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1.
Sci Rep ; 11(1): 17797, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493740

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and has extremely high morbidity and mortality. Although many existing studies have focused on the identification of biomarkers, little information has been uncovered regarding the PBMC RNA profile of HCC. We attempted to create a profile throughout using expression of peripheral blood mononuclear cell (PBMC) RNA using RNA-seq technology and compared the transcriptome between HCC patients and healthy controls. Seventeen patients and 17 matched healthy controls were included in this study, and PBMC RNA was sequenced from all samples. Sequencing data were analyzed using bioinformatics tools, and quantitative reverse transcription PCR (qRT-PCR) was used for selected validation of DEGs. A total of 1,578 dysregulated genes were found in the PBMC samples, including 1,334 upregulated genes and 244 downregulated genes. GO enrichment and KEGG studies revealed that HCC is closely linked to differentially expressed genes (DEGs) implicated in the immune response. Expression of 6 selected genes (SELENBP1, SLC4A1, SLC26A8, HSPA8P4, CALM1, and RPL7p24) was confirmed by qRT-PCR, and higher sensitivity and specificity were obtained by ROC analysis of the 6 genes. CALM1 was found to gradually decrease as tumors enlarged. Nearly the opposite expression modes were obtained when compared to tumor sequencing data. Immune cell populations exhibited significant differences between HCC and controls. These findings suggest a potential biomarker for the diagnosis of HCC. This study provides new perspectives for liver cancer development and possible future successful clinical diagnosis.

2.
J Natl Cancer Inst ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473310

RESUMO

BACKGROUND: Cystoscopy plays an important role in bladder cancer (BCa) diagnosis and treatment, but its sensitivity needs improvement. Artificial intelligence has shown promise in endoscopy, but few cystoscopic applications have been reported. We report a Cystoscopy Artificial Intelligence Diagnostic System (CAIDS) for BCa diagnosis. METHODS: In total, 69,204 images from 10,729 consecutive patients from six hospitals were collected and divided into training, internal validation, and external validation sets. The CAIDS was built using a pyramid scene parsing network and transfer learning. A subset (n = 260) of the validation sets was used for a performance comparison between the CAIDS and urologists for complex lesion detection. The diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values and 95% confidence intervals (CIs) were calculated using the Clopper-Pearson method. RESULTS: The diagnostic accuracies of the CAIDS were 0.977 (95% CI = 0.974-0.979) in the internal validation set and 0.990 (95% CI = 0.979-0.996), 0.982 (95% CI = 0.974-0.988), 0.978 (95% CI = 0.959-0.989), and 0.991 (95% CI = 0.987-0.994) in different external validation sets. In the CAIDS versus urologists' comparisons, the CAIDS showed high accuracy and sensitivity (accuracy = 0.939, 95% CI = 0.902-0.964; and sensitivity = 0.954, 95% CI = 0.902-0.983) with a short latency of 12 s, much more accurate and quicker than the expert urologists. CONCLUSIONS: The CAIDS achieved accurate BCa detection with a short latency. The CAIDS may provide many clinical benefits, from increasing the diagnostic accuracy for BCa, even for commonly misdiagnosed cases such as flat cancerous tissue (carcinoma in situ), to reducing the operation time for cystoscopy.

