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MicroRNAs (miRNAs) have gained a prominent role as biomarkers in prostate cancer (PCa). Our study aimed to evaluate the potential suppressive effect of miR-137 in a model of advanced PCa with and without diet-induced hypercholesterolemia. In vitro, PC-3 cells were treated with 50 pmol of mimic miR-137 for 24 h, and gene and protein expression levels of SRC-1, SRC-2, SRC-3, and AR were evaluated by qPCR and immunofluorescence. We also assessed migration rate, invasion, colony-forming ability, and flow cytometry assays (apoptosis and cell cycle) after 24 h of miRNA treatment. For in vivo experiments, 16 male NOD/SCID mice were used to evaluate the effect of restoring miR-137 expression together with cholesterol. The animals were fed a standard (SD) or hypercholesterolemic (HCOL) diet for 21 days. After this, we xenografted PC-3 LUC-MC6 cells into their subcutaneous tissue. Tumor volume and bioluminescence intensity were measured weekly. After the tumors reached 50 mm3, we started intratumor treatments with a miR-137 mimic, at a dose of 6 μg weekly for four weeks. Ultimately, the animals were killed, and the xenografts were resected and analyzed for gene and protein expression. The animals’ serum was collected to evaluate the lipid profile. The in vitro results showed that miR-137 could inhibit the transcription and translation of the p160 family, SRC-1, SRC-2, and SRC-3, and indirectly reduce the expression of AR. After these analyses, it was determined that increased miR-137 inhibits cell migration and invasion and impacts reduced proliferation and increased apoptosis rates. The in vivo results demonstrated that tumor growth was arrested after the intratumoral restoration of miR-137, and proliferation levels were reduced in the SD and HCOL groups. Interestingly, the tumor growth retention response was more significant in the HCOL group. We conclude that miR-137 is a potential therapeutic miRNA that, in association with androgen precursors, can restore and reinstate the AR-mediated axis of transcription and transactivation of androgenic pathway homeostasis. Further studies involving the miR-137/coregulator/AR/cholesterol axis should be conducted to evaluate this miR in a clinical context.

Telomere dysfunction is one of the hallmarks of cancer, which puts telomere-associated genes in a prominent position in oncology. The CTC1-STN1-TEN1 (CST) complex is vital for telomere maintenance and participates in several steps of DNA metabolism, such as repair and replication, essential functions for malignant cells. Despite this, little is known about these genes in cancer biology. Here, using bioinformatics tools, we performed a study in 33 cancer types and over 10,000 TCGA samples analyzing the role of the CST complex in cancer. We obtained the somatic landscape and gene expression patterns of each of the subunits of the complex studied. Furthermore, we show that CST is important for genetic stability and nucleic acid metabolism in cancer. We identify possible interactors, transcription factors, and microRNAs associated with CST and two drugs that may disrupt their pathways. In addition, we show that CST gene expression is associated with cancer survival and recurrence in several tumor types. Finally, we show negative and positive correlations between immune checkpoint genes and CST in different types of cancer. With this work, we corroborate the importance of these genes in cancer biology and open perspectives for their use in other works in the field.

Resumen Introduccion Diversos estudios han demostrado que los cambios en el gen RA pueden estar asociados a un fenotipo de enfermedad mas agresivo e incluso al cancer de prostata resistente a la castracion. Por este motivo, hemos investigado las alteraciones citogenicas y moleculares asociadas al RA. Materiales y metodos Para evaluar la metilacion del RA, realizamos un analisis citogenetico-molecular mediante hibridacion fluorescente in situ que utiliza sondas especificas para el gen del RA (Xq11.12) y el centromero del cromosoma X. Respecto a la actividad del RA, realizamos un analisis cualitativo de la actividad del receptor de androgenos humano. Para analizar la expresion del RA en las lineas celulares PC3 y LNCaP, utilizamos ensayos de qPCR. Resultados En el ensayo qPCR, encontramos una regulacion a la baja del RA en la linea celular PC3 en comparacion con la LNCaP. Hallamos la presencia de polisomia del cromosoma X en las lineas celulares PC-3 y LNCaP mediante el ensayo FISH. En el ensayo HUMARA-Q encontramos la presencia de dos cromosomas X/celula y actividad en ambos RA de la linea celular PC-3. En las celulas LNCaP hallamos la presencia de dos cromosomas X/celula y la metilacion de solo un RA. Conclusion El fenotipo del cancer de prostata resistente a la castracion representa un gran desafio en el tratamiento urologico. Estos cromosomas X y las alteraciones ligadas al RA pueden contribuir a una mejor comprension de la enfermedad; sin embargo, deben realizarse mas estudios para arrojar mas luz sobre el papel del RA en el fenotipo del cancer de prostata resistente a la castracion.

