RESUMEN
Non-covalent complexes of glycolytic enzymes, called metabolons, were postulated in the 1970s, but the concept has been controversial. Here we show that a c-Myc-responsive long noncoding RNA (lncRNA) that we call glycoLINC (gLINC) acts as a backbone for metabolon formation between all four glycolytic payoff phase enzymes (PGK1, PGAM1, ENO1, and PKM2) along with lactate dehydrogenase A (LDHA). The gLINC metabolon enhances glycolytic flux, increases ATP production, and enables cell survival under serine deprivation. Furthermore, gLINC overexpression in cancer cells promotes xenograft growth in mice fed a diet deprived of serine, suggesting that cancer cells employ gLINC during metabolic reprogramming. We propose that gLINC makes a functional contribution to cancer cell adaptation and provide the first example of a lncRNA-facilitated metabolon.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Proteínas Portadoras/metabolismo , Proteínas de Unión al ADN/metabolismo , Glucólisis , Proteínas de la Membrana/metabolismo , Neoplasias/enzimología , Fosfoglicerato Quinasa/metabolismo , Fosfoglicerato Mutasa/metabolismo , Fosfopiruvato Hidratasa/metabolismo , ARN Largo no Codificante/metabolismo , Hormonas Tiroideas/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Biomarcadores de Tumor/genética , Proteínas Portadoras/genética , Proliferación Celular , Proteínas de Unión al ADN/genética , Femenino , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Células HeLa , Células Hep G2 , Humanos , L-Lactato Deshidrogenasa/genética , L-Lactato Deshidrogenasa/metabolismo , Proteínas de la Membrana/genética , Ratones Desnudos , Complejos Multienzimáticos , Neoplasias/genética , Neoplasias/patología , Fosfoglicerato Quinasa/genética , Fosfoglicerato Mutasa/genética , Fosfopiruvato Hidratasa/genética , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , ARN Largo no Codificante/genética , Serina/deficiencia , Hormonas Tiroideas/genética , Carga Tumoral , Proteínas Supresoras de Tumor/genética , Proteínas de Unión a Hormona TiroideRESUMEN
Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS), a prevalent urological ailment, exerts a profound influence upon the well-being of the males. Autoimmunity driven by Th17 cells has been postulated as a potential factor in CP/CPPS pathogenesis. Nonetheless, elucidating the precise mechanisms governing Th17 cell recruitment to the prostate, triggering inflammation, remained an urgent inquiry. This study illuminated that CCL20 played a pivotal role in attracting Th17 cells to the prostate, thereby contributing to prostatitis development. Furthermore, it identified prostate stromal cells and immune cells as likely sources of CCL20. Additionally, this research unveiled that IL-17A, released by Th17 cells, could stimulate macrophages to produce CCL20 through the NF-κB/MAPK/PI3K pathway. The interplay between IL-17A and CCL20 establishes a positive feedback loop, which might serve as a critical mechanism underpinning the development of chronic prostatitis, thus adding complexity to its treatment challenges.
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Enfermedades Autoinmunes , Quimiocina CCL20 , Quimiotaxis , Interleucina-17 , Prostatitis , Células Th17 , Masculino , Prostatitis/inmunología , Prostatitis/patología , Prostatitis/metabolismo , Células Th17/inmunología , Células Th17/metabolismo , Quimiocina CCL20/metabolismo , Quimiocina CCL20/genética , Animales , Interleucina-17/metabolismo , Interleucina-17/inmunología , Ratones , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/metabolismo , Enfermedades Autoinmunes/patología , Macrófagos/metabolismo , Macrófagos/inmunología , Modelos Animales de Enfermedad , FN-kappa B/metabolismo , Transducción de Señal , Humanos , Ratones Endogámicos C57BL , Próstata/patología , Próstata/metabolismo , Próstata/inmunología , Fosfatidilinositol 3-Quinasas/metabolismo , AutoinmunidadRESUMEN
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a poorly understood disease. Accumulating evidence suggests that autoimmune dysfunction is involved in the development of CP/CPPS. Interleukin-17 (IL-17) is associated with the occurrence and development of several chronic autoimmune inflammatory diseases. However, the molecular mechanisms underlying the role of IL-17 in CP/CPPS are not clear. We confirmed that IL-17 was increased in the prostate tissues of experimental autoimmune prostatitis (EAP) mice. Corresponding to the increase of IL-17, neutrophil infiltration and the levels of CXCL1 and CXCL2 (CXC chemokine ligands 1 and 2) were also increased in the prostate of EAP. Treatment of EAP mice with an IL-17-neutralizing monoclonal antibody (mAb) decreased the number of infiltrated neutrophils and CXCL1 and CXCL2 levels. Depletion of neutrophils using anti-Ly6G antibodies ameliorated the inflammatory changes and hyperalgesia caused by EAP. Fucoidan, a could potent inhibitor of neutrophil migration, also ameliorate the manifestations of EAP. Our findings suggested that IL-17 promoted the production of CXCL1 and CXCL2, which triggered neutrophil chemotaxis to prostate tissues. Fucoidan might be a potential drug for the treatment of EAP via the effective inhibition of neutrophil infiltration.