3.
Microvasc Res ; 139: 104257, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34534572

RESUMO

OBJECTIVE: Amiodarone is the first choice for the treatment of arrhythmia, but it is easy to cause extravasation during infusion, after extravasation, it often cause skin injury. The healing of skin injury induced by amiodarone is an inflammatory process. Chrysin, a natural flavonoid, has been investigated to have anti-inflammatory and antioxidant effects. It was reported that chrysin can promote wound healing. So this study aims to investigate the effect of chrysin on amiodarone extravasation-induced skin injury model in rats. METHODS: The rat model of skin extravasation injury was established by subcutaneous injection of 0.5 mL of amiodarone. After successful modeling, the rats were randomly assigned to the five groups: control group, 10% DMSO group, and low-dose, medium-dose, and high-dose chrysin groups (10, 20 and 40 mg/mL). The extravasation injury model was given locally on the same day for seven days. On day 0, 3, 7 and 10 of administration, the lesion's image were taken to calculate the area, and the tissue of the lesion were collected for H&E staining. Then, the level of IL-6 and TNF-α were measured by ELISA, and the protein expression level of bFGF in the wound tissue were detected by immunohistochemical staining. RESULTS: It was found that chrysin groups (20 and 40 mg/mL) compared to contronl group and 10% DMSO solvent group significantly decreased area injury, IL-6 and TNF-α(P < 0.05) on day 3, 7, 10. On the other hand, the chrysin group (40 mg/mL) compared to contronl group and 10% DMSO group significantly increase bFGF(P < 0.05) on day 3, 7. CONCLUSION: Chrysin were effective in reducing injury area, reducing inflammation, and promoting the secretion of bFGF, it can promote the healing of skin injury induced by amiodarone extravasation in rats. These findings provide a good theoretical and experimental basis for the prevention and treatment of amiodarone extravasation-induced skin injury, and provide evidence for finding potential healing agents for the prevention and treatment of amiodarone and other corrosive extravasation-induced injuries from the molecular and cytological levels, thus solving the clinical problems.

4.
J Chem Phys ; 155(3): 035101, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34293874

RESUMO

Escherichia coli adenylate kinase (AK) is composed of CORE domain and two branch domains: LID and AMP-binding domain (AMPbd). AK exhibits considerable allostery in a reversible phosphoryl transfer reaction, which is largely attributed to the relative motion of LID and AMPbd with respect to CORE. Such an allosteric conformational change is also evident in the absence of ligands. Recent studies showed that the mutations in branch domains can adjust dynamic allostery and alter the substrate affinity and enzyme activity. In this work, we use all-atom molecular dynamics simulation to study the impacts of mutations in branch domains on AK's dynamic allostery by comparing two double mutants, i.e., LID mutant (Val135Gly, Val142Gly) and AMPbd mutant (Ala37Gly, Ala55Gly), with wild-type. Two mutants undergo considerable conformational fluctuation and exhibit deviation from the initially extended apo state to more compact structures. The LID domain in the LID mutant adjusts its relative position and firmly adheres to CORE. More strikingly, AMPbd mutations affect the relative positions of both the AMPbd domain and remote LID domain. Both domains undergo considerable movement, especially the inherent hinge swing motion of the flexible LID domain. In both mutants, the mutations can enhance the inter-domain interaction. The results about the conformation change of AK in both mutants are in line with the experiment of AK's affinity and activity. As revealed by our findings, the flexibility of branch domains and their inherent motions, especially LID domain, is highly relevant to dynamic allostery in the AK system.


Assuntos
Adenilato Quinase/metabolismo , Mutação , Adenilato Quinase/química , Adenilato Quinase/genética , Regulação Alostérica , Escherichia coli/enzimologia , Conformação Proteica , Domínios Proteicos
5.
Sensors (Basel) ; 21(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34072094

RESUMO

Continuous movements of the hand contain discrete expressions of meaning, forming a variety of semantic gestures. For example, it is generally considered that the bending of the finger includes three semantic states of bending, half bending, and straightening. However, there is still no research on the number of semantic states that can be conveyed by each movement primitive of the hand, especially the interval of each semantic state and the representative movement angle. To clarify these issues, we conducted experiments of perception and expression. Experiments 1 and 2 focused on perceivable semantic levels and boundaries of different motion primitive units from the perspective of visual semantic perception. Experiment 3 verified and optimized the segmentation results obtained above and further determined the typical motion values of each semantic state. Furthermore, in Experiment 4, the empirical application of the above semantic state segmentation was illustrated by using Leap Motion as an example. We ended up with the discrete gesture semantic expression space both in the real world and Leap Motion Digital World, containing the clearly defined number of semantic states of each hand motion primitive unit and boundaries and typical motion angle values of each state. Construction of this quantitative semantic expression will play a role in guiding and advancing research in the fields of gesture coding, gesture recognition, and gesture design.


