RESUMO
OBJECTIVE: To explore the effect of a novel transurethral thulium laser vapoenucleation of the prostate with low-power conventional pulse mode (LP-ThuVEP) on sexual function in patients with benign prostatic hyperplasia (BPH). METHODS: 89 BPH patients admitted to Department of Urology, Jintan People's Hospital, Affiliated to Jiangsu University, from January 2022 to June 2023 were selected and randomly divided into the LP-ThuLEP group (45 cases) and the transurethral plasma kinetic resection of the prostate (TUPKRP) group (44 cases). Perioperative indicators were recorded, and the IPSS, Qmax, Qavg, PVR, and QoL of the two groups of patients before surgery and 3 months and 6 months after surgery were comparatively analyzed. The effect of surgery on male sexual function was evaluated through the International Index of Erectile Function-5 (IIEF-5) score and the Male Sexual Health Questionnaire-Ejaculatory Dysfunction (MSHQ-EjD) score. RESULTS: Compared with the TUPKRP group, the LP-ThuVEP group had no statistically significant difference in operation time (P>0.05), but there were statistical differences in bladder irrigation time and indwelling urinary catheter time (P<0.05) and significant statistical differences in the decrease in hemoglobin on the day of surgery and the disappearance time of gross hematuria induced by defecation after surgery (P<0.001). The perioperative complications of the two groups were comparable. Among the urinary tract symptom indicators, the LP-ThuVEP group had statistically significant differences in IPSS score, QoL score, and PVR compared with the TUPKRP group 3 months after surgery (P<0.05). In terms of male sexual function, there was a statistical difference in IIEF-5 scores between the two groups at 3 months and 6 months after surgery (P<0.05); Except that there was no statistical difference in the ejaculation-related satisfaction scores between the two groups at 3 months after surgery (P>0.05), there had all significant statistical differences in ejaculation function and satisfaction scores between and within the groups at 3 months and 6 months after surgery (P<0.001). CONCLUSION: Compared with TUPKRP, the LP-ThuVEP can also effectively relieve urinary tract obstruction caused by BPH and has the advantages of less damage and faster recovery of erectile function and ejaculatory function of patients.
Assuntos
Disfunção Erétil , Terapia a Laser , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Humanos , Masculino , Próstata/cirurgia , Hiperplasia Prostática/cirurgia , Disfunção Erétil/cirurgia , Qualidade de Vida , Resultado do TratamentoRESUMO
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.
Assuntos
Terapia a Laser , Macrófagos/enzimologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Estresse Oxidativo , Próstata/cirurgia , Espécies Reativas de Oxigênio/metabolismo , Cicatrização , Animais , Antioxidantes/farmacologia , Apoptose , Movimento Celular , Proliferação de Células , Técnicas de Cocultura , Cães , Células Epiteliais/enzimologia , Células Epiteliais/patologia , Transição Epitelial-Mesenquimal , Humanos , Terapia a Laser/instrumentação , Lasers , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Fenótipo , Próstata/enzimologia , Próstata/patologia , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais , Células Estromais/enzimologia , Células Estromais/patologia , Células THP-1 , Túlio , Fatores de Tempo , Cicatrização/efeitos dos fármacosRESUMO
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.
Assuntos
Androgênios , Complicações Intraoperatórias , Próstata , Testosterona/análogos & derivados , Ressecção Transuretral da Próstata/efeitos adversos , Uretra , Androgênios/administração & dosagem , Androgênios/efeitos adversos , Androgênios/metabolismo , Animais , Modelos Animais de Doenças , Cães , Complicações Intraoperatórias/metabolismo , Complicações Intraoperatórias/fisiopatologia , Complicações Intraoperatórias/terapia , Macrófagos/patologia , Macrófagos/fisiologia , Masculino , Próstata/patologia , Próstata/cirurgia , Reepitelização/efeitos dos fármacos , Reepitelização/fisiologia , Estatística como Assunto , Testosterona/administração & dosagem , Testosterona/efeitos adversos , Testosterona/metabolismo , Túlio/farmacologia , Ressecção Transuretral da Próstata/métodos , Uretra/lesões , Uretra/patologia , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologiaRESUMO
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.