BACKGROUND Bladder cancer is the leading transitional cell carcinoma affecting men and women with high morbidity and mortality rates, justifying the need to develop new molecular target therapies using microRNAs. This study aimed to evaluate the behavior of the T24 cell line after transfection with miR-Let-7c precursor mimic through invasion, migration, apoptosis, and cell cycle assays. METHODS AND RESULTS: T24 cell was transfected with the Let-7c mimic and its respective control and evaluated after 24 h. The expression levels of miR-Let-7c were analyzed by qPCR. We performed wound healing, Matrigel and flow cytometry, apoptosis, and cell cycle assays to determine its effect on cellular processes. Cells transfected with miR-Let-7c showed increased apoptosis rates (p = 0.019), decreased migration 24 h (p = 0.031) and 48 h (p = 0.0006), invasion potential (p = 0.0007), and cell proliferation (p = 0.002). CONCLUSIONS Our results demonstrate that miR-Let-7c can act in different pathways of the carcinogenic cellular processes of muscle-invasive urothelial carcinoma cells, inhibiting cell proliferation and increasing apoptosis levels, consequently limiting their invasion potential. However, further studies should be carried out better to elucidate this microRNA's role in high-grade urothelial carcinomas and unveil which targets this microRNA may present, which are intrinsically related to the cancer survival pathways.

Introduction: specialists have an urge for biomarkers that can discriminate indolent prostate cancer from aggressive tumors. Ki67 is a proliferation marker, and its expression is associated with the aggressiveness of several cancers. Objective: analyze the expression of Ki67 in prostate cancer samples correlating with the aggressiveness of the disease. Methods: Ki67 mRNA levels were determined utilizing data from a TCGA cohort (Tumor(n)=492 and control(n)=52). The protein expression was determined on 94 biopsies from patients by immunohistochemical assay. Results: in mRNA, the Ki67 upregulation is associated with cancer tissue (p

COVID-19 represents a public health emergency, whose mechanism of which is not fully understood. It is speculated that microRNAs may play a crucial role in host cells after infection by SARS-CoV-2. Thus, our study aimed to analyze the expression of miR-200c-3p in saliva samples from patients with COVID-19. One handred eleven samples from patients with COVID-19 were divided into 4 groups. Group I: 39 patients negative for Covid-19; Group II: 37 positive and symptomatic patients, with no indication of hospitalization; Group III: 21 patients with respiratory disorders (hospitalized); Group IV: 14 patients with severe conditions (oxygen therapy). The expression levels of miR-200c-3p were determined using qPCR. We found greater expression of miR-200c-3p in patients in group IV (p

To compare tissue trauma between Retropubic Radical Prostatectomy and Robotically Assisted Laparoscopic Radical Prostatectomy by inflammatory mediators. Serum samples from 40 patients submitted to RALP and 20 patients submitted to RRP were withdrawn at four different time points. The cytokines IL-4, IL-8, IL-6, IL-1B, IL-10 and TNF-α were detected using ELISA/Multiplex assays and xMAP-Luminex®. With both techniques, IL-10 and IL-6 were higher in T4 than in T1-T3 (p = 0.001). IL-10 and IL-6 were higher in T4 in open surgery than in robotic surgery (p = 0.000 and p = 0.001, respectively). Compared with both groups, IL-6 and IL-10 were higher in T4 in open surgery than in robotic surgery. Thus, we can postulate that RALP causes less tissue trauma than classical RRP, as indicated by the more limited increase in inflammatory mediators such as IL-6 and IL-10.