Assuntos
Articulação da Mão , Semântica , Gestos , Mãos , Movimento , Percepção
6.
Neurosci Lett ; 749: 135755, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33610671

RESUMO

Shape and spirit similarity are two kinds of common artistic modes in concept visualization. The adoption depends on the designers' subjective preference and judgment, which may cause potential risks for semantic communication. This article used pairs of real image-concrete word as the roots, and contrasted four kinds of multimodal mappings such as shape similarity-concrete concept, shape similarity-abstract concept, spirit similarity-concrete concept, and spirit similarity-abstract concept to compare the matching difference through the S1(picture)-S2(word) paradigm. The behavioral results showed that shape similarity had advantages in both matching rate and reaction time over spirit similarity, but the difference was more significant to the concrete word than to the abstract word. The ERPs showed that the N1, P2, and N400 components had alike effects with the behavioral results, but the mappings of spirit similarity-concrete concept elicited the largest positivity of P600, suggesting the complicated mechanisms of semantic integration and concreteness effect in the multimodal mappings. This study proves that the concrete concept should be visualized according to its appearance, not the most striking feature or function; but the visulization of abstract concept shows less difference after a concreteness transition.


Assuntos
Encéfalo/fisiologia , Cognição/fisiologia , Formação de Conceito/fisiologia , Potenciais Evocados/fisiologia , Adulto , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Tempo de Reação , Leitura
7.
World J Urol ; 39(8): 3025-3033, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33388914

RESUMO

PURPOSE: To describe the novel technique of photoselective sharp enucleation of the prostate (PSEP) with a front-firing 532-nm laser and evaluate its efficacy and safety. METHODS: A seven-step standardized surgical procedure was established, and PSEP was performed in an en bloc or lobulate manner according to the size of the middle lobe of the prostate. The following clinical data of 583 patients who underwent PSEP in our center from November 2016 to May 2018 were retrospectively reviewed: maximum flow rate (Qmax), International Prostate Symptom Score (IPSS), quality of life score (Qols), post-void residual volume (PVR), prostate volume, operation time, serum prostate-specific antigen (PSA) concentration, and complications at 1, 6, and 12 months postoperatively. RESULTS: Of the 583 patients, 475 had complete clinical information and were included in the study. The median operation time was 39 min. There were significant improvements in the Qmax, IPSS, Qols, PVR and PSA concentration at each follow-up time point postoperatively. Postoperative hemorrhage occurred in 22 patients (4.6%), urinary retention in 29 (6.1%), urinary tract infection in 55 (11.6%), bladder neck contracture in 8 (1.7%), urethral strictures in 11 (2.3%), and stress urinary incontinence in 9 (1.9%). CONCLUSIONS: PSEP is effective and safe for the treatment of benign prostatic hyperplasia. The innovative technique integrates the excellent hemostatic property of the 532-nm laser and the high efficiency of enucleation. It decreases the occurrence of postoperative incontinence associated with "blunt" enucleation of 532-nm laser and eliminates the lack of tissue samples problem associated with photoselective vaporization of the prostate.

8.
BJU Int ; 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33248014

RESUMO

OBJECTIVES: To compare the occurrence of emptying dysfunction between surgical techniques for orthotopic neobladder suspended with round ligament (rONB) and the standard procedure (sONB). PATIENTS AND METHODS: A prospective randomised controlled trial was performed in a single centre of female patients undergoing creation of an ONB using rONB or sONB. Patients were followed for ≥24 months after ONB. The primary endpoints were significant post-void residual urine volume (sPVR) and need for clean intermittent catheterisation (CIC) at 24 months postoperatively. The secondary endpoints included early and late complications, urodynamic profile, and ONB continence. RESULTS: Between January 2011 and October 2017, the trial enrolled 85 patients, of whom 82 were randomised. A total of 41 patients had a rONB and 41 a sONB. At 24 months, 17 of the 37 patients with a sONB and nine of the 39 patients with a rONB had a sPVR. The cumulative risk of a sPVR was significantly lower in the rONB group (23.1%) vs the sONB group (45.9%) (hazard ratio [HR] 0.43, 95% confidence interval [CI], 0.19-0.96; P = 0.040). In all, 15 of the 37 patients with a sONB and four of the 39 patients with a rONB needed CIC. The cumulative risk of requiring CIC was significantly lower in the rONB group (10.3%) vs the sONB group (40.5%) (HR 0.22, 95% CI 0.07-0.67; P = 0.008) at 24 months. Multivariable Cox regression analysis also showed that the rONB type was an independently protective factor for sPVR and CIC. The rates of early (0-90 days) and late complication (>90 days) were 54.1% and 13.5% in the sONB group, and 64.1% and 10.3% in the rONB group, respectively. There were no significant differences in complications, urodynamic profile or ONB continence. A major limitation is the small sample size at a single centre. CONCLUSION: Posterior support with round ligament for an ONB significantly improved the emptying of the ONB and resulted in a reduced need for CIC. The surgical modification is a feasible and safe technique without additional complication-related surgeries.