Asunto(s)
Enfermedades Autoinmunes , Dolor Crónico , Prostatitis , Animales , Quimiocina CXCL1 , Quimiocina CXCL2 , Enfermedad Crónica , Modelos Animales de Enfermedad , Humanos , Interleucina-17 , Masculino , Ratones , Infiltración Neutrófila , Dolor Pélvico , Prostatitis/tratamiento farmacológicoRESUMEN
Prostate cancer (PCa) is a most common malignancy in males. It has a greater heterogeneity than other cancers, which poses a real challenge to the clinical diagnosis, classification and prognostic monitoring. At present, high-, medium- and low-risk PCa patients are classified mainly by Gleason scores and the PSA level, which, however, fail to reveal the diverse molecular heterogeneity and precisely distinguish the molecular subtypes of PCa. With the development of high-throughput sequencing, more and more studies on the molecular classification of the malignancy have paved the theoretical ground for the early diagnosis, efficacy prediction and individualized treatment of PCa. This study reviews the molecular classification, prognosis prediction and individualized treatment of PCa to date, hoping to contribute to the development of the precise treatment of PCa.
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Neoplasias de la Próstata , Masculino , Humanos , Pronóstico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/terapia , Clasificación del Tumor , Prostatectomía , Antígeno Prostático EspecíficoRESUMEN
OBJECTIVE: To investigate the prevalence of and risk factors for prostate calcification (PCal) in ≥40 years old males with benign prostatic enlargement (BPE) found in health checkup. METHODS: We retrospectively analyzed the data on 671 ≥40-year-old men found with BPE in health checkup and investigated the prevalence of and risk factors for PCal in BPE males aged ≥40 years by univariate and multivariate analyses. RESULTS: Among 1 582 men aged ≥40 years undergoing health checkup, 671 were found with BPE and 274 (17.3%) with both BPE and PCal. The incidence rate of PCal was 40.8% (274/671) in the BPE patients, which was increased with age (trend χ2 = 5.289, P = 0.021), with statistically significant differences in different age groups (χ2 = 9.243, P = 0.026). Significant differences were also observed in age, height, estimated glomerular filtration rate (eGFR), urine pH level and the number of cases of uneven prostatic echoes between the BPE patients with and those without PCal (P < 0.05). Logistic regression analysis showed that age (OR = 1.027, 95% CI: 1.010ï¼1.044), urine pH (OR = 1.446, 95% CI: 1.148ï¼1.823) and uneven prostatic echoes (OR = 2.150, 95% CI: 1.108ï¼4.174) were the associated factors for PCal in BPE patients aged ≥40 years. CONCLUSION: The incidence rate of PCal is high and increased with age in BPE patients aged ≥40 years, and age, urine pH and uneven prostatic echoes are associated factors for PCal in this cohort.
Asunto(s)
Próstata , Hiperplasia Prostática , Masculino , Humanos , Adulto , Estudios Retrospectivos , Prevalencia , Hiperplasia Prostática/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: A growing number of studies indicate that circular RNAs (circRNAs) play critical roles in human diseases, and show great potential as biomarkers and therapeutic targets. This study aimed to investigate the expression and function of circANKS1B in prostate cancer (PC). METHODS: The expression of circANKS1B and miR-152-3p was analyzed by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Cell migration and invasion were measured using a transwell assay. The interaction between circANKS1B and miR-152-3p was confirmed by a dual-luciferase reporter gene assay. Rescue experiments were conducted to determine whether circANKS1B regulated the invasion of PC cells via the circANKS1B-miR-152-3p-TGF-α pathway. RESULTS: The expression of circANKS1B was markedly upregulated in both PC cells and tissues. Moreover, high circANKS1B expression was associated with poor prognosis in PC patients. Dual-luciferase reporter assay indicated that circANKS1B directly bound to miR-152-3p. Furthermore, circANKS1B negatively regulated miR-152-3p expression. Knockdown of circANKS1B markedly suppressed cell migration and invasion and TGF-α expression in PC cells, whereas the effects of circANKS1B silencing were reversed by miR-152-3p deficiency. In addition, the impact of miR-152-3p silencing on invasion of circANKS1B-deficient PC cells was also abrogated by TGF-α deficiency. Overall, circANKS1B acts as a sponge for miR-152-3p to promote PC progression by upregulating TGF-α expression. CONCLUSION: Our findings reveal that circANKS1B may be a potential prognostic biomarker and therapeutic target for PC.