Radical prostatectomy, a standard management approach for localized Prostate Cancer (PC), may cause a stress response associated with immune modulating effects. Regional anesthesia was hypothesized to reduce the immune effects of surgery by minimizing the neuroendocrine surgical stress response, thus mitigating tumor cells dissemination. Our primary objective was to investigate whether the use of spinal blocks attenuates PC tumor cells dissemination on an animal model. We also assessed the number of circulating NK cells and the amount of inflammatory and anti-inflammatory cytokines.A subcutaneous tumor model, with PC-3M cell line transfected with a luciferase-producing gene (PC-3M-luc-C6) was used. After proper tumor establishment and before tumors became metastatic, animals were submitted to tumor excision surgeries under general or combined (general and spinal) anesthesia. A control group was only anesthetized with general anesthesia.The subcutaneous tumor model with PC-3M-luc-C6 cells was effective in causing distant metastasis after 35 days. The number of circulating tumor cells increased in animals that underwent surgery under general anesthesia alone compared to the group submitted to combined anesthesia. Interleukin 6 levels were different in all groups, with increase in the general anesthesia group.Our results suggest that combination of spinal and general anesthesia may attenuate the suppression of innate tumor immunity and it might be related to a reduction in the neuroendocrine response to surgery.Animal Ethics Committee 1332/2019.

Introduction: Coronavirus disease 2019 (COVID-19) has become one of the more dramatic health problems in the century. This disease has enormous consequence for the health care worldwide. In addition to high mortality rate, patients recovered from COVID-19 present short and long-term cardiovascular sequelae including chest pain, myocardial dysfunction, arrhythmia, dyspnea, breathlessness, postural tachycardia syndrome, and thrombotic complications. The explanations for these clinical manifestations are still uncertain but can involve a constellation of physiological alterations. Hypothesis: To test if COVID-19 survivors have augmented sympathetic outflow, diminished endothelial function, elevated aortic stiffness, and reduced physical capacity compared to healthy individuals. Methods: Nineteen COVID-19 survivors [age: 47.0±2.3 years, BMI: 30.1±1.2 Kg/m 2 ] and eighteen well-matched healthy controls (age: 44.0±2.0 years, BMI: 28.4 ±1.2 Kg.m 2 ] were included in study. COVID-19 survivors were evaluated within 6 months of original diagnosis by RT-PCR. Muscle sympathetic nerve activity (MSNA) from fibular nerve (Microneurography), brachial artery flow-mediated dilation (BAFMD; Doppler-Ultrasound), carotid-femoral pulse wave velocity (cf-PWV; Complior), beat-to-beat blood pressure (Peripheral BP; Finometer), heart rate (HR; Electrocardiography) and peak oxygen uptake (VO 2peak , Cardiopulmonary exercise testing) were measured in both groups. Results: MSNA was higher in COVID-19 survivors compared to controls (33.0±1.0 vs. 22.0±1.0 bursts/min, p =0.001). Both BAFMD and VO 2peak were lower in COVID-19 survivors compared to controls (4.6±0.7 vs. 8.2 ±0.8%, p =0.005 and 22.2±1.5 vs. 29.7±1.6 mL/Kg/min p =0.001, respectively). Although COVID-19 survivors had greater cf-PWV than controls (8.6±0.5 m/s vs. 7.4±0.4 m/s, p =0.03), BP and HR were not different between groups. Conclusions: Our study revealed that patients recently recovered from COVID-19 have abnormal neurovascular control, vascular alterations and reduced physical capacity. These findings strongly indicate the need of further long-term investigations to uncover cardiovascular sequelae provoked by COVID-19.

