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1.
Environ Res ; 221: 115218, 2023 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-36608761

RESUMEN

The regulation of bacterial quorum sensing (QS) has been used to inhibit biofouling in wastewater treatment plants and the formation of biofilms. In contrast to traditional QS regulation strategies, this study aimed to obstruct the transmembrane transport process of QS signals to decrease their extracellular accumulation. Three phytochemicals, astragaloside IV, eugenol, and baicalin were selected, their effects on biofilm formation by Pseudomonas aeruginosa PA14 were studied, and the mechanisms determined. The inhibition efficiency of biofilm formation by 50 mg/L astragaloside IV, 1 mg/L eugenol, and 1 mg/L baicalin were 37%, 26%, and 26%, respectively. Confocal laser scanning microscopy and analysis of extracellular polymeric substances indicated that the three inhibitors affected the structure and composition of the biofilms. Furthermore, bacterial motility and a variety of QS-related virulence factors were suppressed by the inhibitor treatment due to changes in bacterial QS. Notably, the three inhibitors all decreased the extracellular concentration of the QS signaling molecule 3-oxo-C12-homoseine lactone by affecting the function of efflux pump MexAB-OprM. This indirectly interfered with the bacterial QS system and thus inhibited biofilm formation. In conclusion, this study revealed the inhibitory effects and inhibition mechanism of three phytochemicals on efflux pump and QS of P. aeruginosa and realized the inhibition on biofilm formation. We update the efflux pump inhibitor library and provide a new way for biofilm contamination control.


Asunto(s)
Percepción de Quorum , Saponinas , Eugenol/farmacología , Biopelículas , Saponinas/farmacología , Antibacterianos/farmacología , Proteínas Bacterianas
2.
Cancer Sci ; 111(2): 369-382, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31833612

RESUMEN

The androgen receptor (AR) pathway is critical for prostate cancer carcinogenesis and development; however, after 18-24 months of AR blocking therapy, patients invariably progress to castration-resistant prostate cancer (CRPC), which remains an urgent problem to be solved. Therefore, finding key molecules that interact with AR as novel strategies to treat prostate cancer and even CRPC is desperately needed. In the current study, we focused on the regulation of RNA-binding proteins (RBPs) associated with AR and determined that the mRNA and protein levels of AR were highly correlated with Musashi2 (MSI2) levels. MSI2 was upregulated in prostate cancer specimens and significantly correlated with advanced tumor grades. Downregulation of MSI2 in both androgen sensitive and insensitive prostate cancer cells inhibited tumor formation in vivo and decreased cell growth in vitro, which could be reversed by AR overexpression. Mechanistically, MSI2 directly bound to the 3'-untranslated region (UTR) of AR mRNA to increase its stability and, thus, enhanced its transcriptional activity. Our findings illustrate a previously unknown regulatory mechanism in prostate cancer cell proliferation regulated by the MSI2-AR axis and provide novel evidence towards a strategy against prostate cancer.


Asunto(s)
Neoplasias de la Próstata/patología , Proteínas de Unión al ARN/metabolismo , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Regiones no Traducidas 3' , Animales , Línea Celular Tumoral , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones , Clasificación del Tumor , Trasplante de Neoplasias , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Estabilidad del ARN , Receptores Androgénicos/química , Regulación hacia Arriba
3.
J Cell Mol Med ; 23(10): 6578-6594, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31449345

RESUMEN

Quaking homolog (QKI) is a member of the RNA-binding signal transduction and activator of proteins family. Previous studies showed that QKI possesses the tumour suppressor activity in human cancers by interacting with the 3'-untraslated region (3'-UTR) of various gene transcripts via the STAR domain. This study first assessed the association of QKI-6 expression with clinicopathological and survival data from bladder cancer patients and then investigated the underlying molecular mechanisms. Bladder cancer tissues (n = 223) were subjected to immunohistochemistry, and tumour cell lines and nude mice were used for different in vitro and in vivo assays following QKI-6 overexpression or knockdown. QKI-6 down-regulation was associated with advanced tumour TNM stages and poor patient overall survival. QKI-6 overexpression inhibited bladder cancer cell growth and invasion capacity, but induced tumour cell apoptosis and cell cycle arrest. Furthermore, ectopic expression of QKI-6 reduced tumour xenograft growth and expression of proliferation markers, Ki67 and PCNA. However, knockdown of QKI-6 expression had opposite effects in vitro and in vivo. QKI-6 inhibited expression of E2 transcription factor 3 (E2F3) by directly binding to the E2F3 3'-UTR, whereas E2F3 induced QKI-6 transcription by binding to the QKI-6 promoter in negative feedback mechanism. QKI-6 expression also suppressed activity and expression of nuclear factor-κB (NF-κB) signalling proteins in vitro, implying a novel multilevel regulatory network downstream of QKI-6. In conclusion, QKI-6 down-regulation contributes to bladder cancer development and progression.