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Péptidos y Proteínas de Señalización Intracelular/genética , MicroARNs/fisiología , Neoplasias de la Próstata/genética , ARN Circular/fisiología , Factor de Crecimiento Transformador alfa/genética , Anciano , Línea Celular Tumoral , Movimiento Celular/genética , Progresión de la Enfermedad , Expresión Génica/fisiología , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica/genética , Células PC-3 , Pronóstico , ARN Circular/genética , Regulación hacia Arriba/genéticaRESUMEN
BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male genitourinary system disease. As a neuroendocrine hormone, melatonin possesses a variety of biological functions, among which its anti-inflammatory effects have recently drawn substantial attention. The purpose of the current research was to study the effect of melatonin on CP/CPPS and the underlying mechanisms using a mouse model of experimental autoimmune prostatitis (EAP). METHODS: The EAP mouse model was successfully established by subcutaneously injecting a mixture of prostate antigen and complete Freund's adjuvant. On Day 42, hematoxylin-eosin staining was used to evaluate the histological appearance of prostate tissues. Chronic pelvic pain development was assessed by suprapubic allodynia. The levels of inflammation-related cytokines, such as interferon-γ, interleukin (IL)-17, and IL-1ß, were detected by enzyme-linked immunosorbent assay. Then, we explored the anti-inflammatory effects of melatonin on CP/CPPS by Western blotting and immunohistochemical staining, by measuring the expression of silent information regulator 1 (Sirt1) and NLRP3 inflammasome-related proteins in EAP mice. RESULTS: The EAP model mice exhibited severe diffuse leukocyte infiltration and significantly increased pelvic pain compared to the control mice. In the melatonin treatment group, the histological appearance of the prostate tissues, pelvic pain development, and the levels of proinflammatory cytokines were significantly alleviated compared to the EAP + dimethyl sulfoxide group. Furthermore, we found that the protective effects of melatonin were achieved through activation of the Sirt1 pathway and downregulation of the NLRP3 inflammasome. CONCLUSIONS: The results indicated that melatonin could attenuate prostate inflammation and pelvic pain by inhibiting the NLRP3 inflammasomes signaling pathway through the activation of Sirt1 in mice with EAP, and these efforts should provide a promising therapeutic strategy for CP/CPPS.
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Antiinflamatorios/uso terapéutico , Inflamasomas/metabolismo , Melatonina/uso terapéutico , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Dolor Pélvico/tratamiento farmacológico , Prostatitis/tratamiento farmacológico , Sirtuina 1/metabolismo , Animales , Antiinflamatorios/farmacología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Masculino , Melatonina/farmacología , Ratones , Dimensión del Dolor , Dolor Pélvico/metabolismo , Prostatitis/metabolismoRESUMEN
Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) is a complicated syndrome characterized by genitourinary pain in the absence of bacterial infection. Th17 cell-driven autoimmunity has been proposed as a cause of CP/CPPS. However, the factors that promote Th17-driven autoimmunity in experimental autoimmune prostatitis (EAP) and the molecular mechanisms are still largely unknown. Here, we showed that Th17 cells were excessively activated, and blockade of IL-17A could effectively ameliorate various symptoms in EAP. Furthermore, we revealed that calcium/calmodulin-dependent kinase ⠣ (CaMK4), especially Thr196 p-CaMK4 was increased in the Th17 cells of the EAP group, which were activated by intracellular cytosolic Ca2+ . Pharmacologic and genetic inhibition of CaMK4 decreased the proportion of Th17 cells, and the protein and mRNA level of IL-17A, IL-22, and RORγt. The phosphorylation of CaMK4 was dependent on the increase in intracellular cytosolic Ca2+ concentration in Th17 cells. A mechanistic study demonstrated that inhibition of CaMK4 reduced IL-17A production by decreasing the phosphorylation of Akt-mTOR, which was well accepted to positively regulate Th17 differentiation. Collectively, our results demonstrated that Ca2+ -CaMK4-Akt/mTOR-IL-17A axis inhibition may serve as a promising therapeutic strategy for CP/CPPS.
