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1.
Cancer Med ; 12(24): 21820-21829, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38014481

RESUMO

BACKGROUND: Prediction of clinically significant prostate cancer (csPCa) is essential to select biopsy-naive patients for prostate biopsy. This study was to develop and validate a nomogram based on clinicodemographic parameters and exclude csPCa using prostate-specific antigen density (PSAD) stratification. METHODS: Independent predictors were determined via univariate and multivariate logistic analysis and adopted for developing a predictive nomogram, which was assessed in terms of discrimination, calibration, and net benefit. Different PSAD thresholds were used for deciding immediate biopsies in patients with Prostate Imaging-Reporting and Data System (PI-RADS) 3 lesions. RESULTS: A total of 932 consecutive patients who underwent ultrasound-guided transperineal cognitive biopsy were enrolled in our study. In the development cohort, age (odds ratio [OR], 1.075; 95% confidence interval [CI], 1.036-1.114), PSAD (OR, 6.003; 95% CI, 2.826-12.751), and PI-RADS (OR, 3.419; 95% CI, 2.453-4.766) were significant predictors for csPCa. On internal and external validation, this nomogram showed high areas under the curve of 0.943, 0.922, and 0.897, and low Brier scores of 0.092, 0.102, and 0.133 and insignificant unreliability tests of 0.713, 0.490, and 0.859, respectively. Decision curve analysis revealed this model could markedly improve clinical net benefit. The probability of excluding csPCa was 98.51% in patients with PI-RADS 3 lesions and PSAD <0.2 ng/ml2 . CONCLUSION: This novel nomogram including age, PSAD, and PI-RADS could be applied to accurately predict csPCa, and 44.08% of patients with equivocal imaging findings plus PSAD <0.2 ng/ml2 could safely forgo biopsy.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Nomogramas , Antígeno Prostático Específico , Imageamento por Ressonância Magnética/métodos , Biópsia Guiada por Imagem/métodos , Estudos Retrospectivos
2.
Front Oncol ; 13: 1067987, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37035172

RESUMO

Background: There is growing evidence that immune cells are strongly associated with the prognosis and treatment of clear cell renal cell carcinoma (ccRCC). Our aim is to construct an immune subtype-related model to predict the prognosis of ccRCC patients and to provide guidance for finding appropriate treatment strategies. Methods: Based on single-cell analysis of the GSE152938 dataset from the GEO database, we defined the immune subtype-related genes in ccRCC. Immediately afterwards, we used Cox regression and Lasso regression to build a prognostic model based on TCGA database. Then, we carried out a series of evaluation analyses around the model. Finally, we proved the role of VMP1 in ccRCC by cellular assays. Result: Initially, based on TCGA ccRCC patient data and GEO ccRCC single-cell data, we successfully constructed a prognostic model consisting of five genes. Survival analysis showed that the higher the risk score, the worse the prognosis. We also found that the model had high predictive accuracy for patient prognosis through ROC analysis. In addition, we found that patients in the high-risk group had stronger immune cell infiltration and higher levels of immune checkpoint gene expression. Finally, cellular experiments demonstrated that when the VMP1 gene was knocked down, 786-O cells showed reduced proliferation, migration, and invasion ability and increased levels of apoptosis. Conclusion: Our study can provide a reference for the diagnosis and treatment of patients with ccRCC.

3.
Int J Surg ; 109(5): 1342-1349, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37026834

RESUMO

BACKGROUND: Peripheral electrical nerve stimulation is a routinely recommended treatment for non-neurogenic overactive bladder but has not been approved for patients with neurogenic lower urinary tract dysfunction (NLUTD). This systematic review and meta-analysis was to elucidate the efficacy and safety of electrostimulation and thus provide firm evidence for treating NLUTD. MATERIALS AND METHODS: We systematically performed the literature search through PubMed, Web of Science, and Cochrane Library databases in March 2022. The eligible studies were identified across the inclusion criteria and the data on urodynamic outcomes, voiding diary parameters, and safety was collected to quantitatively synthesize the pooled mean differences (MDs) with 95% CIs. Subgroup analyses and sensitivity analyses were subsequently used to investigate the possible heterogeneity. This report was achieved in accordance with the preferred reporting items for systematic reviews and meta-analyses statement. RESULTS: A total of 10 studies involving 464 subjects and 8 studies with 400 patients were included for systematic review and meta-analysis, respectively. The pooled effect estimates indicated that electrostimulation could significantly improve urodynamic outcomes, including maximum cystometric capacity (MD=55.72, 95% CI 15.73, 95.72), maximum flow rate (MD=4.71, 95% CI 1.78, 7.65), maximal detrusor pressure (MD=-10.59, 95% CI -11.45, -9.73), voided volume (MD=58.14, 95% CI 42.97, 73.31), and post-void residual (MD=-32.46, 95% CI -46.63, -18.29); for voiding diary parameters, patients undergoing electrostimulation showed lower MDs of incontinence episodes per 24 h (MD=-2.45, 95% CI -4.69, -0.20) and overactive bladder symptom score (MD=-4.46, 95% CI -6.00, -2.91). In addition to surface redness and swelling, no stimulation-related severe adverse events were reported else. CONCLUSIONS: The current evidence demonstrated that peripheral electrical nerve stimulation might be effective and safe for managing NLUTD, whereas more reliable data from large-scale randomized controlled trials are necessary to strengthen this concept.