Asunto(s)
Factor de Transcripción E2F3/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , FN-kappa B/metabolismo , Proteínas de Unión al ARN/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Regiones no Traducidas 3' , Animales , Apoptosis/genética , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación hacia Abajo , Factor de Transcripción E2F3/genética , Femenino , Humanos , Antígeno Ki-67/metabolismo , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , FN-kappa B/antagonistas & inhibidores , Estadificación de Neoplasias , Antígeno Nuclear de Célula en Proliferación/metabolismo , Proteínas de Unión al ARN/genética , Transducción de Señal/genética , Trasplante Heterólogo , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología
4.
Prostate ; 79(11): 1238-1255, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31124594

RESUMEN

BACKGROUND: This study investigated shallow heat injury to prostate stromal fibroblasts and epithelial cells and their interaction to regulate the wound healing and the underlying molecular events. METHODS: Prostate stromal fibroblasts and epithelial cells were cultured individually or cocultured and subjected to shallow heat injury for assessments of cell proliferation, migration, apoptosis, cell cycle distribution, and gene expression. The supernatant of heat-injured WPMY-1 cells was collected for exosome extraction and assessments. Furthermore, beagle dogs received thulium laser resection of the prostate (TmLRP) and randomly divided into Gefitinib, GW4869, and control treatment for the histological analysis, tissue re-epithelialization, and epidermal growth factor receptor (EGFR) expression on the prostatic wound surface. Immunofluorescence was to evaluate p63-positive basal progenitor cell trans-differentiation and macrophage polarization and ELISA was to detect cytokine levels in beagles' urine. RESULTS: Shallow heat injury caused these cells to enter a stressed state and enhanced their crosstalk. The prostate stromal fibroblasts produced and secreted more exosomal-EGFR and other cytokines and chemokines after shallow heat injury, resulting in increased proliferation and migration of prostate epithelial cells during wound healing. The wound healing of the canine prostatic urethra following the TmLRP procedure was slower in the Gefitinib and GW4869 treatment group than in the control group of animals. Immunofluorescence and ELISA showed that reduced EGFR expression interrupted macrophage polarization but increased the inflammatory response. CONCLUSIONS: Shallow heat injury was able to promote the interaction of prostate stromal cells with prostate epithelial cells to enhance wound healing. Stromal-derived exosomal-EGFR plays a crucial role in the balance of the macrophage polarization and prostatic wound healing.


Asunto(s)
FN-kappa B/metabolismo , Próstata/metabolismo , Células del Estroma/metabolismo , Cicatrización de Heridas/fisiología , Línea Celular , Proliferación Celular , Receptores ErbB/metabolismo , Calor , Humanos , Rayos Láser , Masculino , Próstata/citología , Transducción de Señal/fisiología , Células del Estroma/citología , Tulio
5.
Toxicol Appl Pharmacol ; 366: 83-95, 2019 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-30690042

RESUMEN

Thulium laser resection of the prostate (TmLRP), a major treatment for benign prostatic hyperplasia (BPH), has several postoperative complications that affect the patients' quality of life. The aim of this study was to investigate the effect of the M1 macrophage-secreted reactive oxygen species (ROS) on prostatic wound healing, and the role of MAPK signaling in this process. A co-culture model in vitro was established using macrophages and prostate epithelial or stromal cells. Cell proliferation, migration, apoptosis, MAPK pathway-related gene expression levels were evaluated by standard assays. In addition, an in vivo model of prostatectomy was established in beagles by subjecting them to TmLRP, and were either treated with N-acetyl-L-cysteine (NAC) and or placebo. Wound healing and re-epithelialization were analyzed histopathologically in both groups, in addition to macrophage polarization, oxidative stress levels and MAPK pathway-related proteins expressions. Intracellular ROS levels were significantly increased in the prostate epithelial and stromal cells following co-culture with M1-like macrophages and H2O2 exposure via MAPK activation, which affected their proliferation, migration and apoptosis, and delayed the wound healing process. The cellular functions and wound healing capacity of the prostate cells were restored by blocking or clearing the macrophage-secreted ROS. In the beagle model, increased ROS levels impaired cellular functions, and appropriate removing ROS accelerated the wound healing process.


Asunto(s)
Terapia por Láser , Macrófagos/enzimología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Estrés Oxidativo , Próstata/cirugía , Especies Reactivas de Oxígeno/metabolismo , Cicatrización de Heridas , Animales , Antioxidantes/farmacología , Apoptosis , Movimiento Celular , Proliferación Celular , Técnicas de Cocultivo , Perros , Células Epiteliales/enzimología , Células Epiteliales/patología , Transición Epitelial-Mesenquimal , Humanos , Terapia por Láser/instrumentación , Rayos Láser , Macrófagos/efectos de los fármacos , Macrófagos/patología , Masculino , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Estrés Oxidativo/efectos de los fármacos , Fenotipo , Próstata/enzimología , Próstata/patología , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal , Células del Estroma/enzimología , Células del Estroma/patología , Células THP-1 , Tulio , Factores de Tiempo , Cicatrización de Heridas/efectos de los fármacos
6.
Prostate ; 78(3): 193-201, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29171041