Background Telomere dysfunction is one of the hallmarks of cancer and is crucial to prostate carcinogenesis. TERF1 is a gene essential to telomere maintenance, and its dysfunction has already been associates with several cancers. TERF1 is a target of miR-155, and this microRNA can inhibit its expression and promotes carcinogenesis in breast cancer. We aim to analyze TERF1, in gene and mRNA level, involvement in prostate cancer progression. Results Alterations in TERF1 DNA were evaluated using datasets of primary tumor and castration-resistant tumors (CRPC) deposited in cBioportal. The expression of TERF1 mRNA levels was assessed utilizing TCGA datasets, clinical specimens, and metastatic prostate cancer cell lines (LNCaP, DU145, and PC3). Six percent of localized prostate cancer presents alterations in TERF1 (the majority of that was amplifications). In the CRPC cohort, 26% of samples had TERF1 amplification. Patients with TERF1 alterations had the worst overall survival only on localized cancer cohort (p = 0.0027). In the TCGA cohort, mRNA levels of TERF1 were downregulated in comparison with normal tissue (p = 0.0013) and upregulated in tumors that invade lymph nodes (p = 0.0059). The upregulation of TERF1 is also associated with worst overall survival (p = 0.0028) and disease-free survival (p = 0.0023). There is a positive correlation between TERF1 and androgen receptor expression in cancer tissue (r = 0.53, p < 0.00001) but not on normal tissue (r = − 0.16, p = 0.12). In the clinical specimens, there is no detectable expression of TERF1 and upregulation of miR-155 (p = 0.0348). In cell lines, TERF1 expression was higher in LNCaP and was progressively lower in DU145 and PC3 (p = 0.0327) with no differences in miR-155 expression. Conclusion Amplification/upregulation of TERF1 was associated with the worst prognostic in localized prostate cancer. Our results corroborate that miR-155 regulates TERF1 expression in prostate cancer. TERF1 has the potential to become a biomarker in prostate cancer.

The new identified protein telomeric zinc-finger associated protein (TZAP) is a negative regulator of telomere length. Since telomere length and telomere maintenance mechanisms are essential to cancer progression, TZAP is considered a new player in cancer biology. Here we aimed to analyze TZAP using the Cancer Genome Atlas data in a Pan-Cancer approach. We gathering data from TCGA Pan-Cancer studies utilizing cBioPortal, GEPIA and UALCAN. In total we analyzed 33 types of cancer (n=9664) and their respective controls (n=711). TZAP is transcribed in all cancers but less than 5% of all tumors show any somatic changes. TZAP was downregulated in kidney chromophobe carcinoma, and upregulated in esophageal cancer, head and neck squamous cell carcinomas, kidney renal clear cell carcinoma and in liver hepatocellular carcinoma. Globally, TZAP expression is related to favorable prognosis, associated to better overall and disease-free survival. Looking to specific tumors, TZAP expression has a dual behavior. Its downregulation is associated with poor prognosis in cervical squamous cell carcinoma, in kidney renal clear cell carcinoma, kidney papillary cell carcinoma, lung adenocarcinoma and pancreas adenocarcinoma. On the contrary, in adrenocortical carcinoma, colon and rectal cancer, brain lower grade glioma and prostate adenocarcinoma the upregulation of TZAP is related with poor prognosis. TZAP expression has a positive correlation with TRF1 and TRF2 in normal tissue but not in cancer. Our analyses indicate that TZAP has an important role in oncology and may be considered as a potential biomarker.

Background: Peyronie’s disease (PD) is characterized by the formation of fibrous plaque in tunica albuginea, causing several problems in patients. The etiology of this disease is not fully understood, and there are few effective treatments. To better understand the molecular pathways of PD, we studied miR-29b, a microRNA that could be involved with this illness. MicroRNAs are endogenous molecules that act by inhibiting messenger RNA. MiR-29b regulates 11 of 20 collagen genes and the TGF-β1 gene, which are related to PD progression. Methods: We compared miR-29b expression in 11 patients with PD and 14 patients without PD (control group). For the patients with PD, we utilized samples from the fibrous plaque ( n = 9), from the tunica albuginea ( n = 11), and from the corpus cavernosum ( n = 8). For the control group, we utilized samples from the tunica albuginea ( n = 14) and from the corpus cavernosum ( n = 10). MiR-29b expression was determined by q-PCR. Results: We found a downregulation of miR-29b in the fibrous plaque, tunica albuginea and corpus cavernosum of patients with PD in comparison with the control group ( p = 0.0484, p = 0.0025, and p = 0.0016, respectively). Conclusion: Although our study has a small sample, we showed for the first time an evidence that the downregulation of miR-29b is associated with PD.