Assuntos
Bexiga Urinaria Neurogênica , Bexiga Urinária Hiperativa , Incontinência Urinária , Humanos , Bexiga Urinária Hiperativa/terapia , Bexiga Urinaria Neurogênica/terapia , Urodinâmica , Bexiga Urinária
4.
Front Oncol ; 12: 906370, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35646683

RESUMO

Objective: This meta-analysis was to investigate the effects of neoadjuvant chemohormonal therapy (NCHT) on patients with prostate cancer (PCa) before radical prostatectomy (RP) and attempt to provide meaningful evidence. Methods: A systematic search was performed using the PubMed, Web of Science, and Cochrane Library databases in February 2022 based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The relevant studies were critically screened and we extracted the data of demography, postoperative pathology, and survival to calculate the pooled effect sizes. Subgroup analyses and sensitivity analyses were used to explore the source of heterogeneity. Results: Six identified studies involving 1717 subjects were included according to the selection criteria. There was no significant difference between NCHT plus RP and RP alone groups regarding lymph node involvement (risk ratio [RR]=1.03, 95% confidence interval [CI]: 0.57-1.87, P=0.92). However, NCHT prior to RP significantly decreased the rates of positive surgical margin (PSM, RR=0.35, 95% CI: 0.22-0.55, P<0.0001) and seminal vesicle invasion (SVI, RR=0.78, 95% CI: 0.65-0.95, P=0.01), and increase pathological downstaging (RR=1.64, 95% CI: 1.17-2.29, P=0.004). Additionally, biochemical recurrence-free survival (BRFS) and overall survival (OS) were significantly prolonged under the administration of NCHT (HR=0.54, 95% CI: 0.34-0.85, P=0.008 and HR=0.67, 95% CI: 0.48-0.94, P=0.02, respectively). Conclusions: Compared to the RP alone group, patients with NCHT plus RP showed significant improvements in PSM, SVI, pathological downstaging, BRFS, and OS, whereas further multicenter randomized controlled trials are needed to consolidate this concept.

5.
J Med Food ; 25(7): 722-731, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35758826

RESUMO

Interstitial cystitis (IC) is featured by apoptosis and chronic inflammation in bladder tissue. We aimed to evaluate the effect of echinacoside (ECH), which is known to modulate inflammation and apoptosis on IC using relevant models. We established a mouse model of cystitis using cyclophosphamide (CYP) and treated human urothelium cells (SV-HUC-1) with lipopolysaccharide (LPS) + ATP as in vitro model. The bladder function was tested by urodynamics. Apoptosis of bladder cells was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Expressions of apoptosis-associated and inflammation-related proteins were assessed using western blotting. Treatment with ECH significantly improved bladder function, reduced inflammatory damage, and decreased apoptosis in the models. Furthermore, ECH decreased the phosphorylation levels of IκB and NF-κB(p65), and upregulated the expression of peroxisome proliferator-activated receptor gamma (PPARγ), which are related to apoptosis and inflammation in CYP-induced mouse cystitis. Moreover, ECH did not reduce apoptosis of urothelial cells after treatment with PPARγ antagonist GW9662. Our findings suggest that ECH might have protective effect against IC in bladder and be mediated through modulation of the PPARγ/NF-κB pathway.