RESUMEN

BACKGROUND: Increased prostatic smooth muscle tone and hyperplastic growth contribute to urethral obstruction and voiding symptoms in benign prostatic hyperplasia (BPH). It has been suggested that different proliferative potential of stromal cells between transition zone (TZ) and adjoining regions of the prostate plays a significant role in the development of BPH. However, the molecular mechanisms of this hyperplastic process remain unclear. We found tumor necrosis factor receptor-associated factor 6 (TRAF6) highly expressed in TZ stromal cells compared to peripheral zone (PZ) stromal cells by gene array analyzes. Therefore, we aim to study the potential mechanisms of stromal TRAF6 in promoting BPH progression. METHODS: Stromal cells obtained from BPH-derived primary cultures. The TRAF6-siRNA vector were constructed and transfected into cultured human BPH primary TZ stromal cells, and TRAF6-overexpressing vector were constructed and transfected into cultured human BPH primary PZ stromal cells. Stromal cells were recombined with BPH-1 cells then subcutaneously inoculated into the kidney capsule of male nude mice. Cell proliferation was evaluated by CCK-8 assay. Multiple proteins in the Akt/mTOR pathway were assessed using western blot. RESULTS: TRAF6 levels were increased in TZ stroma compared with PZ stroma of BPH. The in vitro cell culture and in vivo cell recombination revealed that selective downregulation of TRAF6 in TZ stromal cells led to suppression of the proliferation, while upregulation of TRAF6 in PZ stromal cells enhanced the proliferation. We found that the Phosphorylation and Ubiquitination of Akt as well as the Phosphorylation of mTOR, P70S6K were decreased when TRAF6 was downregulated in primary cultured TZ stromal cells of BPH. CONCLUSIONS: TRAF6 can promote the proliferation of stromal cells of BPH via Akt/mTOR signaling. Our results may make stromal TRAF6 responsible for zonal characteristic of BPH and as a promising therapeutic strategy for BPH treatment.


Asunto(s)
Proliferación Celular/fisiología , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células del Estroma/metabolismo , Factor 6 Asociado a Receptor de TNF/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Animales , Humanos , Péptidos y Proteínas de Señalización Intracelular , Masculino , Ratones , Ratones Desnudos , Transducción de Señal/fisiología , Factor 6 Asociado a Receptor de TNF/genética
7.
Prostate ; 77(7): 708-717, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28168722

RESUMEN

BACKGROUND: Complications after a thulium laser resection of the prostate (TmLRP) are related to re-epithelialization of the prostatic urethra. Since prostate growth and development are induced by androgen, the aim of this study was to determine the role and explore the mechanism of androgen in wound healing of the prostatic urethra. METHODS: Beagles that received TmLRPs were randomly distributed into a castration group, a testosterone undecanoate (TU) group, and a control group. The prostate wound was assessed once a week using a cystoscope. Histological analysis was then carried out to study the re-epithelialization of the prostatic urethra in each group. The inflammatory response in the wound tissue and urine was also investigated. RESULTS: The healing of the prostatic urethra after a TmLRP was more rapid in the castration group and slower in the TU group than that in the control group. Castration accelerated re-epithelialization by promoting basal cell proliferation in the wound surface and beneath the wound and by accelerating the differentiation of basal cells into urothelial cells. Castration reduced the duration of the inflammatory phase and induced the conversion of M1 macrophages to M2 macrophages, thus accelerating the maturation of the wound. By contrast, androgen supplementation enhanced the inflammatory response and prolonged the inflammatory phase. Moreover, the anti-inflammatory phase was delayed and weakened. CONCLUSION: Androgen deprivation promotes re-epithelialization of the wound, regulates the inflammatory response, and accelerates wound healing of the prostatic urethra after a TmLRP. Prostate 77:708-717, 2017. © 2017 Wiley Periodicals, Inc.


Asunto(s)
Andrógenos , Complicaciones Intraoperatorias , Próstata , Testosterona/análogos & derivados , Resección Transuretral de la Próstata/efectos adversos , Uretra , Andrógenos/administración & dosificación , Andrógenos/efectos adversos , Andrógenos/metabolismo , Animales , Modelos Animales de Enfermedad , Perros , Complicaciones Intraoperatorias/metabolismo , Complicaciones Intraoperatorias/fisiopatología , Complicaciones Intraoperatorias/terapia , Macrófagos/patología , Macrófagos/fisiología , Masculino , Próstata/patología , Próstata/cirugía , Repitelización/efectos de los fármacos , Repitelización/fisiología , Estadística como Asunto , Testosterona/administración & dosificación , Testosterona/efectos adversos , Testosterona/metabolismo , Tulio/farmacología , Resección Transuretral de la Próstata/métodos , Uretra/lesiones , Uretra/patología , Cicatrización de Heridas/efectos de los fármacos , Cicatrización de Heridas/fisiología
8.
Biochem Biophys Res Commun ; 470(3): 721-727, 2016 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-26797523