Assuntos
Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , RNA Longo não Codificante/metabolismo , Proliferação de Células , Humanos , Masculino , Invasividade Neoplásica , Regulação para CimaRESUMO
OBJECTIVE: To explore the expression patterns of cadherins (N-cadherin and E-cadherin) in urothelial carcinomas and understand the values of N-E cadherin switch in the predictions of postoperative recurrence and prognosis. METHODS: The expressions of N-cadherin and E-cadherin were measured by immunohistochemistry in 64 transurethral bladder tumor resection (TURBT) or partial cystectomy samples (48 cases) in 2005 by the method of streptavidin-biotin peroxidase. RESULTS: A positive expression of N-cadherin and a negative expression of E-cadherin were noted in 27 (42.2%) and 16 (25.0%) specimens respectively. Patients with more poorly differentiated bladder cancer were accompanied with a higher expression of N-cadherin and a lower expression of E-cadherin (both P < 0.05). A positive expression of N-cadherin decreased the recurrence-free and cancer-related survival rates while a negative expression of E-cadherin was correlated with a lower cancer-related survival rate (all P < 0.05). No significant association was found between the expression of E-cadherin and the recurrence-free survival rate. Furthermore, the N-E cadherin switch (a negative expression of E-cadherin and a positive expression of N-cadherin) showed a higher predictive power in both recurrence-free and cancer-related survival according to multivariate analysis (HR = 0.428, 95%CI: 0.217 - 0.845, HR = 0.098, 95%CI: 0.013 - 0.767). No significant association was found between the expressions of two cadherins and postoperative progression. CONCLUSION: Although the expressions of E-cadherin and N-cadherin appear to be correlated with survival outcomes in bladder cancer, N-E cadherin switch may be a better predicator for postoperative recurrence and cancer-related survival.
Assuntos
Caderinas/metabolismo , Carcinoma de Células de Transição/patologia , Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Carcinoma de Células de Transição/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/metabolismoRESUMO
Background: M2 macrophages are well accepted to promote cancer progression in the prostate cancer (PCa). Paracrine is the principally studied mode of communication between M2 macrophages and tumor cells. In addition to this, we present here a novel model to demonstrate these cellular communications. Methods: PCa cells were co-cultured with THP-1/ human peripheral blood mononuclear cells derived M2 macrophages in direct contact manner. Cancer cell proliferation and invasion were examined to explain how direct contact communicates. Cell-based findings were validated in two xenograft models and patients samples. Results: M2 macrophage direct contact induced a higher proliferation and invasion in PCa cells when compared with noncontact coculture manner. In direct contact manner, NOTCH1 pathway was greatly activated in PCa cells, induced by elevated γ-secretase activity and higher coactivator MAML2 expression. Additionally, blocking γ-secretase activity and depletion of MAML2 completely abolished M2 macrophage direct contact-mediated PCa cell proliferation and invasion. In vivo, inhibiting NOTCH1 signalling impaired M2 macrophage-mediated PCa tumor growth and lung metastasis. Notably, M2 macrophage infiltration as well as high NOTCH1 signaling in cancer cells indicated more aggressive features and worse survival in PCa patients. Conclusion: Our results demonstrated the cell-cell direct contact pattern is an important way in PCa microenvironment cell communication. In this manner, elevated γ-secretase activity and MAML2 expression induced higher NOTCH1 signalling in PCa cells, which increased tumor cells proliferation and invasion. This potentially provided a therapeutic target for PCa.
Assuntos
Neoplasias da Próstata , Macrófagos Associados a Tumor , Masculino , Humanos , Secretases da Proteína Precursora do Amiloide , Leucócitos Mononucleares/metabolismo , Linhagem Celular Tumoral , Neoplasias da Próstata/metabolismo , Proliferação de Células , Microambiente Tumoral , Receptor Notch1/genéticaRESUMO
OBJECTIVE: To investigate the long-term efficacy of ureteral reconstruction with tubularized peritoneal free grafts for the treatment of avulsion of ureteral mucosa in animal models. METHODS: The model of avulsion of ureteral mucosa was established in 12 adult dogs. Then they were divided into Group A (n = 6, length of avulsed mucosa at 4 cm) and Group B (n = 6, length of avulsed mucosa at 6 cm). And the tubularized peritoneal free grafts and ureteral stents were implanted into the injured ureters. The curative effect was observed by intravenous urethrogram (IVU) and histological examination at Week 24 post-operation. RESULTS: Severe stenosis was observed by IVU in 1 dogs in Groups A and B respectively. In the remaining 10 dogs, IVU showed normal size and morphology of kidneys. There was no hydronephrosis. And no obvious stricture of ureteral part was observed for mucosa substitutes made of peritoneal free grafts. In all 10 dogs without stenosis of both groups, peritoneal membrane was replaced by integrated transitional epithelium. And there was no obvious stricture. Collagen fibers were arranged parallel to mucosal surface. CONCLUSION: For avulsion of ureteral mucosa under 6 cm, reconstruction with tubularized peritoneal free grafts as mucosa substitutes is an effective method. And its long-term efficacy is satisfactory.