Asunto(s)
Enfermedades Autoinmunes/inmunología , Proteína Quinasa Tipo 4 Dependiente de Calcio Calmodulina/metabolismo , Activación de Linfocitos , Prostatitis/inmunología , Transducción de Señal , Células Th17/inmunología , Animales , Calcio/metabolismo , Proteína Quinasa Tipo 4 Dependiente de Calcio Calmodulina/genética , Interleucina-17/metabolismo , Interleucinas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Interleucina-22RESUMEN
OBJECTIVE: To investigate the efficiency and complications of modified urethral reconstruction with lingual mucosa in the treatment of complicated anterior urethral stricture (CAUS). METHODS: We retrospectively studied the clinical data on 10 cases of CAUS treated by modified urethral reconstruction with lingual mucosa from December 2017 to June 2019 concerning the age of the patients and the causes, location and length of urethral stricture. We statistically analyzed the pre- and post-operative maximum urine flow rate (Qmax), scores on Mental Status Scale in Non-psychiatric Settings (MSSNS) and quality of life (QOL) scores and observed post-operative complications such as abnormal taste, tongue numbness, urinary tract infection, urethral diverticulum, and urethral stricture. RESULTS: Compared with the baseline, Qmax was significantly improved and the MSSNS and QOL scores dramatically decreased at 3, 6 and 12 months after surgery (P < 0.01). Paraurethral infection developed in 1 case postoperatively, which was cured after dressing change, external urethral orifice stenosis occurred in another, which was improved after regular urethral orifice expansion, and mild tongue numbness was found in 2 cases at 1 month but gradually restored to abnormal. Urethrography showed no urethral diverticulum before catheter removal. CONCLUSIONS: Lingual mucosa is an ideal alternative material for urethral reconstruction in the treatment of CAUS, and lateral lingual mucosa can be easily obtained. Modified urethral reconstruction by embedding lingual mucosa in the dorsal base of the urethra, with the advantages of definite effectiveness and few postoperative complications, is worthy of clinical application.
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Estrechez Uretral , Humanos , Masculino , Membrana Mucosa , Calidad de Vida , Estudios Retrospectivos , Lengua , Uretra , Estrechez Uretral/etiología , Estrechez Uretral/cirugíaRESUMEN
BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disease in males. Eriocalyxin B (EriB), a natural diterpenoid purified from Isodon eriocalyx var. laxiflora, was previously reported to have antitumor effects via multiple immune-related pathways. In this study, we investigated the effect of EriB on CP/CPPS using a mouse model of experimental autoimmune prostatitis (EAP) and explored its potential mechanisms. METHODS: The EAP model was established in nonobese diabetic mice by intradermal injecting a mixture of prostate antigens and Complete Freund's Adjuvant on days 0 and 28. Then, EAP mice received daily intraperitoneal injections of EriB (5 or 10 mg/kg/d) for 14 days, from days 28 to 42 (EAP+EriB5 or EAP+EriB10 groups). The histopathological appearance of the prostate tissues was evaluated. Chronic pelvic pain development was assessed by cutaneous allodynia. Inflammatory cytokines were measured by enzyme-linked immunosorbent assay tests. We then explored anti-inflammatory potential mechanisms of EriB by studying the effects of PI3K inhibitor wortmannin (EAP+EriB10+Wort group) and NF-κB inhibitor SC75741 (EAP+EriB10+SC group) on prostate inflammation and pelvic pain using this model. RESULTS: Histological analyses revealed significant prostate inflammation in EAP mice compared with control mice. Significantly increased pelvic pain was detected in EAP mice (P < .05). Compared with the EAP+Veh group, chronic pain development, histological appearance, and cytokine levels demonstrated that EriB could alleviate the severity of EAP in a dose-dependent manner though upregulation of the PI3K/Akt/mTOR pathway and downregulation of the NF-κB pathway. Further mechanism research demonstrated that the PI3K/AKT/mTOR pathway could be blocked by wortmannin, but was not affected by SC75741. In addition, the NF-κB pathway could be further inhibited by SC75741 compared with the EAP+EriB10+Veh group. However, wortmannin could reactivate the NF-κB pathway, indicating that the PI3K/AKT/mTOR pathway negatively regulates the NF-κB pathway during EriB treatment. CONCLUSIONS: The results of the present study suggested that EriB could alleviate the severity of prostatic inflammation and pelvic pain in an EAP mouse model. These findings may broaden the value of EriB as a promising candidate for the treatment of CP/CPPS.