RESUMEN

Long non-coding RNAs (lncRNAs) are emerging as key molecules in human cancer genesis and progression, including prostate cancer. Large amount of lncRNAs have been found that differentially expressed between prostate cancer tissues and normal prostate tissues. Whether these lncRNAs could serve as a novel biomarker for prostate cancer diagnosis or prognosis, and their biological functions in prostate cancer need further investigation. In the present study, we identified that lncRNA lnc-MX1-1 is over-expressed in prostate cancer tissues compared with their adjacent normal prostate tissues by gene expression array profiling. The expression of lnc-MX1-1 in 60 prostate cancer cases was determined by real-time quantitative PCR and the correlations between lnc-MX1-1 expression and patients' clinical features were further analyzed. Next, we impaired lnc-MX1-1 expression using RNAi in LNCaP and 22Rv1 prostate cancer cells to explore the effects of lnc-MX1-1 on proliferation and invasiveness of the cells. Our results showed that there was a significant association between over-expression of lnc-MX1-1 and patients' clinical features such as PSA, Gleason score, metastasis, and recurrence free survival. Moreover, knockdown of lnc-MX1-1 reduced both proliferation and invasiveness of LNCaP and 22Rv1 cells. In conclusion, the results suggest that lnc-MX1-1 may serve as a potential biomarker and therapeutic target for prostate cancer.


Asunto(s)
Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , ARN Largo no Codificante/metabolismo , Proliferación Celular , Humanos , Masculino , Invasividad Neoplásica , Regulación hacia Arriba
9.
Water Res ; 259: 121851, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38851110

RESUMEN

Overuse of antibiotics has led to their existence in nitrogen-containing water. The impacts of antibiotics on bio-denitrification and the metabolic response of denitrifiers to antibiotics are unclear. We systematically analyzed the effect of ciprofloxacin (CIP) on bio-denitrification and found that 5 mg/L CIP greatly inhibited denitrification with a model denitrifier (Paracoccus denitrificans). Nitrate reduction decreased by 32.89 % and nitrous oxide emission increased by 75.53 %. The balance analysis of carbon and nitrogen metabolism during denitrification showed that CIP exposure blocked electron transfer and reduced the flow of substrate metabolism used for denitrification. Proteomics results showed that CIP exposure induced denitrifiers to use the pentose phosphate pathway more for substrate metabolism. This caused a substrate preference to generate NADPH to prevent cellular damage rather than NADH for denitrification. Notably, despite denitrifiers having antioxidant defenses, they could not completely prevent oxidative damage caused by CIP exposure. The effect of CIP exposure on denitrifiers after removal of extracellular polymeric substances (EPS) demonstrated that EPS around denitrifiers formed a barrier against CIP. Fluorescence and infrared spectroscopy revealed that the binding effect of proteins in EPS to CIP prevented damage. This study shows that denitrifiers resist antibiotic stress through different intracellular and extracellular defense strategies.


Asunto(s)
Antibacterianos , Ciprofloxacina , Desnitrificación , Ciprofloxacina/farmacología , Antibacterianos/farmacología , Paracoccus denitrificans/metabolismo
10.
Free Radic Biol Med ; 195: 132-144, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36584797

RESUMEN

Tubulointerstitial fibrosis (TIF) is essential during the development of end-stage kidney disease (ESKD) and is associated with the impairment of fatty acid oxidation (FAO). Kruppel-like factor 14 (KLF14) is an important gene in lipid metabolism, but its role in TIF remains unknown. TGF-ß-stimulated HK-2 cells and mouse unilateral ureteral obstruction (UUO) were used as renal fibrosis models. The role of KLF14 in the process of renal fibrosis was verified by gene knockout mice, genetic or pharmacological interference in animal model and cell model respectively. In the current study, we found that KLF14 expression increased after activation of the TGF-ß signaling pathway during TIF. In KLF14-/- mice, more severe fibrosis was observed after unilateral ureteral obstruction (UUO) was induced. In human HK2 cells, knockdown of KLF14 led to more severe fibrosis induced by TGF-ß1, while overexpression of KLF14 partially attenuated this process. Specifically, KLF14 deficiency decreased mitochondrial FAO activity, resulting in lipid accumulation. Thus, the energy supply to the cells was insufficient, finally resulting in TIF. We further proved that KLF14 could target peroxisome proliferator activated receptor alpha (PPARα) as a transcriptional activator. This study identified the upregulation of KLF14 expression in response to kidney stress during the process of fibrosis. Upon TIF, the activated TGF-ß signaling pathway can enhance KLF14 expression, while the upregulation of KLF14 expression can decrease the degree of TIF by improving FAO activity in tubular epithelial cells and recovering the energy supply mediated by PPARα.