9.
Asian J Urol ; 7(3): 291-300, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32742929

RESUMO

Objective: To investigate oncological outcomes in patients with bladder cancer who underwent minimally invasive radical cystectomy (MIRC) or open radical cystectomy (ORC). Methods: We identified patients with bladder cancer who underwent radical cystectomy (RC) in 13 centers of the Chinese Bladder Cancer Consortium (CBCC). Perioperative outcomes were compared between MIRC and ORC. The influence of surgical approaches on overall survival (OS) and cancer-specific survival (CSS) in the entire study group and subgroups classified according to pathologic stage or lymph node (LN) status was assessed with the log-rank test. Multivariable Cox proportional hazard models were used to evaluate the association among OS, CSS and risk factors of interest. Results: Of 2 098 patients who underwent RC, 1 243 patients underwent MIRC (1 087 laparoscopic RC and 156 robotic-assisted RC, respectively), while 855 patients underwent ORC. No significant differences were noted in positive surgical margin rate and 90-day postoperative mortality rate. MIRC was associated with less estimated blood loss, more LN yield, higher rate of neobladder diversion, longer operative time, and longer length of hospital stay. There was no significant difference in OS and CSS according to surgical approaches (p=0.653, and 0.816, respectively). Subgroup analysis revealed that OS and CSS were not significantly different regardless of the status of extravesical involvement or LN involvement. Multivariable Cox regression analyses showed that the surgical approach was not a significant predictor of OS and CSS. Conclusions: Our study showed that MIRC was comparable to conventional ORC in terms of OS and CSS.

10.
Org Lett ; 22(12): 4908-4913, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32519870

RESUMO

In this paper, a visible-light-promoted cross-coupling of 4-alkyl-1,4-dihydropyridines with thio-/selenium sulfonates under transition-metal-free conditions is described. This strategy features easily available substrates, mild reaction conditions, high yields, and high chemoselectivity. A novel synthetic route for the construction of a sulfide or selenide Csp3-S or Csp3-Se bond under transition-metal-free conditions without an additive oxidant or base is developed. This method is well extended to the synthesis of a class of thiolated or selenylated glycosides that has not been explored before. Sulfoxides were also successfully chemoselectively observed via a facile variation of the atmosphere under photocatalyzed conditions.

11.
BMC Urol ; 20(1): 36, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228552

RESUMO

BACKGROUND: To evaluate the efficacy of submucosal injection of triamcinolone acetonide for the treatment of type II/III interstitial cystitis/bladder pain syndrome. METHODS: A retrospective analysis of the clinical data of type II/III interstitial cystitis/bladder pain syndrome patients treated in our department from April 2016 to August 2018 was conducted, and changes in International Prostate Symptom Scores and the Pelvic Pain and Urgency/Frequency symptom scale after surgery were evaluated to explore factors that may affect patient outcomes. RESULTS: A total of 27 female patients and 8 male patients were enrolled, with type II patients accounting for 62.9% of the sample, and the median follow-up duration was 31 months (range: 12-40 months). Twenty-two patients (74.3%) had significantly improved questionnaire scores at 4 weeks postoperatively. Treatment efficacy was sustained for at least 1 year in 15 patients, and persistent effectiveness was noted in 10 (28.6%) patients. Patients with an advanced age (p = 0.015), high pain scores (p = 0.040), and higher International Prostate Symptom Scores (p = 0.037) and Pelvic Pain and Urgency/Frequency symptom scale scores (p = 0.020) were more likely to benefit from submucosal injection of triamcinolone acetonide. Gender, disease duration, and the presence of Hunner's lesions had no predictive value for treatment outcomes. CONCLUSION: Submucosal injection of triamcinolone acetonide can improve the clinical symptoms and quality of life in both men and women with type II/III interstitial cystitis/bladder pain syndrome. Patients with an advanced age and more severe interstitial cystitis/bladder pain syndrome related symptoms may benefit more from triamcinolone acetonide injection.