Assuntos
Cistite Intersticial , Cistite , Animais , Ciclofosfamida , Cistite/induzido quimicamente , Cistite/tratamento farmacológico , Cistite Intersticial/induzido quimicamente , Cistite Intersticial/metabolismo , Glicosídeos , Humanos , Inflamação/metabolismo , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Bexiga Urinária/metabolismo
6.
Cell Biol Int ; 46(1): 83-95, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34519127

RESUMO

Dysregulated hematological and neurological expressed 1-like (HN1L) has been implicated in carcinogenesis of difference cancers, including hepatocellular carcinoma and breast cancer. However, the role of HN1L in the progression of prostate cancer (PCA) remains unknown. Therefore, we aimed to investigate the role of HN1L in stemness and progression of PCA. The expression of HN1L in PCA tissues and cells was determined by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), western blot analysis, and/or immunohistochemistry (IHC). CD133+ cells were sorted from PCA cells using magnetic fluorescence cell sorting technology and were considered as cancer stem cells (CSCs). Sphere formation assays, transwell assays, and animal experiments were conducted to assess cell stemness, migration, invasion, and in vivo tumorigenesis, respectively. The results showed that HN1L expression was higher in PCA tissues and cells as compared with normal tissues and cells, as well as in CD133+ cells as compared with CD133- cells. HN1L knockdown significantly decreased the expression levels of CSC markers including OCT4 (POU class 5 homeobox 1), CD44, and SRY-box transcription factor 2, inhibited cell migration, invasion, and tumorigenesis and decreased the number of tumor spheroids and CD133+ cell population. Furthermore, we found that HN1L could bind to forkhead box P2 (FOXP2) and positively regulated transforming growth factor-ß (TGF-ß) expression via upregulation of FOXP2. In addition, the overexpression of TGF-ß in HN1L-knockdown PCA cells increased the number of tumor spheroids and CD133+ cell population, as well as enhanced cell migration and invasion. Collectively, this study demonstrates that HN1L promotes stem cell-like properties and cancer progression by targeting FOXP2 through TGF-ß signaling pathway in PCA.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neoplasias da Próstata/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Antígeno AC133/genética , Antígeno AC133/metabolismo , Animais , Movimento Celular , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Endogâmicos BALB C , Proteínas Associadas aos Microtúbulos/genética , Invasividade Neoplásica , Células-Tronco Neoplásicas/patologia , Células PC-3 , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Transdução de Sinais , Esferoides Celulares , Fator de Crescimento Transformador beta/genética
7.
Front Surg ; 8: 710594, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540886

RESUMO

Purpose: The purpose of this study is to evaluate the efficacy of management and follow-up practices in repeat retropubic mid-urethral synthetic sling (MUS) procedure after transobturator tape/tension-free vaginal tape-obturator (TOT/TVT-O) failure, and to clarify the possible etiology of recurrent stress urinary incontinence. Methods: The charts of all women patients who underwent tension-free vaginal tape (TVT) slings after previous failed transobturator MUS procedures between February 2012 and November 2018 at a single center were reviewed retrospectively. The transperineal ultrasound was performed to assess the pre-operative or post-operative urethral mobility and location of the slings. Furthermore, some essential evaluations were also made, mainly including medical history, physical examination, 1 h pad test, and urodynamic study. Finally, primary outcomes were evaluated according to the above items at 3, 6, and 12 months after the second operation, respectively. Results: Thirty-five patients were included in the primary transobturator MUS sling procedure. At the 6 months follow-up, 32 (91.42%) patients were socially continent and negative in 1 h pad test. The transperineal ultrasound measurement results revealed that the bladder neck descent (BND) values were significantly decreased after the repeat sling operation, and better urinary continence function was observed according to the post-operative urodynamic study. Multifactorial etiologies resulted in recurrent stress urinary incontinence (SUI), including poor surgical technique, inadequate sling tension when treating ISD, and inappropriate sling position. Then the detail of the surgical procedure varied with the results of pre-operative evaluations, affecting the validity of the second sling. Conclusion: Recurrent SUI has resulted from multi factors, pre-operative urodynamic study and transperineal ultrasound might be valuable tools to guide repeat sling operation and predict post-operative outcomes. A repeat TVT procedure may be regarded as a remedial measure for a failed transobturator MUS operation.

8.
Front Cell Infect Microbiol ; 11: 711746, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527602

RESUMO

Interstitial cystitis (IC) is a clinical syndrome characterized by frequency, urgency, and bladder pain or pelvic pain; however, the underlying pathophysiological mechanisms and diagnostic markers are unknown. In this study, microbiome and metabolome analysis were used to explain the urine signatures of IC patients. Urine samples from 20 IC patients and 22 control groups were analyzed by using 16S rRNA sequence and liquid chromatography coupled with mass spectrometry. Four opportunistic pathogen genera, including Serratia, Brevibacterium, Porphyromonas, and Citrobacter, were significantly upregulated in IC group. The altered metabolite signatures of the metabolome may be related to sphingosine metabolism, amino acid metabolism, and fatty acid biosynthesis. Meanwhile, the associations were observed between different metabolites and microbiomes of IC. The present study suggests that the combined signatures of IC in urine microbiome and metabolome may become its prospective diagnostic markers.