Asunto(s)
Enfermedades Renales , Factores de Transcripción de Tipo Kruppel , PPAR alfa , Obstrucción Ureteral , Animales , Humanos , Ratones , Ácidos Grasos/metabolismo , Fibrosis , Riñón/metabolismo , Enfermedades Renales/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Metabolismo de los Lípidos/genética , PPAR alfa/genética , PPAR alfa/metabolismo , Factor de Crecimiento Transformador beta1/genética , Regulación hacia Arriba , Obstrucción Ureteral/genética , Ratones Noqueados
11.
Bioresour Technol ; 379: 129039, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37037332

RESUMEN

A highly efficient aerobic denitrifying microbe was isolated from sewage sludge by using a denitrifier enrichment strategy based on decreasing carbon content. The microbe was identified as Pseudomonas mendocina HITSZ-D1 (hereafter, D1). Investigation of the conditions under which D1 grew and denitrified revealed that it performed good growth and nitrate removal performance under a wide range of conditions. In particular, D1 rapidly removed all types of inorganic nitrogen without accumulation of the intermediate products nitrite and nitrous oxide. Overall, D1 showed a total nitrogen removal efficiency >96% at a C/N ratio of 8. The biotransformation modes and fates of three typical types of inorganic nitrogen were also assessed. Moreover, D1 had significantly higher denitrification efficiency and enzyme activities than other aerobic denitrifying microbes (Paracoccus denitrificans, Pseudomonas aeruginosa, and Pseudomonas putida). These results suggest that D1 has great potential for treating wastewater containing high concentrations of nitrogen.


Asunto(s)
Nitritos , Pseudomonas mendocina , Nitritos/metabolismo , Pseudomonas mendocina/metabolismo , Aguas del Alcantarillado , Desnitrificación , Nitratos/metabolismo , Nitrógeno/metabolismo , Nitrificación , Aerobiosis
12.
J Orthop Surg Res ; 17(1): 108, 2022 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-35184732

RESUMEN

OBJECTIVES: Internal fixation with multiple cannulated compression screws is an optional treatment for femoral neck fracture. Recently, fully threaded cannulated compression screws (FTCCS) have been introduced to fix fresh femoral neck fractures (FNF). The purpose of this study was to investigate the effectiveness of FTCCS. PATIENTS AND METHODS: Patients with FNF fixed by multiple FTCCS from February 1st, 2014 to August 31st, 2017 were included in this study. They were followed for at least 12 months postoperatively. Nonunion, osteonecrosis of the femoral head (ONFH), fixation failure, reoperation, and femoral neck shortening (FNS) were used to evaluate the outcomes. Risk factors including age, sex, fracture side, fracture displacement, fracture stability, fixation configuration, and screw numbers were analyzed. RESULTS: A total of 113 patients including 67 males and 46 females with an average age of 48.4 ± 13.4 years were included. The mean duration of follow-up was 27.1 months (range: 12-51 months). The incidence of nonunion, ONFH, fixation failure, and reoperation was 15.9%, 22.1%, 8.8%, and 24.8%, respectively. The rates of nonunion and reoperation were significantly higher in displaced fractures and unstable fractures. And patients with an unstable fracture had a higher risk of internal fixation failure. The median length of FNS was 2.9 mm (interquartile range: 0.9-6.5 mm, range: 0-17.5 mm). Age was a significant risk factor for FNS. CONCLUSIONS: The screw fixation method with FTCCS provided encouraging clinical results which may be a rational choice for the treatment of fresh FNF. Displaced fractures and unstable fractures were attributed to the higher incidence of complications. TRIAL REGISTRATION: ChiCTR, ChiCTR1800017200. Registered 17 July 2018-Retrospectively registered, http: www.chictr.org.cn/showprojen.aspx?proj=29182 .


Asunto(s)
Tornillos Óseos , Fracturas del Cuello Femoral/cirugía , Cuello Femoral/cirugía , Fijación Interna de Fracturas/métodos , Adulto , Anciano , Femenino , Fracturas del Cuello Femoral/diagnóstico por imagen , Cuello Femoral/diagnóstico por imagen , Fijación Interna de Fracturas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
13.
J Bone Joint Surg Am ; 104(23): 2108-2116, 2022 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-36325763

RESUMEN

BACKGROUND: There is currently no ideal treatment for osteochondral lesions of the femoral head (OLFH) in young patients. METHODS: We performed a 1-year single-arm study and 2 additional years of follow-up of patients with a large (defined as >3 cm 2 ) OLFH treated with insertion of autologous costal cartilage graft (ACCG) to restore femoral head congruity after lesion debridement. Twenty patients ≤40 years old who had substantial hip pain and/or dysfunction after nonoperative treatment were enrolled at a single center. The primary outcome was the change in Harris hip score (HHS) from baseline to 12 months postoperatively. Secondary outcomes included the EuroQol visual analogue scale (EQ VAS), hip joint space width, subchondral integrity on computed tomography scanning, repair tissue status evaluated with the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and evaluation of cartilage biochemistry by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping. RESULTS: All 20 enrolled patients (31.02 ± 7.19 years old, 8 female and 12 male) completed the initial study and the 2 years of additional follow-up. The HHS improved from 61.89 ± 6.47 at baseline to 89.23 ± 2.62 at 12 months and 94.79 ± 2.72 at 36 months. The EQ VAS increased by 17.00 ± 8.77 at 12 months and by 21.70 ± 7.99 at 36 months (p < 0.001 for both). Complete integration of the ACCG with the bone was observed by 12 months in all 20 patients. The median MOCART score was 85 (interquartile range [IQR], 75 to 95) at 12 months and 75 (IQR, 65 to 85) at the last follow-up (range, 24 to 38 months). The ACCG demonstrated magnetic resonance properties very similar to hyaline cartilage; the median ratio between the relaxation times of the ACCG and recipient cartilage was 0.95 (IQR, 0.90 to 0.99) at 12 months and 0.97 (IQR, 0.92 to 1.00) at the last follow-up. CONCLUSIONS: ACCG is a feasible method for improving hip function and quality of life for at least 3 years in young patients who were unsatisfied with nonoperative treatment of an OLFH. Promising long-term outcomes may be possible because of the good integration between the recipient femoral head and the implanted ACCG. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.