Bladder cancer is the leading transitional cell carcinoma affecting men and women with high morbidity and mortality rates, justifying the need to develop new molecular target therapies using microRNAs. This study aimed to evaluate the behavior of the T24 cell line after transfection with miR-Let-7c precursor mimic through invasion, migration, apoptosis, and cell cycle assays. METHODS AND RESULTS: T24 cell was transfected with the Let-7c mimic and its respective control and evaluated after 24 h. The expression levels of miR-Let-7c were analyzed by qPCR. We performed wound healing, Matrigel and flow cytometry, apoptosis, and cell cycle assays to determine its effect on cellular processes. Cells transfected with miR-Let-7c showed increased apoptosis rates (p = 0.019), decreased migration 24 h (p = 0.031) and 48 h (p = 0.0006), invasion potential (p = 0.0007), and cell proliferation (p = 0.002).Our results demonstrate that miR-Let-7c can act in different pathways of the carcinogenic cellular processes of muscle-invasive urothelial carcinoma cells, inhibiting cell proliferation and increasing apoptosis levels, consequently limiting their invasion potential. However, further studies should be carried out better to elucidate this microRNA's role in high-grade urothelial carcinomas and unveil which targets this microRNA may present, which are intrinsically related to the cancer survival pathways.

Objective To evaluate the synergic effects of a novel oral supplement formulation, containing prebiotics, yeast β-glucans, minerals and silymarin (Silybum marianum), on lipid and glycidic metabolism, inflammatory and mitochondrial proteins of the liver, in control and high-fat diet-induced obese mice. Methods After an acclimation period, 32 male C57BL/6 mice were divided into the following groups: nonfat diet (NFD) vehicle, NFD supplemented, high-fat diet (HFD) vehicle and HFD supplemented. The vehicle and experimental formulation were administered orally by gavage once a day during the last four weeks of the diet (28 consecutive days). We then evaluated energy homeostasis, inflammation, and mitochondrial protein expression in these groups of mice. Results After four weeks of supplementation, study groups experienced reduced glycemia, dyslipidemia, fat, and hepatic fibrosis levels. Additionally, proliferator-activated receptor-α, AMP-activated protein kinase-1α, peroxisome proliferator-activated receptor γ co-activator -1α, and mitochondrial transcription factor A expression levels were augmented; however, levels of inhibitor of nuclear factor-κB kinase subunit α and p65 nuclear factor-κB expression, and oxidative markers were reduced. Notably, the cortisol/C-reactive protein ratio, a well-characterized marker of the hypothalamic–pituitary–adrenal axis immune interface status, was found to be modulated by the supplement. Conclusion We discovered that the novel supplement was able to modify different antioxidant, metabolic and inflammatory pathways, improving the energy homeostasis and inflammatory status, and consequently alleviated hepatic steatosis.

The infection by COVID-19 is a serious global public health problem. An efficient way to improve this disease's clinical management would be to characterize patients at higher risk of progressing to critically severe infection using prognostic biomarkers. The telomere length could be used for this purpose. Telomeres are responsible for controlling the number of maximum cell divisions. The telomere length is a biomarker of aging and several diseases. We aimed to compare leukocyte telomere length (LTL) between patients without COVID-19 and patients with different clinical severity of the infection. Were included 53 patients who underwent SARS-CoV-2 PCR divided in four groups. The first group was composed by patients with a negative diagnosis for COVID-19 (n = 12). The other three groups consisted of patients with a confirmed diagnosis of COVID-19 divided according to the severity of the disease: mild (n = 15), moderate (n = 17) and severe (n = 9). The LTL was determined by Q-PCR. The severe group had the shortest LTL, followed by the moderate group. The negative and mild groups showed no differences. There is an increase of patients with hypertension (p = 0.0099) and diabetes (p = 0.0067) in moderate and severe groups. Severe group was composed by older patients in comparison with the other three groups (p = 0.0083). Regarding sex, there was no significant difference between groups (p = 0.6279). In an ordinal regression model, only LTL and diabetes were significantly associated with disease severity. Shorter telomere length was significantly associated with the severity of COVID-19 infection, which can be useful as a biomarker or to better understand the SARS-CoV-2 pathophysiology., Highlights ● Telomere length is a biomarker in several diseases, including infections. ● Experimental report that associated leukocyte telomere length with severity of SARS-CoV-2. ● Leukocyte telomere length could be used to stratify patients with a greater risk of severe illness.