Assuntos
Cistite Intersticial , Microbiota , Biomarcadores , Humanos , Metaboloma , Estudos Prospectivos , RNA Ribossômico 16S/genética
9.
Stem Cells Dev ; 30(18): 934-945, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34289746

RESUMO

Prostate cancer (PCa) is a malignant tumor that originates in the male genitourinary system. Downregulation of death-associated protein kinase 1 (DAPK1) is closely related to PCa. Little is known about the functional role of DAPK1 in regulating cancer stem cell (CSC)-like characteristics of PCa cells, and we have conducted research on this topic. Compared with tumor-adjacent normal tissues, DAPK1 was severely downregulated in tumor tissues of PCa patients. DAPK1 expression was also reduced in PCa cell lines with respect to that in normal prostate cells. Moreover, we sorted PCa-CSCs (PCa-CD133+ cells) from PCa cells. PCa-CD133+ cells also exhibited a reduced DAPK1 level and elevated levels of stem cell markers (CD44, OCT4, and SOX2). DAPK1 knockdown promoted sphere formation and enhanced the proportions of PCa-CD133+/PCa-CD133- cells. Inhibition of DAPK1 also accelerated migration and invasion of PCa-CD133+ cells. In addition, DAPK1 interacted with zinc finger E-box-binding homeobox-1 (ZEB1) and repressed ZEB1 expression in PCa-CD133+ cells. DAPK1 suppressed Hippo/YAP signaling pathway by interacting with ZEB1. Finally, we generated a tumor xenograft model to verify the effect of PCa-CD133+ cells following DAPK1 overexpression on tumor growth of PCa. DAPK1 overexpression inhibited tumor growth of PCa and repressed the expression of ZEB1, YAP, and TAZ in the tumor tissues of PCa mice. In conclusion, reduced DAPK1 expression promoted stem cell-like characteristics of PCa cells through activating ZEB1 via Hippo/YAP signaling pathway. Taken together, this work sheds lights on the potential of DAPK1 as a target for PCa therapeutics from bench to clinic.


Assuntos
Próstata , Neoplasias da Próstata , Animais , Linhagem Celular Tumoral , Proliferação de Células , Proteínas Quinases Associadas com Morte Celular/genética , Proteínas Quinases Associadas com Morte Celular/metabolismo , Regulação para Baixo , Humanos , Masculino , Camundongos , Células-Tronco Neoplásicas/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Transdução de Sinais , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo
10.
Oxid Med Cell Longev ; 2021: 4009308, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34306306

RESUMO

OBJECTIVE: To investigate the protective effect and molecular mechanism of nuclear factor E2-related factor 2 (Nrf2) pathway in interstitial cystitis (IC). METHODS: We established a mouse model of IC by cyclophosphamide (CYP) in wild-type mice and Nrf2 gene knockout mice. We examined the histological and functional alterations, the changes of oxidative stress markers, and the expression of the antioxidant genes downstream of Nrf2 pathway. RESULTS: After CYP administration, the mice showed urinary frequency and urgency, pain sensitization, decreased contractility, bladder edema, and oxidative stress disorder. Notably, the Nrf2-/- CYP mice had more severe symptoms. The mRNA and protein levels of antioxidant genes downstream of Nrf2 pathway were significantly upregulated in the Nrf2+/+ CYP mice, while there were no significant changes in the Nrf2-/- CYP mice. CONCLUSION: Nrf2 pathway protects bladder injury and ameliorates bladder dysfunction in IC, possibly by upregulating antioxidant genes and inhibiting oxidative stress.