Asunto(s)
Cartílago Costal , Humanos , Femenino , Masculino , Adulto , Adulto Joven , Cabeza Femoral/diagnóstico por imagen , Cabeza Femoral/cirugía , Calidad de Vida
14.
Asian J Androl ; 23(4): 415-420, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33473011

RESUMEN

To improve the diagnostic efficiency of prostate cancer (PCa) and reduce unnecessary biopsies, we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen (PSA) density (PZ-PSAD). Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital (Shanghai, China) between January 2012 and January 2018 were retrospectively identified (n = 529). Another group of patients with benign prostatic hyperplasia (n = 100) were randomly preselected to obtain the PSA density of the non-PCa cohort (N-PSAD). Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging (mpMRI) and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm. Receiver operating characteristic (ROC) curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level, and the area under the ROC curve (AUC) of PZ-PSAD was higher than that of PSA, PSA density (PSAD), and transition zone PSA density (TZ-PSAD). PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography (TRUS) and mpMRI results. When TRUS and mpMRI findings were ambiguous to predict PCa (PIRADS score ≤3), PZ-PSAD could increase the positive rate of biopsy from 21.7% to 54.7%, and help 63.8% (150/235) of patients avoid unnecessary prostate biopsy. In patients whose PSA was 4.0-10.0 ng ml-1, 10.1-20.0 ng ml-1, and >20.0 ng ml-1, the ideal PZ-PSAD cut-off value for predicting clinically significant PCa was 0.019 ng ml-2, 0.297 ng ml-2, and 1.180 ng ml-2, respectively (sensitivity >90%). Compared with PSA, PSAD, and TZ-PSAD, the efficiency of PZ-PSAD for predicting PCa is the highest, leading to fewer missed diagnoses and unnecessary biopsies.


Asunto(s)
Valor Predictivo de las Pruebas , Antígeno Prostático Específico/análisis , Neoplasias de la Próstata/diagnóstico , Anciano , Anciano de 80 o más Años , China , Estudios de Cohortes , Humanos , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Estudios Retrospectivos , Sensibilidad y Especificidad , Estadísticas no Paramétricas
15.
Cancer Lett ; 503: 138-150, 2021 04 10.
Artículo en Inglés | MEDLINE | ID: mdl-33503448

RESUMEN

The androgen receptor (AR) is expressed in prostate fibroblasts in addition to normal prostate epithelial cells and prostate cancer (PCa) cells. Moreover, AR activation in fibroblasts dramatically influences prostate cancer (PCa) cell behavior. Androgen deprivation leads to deregulation of AR downstream target genes in both fibroblasts and PCa cells. Here, we identified LIM domain only 2 (LMO2) as an AR target gene in prostate fibroblasts using ChIP-seq and revealed that LMO2 can be repressed directly by AR through binding to androgen response elements (AREs), which results in LMO2 overexpression after AR deactivation due to normal prostate fibroblasts to cancer-associated fibroblasts (CAFs) transformation or androgen deprivation therapy. Next, we investigated the mechanisms of LMO2 overexpression in fibroblasts and the role of this event in non-cell-autonomous promotion of PCa cells growth in the androgen-independent manner through paracrine release of IL-11 and FGF-9. Collectively, our data suggest that AR deactivation deregulates LMO2 expression in prostate fibroblasts, which induces castration resistance in PCa cells non-cell-autonomously through IL-11 and FGF-9.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Benzamidas/farmacología , Fibroblastos Asociados al Cáncer/metabolismo , Proteínas con Dominio LIM/metabolismo , Nitrilos/farmacología , Feniltiohidantoína/farmacología , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Receptores Androgénicos/metabolismo , Regulación hacia Arriba , Animales , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Secuenciación de Inmunoprecipitación de Cromatina , Factor 9 de Crecimiento de Fibroblastos/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Interleucina-11/metabolismo , Masculino , Ratones , Comunicación Paracrina , Cultivo Primario de Células , Activación Transcripcional/efectos de los fármacos
16.
J Exp Clin Cancer Res ; 39(1): 28, 2020 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-32019578

