , Neoplasias da Próstata/genética , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genéticaRESUMO
OBJECTIVE: To explore the clinical features, treatment and prognosis of ductal adenocarcinoma of the prostate (DAP) and get a deeper insight into the malignancy. METHODS: We retrospectively studied the clinical data on 45 cases of confirmed DAP, 26 in the high-risk group and 19 in the medium-risk group, treated from January 2013 to September 2020. We compared the time and rate of biochemical recurrence and the rate of imaging progression between the two groups of patients, and evaluated the effect of palliative transurethral bipolar plasma resection of the prostate (pTU-PKRP) on the lower urinary tract symptoms (LUTS). RESULTS: Of the 45 cases of DAP, 4 (8.9%) were of the simple type, and 41 (91.1%) complicated by prostatic acinar carcinoma (PAA). And of the latter 41 cases, 9 (21.9%) were complicated by neuroendocrine differentiation and another 4 (9.8%) by intraductal carcinoma. The time to biochemical recurrence was longer in the medium-risk than in the high-risk group (P < 0.05). No statistically significant differences were observed in the rates of biochemical recurrence and imaging progression between the two groups (P > 0.05). The maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), IPSS and QOL of the patients were significantly improved at 6 months after pTU-PKRP compared with the baseline (P < 0.05). CONCLUSION: Radical prostatectomy can improve the prognosis of early DAP, while for advanced DAP with serious LUTS, pTU-PKRP can improve the quality of life of the patients.
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Adenocarcinoma , Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Neoplasias da Próstata , Ressecção Transuretral da Próstata , Masculino , Humanos , Próstata/patologia , Qualidade de Vida , Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata/métodos , Estudos Retrospectivos , Neoplasias da Próstata/patologia , Resultado do Tratamento , Sintomas do Trato Urinário Inferior/patologia , Adenocarcinoma/cirurgiaRESUMO
BACKGROUND: For certain human cancers, sperm associated antigen 5 (SPAG5) exerts important functions for their development and progression. However, whether RNA interference (RNAi) targeting SPAG5 has antitumor effects has not been determined clinically. RESULTS: The results indicated that Fe-doped chrysotile nanotubes (FeSiNTs) with a relatively uniform outer diameter (15-25 nm) and inner diameter (7-8 nm), and a length of several hundred nanometers, which delivered an siRNA against the SPAG5 oncogene (siSPAG5) efficiently. The nanomaterials were designed to prolong the half-life of siSPAG5 in blood, increase tumor cell-specific uptake, and maximize the efficiency of SPAG5 silencing. In vitro, FeSiNTs carrying siSPAG5 inhibited the growth, migration, and invasion of bladder cancer cells. In vivo, the FeSiNTs inhibited growth and metastasis in three models of bladder tumors (a tail vein injection lung metastatic model, an in-situ bladder cancer model, and a subcutaneous model) with no obvious toxicities. Mechanistically, we showed that FeSiNTs/siSPAG5 repressed PI3K/AKT/mTOR signaling, which suppressed the growth and progression of tumor cells. CONCLUSIONS: The results highlight that FeSiNTs/siSPAG5 caused no activation of the innate immune response nor any systemic toxicity, indicating the possible therapeutic utility of FeSiNTs/siSPAG5 to deliver siSPAG5 to treat bladder cancer.
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Asbestos Serpentinas/farmacologia , Proteínas de Ciclo Celular/genética , Nanotubos/química , RNA Interferente Pequeno/química , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Inativação Gênica , Terapia Genética/métodos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Interferência de RNA , Ratos , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologiaRESUMO
Clinically, patients with urothelial carcinoma of the bladder (UCB) with tumor metastasis are incurable. To find new therapeutic strategies, the mechanisms underlying UCB invasion and metastasis should be further investigated. In this study, zinc finger and homeobox 3 (ZHX3) was first screened as a critical oncogenic factor associated with poor prognosis in a UCB dataset from The Cancer Genome Atlas (TCGA). These results were also confirmed in a large cohort of clinical UCB clinical samples. Next, we found that ZHX3 could promote the migration and invasion capacities of UCB cells both in vitro and in vivo. Mechanistically, coimmunoprecipitation (coIP) and mass spectrometry (MS) analysis indicated that ZHX3 was a target of tripartite motif 21 (TRIM21), which mediates its ubiquitination, and subsequent degradation. Notably, RNA-seq analysis showed that ZHX3 repressed the expression of regulator of G protein signaling 2 (RGS2). Generally, our results suggest that ZHX3 plays an oncogenic role in UCB pathogenesis and might serve as a novel therapeutic target for UCB.
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Carcinoma de Células de Transição/metabolismo , Proteínas de Homeodomínio/metabolismo , Proteínas RGS/metabolismo , Proteínas Repressoras/metabolismo , Ribonucleoproteínas/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Animais , Carcinoma de Células de Transição/etiologia , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/secundário , Linhagem Celular Tumoral , Movimento Celular , Progressão da Doença , Regulação para Baixo , Feminino , Proteínas de Homeodomínio/genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/metabolismo , Prognóstico , Proteínas RGS/genética , RNA Interferente Pequeno , Proteínas Repressoras/genética , Ubiquitinação , Regulação para Cima , Neoplasias da Bexiga Urinária/etiologia , Neoplasias da Bexiga Urinária/patologia , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
Purpose: Benign prostatic hyperplasia-associated massive hemorrhage is a urological emergency. We evaluated the outcome from immediate transurethral plasma kinetic enucleation of the prostate gland (i-TUPKEP) for BHM treatment. Methods: We retrospectively analyzed the records of 49 patients with acute BMH who underwent i-TUPKEP between January 2014 and November 2018 at our institution. The hemostatic effect, International Prostate Symptom Score (IPSS), and quality of life (QoL) score were evaluated preoperatively as well as 3, 6, and 12 months postoperatively. Postoperative follow-up also included measurement of the peak flow rate (Qmax) and post-void residual urine volume (PVR). Clinical characteristics, weight of resected tissue, duration of bladder irrigation, duration of hospital stay, complications, as well as the time required for enucleation and resection, were recorded. Results: BMH causes were attributed to transurethral surgery (17/49, 34.7%), violent catheterization (13/49, 26.5%), cystoscopy (10/49, 20.4%), and urethral dilatation (9/49, 18.4%). Bleeding was from different sites of prostate-gland tissues during i-TURKEP. i-TUPKEP-controlled BMH effectively induced immediate, notable, and lasting improvements in the IPSS and QoL score. Qmax was close to normal, and the PVR was within the physiological range, postoperatively. Long-term complications were not observed. Conclusion: Our preliminary data suggest that i-TUPKEP is a feasible method for controlling BHM and relieving BPH symptoms.
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Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms are common clinical concerns that affect aging men all over the world. The underlying molecular and cellular mechanisms remain elusive. Over the past few years, a number of animal models of BPH, including spontaneous model, BPH-induction model, xenograft model, metabolic syndrome model, mechanical obstruction model, and transgenic model, have been established that may provide useful tools to fill these critical knowledge gaps. In this review, we therefore outlined the present status quo for animal models of BPH, comparing the pros and cons with respect to their ability to mimic the etiological, histological, and clinical hallmarks of BPH and discussed their applicability for future research.