Assuntos
Cistite/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Bexiga Urinária/metabolismo , Animais , Antioxidantes/metabolismo , Ciclofosfamida/farmacologia , Cistite/induzido quimicamente , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Substâncias Protetoras/farmacologia
11.
Exp Ther Med ; 21(5): 501, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33791010

RESUMO

Diabetic cystopathy (DCP) is one of the most common complications of diabetes mellitus (DM). A previous study reported that caffeine may improve bladder dysfunction in rats with DM. The aim of the present study was to investigate the mechanisms behind the capacity for caffeine to improve bladder function in rats with DM. Sprague Dawley rats were divided into four groups: control, caffeine, DM and DM plus caffeine treatment (DM + caffeine). Bladder function was measured by urodynamic analyses. The levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and calcitonin gene-related peptide (CGRP) in the bladder tissue were detected by ELISA. Apoptosis in the dorsal root ganglion (DRG) was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, cleaved caspase-3, caspase-9 and cleaved caspase-9 proteins in the DRG were detected by western blotting. Following treatment with caffeine, the urination time and micturition interval of rats with DM were improved, the bladder wet weight was decreased, and the maximum voiding pressure was increased. Relative to that in the DM group, the expression levels of NGF, BDNF and CGRP in the bladder tissue of DM + caffeine rats increased; cellular apoptosis in the DRG of DM + caffeine rates decreased; and the expression levels of Bcl-2, Bax, cleaved caspase-3 and cleaved caspase-9 proteins in the DRG of DM + caffeine rats were restored to a certain extent. In conclusion, caffeine promotes bladder function in rats with DM through a protective effect on DRG.

12.
Zhonghua Nan Ke Xue ; 26(9): 838-843, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33377710

RESUMO

Radical prostatectomy is a standard surgical strategy for prostate cancer though with a few postoperative complications such as urinary incontinence, erectile dysfunction and vesicle urethral anastomotic stricture. Post-prostatectomy incontinence, as a common complication seriously affecting the patient's quality of life, is mainly diagnosed according to the clinical symptoms and the results of urodynamic and imaging examinations. Patients with post-prostatectomy incontinence may undergo corresponding anatomic and functional changes, which can be clearly and directly observed in imaging examination. This review focuses on the advances in the imaging studies of post-prostatectomy urinary incontinence from the perspectives of MRI, ultrasound and cystourethrography.


Assuntos
Prostatectomia/efeitos adversos , Incontinência Urinária , Humanos , Masculino , Neoplasias da Próstata/cirurgia , Qualidade de Vida , Incontinência Urinária/diagnóstico por imagem , Incontinência Urinária/etiologia , Urodinâmica
13.
Int J Surg ; 84: 13-17, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33080412

RESUMO

BACKGROUND: Sacral neuromodulation (SNM) has been widely used to treat lower urinary tract dysfunction. Studies have shown a higher conversion rate among female patients than among male patients. However, the influence of gender on the clinical effectiveness of SNM remains unclear. We aimed to confirm whether patients of both genders show similar benefits after SNM treatment. MATERIALS AND METHODS: Clinical data of patients with lower urinary tract symptoms associated with pelvic floor dysfunction (overactive bladder, neurogenic bladder, interstitial cystitis/painful bladder syndrome, idiopathic urinary retention) treated with SNM in 10 medical centres in China between January 2012 and December 2016 were retrospectively collected. The patients were classified by gender. Variations in objective (voiding diary) and subjective scores in the baseline, testing, and last follow-up periods were compared. Data were analysed using statistical measures. RESULTS: The study included 203 patients (93 males, 110 females). There were no statistical differences in baseline information between the two groups, both groups showed improvement over time. Unsatisfactory improvement was observed in the quality of life and sexual life scores of both groups over the entire treatment period (all p>0.05). Although there was a difference in the maximum voiding volume between the groups at baseline, no difference was observed at the last follow-up (p = 0.004, p = 0.044, p = 0.124), unlike in the average volume where a difference was noted at the last follow-up (p = 0.085, p = 0.964, p = 0.031). While there were no differences in quality of life, sexual life, or pelvic pain and urinary urgency frequency scores at baseline, a significant difference was observed at the last follow-up, and the degree of improvement was less among female patients (p = 0.836, p = 0.131, p = 0.015; p = 0.294, p = 0.265, p = 0.013; p = 0.299, p = 0.087, p = 0.015). CONCLUSION: SNM treatment elicited a similar effect on patients of both gender; however, a significant difference was observed regarding patient satisfaction with the treatment. Further preoperative patient education, especially, for female patients with interstitial cystitis/painful bladder syndrome may improve patient satisfaction.