RESUMEN

BACKGROUND: Sirtuin-7 (SIRT7) is associated with the maintenance of tumorigenesis. However, its functional roles and oncogenic mechanisms in prostate cancer (PCa) are poorly understood. Here, we investigated the roles and underlying molecular mechanisms of SIRT7 in PCa cell growth and androgen-induced autophagy. METHODS: The LNCap and 22Rv1 PCa cell lines were subjected to quantitative reverse transcription (RT)-PCR to characterize their genes encoding SIRT7, AR, and SMAD4. The proteins produced from these genes were quantified by western blotting and immunoprecipitation analysis. SIRT7-depleted cells were produced by transfection with plasmid vectors bearing short hairpin RNAs against SIRT7. The proliferation of each cell line was assessed by CCK8 and EdU assays. Autophagic flux was tracked by mRFP-GFP-LC3 adenovirus under an immunofluorescence microscope. Apoptosis was evaluated by flow cytometry. Tumors were induced in mouse axillae by injection of the cell lines into mice. Tumor morphology was examined by immunohistochemistry and relative tumor growth and metastases were compared by a bioluminescence-based in vivo imaging system. RESULTS: SIRT7 depletion significantly inhibited cell proliferation, androgen-induced autophagy, and invasion in LNCap and 22Rv1 cells (in vitro) and mouse xenograft tumors induced by injection of these cells (in vivo). SIRT7 knockdown also increased the sensitivity of PCa cells to radiation. Immunohistochemical analysis of 93 specimens and bioinformatic analysis revealed that SIRT7 expression was positively associated with androgen receptor (AR). Moreover, the AR signal pathway participated in SIRT7-mediated regulation of PCa cell proliferation, autophagy, and invasion. SIRT7 depletion downregulated the AR signal pathway by upregulating the level of SMAD4 protein in PCa cells. CONCLUSION: SIRT7 plays an important role in the development and progression of human PCa and may be a promising prognostic marker for prostate cancer.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Receptores Androgénicos/metabolismo , Transducción de Señal , Sirtuinas/genética , Sirtuinas/metabolismo , Animales , Apoptosis/genética , Autofagia , Biomarcadores de Tumor , Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Humanos , Masculino , Ratones , Metástasis de la Neoplasia , Pronóstico , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Tolerancia a Radiación/genética , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Acta Biomater ; 88: 392-405, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30753941

RESUMEN

Benign prostatic hyperplasia (BPH) patients experience complications after surgery. We studied oxidative stress scavenging by porous Se@SiO2 nanospheres in prostatic urethra wound healing after transurethral resection of the prostate (TURP). Beagle dogs were randomly distributed into two groups after establishing TURP models. Wound recovery and oxidative stress levels were evaluated. Re-epithelialization and the macrophage distribution at the wound site were assessed by histology. The mechanism by which porous Se@SiO2 nanospheres regulated macrophage polarization was investigated by qRT-PCR, western blotting, flow cytometry, immunofluorescence and dual luciferase reporter gene assays. Our results demonstrated that Porous Se@SiO2 nanosphere-coated catheters advance re-epithelization of the prostatic urethra, accelerating wound healing in beagle dogs after TURP, and improve the antioxidant capacity to inhibit oxidative stress and induced an M2 phenotype transition of macrophages at the wound. By restraining the function of reactive oxygen species (ROS), porous Se@SiO2 nanospheres downregulated Ikk, IκB and p65 phosphorylation to block the downstream NF-κB pathway in macrophages in vitro. Since activation of NF-κB signaling cascades drives macrophage polarization, porous Se@SiO2 nanospheres promoted macrophage phenotype conversion from M1 to M2. Our findings suggest that porous Se@SiO2 nanosphere-coated catheters promote postoperative wound recovery in the prostatic urethra by promoting macrophage polarization toward the M2 phenotype through suppression of the ROS-NF-κB pathway, attenuating the inflammatory response. STATEMENT OF SIGNIFICANCE: The inability to effectively control post-operative inflammatory responses after surgical treatment of benign prostatic hyperplasia (BPH) remains a challenge to researchers and surgeons, as it can lead to indirect cell death and ultimately delay wound healing. Macrophages at the wound site work as pivotal regulators of local inflammatory response. Here, we designed and produced a new type of catheter with a coating of porous Se@SiO2 nanosphere and demonstrated its role in promoting prostatic urethra wound repair by shifting macrophage polarization toward the anti-inflammatory M2 phenotype via suppressing ROS-NF-κB pathway. These results indicate that the use of porous Se@SiO2 nanosphere-coated catheter may provide a therapeutic strategy for postoperative complications during prostatic urethra wound healing to improve patient quality of life.


Asunto(s)
Catéteres , Materiales Biocompatibles Revestidos/farmacología , Macrófagos/patología , Nanosferas/química , Transducción de Señal , Dióxido de Silicio/química , Uretra/patología , Cicatrización de Heridas/efectos de los fármacos , Animales , Polaridad Celular , Perros , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , FN-kappa B/metabolismo , Nanosferas/ultraestructura , Estrés Oxidativo/efectos de los fármacos , Porosidad , Próstata/patología , Próstata/cirugía , Repitelización/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Selenio/química , Células THP-1 , Resección Transuretral de la Próstata , Uretra/efectos de los fármacos
18.
Asian J Androl ; 21(6): 612-617, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31006712