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Diterpenos/uso terapéutico , Dolor Pélvico/tratamiento farmacológico , Próstata/efectos de los fármacos , Prostatitis/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Diterpenos/farmacología , Masculino , Ratones , FN-kappa B/antagonistas & inhibidores , Dolor Pélvico/patología , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Próstata/patología , Prostatitis/patología , Transducción de Señal/efectos de los fármacos , Wortmanina/farmacologíaRESUMEN
BACKGROUND: Depressive symptoms are found in approximately 78% of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) patients, but the pathological mechanisms remain unknown. Increasing evidence suggests that abnormal gut microbiota may play an important role in depression. Thus, we aimed to investigate whether gut microbiota contributes to CP/CPPS-associated depression by using a mouse model of experimental autoimmune prostatitis (EAP). METHODS: Male nonobese diabetic mice were immunized twice by subcutaneous injection of prostate antigen and adjuvant. Behavioral tests consisted of an open field test, sucrose preference test, forced swimming tests, and tail suspension test was used to confirm the depression-like symptoms that were induced by EAP. Then, fecal samples were collected, and 16S ribosomal RNA gene sequencing was performed to detect differences in gut microbiota composition between control and EAP group. Additionally, fecal bacteria from the control and EAP mice were transplanted into antibiotics-induced pseudo-germ-free mice to investigate the effects on host behaviors and the composition of gut bacteria. RESULTS: EAP was successfully established and exhibited depressive-like behaviors in mice. The 16S rRNA analysis of fecal samples indicated the abnormal composition of gut microbiota in the EAP mice compared to the control mice. In the fecal microbiota transplant study, antibiotics-treated pseudo-germ-free mice presented depressive states as compared to naïve mice. Fecal bacteria transplant from EAP mice, but not from control mice, into the pseudo-germ-free mice, significantly exaggerated host depression-like behaviors. Moreover, fecal bacteria transplants from control and EAP mice induced distinct alterations in α-diversity and ß-diversity indices. In all, 24 bacteria at six phylogenetic levels were remarkably changed by the fecal bacteria transplantation. CONCLUSIONS: Abnormal gut microbiota composition after EAP induction may contribute to the development of depression in mice. A therapeutic strategy that targets gut microbiota may provide an alternative treatment for alleviating this condition.
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Conducta Animal/fisiología , Depresión/microbiología , Microbioma Gastrointestinal/fisiología , Prostatitis/microbiología , Prostatitis/psicología , Animales , Antibacterianos/farmacología , Enfermedad Crónica , Depresión/inmunología , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/inmunología , Masculino , Ratones , Ratones Endogámicos NOD , Prostatitis/inmunología , Distribución AleatoriaRESUMEN
OBJECTIVE: To evaluate the clinical effect and safety of transurethral 180 W front-firing GreenLight laser vaporization of the prostate (PVP) in the treatment of benign prostatic hyperplasia (BPH). METHODS: A total of 61 BPH patients underwent 180W front-firing GreenLight laser PVP (n = 30, the PVP group) or transurethral plasmakinetic resection of the prostate (n = 31, the control group) from March to December 2019. We collected the pre-, intra- and post-operative clinical data and compared them between the two groups of patients. RESULTS: Operations were successfully completed in all the cases with no blood transfusion or serious complications. Compared with the controls, the patients of the PVP group showed remarkably less intra-operative blood loss (ï¼»62.3 ± 15.9ï¼½ vs ï¼»48.8 ± 9.6ï¼½ ml, P < 0.05), shorter operation time (ï¼»75.0 ± 9.9ï¼½ vs ï¼»57.5 ± 19.0ï¼½ min, P < 0.05), postoperative bladder lavage time (ï¼»64.4 ± 10.5ï¼½ vs ï¼»25.2 ± 11.5ï¼½ h, P < 0.05), catheter-indwelling time (ï¼»5.1 ± 0.5ï¼½ vs ï¼»2.5 ± 0.5ï¼½ d, P < 0.05) and hospitalization time (ï¼»7.3 ± 1.7ï¼½ vs ï¼»4.1 ± 0.6ï¼½ d, P < 0.05), and a lower incidence of postoperative hematuria (12.9% ï¼»4/31ï¼½ vs 0% ï¼»0/30ï¼½, P < 0.05). No statistically significant differences, however, were found between the two groups in the incidence rates of capsular perforation, transurethral resection syndrome (TURS), urinary incontinence, urethral stricture and post-extubation urinary retention. Significant improvement was observed in IPSS, QOL, Qmax and PVR in both groups post-operatively (P < 0.05). CONCLUSIONS: Compared with transurethral plasmakinetic resection of the prostate, 180W front-firing GreenLight laser PVP, with the advantages of less bleeding, shorter catheter-indwelling time and faster recovery, is safer and more effective for the treatment of BPH, with no need for drug withdrawal for those taking anticoagulants, and especially applicable to the elderly and high-risk patients.