Assuntos
Peritônio/transplante , Procedimentos de Cirurgia Plástica/métodos , Doenças Ureterais/cirurgia , Animais , Modelos Animais de Doenças , Cães , Mucosa/patologia , Doenças Ureterais/patologiaRESUMO
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.
Assuntos
Valor Preditivo dos Testes , Antígeno Prostático Específico/análise , Neoplasias da Próstata/diagnóstico , Idoso , Idoso de 80 Anos ou mais , China , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Estudos Retrospectivos , Sensibilidade e Especificidade , Estatísticas não ParamétricasRESUMO
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.
Assuntos
Catéteres , Materiais Revestidos Biocompatíveis/farmacologia , Macrófagos/patologia , Nanosferas/química , Transdução de Sinais , Dióxido de Silício/química , Uretra/patologia , Cicatrização/efeitos dos fármacos , Animais , Polaridade Celular , Cães , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , NF-kappa B/metabolismo , Nanosferas/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Porosidade , Próstata/patologia , Próstata/cirurgia , Reepitelização/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Selênio/química , Células THP-1 , Ressecção Transuretral da Próstata , Uretra/efeitos dos fármacosRESUMO
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.
Assuntos
Inibidores de 5-alfa Redutase/farmacologia , Fator de Crescimento Insulin-Like I/metabolismo , Próstata/citologia , Próstata/efeitos dos fármacos , Animais , Autofagia/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Nus , Proteínas Associadas aos Microtúbulos/metabolismo , Próstata/metabolismo , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Receptores Androgênicos/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismoRESUMO
OBJECTIVE: To investigate the clinical and pathological features, diagnosis and treatment of cystic lymphangioma of the spermatic cord. METHODS: One case of cystic lymphangioma of the spermatic cord in a 71-year-old patient was retrospectively analyzed and the relevant literature was reviewed. RESULTS: The patient, presented with spermatic cord hydrocele, was treated by local excision of the tumor, which was pathologically diagnosed as cystic lymphangioma. No relapse was found during a 3-month follow-up after the operation. CONCLUSION: Lymphangioma of the spermatic cord is a benign tumor. Preoperation ultrasonography and CT are important for determining the location and nature of lymphangioma. Surgical excision is an effective option for the treatment of cystic lymphangioma of the spermatic cord.
Assuntos
Neoplasias dos Genitais Masculinos/diagnóstico , Linfangioma Cístico/diagnóstico , Cordão Espermático/patologia , Idoso , Neoplasias dos Genitais Masculinos/cirurgia , Humanos , Linfangioma Cístico/cirurgia , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the curative effects of different reconstruction methods in the treatment of avulsion of ureteral mucosa. METHODS: Twenty adult dogs were randomly divided into 4 equal groups: Group III (control group in which the ureter was incised and a ureteral stent was placed therein), Group II (the ureter was incised and a ureteral mucosal avulsion about 5 cm in length was created and the avulsed mucosa was replaced to the original position and a ureteral stent was placed in addition), Group III (a piece of bladder mucosa was incised and grafted to the avulsed ureter mucosa and a ureteral stent was placed in addition), and Group IV (a tubularized peritoneal free graft and a ureteral stent were placed in the avulsed ureter). Ten weeks later intravenous pyelography (IVP) was conducted to observe the images of ureter. Then the dogs were killed and pathological examination of the reconstructed ureter was conducted. RESULTS: IVP showed atresia and stenosis in all control group dogs. No obvious stenosis was observed in Groups II and IV. Pathological examination showed that the newly grown mucosa was similar to the normal ureter structure in Groups II and IV. In Group III one dog died, slight distension of ureter superior to the reconstructed part was found in 2 dogs, and no obvious stenosis was observed in 3 dogs. CONCLUSION: Orthotopic replacement and tabularized peritoneal free grafting with placement of ureter stent are effective in treatment of avulsion of ureter mucosa. Bladder mucosa can be used as selectable material.