RESUMEN

This study compared the diagnostic efficacy of transrectal ultrasound (TRUS)-guided prostate biopsy (TRBx) and transperineal prostate biopsy (TPBx) in patients with suspected prostate cancer (PCa). We enrolled 2962 men who underwent transrectal (n = 1216) or transperineal (n = 1746) systematic 12-core prostate biopsy. Clinical data including age, prostate-specific antigen (PSA) level, and prostate volume (PV) were recorded. To minimize confounding, we performed propensity score-matching analysis. We measured and compared PCa detection rates between TRBx and TPBx, which were stratified by clinical characteristics and Gleason scores. The effects of clinical characteristics on PCa detection rate were assessed by logistic regression. For all patients, TPBx detected a higher proportion of clinically significant PCa (P < 0.001). Logistic regression analyses illustrated that PV had a smaller impact on PCa detection rate of TPBx compared with TRBx. Propensity score-matching analysis showed that the detection rates in TRBx were higher than those in TPBx for patients aged >- 80 years (80.4% vs 56.5%, P = 0.004) and with PSA level 20.1-100.0 ng ml-1 (80.8% vs 69.1%, P = 0.040). In conclusion, TPBx was associated with a higher detection rate of clinically significant PCa than TRBx was; however, because of the high detection rate at certain ages and PSA levels, biopsy approaches should be optimized according to patents' clinical characteristics.


Asunto(s)
Biopsia/métodos , Próstata/patología , Neoplasias de la Próstata/diagnóstico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Perineo , Puntaje de Propensión , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/patología , Recto
19.
Cell Prolif ; 52(3): e12590, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30883989

RESUMEN

OBJECTIVES: 5α-reductase inhibitor (5-ARI) is a commonly used medicine in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Our study mainly focuses on the mechanism of BPH development after 5ARI treatment. MATERIALS AND METHODS: Prostate specimens from patients were collected. Insulin-like growth factor 1 (IGF-1), Beclin-1, LC3 levels, was analysed by immunohistochemistry. The role IGF-1 on autophagic flux in prostate epithelial cells was studied. Additionally, effect of autophagy on recombinant grafts consisting of prostate stromal and epithelial cells in nude mice was investigated. RESULTS: We demonstrated that IGF-1 expression is down-regulated in prostate fibroblasts after long-term 5-ARI application. A decrease in IGF-1 levels was found to activate autophagic flux through the mTOR pathway in prostate epithelial cells, while the inhibition of IGF-1 receptor function induced autophagy in prostate epithelial cells. In addition, we revealed that blocking autophagic flux initiation can reduce the volume of recombinant grafts in vivo. Finally, our findings suggest that long-term 5-ARI application reduces IGF-1 secretion by prostatic stromal cells, thereby inducing autophagy of prostatic epithelial cells, which is one of the mechanisms underlying BPH pathogenesis and progression. CONCLUSIONS: Focusing on the autophagy induced by low levels of IGF-1 in prostatic epithelial cells, after elucidating AR signalling impairment of prostate stromal cells, might provide a novel strategy for the treatment and prevention of BPH development.


Asunto(s)
Inhibidores de 5-alfa-Reductasa/farmacología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Próstata/citología , Próstata/efectos de los fármacos , Animales , Autofagia/efectos de los fármacos , Beclina-1/metabolismo , Células Cultivadas , Regulación hacia Abajo/efectos de los fármacos , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Xenoinjertos , Humanos , Masculino , Ratones , Ratones Desnudos , Proteínas Asociadas a Microtúbulos/metabolismo , Próstata/metabolismo , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Receptores Androgénicos/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo
20.
Cell Death Dis ; 9(4): 431, 2018 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-29568063

RESUMEN

The activation of androgen receptor (AR) signaling plays an essential role in both prostate stromal cells and epithelial cells during the development of benign prostatic hyperplasia (BPH). Here we demonstrated that androgen ablation after 5α-reductase inhibitor (5-ARI) treatment induced autophagy in prostate stromal fibroblasts inhibiting cell apoptosis. In addition, we found that ATG9A expression was increased after androgen ablation, which facilitated autophagic flux development. Knockdown of ATG9A not only inhibited autophagy notably in prostate stromal fibroblasts, but also reduced the volumes of prostate stromal fibroblast and epithelial cell recombinant grafts in nude mice. In conclusion, our findings suggested that ATG9A upregulation after long-term 5-ARI treatment constitutes a possible mechanism of BPH progression. Thus, combined treatment with 5-ARI and autophagy inhibitory agents would reduce the risk of BPH progression.


Asunto(s)
Proteínas Relacionadas con la Autofagia/metabolismo , Autofagia , Proteínas de la Membrana/metabolismo , Hiperplasia Prostática/patología , Transducción de Señal , Proteínas de Transporte Vesicular/metabolismo , Inhibidores de 5-alfa-Reductasa/farmacología , Animales , Autofagia/efectos de los fármacos , Proteínas Relacionadas con la Autofagia/antagonistas & inhibidores , Proteínas Relacionadas con la Autofagia/genética , Células Cultivadas , Progresión de la Enfermedad , Fibroblastos/citología , Fibroblastos/metabolismo , Humanos , Masculino , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/genética , Ratones , Ratones Desnudos , Proteínas Asociadas a Microtúbulos/metabolismo , Próstata/citología , Hiperplasia Prostática/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Regulación hacia Arriba , Proteínas de Transporte Vesicular/antagonistas & inhibidores , Proteínas de Transporte Vesicular/genética
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