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Terapia por Láser , Hiperplasia Prostática , Anciano , Humanos , Masculino , Hiperplasia Prostática/cirugía , Calidad de Vida , Resección Transuretral de la Próstata , Resultado del TratamientoRESUMEN
OBJECTIVE: To find the causes of the failure in the first catheter removal (CR) after transurethral resection of the prostate (TURP) and the related risk factors. METHODS: We collected the clinical data on 285 BPH patients treated by TURP from June 2015 to May 2018. We divided the cases into a successful CR (SCR) and a failed CR (FCR) group and investigated the risk factors for the first CR after TURP by multivariate logistic regression analysis. RESULTS: CR was successfully performed in 246 and failed in 39 of the 285 cases. In the FCR group, post-CR urinary retention occurred in 15 cases immediately after, severe urinary tract irritation in 13, massive gross hematuria in 7 and urinary incontinence in 4 within 1 month. Multivariate logistic regression analysis showed that the independent risk factors for CR failure included IPSS (OR = 5.106, P = 0.013), preoperative urinary tract infection (OR = 3.835, P = 0.041), prostate volume (OR = 4.160, P = 0.011) and catheter compression time (OR = 4.051, P = 0.017). CONCLUSIONS: The common causes of the failure in catheter removal after TURP included early postoperative urinary retention, urinary infection, secondary hematuria and urinary incontinence.
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Catéteres , Remoción de Dispositivos/efectos adversos , Hiperplasia Prostática , Resección Transuretral de la Próstata , Humanos , Masculino , Hiperplasia Prostática/cirugía , Factores de Riesgo , Resección Transuretral de la Próstata/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent disease of the urogenital system. Alcohol has been reported to be closely related to CP/CPPS. Thus, we intended to verify the role of alcohol in CP/CPPS and determine the underlying mechanism. METHODS: We induced experimental autoimmune prostatitis (EAP) mouse model by intradermally injecting a mixture of prostate antigens (PAgs) and complete Freund's adjuvant on days 0 and 28. Mice were treated with alcohol (control-alcohol and EAP-alcohol groups) or vehicle (control-vehicle, and EAP-vehicle groups) from day 32 to 42. Forty-two days after PAg injection, the pathological appearance of the prostate tissues was evaluated, and histological analyses of the prostate were performed. Chronic pelvic pain was assessed by applying von Frey filaments to the lower abdomen. Proinflammatory cytokines were detected by enzyme-linked immunosorbent assay tests. Then, we explored the effects of the NLRP3 inhibitor MCC950 on chronic pelvic pain and prostatic inflammation in this model. RESULTS: Histological analyses showed diffuse inflammation in the stromal tissues that were characterized by severe infiltration of neutrophils and mononuclear cells in mice in the EAP-alcohol group compared with EAP-vehicle group. Chronic pain tests showed that the response frequency was significantly increased using a von Frey filament at forces of 0.4, 1.0, and 4.0 g in EAP-alcohol group compared with EAP-vehicle (P < .05). The levels of proinflammatory cytokines, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-17, and IL-1ß were all significantly elevated in EAP-alcohol group compared with the EAP-vehicle group (P < .05). However, between the control-alcohol and control-vehicle groups, chronic pain tests, histological assays, and cytokine determinations showed no differences. Furthermore, our results demonstrated that MCC950 could decrease the expression level of NLRP3 inflammasome-related proteins including NLRP3, ASC, and caspase-1. The chronic pain tests, histological assays, and cytokine determinations showed that MCC950 could attenuate the chronic pain and prostatic inflammation through the inhibition of the NLRP3 inflammasome. CONCLUSIONS: This study indicated that alcohol could aggravate the severity of prostatic inflammation in EAP model though activating the NLRP3 inflammasome. Furthermore, the role of MCC950 in inhibiting NLRP3 inflammasome and decreasing IL-1ß secretion to alleviate EAP severity may show that it is a promising therapeutic agent for CP/CPPS.
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Enfermedades Autoinmunes/inmunología , Etanol/farmacología , Dolor Pélvico/inmunología , Próstata/inmunología , Prostatitis/inmunología , Alcoholes/farmacología , Animales , Enfermedades Autoinmunes/patología , Dolor Crónico/inmunología , Citocinas/inmunología , Modelos Animales de Enfermedad , Furanos/farmacología , Compuestos Heterocíclicos de 4 o más Anillos , Indenos , Inflamasomas/inmunología , Inflamación/inmunología , Masculino , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología , Próstata/efectos de los fármacos , Próstata/patología , Prostatitis/patología , Ratas , Ratas Wistar , Sulfonamidas/farmacología , SulfonasRESUMEN
Long non-coding RNAs (lncRNA) are a cluster of non-coding RNAs with a length of more than 200 nucleotides, which, formerly considered as "transcriptional noise" of DNA, have now been proved to be widely involved in the regulation of gene expressions and play pivotal roles in the proliferation, differentiation and apoptosis of cells and the development and progression of tumors. Recent studies show that a series of lncRNAs participate in the regulation of the progression of prostate cancer, including the transition of the cancer cells from hormone-sensitive to castration-resistant. Androgen receptor (AR) has been proved by clinicians and researchers to be a key regulating factor in the initiation and progression of prostate cancer. Abundant evidence shows that lncRNAs can influence the AR signaling pathway and thus the progression and drug resistance of prostate cancer. Therefore, a clarification of the interaction between AR and lncRNA will help us better understand the biological mechanisms of tumorigenesis and provide some ideas for the treatment of prostate cancer.