Assuntos
Anti-Inflamatórios/uso terapêutico , Cistite Intersticial/tratamento farmacológico , Triancinolona Acetonida/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistoscopia/métodos , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Membrana Mucosa , Estudos Retrospectivos , Resultado do Tratamento
12.
BMC Urol ; 20(1): 31, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32192483

RESUMO

BACKGROUND: A routine blood examination is one of the most rapid, convenient and inexpensive clinical examinations that can reflect a patient's inflammatory status and other blood conditions, and the prognostic value of routine preoperative blood parameters in MIBC patients is still unclear, so we evaluated the prognostic value of routine preoperative blood parameters in muscle-invasive bladder cancer (MIBC) following radical cystectomy (RC). METHODS: Data on 202 patients with MIBC who underwent RC at our institution were retrospectively collected between October 2007 and August 2018. The median preoperative neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and hemoglobin (HGB) values were used as cutoffs to form the low and high NLR, low and high PLR, and low and high HGB groups, respectively. The clinicopathologic characteristics of each group were compared by chi-square and t tests. Kaplan-Meier survival and multivariate Cox regression analyses were used to analyze prognosis. RESULTS: The median NLR, PLR and HGB values were 2.42, 112 and 125 g/L, respectively. Kaplan-Meier results showed that the low HGB group had poor progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). A high NLR and high PLR groups correlated only with poor OS. Multivariate Cox analyses showed that pathological T3/4 stage, positive lymph node status and low HGB were independent risk factors for PFS, CSS and OS, and age was the only independent risk factor for OS. CONCLUSION: Preoperative peripheral blood HGB is an independent risk factor for the prognosis of MIBC patients. These data suggest that HGB may be a useful prognostic marker for MIBC patients undergoing RC.


Assuntos
Carcinoma de Células de Transição/sangue , Cistectomia , Hemoglobinas/metabolismo , Contagem de Linfócitos , Neutrófilos , Contagem de Plaquetas , Neoplasias da Bexiga Urinária/sangue , Bexiga Urinária/patologia , Idoso , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Causas de Morte , Feminino , Humanos , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Período Pré-Operatório , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
13.
Urology ; 138: 45-51, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32006548

RESUMO

OBJECTIVE: To illustrate our refinement technique for robotic intracorporeal orthotopic Hautmann neobladder with adherence to open surgical principles and evaluate perioperative and functional outcomes. PATIENTS AND METHODS: Robot-assisted radical cystectomy with intracorporeal Hautmann orthotopic neobladder was performed by the same surgeon in 40 patients with bladder cancer from November 2017 to March 2019. Baseline demographics, pathologic data, 90-day complications, and functional outcomes at both 6 and 12 months were evaluated with questionnaire and urodynamic analysis. RESULTS: Median follow-up was 14 months (range 4-20). Median operative time was 320 (230-500) minutes, and the estimated blood loss was 300 (100-2000) mL. No conversion to the open technique was reported. The overall 90-day complication rate was 45%, and the high-grade complication rate was only 10%. The daytime satisfactory continence rate was 90% at both 6 months (30 patients) and 12 months (20 patients), while the night-time satisfactory continence rate was 76.7% and 80.0% at 6 months and 12 months, respectively. One patient underwent clean intermittent catheterization. The cohort had minimal postvoid residual volume, normal compliance, and a mean capacity of 328.7 cm3 (range 170-500) at 6 months postoperatively. CONCLUSION: Our preliminary data indicate that robotic intracorporeal Hautmann neobladder configuration is a feasible surgical technique and can achieve a low pressure and sufficient capacity for satisfactory early voiding patterns. Refinement of the stepwise process can effectively decrease the time of the operation. Long-term functional and oncological outcomes remain to be evaluated with longer follow-up and more cases.