Assuntos
Procedimentos de Cirurgia Plástica/métodos , Doenças Ureterais/cirurgia , Animais , Cães , Mucosa/patologia , Distribuição Aleatória , Doenças Ureterais/patologia , Bexiga UrináriaRESUMO
OBJECTIVES: Aberrant androgen receptor (AR) signaling functions are implicated in prostate cancer (PCa) pathogenesis. Here, we studied interactions between miR-185 and the bromodomain containing 8 isoform 2 (BRD8 ISO2) to investigate indirect mechanisms of miR-185 with respect to AR function through BRD8 ISO2 in PCa. METHODS: Putative miRNA response element (MRE) of miR-185 in 3'-untranslated region (3'-UTR) of BRD8 ISO2 mRNA was predicted by software and confirmed using dual-luciferase assays and Ago2 immunoprecipitation. BRD8 and AR expression were determined by qRT-PCR and Western blot in PCa cells and tissues. MMTV-Fluc reporter plasmids and dual-luciferase assays were used to evaluate AR activity. RESULTS: MRE prediction, dual-luciferase assays and Ago2 immunoprecipitation confirmed that miR-185 is capable of binding the 3'-UTR of BRD8 ISO2 mRNA. QRT-PCR and Western blot indicated that BRD8 ISO2 expression is decreased by miR-185 mimic transfection while increased by miR-185 inhibitor transfection. MMTV-Fluc reporter assays revealed that miR-185 can attenuate AR function by suppressing BRD8 ISO2. Additionally, Pearson's correlation analyses confirmed that BRD8 ISO2 mRNA expression is inversely correlated with miR-185 expression in clinical specimens. CONCLUSION: In addition to suppression of AR expression, miR-185 can attenuate AR function indirectly by suppressing BRD8 ISO2. MiR-185 and BRD8 ISO2 may be possible therapeutic targets for PCa treatment.
Assuntos
MicroRNAs/metabolismo , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/metabolismo , Receptores dos Hormônios Tireóideos/metabolismo , Regiões 3' não Traduzidas , Antagonistas de Receptores de Andrógenos/metabolismo , Sítios de Ligação , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Variação Genética , Humanos , Masculino , Neoplasias da Próstata/genética , Ligação Proteica , Biossíntese de Proteínas , Domínios Proteicos , Isoformas de Proteínas/metabolismo , RNA Mensageiro/metabolismo , Receptores dos Hormônios Tireóideos/genética , Fatores de TranscriçãoRESUMO
OBJECTIVE: To investigate the effect of creatine phosphate sodium (sodium phosphocreatine) on miRNA378, miRNA378* and calumenin mRNA in adriamycin-injured suckling mouse myocardium. METHODS: The suckling mouse myocardium of primary culture were randomly divided into control group, adriamycin group and treatment group. To identify the suckling mouse myocardium, Smooth muscle actin-α (α-SMA) was monitored by immunohistochemical method. Cardiac function was evaluated by transthoracic echocardiography. The mRNA change of miRNA378, miRNA378* and calumenin mRNA were detected by quantitative real-time PCR. The expression of calumenin and GRP78 were identified by western blot. RESULTS: Mitochondrial damage and vacuolization were found in adriamycin-induced suckling mouse myocardium compared with control group, while creatine phosphate sodium could reduce this phenomenon. Compared with the control group, the mRNA of miRNA378, miRNA378* and calumenin in adriamycin group was reduced, while creatine phosphate sodium could increase this phenomenon. The expression of calumenin and GRP78 were decreased after adriamycin treatment in suckling mouse myocardiums, creatine phosphate sodium increased the expression of calumenin and GRP78. CONCLUSIONS: The results of this experiment might be closely related to the effects of that creatine phosphate sodium reduced the pathological mechanism of suckling mouse myocardium with myocarditis caused by adriamycin.