Asunto(s)
Neoplasias de la Próstata/genética , ARN Largo no Codificante/genética , Receptores Androgénicos/genética , Andrógenos , Carcinogénesis , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Transducción de SeñalRESUMEN
OBJECTIVES: This study aims to investigate the effects and molecular mechanisms of apigenin (ApI) on renal ischemia/reperfusion (I/R) injury in vivo and in vitro. METHODS: In vivo, the left renal artery was clamped for 45 min and the right kidney was removed to study renal I/R injury on Sprague-Dawley (SD) rats. ApI was injected at 60 min before renal ischemia. In vitro, renal tubular epithelial cells (HK-2) were pretreated with or without ApI (20 uM) for 60 min and then treated with hypoxia/reoxygenation (H/R). Renal function, histology, cells apoptosis, and cell viability were tested. Furthermore, the potential molecular mechanisms were assessed. RESULTS: ApI pretreatment could significantly alleviated the renal function and the pathological damage as well as cells apoptosis after I/R injury. Meanwhile, ApI treatment protects H/R induced HK-2 cell apoptosis in vitro. The results of Western blot showed that ApI significantly increased the expressions of B-cell lymphoma 2 (Bcl-2) and phosphor-AKt (p-AKt), Phosphoinositide 3-kinase (PI3K), while down-regulated the expressions of Caspase3 and Bax induced by H/R injury. CONCLUSIONS: ApI pretreatment can protect renal function against I/R injury and prevent renal tubular cells from apoptosis in vivo and in vitro which might through PI3K/Akt mediated mitochondria-dependent apoptosis signaling pathway.
Asunto(s)
Apigenina/farmacología , Apoptosis/efectos de los fármacos , Enfermedades Renales/patología , Sustancias Protectoras/farmacología , Daño por Reperfusión/metabolismo , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Humanos , Riñón/patología , Enfermedades Renales/metabolismo , Masculino , Mitocondrias/metabolismo , Fosfatidilinositol 3-Quinasas , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
Chronic prostatitis is a common male disease with a high incidence rate and a serious impact on the patients' quality of life. The pathogenesis of chronic prostatitis remains unclear though it is considered to be possibly related to infection, inflammation, and abnormal pelvic nerve muscle activity. Recently, a growing number of studies have reported immune imbalance and changes of inflammatory cytokines in patients with chronic prostatitis as well as a close correlation of abnormal immune response with the occurrence of diseases, pelvic pain symptoms, mental symptoms, hyperalgesia, and so on. This review summarizes the latest advances in the studies of immunologic mechanisms of chronic prostatitis.
Asunto(s)
Citocinas/sangre , Prostatitis/inmunología , Enfermedad Crónica , Humanos , Hiperalgesia/inmunología , Masculino , Dolor Pélvico/inmunología , Prostatitis/sangre , Calidad de VidaRESUMEN
Renal cell carcinoma (RCC) is the fifth most common cancer worldwide, and becomes one of the leading causes of genitourinary cancer-related death in both males and females. Genetic alternations, alcohol consumption, occupationally harmful exposure and even obesity are well-established risk factors of RCC. Omentin-1 is a plasma adipokine synthesized in visceral adipose tissue, and its circulating serum concentration alters not only in conditions associated with insulin resistance such as Polycystic Ovary Syndrome (PCOS), but also in colorectal cancer and prostate cancer. To our best knowledge, the relationship between omentin-1 and RCC has not been clarified previously. Thus, we evaluated serum omentin-1 levels in RCC patients in the current matched case-control study. Forty-one patients newly diagnosed with RCC and forty-two healthy controls confirmed by the comprehensive medical examination were assessed. The omentin-1 concentrations were determined via utilizing enzyme-linked immunosorbent assays (ELISA) in the paired groups, in which the patients and healthy controls had no statistically significant differences in gender, age, systolic blood pressure (SBP), diastolic blood pressure (DBP), waist-hip ratio (WHR), estimate glomerular filtration rate (eGFR), body-mass index (BMI) and biochemical parameters. The omentin-1 levels in healthy people were 9.86±1.44ng/mL and the circulating omentin-1 levels were dramatically decreased to 3.62±0.76ng/mL in RCC patients (p<0.001). Besides, we revealed a negative correlation between omentin-1 with WHR (r=-0.261, p=0.017) and BMI (r=-0.310, p=0.004), further indicating BMI was the main influential factor on omentin-1 levels (p=0.0091). Follow-up studies would be conducted to establish the concrete mechanisms underlying the altered circulating levels of omentin-1 and elucidate the interaction between "RCC complex system" and adipose tissues, which may together provide promising and novel pharmacological insights for RCC theragnosis in the near future.