14.
Sci Rep ; 8(1): 17792, 2018 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-30542123

RESUMO

Here, we attempt to better define the long-term outcomes of radical cystectomy (RC) for urothelial carcinoma (UC) in a Chinese population and to investigate the relationship between EZH2 protein expression levels and the clinicopathological parameters and outcomes in patients with UC. We detected the relative EZH2 protein expression levels by immunohistochemistry in tumour specimens from a cohort of 189 Chinese UC patients. In patients who underwent RC, the 5-year cancer-specific survival (CSS) and overall survival (OS) were 69% and 61% respectively. EZH2 expression was increased in UC compared with normal urothelium. The expression levels of EZH2 were elevated in parallel with tumour stage (p = 0.001) and tumour grade (p = 0.001) and were increased in cases with lymph node metastasis compared with node-negative cases (p = 0.018). Kaplan-Meier analyses showed that higher EZH2 expression was related to significantly shorter CSS and OS in patients who underwent RC. High EZH2 expression was associated with worse CSS (HR = 3.51; p = 0.037) and OS (HR = 2.15; p = 0.047) in the univariate analysis, but only lymph node invasion maintained its predictive value for CSS in a multivariate model. This contemporary and homogeneous single-centre series found acceptable outcomes for Chinese UC patients who underwent RC. Clinically, our retrospective studies suggest that EZH2 levels can be used to identify more aggressive phenotypes in UC patients, thereby improving our prognostic knowledge.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Cistectomia/métodos , Feminino , Humanos , Imuno-Histoquímica/métodos , Estimativa de Kaplan-Meier , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Estudos Retrospectivos , Bexiga Urinária/patologia , Urotélio/metabolismo , Urotélio/patologia
15.
Oncol Lett ; 16(5): 6522-6530, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30405791

RESUMO

The aim of the present study was to investigate the activities of novel synthetic epidermal growth factor receptor (EGFR) inhibitors (ZINC05463076, ZINC2102846 and ZINC19901103) against prostate tumors, in vitro models and investigate the potential underlying mechanisms. A panel of prostate tumor cell lines (LNCaP, DU-145, PC-3 and LNCaP-AI cells) were used to evaluate antitumor activity of ZINC05463076, ZINC2102846, and ZINC19901103 in vitro. Cell growth and clonal formation were determined by MTT assay and Soft agar colony formation assay, respectively. An EGFR kinase assay following treatment of the compounds was performed by ELISA. Cell cycle-regulating proteins, including cyclin-dependent kinase (CDK)1, CKD2, CKD4 and inhibitory effects of these compounds on downstream signaling were analyzed by western blotting. Flow cytometry was performed to investigate apoptosis and cell cycle phases of the treated cells. It was revealed that all compounds synthesized in the present study demonstrated significant EGFR inhibition abilities, compared with approved EGFR inhibitor drug gefitinib. Treatment of LNCaP, DU-145, PC3 and LNCaP-AI cells with these compounds revealed cell proliferation inhibition and colony formation suppression dose-dependently in vitro. The agents impaired phosphorylation of EGFR and extracellular signal-regulated kinase 1/2 and suppressed their downstream signaling. In addition, these novel synthetic agents decreased the expression level of survivin, which may induce G1 cell cycle phase arrest and cell apoptosis in PCa cells subsequently. Collectively, ZINC05463076, ZINC2102846 and ZINC19901103 exhibited significant antitumor activity in human prostate tumors in vitro, by inhibiting EGFR and promoting apoptosis, which suggested a rationale for clinical development in prostate tumor therapy.