Assuntos
Terapia por Estimulação Elétrica/métodos , Sintomas do Trato Urinário Inferior/terapia , Adulto , Idoso , Feminino , Humanos , Sintomas do Trato Urinário Inferior/psicologia , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Retrospectivos , Sacro , Caracteres Sexuais
14.
Onco Targets Ther ; 13: 7897-7906, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884284

RESUMO

PURPOSE: Long non-coding RNAs (lncRNAs) are involved in the development of various tumors including prostate cancer. The purpose of this study was to explore the function of a natural antisense RNA, IDH1-AS1, exerting potential carcinogenic effects in prostate cancer through a novel molecular mechanism. MATERIALS AND METHODS: GEPIA and CCLE databases were searched to identify alterations in the expression of IDH1-AS1, which were then verified by RT-qPCR in 20 pairs of matched tumor and normal tissue samples. Subsequently, CCK-8, EdU, and transwell assays were conducted to investigate the carcinogenic effect of IDH1-AS1. RT-qPCR, Western blot, and isocitrate dehydrogenase 1 (IDH1) enzyme activity assays were used to explore the functional relationship between IDH1-AS1 and its sense gene IDH1. RESULTS: IDH1-AS1 expression was found to be significantly increased in prostate cancer tissues and cell lines. IDH1-AS1 knockdown significantly inhibited the proliferation and migration of prostate cancer cells. Interestingly, RT-qPCR and Western blot analyses revealed that IDH1-AS1 did not significantly affect the expression of IDH1 mRNA or protein but was involved in the regulation of IDH1 enzyme activity in prostate cancer cells. CONCLUSION: Our experiments revealed that the carcinogenic effects of IDH1-AS1 in prostate cancer may depend on a new molecular mechanism, which directly alters IDH1 enzyme activity. Our findings indicate that IDH1-AS1 is a novel candidate target for prostate cancer treatment.

15.
Stem Cell Res Ther ; 11(1): 278, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32650831

RESUMO

BACKGROUND: Diabetic cystopathy (DCP) is a chronic complication of diabetes mainly within the submucosal and muscular layers of the bladder due to the hyperglycemia-induced ischemia. As no effective therapies are currently available, the administration of optimized mesenchymal stem cells (MSCs) provides a potential treatment of DCP. Thus far, new strategy, such as genetic modification of MSCs, has been developed and has shown promising outcomes of various disorders. METHODS: This study was conducted using integrin-linked kinase (ILK) gene-modified bone marrow-derived stem cells (BMSCs) for streptozotocin (STZ)-induced diabetic cystopathy in a rat model. In total, 68 male Sprague-Dawley rats were randomized into five groups: sham control (control group, n = 10); DCP model alone (DM group, n = 10); DCP rats intravenously treated with BMSCs (BMSC group, n = 16); DCP rats accepted adenoviral vector-infected BMSCs (Ad-null-BMSC group, n = 16) and DCP rats accepted ILK adenoviral vector-infected BMSCs (Ad-ILK-BMSC group, n = 16). Diabetic rats accepted cell transplantation in the experimental group (2 rats per group) were sacrificed for the bladder tissue on the third day, 7th day, and 14th day of treatment respectively ahead of schedule. At 4 weeks after treatment, all rats in five groups accepted urodynamic studies to evaluate bladder function and were sacrificed for bladder tissue. RESULTS: Our data showed that the underactive bladder function was significantly improved in DCP rats intravenously treated with ILK gene-modified BMSCs compared to those in the DM, BMSCs, and Ad-null-BMSC group. Meanwhile, we found that gene-modified BMSC treatment significantly promoted the activation of the AKT/GSK-3ß pathway by increasing phosphorylation and led to the enhancement of survival. In addition, the expression levels of angiogenesis-related protein vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and stromal cell-derived factor-1 (SDF-1) were significantly higher in the Ad-ILK-BMSC group than that in the DM, BMSCs, and Ad-null-BMSC group as assessed by enzyme-linked immunosorbent assay and western blot. As two indicators of vascular endothelial cell markers, the expression of von Willebrand factor (vWF) and CD31 by western blot and immunofluorescent staining revealed that the percentage of the vascular area of the bladder tissue significantly increased in Ad-ILK-BMSC group compared with the BMSCs and Ad-null-BMSC group on the 14th day of treatment. Histological and immunohistochemical staining (hematoxylin and eosin (HE), vWF, Ki67, and TUNNEL) on the bladder tissue revealed statistically different results between groups. CONCLUSION: ILK gene-modified BMSCs restored the bladder function and histological construction via promoting the process of angiogenesis and protecting cells from high glucose-associated apoptosis in STZ-induced DCP rat model, which provides a potential for the treatment of patients with DCP.