Assuntos
Proteínas de Ligação ao Cálcio/genética , Doxorrubicina/efeitos adversos , MicroRNAs/genética , Miócitos Cardíacos/efeitos dos fármacos , Fosfocreatina/farmacologia , Actinas/metabolismo , Animais , Células Cultivadas , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Camundongos , Miocárdio/patologia , Cultura Primária de Células , RNA Mensageiro/genéticaRESUMO
OBJECTIVE: To investigate the role of fatty acid synthase (FASN) in bladder transitional cell carcinoma (BTCC). METHODS: FASN expression was investigated in non-muscle-invasive BTCC tissue specimens by immunohistochemistry and BTCC cell lines by Western blot. After treatment with FASN-siRNA or FASN inhibitor cerulenin (Cer), the proliferation and apoptosis of BTCC cell lines 5637 and 253 J were determined by cell counting Kit-8 (CCK8) assay and flow cytometry respectively. The expression of p-AKT, cyclin D1 (CCND1), and apoptosis-related proteins were detected by Western blot. RESULTS: High levels of FASN expression were observed in 59% (32/54) of non-muscle-invasive BTCC tissue specimens, and FASN expression was associated with histologic grade (P < .05) and recurrence (P < .05). FASN expression was high in 6 BTCC cell lines. FASN inhibitor Cer and FASN-siRNA produced the increased apoptosis and decreased proliferation of bladder cancer cells, and caused inactivity of AKT and downregulation of CCND1. Furthermore, treatment of BTCC cell lines with Cer resulted in apoptosis via the caspase-dependent pathway involving inactivation of antiapoptotic bcl-2 protein. CONCLUSION: Our data suggest that FASN plays an important role in BTCC development. Targeting FASN may be a new therapeutic strategy for BTCC.
Assuntos
Apoptose/efeitos dos fármacos , Carcinoma de Células de Transição/enzimologia , Carcinoma de Células de Transição/patologia , Cerulenina/farmacologia , Ácido Graxo Sintases/antagonistas & inibidores , Ácido Graxo Sintases/fisiologia , Inibidores da Síntese de Ácidos Graxos/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Neoplasias da Bexiga Urinária/enzimologia , Neoplasias da Bexiga Urinária/patologia , Idoso , Feminino , Humanos , Masculino , Células Tumorais CultivadasRESUMO
The objectives of this study were to investigate the dysplasia, histological malformations, and genetic abnormalities in male rats induced by maternal exposure to di-n-butyl phthalate (DBP). Here we report novel findings concerning developmental abnormalities resulting from prenatal exposure to DBP, which leads to significant anorectal malformations (ARMs) in male rat offspring. The incidence of ARMs was 39.5% in male offspring and all abnormal pups were complicated with secondary megacolon. General images, histological analysis and anatomy examination confirmed the malformation. The development abnormalities such as decreased bodyweight (BW) and anogenital distance (AGD), shortened body lengths (with tail removed), as well as increased abdominal circumference were observed at different developmental stages of ARMs in male rat. The developmental abnormalities in both solid organs (brain, heart, liver, spleen, lung and kidney) and reproductive organs (testes and epididymis) of abnormal pubs on PND35 were also investigated. In addition, the serum testosterone (T) level of ARMs in male rats on PND1 was significantly lower than that of controls with accompanying reduced expression of androgen receptor (AR), sonic hedgehog (Shh) and bone morphogenetic protein 4 (Bmp4) mRNA from tissues of the terminal rectum. These results conclusively demonstrate for the first time that in utero exposure to DBP leads to an increased likelihood for the development of ARMs and subsequent complicating megacolon in male rat offspring.
Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Anormalidades Múltiplas/induzido quimicamente , Canal Anal/anormalidades , Dibutilftalato/toxicidade , Reto/anormalidades , Animais , Animais Recém-Nascidos , Peso Corporal/efeitos dos fármacos , Feminino , Masculino , Megacolo/induzido quimicamente , Plastificantes/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos , Ratos Sprague-Dawley , Testosterona/sangueRESUMO
This paper presents a typical Clinical Information System for ICU and its design and implementation. This system is able to capture and archive vital data from the monitor network, providing a whole digital solution in ICU. These vital data can be used in quantitative analysis in the computer-assisted decision support.
Assuntos
Tomada de Decisões Assistida por Computador , Sistemas de Informação , Unidades de Terapia Intensiva , Monitorização Fisiológica , Design de SoftwareRESUMO
Firstly, IHE technical framework is introduced in this paper, and the sub-framework of Schedule Workflow is also described. Secondly, the development of IHE in Japan and the formation of IHE-J are presented, and in combination with IDS system's practice in IHE-J, some ideas about developing IHE in China and the relative methods of implementation are discussed.