16.
J Int Med Res ; 46(9): 3928-3937, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29936879

RESUMO

Objectives To report on the treatment of urethral recurrence after orthotopic urinary diversion at our institution. Methods We retrospectively reviewed clinical information of urethral recurrence in patients who underwent radical cystectomy and orthotopic urinary diversion between January 1998 and January 2013. Results Of 341 patients, 282 presented for follow-up (median follow-up: 56 months; range: 1-174 months). Eight patients developed local recurrence of urothelial cancer after radical cystectomy. The rate of urethral recurrence (1.4%) in female patients who underwent orthotopic urinary diversion was lower than in male patients (3.3%). The median (range) time to recurrence was 33 (6-120) months after radical cystectomy and orthotopic urinary diversion. Recurrences were treated by transurethral resection of tumour, urethrectomy, neobladder resection, revision of urinary diversion, adjuvant chemotherapy, or radiation therapy, based on individual circumstances. Survival analysis showed that 5-year cancer-specific survival was significantly higher in patients with urethral recurrence alone (83.3%), compared with patients with other recurrences, including pelvic/abdomen recurrence and distant metastasis (26.8%). Conclusions En bloc urethrectomy and revision of urinary diversion remain the principle surgical choices. Selection of transurethral tumour resection was based on tumour stage and was used in carefully chosen patients. Cancer-specific survival might depend on multidisciplinary therapy.


Assuntos
Carcinoma de Células de Transição/cirurgia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Uretrais/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Bexiga Urinária/cirurgia , Derivação Urinária/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/secundário , Cistectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Procedimentos Cirúrgicos Reconstrutivos/efeitos adversos , Reoperação , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Neoplasias Uretrais/secundário , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia
17.
J Nat Prod ; 81(2): 298-306, 2018 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-29394050

RESUMO

Acute myeloid leukemia (AML) is a hematologic malignancy that is characterized by clonal proliferation of myeloid blasts. Despite the progress that has been made in the treatment of various malignant hematopoietic diseases, the effective treatment of AML remains very challenging. Differentiation therapy has emerged as a promising approach for leukemia treatment, and new and effective chemical agents to trigger the differentiation of AML cells, especially drug-resistant cells, are urgently required. Herein, the natural product jungermannenone C, a tetracyclic diterpenoid isolated from liverworts, is reported to induce cell differentiation in AML cells. Interestingly, the unnatural enantiomer of jungermannenone C (1) was found to be more potent than jungermannenone C in inducing cell differentiation. Furthermore, compound 1 targets peroxiredoxins I and II by selectively binding to the conserved cysteine residues and leads to cellular reactive oxygen species accumulation. Accordingly, ent-jungermannenone C (1) shows potential for further investigation as an effective differentiation therapy against AML.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Diterpenos/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Hepatófitas/química , Humanos , Leucemia Mieloide Aguda/metabolismo , Peroxirredoxinas/farmacologia
18.
World J Urol ; 36(1): 41-50, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29080948

RESUMO

PURPOSE: Enhanced recovery after surgery (ERAS) has played an important role in recovery management for radical cystectomy with ileal urinary diversion (RC-IUD). This study is to evaluate ERAS compared with the conventional recovery after surgery (CRAS) for RC-IUD. METHODS: From October 2014 and July 2016, bladder cancer patients scheduled for curative treatment from 25 centers of Chinese Bladder Cancer Consortium were randomly assigned to either ERAS or CRAS group. Primary endpoint was the 30-day complication rate. Secondary endpoints included recovery of fluid and regular diet, flatus, bowel movement, ambulation, and length of stay (LOS) postoperatively. Follow-up period was 30-day postoperatively. RESULTS: There were 144 ERAS and 145 CRAS patients. Postoperative complications occurred in 25.7 and 30.3% of the ERAS and CRAS patients with 55 complications in each group, respectively (p = 0.40). There was no significant difference between groups in major complications (p = 0.82), or type of complications (p = 0.99). The ERAS group had faster recovery of bowel movements (median 88 versus 100 h, p = 0.01), fluid diet tolerance (68 versus 96 h, p < 0.001), regular diet tolerance (125 versus 168 h, p = 0.004), and ambulation (64 versus 72 h, p = 0.047) than the CRAS group, but similar time to flatus and LOS. CONCLUSIONS: ERAS did not increase 30-day complications compared with CRAS after RC. ERAS may be better than CRAS in terms of bowel movement, tolerance of fluid and regular diet, and ambulation.