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Carcinoma de Células Renales/sangre , Citocinas/sangre , Neoplasias Renales/sangre , Lectinas/sangre , Adipoquinas/sangre , Índice de Masa Corporal , Carcinoma de Células Renales/diagnóstico , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Proteínas Ligadas a GPI/sangre , Humanos , Neoplasias Renales/diagnóstico , Modelos Logísticos , Masculino , Persona de Mediana Edad , Relación Cintura-CaderaRESUMEN
OBJECTIVE: To investigate the correlation between the premature ejaculation diagnostic tool (PEDT) and International Index of Erectile Function-15 (IIEF-15) in different types of premature ejaculation (PE). METHODS: We performed a cross-section survey among 352 PE patients received in the andrology clinic from December 2014 to December 2015 and 104 healthy men from the health examination center using basic demographic information (as on age, height, weight, education status, occupation, income, etc.), PEDT results, and IIEF-15 scores of the subjects. RESULTS: The PE patients had remarkably higher PEDT and lower IIEF-15 scores than the healthy men (P<0.01). The PEDT score of the PE patients was negatively correlated with their total IIEF-15 score as well as with the scores in the domains of erectile function, sexual intercourse satisfaction, and overall satisfaction after adjusted for age (P<0.01). The patients with acquired PE (APE) showed a lower IIEF-15 score than those with lifelong PE (LPE) (P<0.01). The PEDT score of the APE patients was correlated negatively with the total IIEF-15 score (r=ï¼0.391, P<0.01) and the scores in the domains of erectile function (r=ï¼0.362, P<0.01) and overall satisfaction (r=ï¼0.621, P<0.01), but not correlated with intercourse satisfaction, sexual orgasm, or sexual desire. The PEDT score of the LPE group was correlated negatively with intercourse satisfaction (r=ï¼0.286, P<0.05) but not correlated with either the total IIEF-15 score or the scores in the domains of erectile function, overall satisfaction, sexual orgasm, or sexual desire. CONCLUSIONS: PE patients have a higher PEDT score and a lower IIEF-15 score than normal males. The PEDT score of APE patients is significantly correlated with the total IIEF-15 score, while that of LPE patients is correlated not with the total IIEF-15 score but with intercourse satisfaction.
Asunto(s)
Coito/psicología , Disfunción Eréctil/fisiopatología , Erección Peniana/fisiología , Eyaculación Prematura/diagnóstico , Adulto , Andrología , Estudios de Casos y Controles , Estudios Transversales , Humanos , Libido , Masculino , Persona de Mediana Edad , Satisfacción Personal , Eyaculación Prematura/fisiopatología , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To compare the effect of transurethral resection of the prostate combined with endocrine therapy (TURP + ET) with that of αlA-blockers combined with ET ((αlA-b + ET) in the treatment of bladder outlet obstruction (BOO) in patients with advanced prostate cancer (PCa), and to investigate the safety of the TURP + ET for the treatment of PCa with BOO. METHODS: We retrospectively analyzed 63 cases of PCa with BOO, 28 treated by αlA-b + ET and the other 35 by TURP + ET. We obtained the residual urine volume (RV), maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), and quality of life score (QoL) before and after treatment along with the overall survival rate of the patients, followed by comparison of the parameters between the two methods. RESULTS: At 3 months after treatment, RV, IPSS, and QoL in the TURP + ET group were significantly decreased from (137.8 ± 27.6) ml, (22.3 ± 3.6), and (4.2 ± 0.8) to (29 ± 13.6) ml, (7.8 ± 2.1), and (1.6 ± 0.5) respectively (P < 0.05), while Qmax increased from (5.6 ± 2.1) ml/s to (17.6 ± 2.7) ml/s (P < 0.05); the former three parameters in the αlA-b + ET group decreased from (133.6 ± 24.9) ml, (21.5 ± 3.2), and (4.7 ± 1.1) to (42 ± 18.3) ml, (12.8 ± 2.6), and (2.5 ± 0.7) respectively (P < 0.05), while the latter one increased from (6.3 ± 2.4) ml/s to (11.7 ± 2.3) ml/s (P < 0.05), all with statistically significant differences between the two groups (P < 0.05). The overall survival rate of the TURP + ET group was not significantly different from that of the αlA-b + ET group (51.4% vs 46.4% , P > 0.05). CONCLUSION: TURP + ET is preferable to αlA-b + ET for its advantage of relieving BOO symptoms in advanced PCa without affecting the overall survival rate of the patients.