Assuntos
Diabetes Mellitus Experimental , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Medula Óssea , Células da Medula Óssea , Diabetes Mellitus Experimental/terapia , Glicogênio Sintase Quinase 3 beta , Humanos , Masculino , Proteínas Serina-Treonina Quinases , Ratos , Ratos Sprague-Dawley , Estreptozocina , Fator A de Crescimento do Endotélio Vascular
16.
Medicine (Baltimore) ; 99(28): e20825, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664075

RESUMO

INTRODUCTION: Primary bladder mucosa-associated lymphoid tissue (MALT) lymphoma is a rare tumor. To date, the PubMed database contains only 39 English articles covering 63 cases of primary bladder MALT lymphoma. Herein, we report a case of this disease and review the current literature. PATIENT CONCERNS: A 77-year-old woman presented with frequent urination, urinary urgency, and dysuria for 3 years. In the past 3 years, the patient's symptoms recurred and progressively worsened, and she was admitted to the hospital. DIAGNOSIS: A histopathological examination revealed the bladder mass as a tumor with high proliferation of atypical B-lymphocytes. Immunohistochemistry showed positive results for CD20, PAX-5, Ki-67, BCL-2, and CD21 and negative results for CD10, MUM1, TDT, and cyclin D1. These data supported the diagnosis of primary bladder MALT lymphoma. INTERVENTIONS: A transurethral resection of bladder tumor was performed to treat the disease. OUTCOMES: The patient was alive and healthy at the 15-month follow-up. CONCLUSION: Primary bladder MALT lymphoma is a rare disease and can be easily missed or misdiagnosed before achieving a histological confirmation. Surgery may be the best choice for both diagnosis and treatment.


Assuntos
Linfoma de Zona Marginal Tipo Células B/patologia , Neoplasias da Bexiga Urinária/patologia , Transtornos Urinários/etiologia , Adolescente , Adulto , Assistência ao Convalescente , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/patologia , Cistoscopia/métodos , Feminino , Humanos , Imuno-Histoquímica/métodos , Linfoma de Zona Marginal Tipo Células B/metabolismo , Linfoma de Zona Marginal Tipo Células B/cirurgia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/cirurgia , Transtornos Urinários/fisiopatologia , Adulto Jovem
17.
Oxid Med Cell Longev ; 2019: 2053149, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885775

RESUMO

Dorsal root ganglion (DRG) neurons, which are sensitive to oxidative stress due to their anatomical and structural characteristics, play a complex role in the initiation and progression of diabetic bladder neuropathy. We investigated the hypothesis that the antioxidant and antiapoptotic effects of CGRP may be partly related to the expression of Nrf2 and HO-1, via the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, thus reducing apoptosis and oxidative stress responses. This study shows that CGRP activates the PI3K/AKT pathway, thereby inducing increased expression of Nrf2 and HO-1 and resulting in the decrease of reactive oxygen species and malondialdehyde levels and reduced neuronal apoptosis. These effects were suppressed by LY294002, an inhibitor of the PI3K/AKT pathway. Therefore, regulation of Nrf2 and HO-1 expression by the PI3K/AKT pathway plays an important role in the regulation of the antioxidant and antiapoptotic responses in DRG cells in a high-glucose culture model.


Assuntos
Apoptose/efeitos dos fármacos , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Glucose/farmacologia , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Cromonas/farmacologia , Feminino , Gânglios Espinais/citologia , Gânglios Espinais/metabolismo , Malondialdeído/metabolismo , Morfolinas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
18.
Neuromodulation ; 22(6): 730-737, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30609180

RESUMO

PURPOSE: This five-year, retrospective, multicenter study evaluated the long-term safety and efficiency of sacral neuromodulation (SNM) in Chinese patients with urinary voiding dysfunction. PATIENTS AND METHODS: This is a Chinese national, multicenter, retrospective study that included 247 patients (51.2% female) who received an implantable pulse generator (IPG) (InterStim, Medtronic, Minneapolis, MN, USA) between 2012 and 2016. Success was considered if the initial ≥50% improvement in any of primary voiding diary variables persisted compared with baseline. The results were further stratified by identifying patients who showed >50% improvement and those although showed <50% improvement but still wanted to receive IPG; these data were collected and analyzed for general improvement. RESULTS: Following test stimulation, 187 patients (43%) declined implantation and 247 (57%) underwent implantation using InterStim®. Among 247 patients, 34 (13.7%) had overactive bladder (OAB), 59 (23.8%) had interstitial cystitis/bladder pain syndrome (IC/BPS), 47 (19%) had idiopathic urinary retention (IUR), and 107 (44.1%) had neurogenic bladder (NB). IPG efficiency rate for OAB, interstitial cystitis/bladder pain syndrome, idiopathic urinary retention, and neurogenic bladder were 42.5, 72.4, 51.6, and 58.8%, respectively. The mean duration of follow-up was 20.1 ± 12.8 months. CONCLUSIONS: SNM appears effective in the long term, with a total IPG implantation rate of approximately 57% (ranging between 42.5 and 72.4% depending on indication). Interstitial cystitis/bladder pain syndrome appear to be the best indication for stage I testing. Chinese neurogenic bladder patients are most inclined to choose SNM. SNM is relatively safe, with low postoperation adverse events of 16.1% and reoperation rate of 3.2% during the follow-up period.