Assuntos
Cistectomia , Cuidados Pós-Operatórios/métodos , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária , China , Cistectomia/métodos , Feminino , Humanos , Íleo/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recuperação de Função Fisiológica
19.
Food Funct ; 8(9): 3259-3270, 2017 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-28828418

RESUMO

The anti-obesity effects of different proanthocyanidin extracts (PE) from Chinese bayberry (Myrica rubra Sieb.et Zucc.) leaves were evaluated in a high-fat (HF) diet-induced obese rat model. The leaves of Chinese bayberry (LCB), a non-desaccharified proanthocyanidin extract (NDPE), and a desaccharified proanthocyanidin extract (DPE) were compared with orlistat, a conventional anti-obesity drug used as a positive control. The rats from all of the PE-treated groups showed obvious weight loss, with the greatest weight loss in the DPE group (P < 0.05). Compared to the HF group, almost all of the PE-treated groups showed significantly reduced levels of serum TC, TG, AST, ALT, ALP, LDL-C, ADP and a LEP/ADP ratio, and increased levels of HDL-C and LEP. Furthermore, the expression levels of SIRT1, PPAR-γ, C/EBP-α, BMP4 and UCP1 were investigated in the liver, kidney, epididymis and abdominal adipose tissue. Compared to the HF group, PPAR-γ and C/EBP-α levels were significantly reduced and SIRT1, BMP4 and UCP1 levels were significantly upregulated in the DPE-treated group. Our results suggested that PE exerted its anti-obesity effects by upregulating the expression of SIRT1, thus inducing the deacetylation of PPAR-γ and downregulating the expression of C/EBP-α, and also upregulating the expression of BMP4 to boost the levels of brown fat.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Myrica/química , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Proantocianidinas/administração & dosagem , Animais , Fármacos Antiobesidade/química , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 4/metabolismo , Frutas/química , Humanos , Masculino , Obesidade/genética , Obesidade/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Extratos Vegetais/química , Folhas de Planta/química , Proantocianidinas/química , Ratos , Ratos Sprague-Dawley , Sirtuína 1/genética , Sirtuína 1/metabolismo
20.
Biomed Pharmacother ; 92: 595-605, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28577498

RESUMO

Erectile dysfunction (ED) is considered to be incapable of obtaining or/and keeping a sufficient erection function to receive the satisfactory during the sexual intercourse. This study aims to investigate the effects of telomerase reverse transcriptase (hTERT) modified adipose tissue derived stem cells (ADSCs) autologously injected into cavernosa of the ED rats on erectile function. The ADSCs were isolated form the rat subcutaneous adipose tissue sample, and identified by examining the CD29 and CD44 molecule. The ED model was established by using 100µg/kg apomorphine (APO). The adenovirus expressing rat hTERT (Ade-hTERT vector) was established, and transfected into ADSCs and injected into ED rat model, respectively. Telomerase activity, cell growth, cell apoptosis were analyzed by using TRAP ELISA assay, CCK8 assay and flow cytometry assay, respectively. The trophic growth factors were examined by using enzyme-linked immunosorbent assay (ELISA). The mRNA and proteins were detected by using semi-quantitative PCR and western blot assay, respectively. Ade-hTERT vector was highly expressed in both ADSCs and ED rat mode. The hTERT expression enhanced the telomerase activity, inhibits cell apoptosis and enhances proliferation of ADSCs (P<0.05). hTERT expression triggers the secretory function of ADSCs and induces differentiative potential of ADSCs. hTERT expression inhibits apoptosis and increases eNOS and nNOS levels in older ED rats compared to the Ade-vector injected ED rats (P<0.05). In conclusion, the hTERT modification could enhance the ADSCs proliferation, and hTERT modified ADSCs could increase the anti-oxidative stress capacity in the ED rat model.


Assuntos
Tecido Adiposo/transplante , Disfunção Erétil/genética , Disfunção Erétil/terapia , Estresse Oxidativo/fisiologia , Transplante de Células-Tronco/métodos , Telomerase/genética , Tecido Adiposo/metabolismo , Animais , Proliferação de Células/fisiologia , Modelos Animais de Doenças , Disfunção Erétil/metabolismo , Masculino , DNA Polimerase Dirigida por RNA/genética , DNA Polimerase Dirigida por RNA/metabolismo , Ratos , Células-Tronco/metabolismo
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