Assuntos
Eletrodos Implantados , Sacro/inervação , Estimulação Elétrica Nervosa Transcutânea/métodos , Transtornos Urinários/epidemiologia , Transtornos Urinários/terapia , Adulto , Idoso , China/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sacro/fisiologia , Fatores de Tempo , Estimulação Elétrica Nervosa Transcutânea/instrumentação , Resultado do Tratamento , Transtornos Urinários/fisiopatologia
19.
Zhonghua Nan Ke Xue ; 25(1): 68-71, 2019.
Artigo em Chinês | MEDLINE | ID: mdl-32212509

RESUMO

OBJECTIVE: To evaluate the efficacy of Huang'e Capsules in the treatment of BPH of the qi-deficiency blood-stasis and damp-heat stagnation type under conditions of extensive use. METHODS: Totally, 605 male patients with BPH of the qi-deficiency blood-stasis and damp-heat stagnation type received oral Huang'e Capsules, tid, 4 capsules per time, for 42 days. We recorded the IPSS, maximum urinary flow rate (Qmax), mean urinary flow rate (Qave), quality of life (QOL) score, and prostate volume of the patients before and after medication. RESULTS: A total of 503 patients completed the whole trial. Compared with the baseline, the patients showed significant decreases after treatment in the IPSS (20.1 ± 5.5 vs 12.6 ± 5.0, P < 0.05), QOL score (4.19 ± 0.90 vs 2.50 ± 0.89, P < 0.05) and prostate volume (ï¼»36.6 ± 15.8ï¼½ vs ï¼»34.0 ± 17.6ï¼½ ml, P < 0.05), but remarkable increases in Qmax (ï¼»12.2 ± 5.8ï¼½ vs ï¼»14.2 ± 6.5ï¼½ ml/s, P < 0.05) and Qave (ï¼»5.91 ± 3.12ï¼½ vs ï¼»6.95 ± 3.45ï¼½ ml/s, P < 0.05). CONCLUSIONS: Huang'e Capsules had a good therapeutic effect on BPH of the qi-deficiency blood-stasis and damp-heat stagnation type.


Assuntos
Medicamentos de Ervas Chinesas , Hiperplasia Prostática , Qi , Cápsulas , Medicamentos de Ervas Chinesas/administração & dosagem , Temperatura Alta , Humanos , Masculino , Hiperplasia Prostática/tratamento farmacológico , Qualidade de Vida , Resultado do Tratamento
20.
Neurourol Urodyn ; 38(1): 81-86, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30411811

RESUMO

AIMS: To examine the protective effects of caffeine in rats with diabetes mellitus (DM) by using urodynamics. METHODS: Female Sprague-Dawley rats (n = 24) were divided into four groups: control group, DM group, DM + caffeine (5 mg/kg/day), and DM + caffeine (10 mg/kg/day). DM was induced by streptozotocin (STZ). Cystometric studies were conducted on all rats. After 8 weeks of treatment with caffeine, the urodynamic parameters, including bladder capacity, residual urine volume, voiding time, and peak voiding pressure, were measured. RESULTS: DM rats had a higher bladder capacity and post-void residual urine volume (PVR), an increased voiding time and peak voiding pressure, and a markedly lower voiding efficiency than the control group rats. After treatment with caffeine, bladder capacity, post-void residual urine volume, and peak voiding pressure were significant lower than those in the DM group, but voiding efficiency was markedly higher. CONCLUSION: The results suggested that caffeine (5 or 10 mg/kg/day) may improve the bladder function at 8 weeks after STZ induction. Thus, this may represent a potential strategy to increase voiding efficiency in diabetes.


Assuntos
Cafeína/uso terapêutico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Diabetes Mellitus Experimental/complicações , Bexiga Urinária/fisiopatologia , Animais , Relação Dose-Resposta a Droga , Feminino , Ratos , Ratos Sprague-Dawley , Retenção Urinária/tratamento farmacológico , Retenção Urinária/etiologia , Retenção Urinária/fisiopatologia , Micção/efeitos dos fármacos , Urodinâmica
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