Background and Purpose: COVID-19 (Coronavirus Disease - 2019) represents a public health emergency because of the elevated transmission rates and associated mortality. There is an urgent need to limit the spread of the virus and to develop an effective antiviral treatment for the patients harboring such disease. This meta-analysis aimed to evaluate the results of the existing randomized clinical trials assessing the use of Hydroxychloroquine (HCQ) to treat COVID-19.Methods: A systematic review was performed on PubMed and Google Scholar according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) recommendations. Information from randomized controlled trials (RCT) was retrieved and included in a meta-analysis.Results: Among 214 studies that were found, 3 were included for in the meta‐ analysis. Patients treated with HCQ had a faster clearance of virus or pneumonia improvement than those that received standard treatment (OR = 7.08, 95% CI 2.79 to 4.12; P = 0.001). Only minor side effects were reported.Conclusions: Although this meta-analysis has found favorable evidence for the use of HCQ in the treatment of COVID-19, the literature does not yet present well-designed clinical studies that demonstrate the effectiveness of this medication. We believe that clinical trials coordinated by standardized guidelines, with complete and quality information, must be carried out worldwide and are urgently needed.

INTRODUCTION AND OBJECTIVE:Cystinuria is an autosomal recessive disease characterized by the failure of the proximal tubule to reabsorb the glomerulus-filtered cystine. Two genes encode the two pro...

Mobile applications ("apps") developed for smartphones and tablets are increasingly used in healthcare, allowing remote patient support or promoting self-health care. Prostate cancer (PC) screening allows for early-stage PC diagnosis, resulting in high rates of curative procedures such as radical prostatectomy. The main complications following surgery are urinary incontinence and erectile dysfunction. However, the exact numbers related to these morbidities are often missing due to brief interviews during consultations in the medical office. Therefore, the aim of this study was to create an app to determine whether response rates to pre- and post-surgical PC questionnaires will increase.The app was built using the IONIC framework system and provided to patients through a prospective randomized study. We included 100 patients divided into two groups: 1. first group used the app (n = 50); and 2. second group responded via validated printed questionnaires (control group) (n = 50). All patients received discharge counseling to respond to the questionnaires 1, 3, 6 and 12 months after the procedure. The app group received verbal guidance on how monitoring would occur, received an SMS containing a username and password providing access to the system and received reminder alerts to respond to the questionnaires.The new app is called UroHealth and is available for download in the Apple App Store or at www.urohealth.com.br. When we evaluated the response rates, we found that 42.9% of the patients answered the preoperative questionnaire in the app group, while 16% responded in the control group (p = 0.003). By the end of the follow-up, we found that 24.5% of the patients answered the questionnaire in the app group, while 4% responded in the control group (p = 0.003).This app enabled almost 6 times more patients to answer long-term follow-up questions after surgical procedures, providing high-quality information regarding morbidity related to treatment. Although our initial results indicate that this app may become a useful tool in obtaining more frequent and realistic answers, thus helping to improve surgical techniques, other ways of reaching the patient should be tested to achieve higher response rates.

Background: Nearly 500,000 new cases of cervical cancer are estimated annually worldwide. Three vaccines are currently licensed to prevent cervical cancer. The success of vaccination depends mainly on the prevalence of HPV genotypes, and many cases of HPV infection have been diagnosed after vaccination. Our aim was to search for HPV genotyping in cervical samples to verify the proportion of women that remain susceptible to infection even after vaccination. Methods: 21,017 liquid-based cervical (LBC) specimens were received for cytology and HPV detection from 2015 to 2018. Before slide preparations for cytology, a 1,000-μL aliquot was taken from the LBC fixative and subjected to automated DNA extraction and multiplex PCR followed by capillary electrophoresis to detect and classify HPV. Results: HPV was detected in 895 (4.3%) specimens. The most prevalent genotype was HPV-16, followed by HPV-58 and HPV-66. A total of 258 (28.8%) cases were positive for high-risk (HR)-HPV types (66, 59, 39, 56, 30, 35, 53, 51, 68, 82, and 70) that are not covered by the HPV vaccines. Conclusion: A significant proportion of HPV types detected in cytological specimens are representative of HR-HPV not covered by the available vaccines. The health system should be aware of the considerable percentage of women who are not being immunized and will continue to need cervical cancer screening.

INTRODUCTION AND OBJECTIVES:Cystinuria is a recessive inherited disorder characterized by impaired tubular reabsorption of cystine and dibasic amino acids ultimately resulting in urolithiasis. Prev...

Currently, the biggest challenge for prostate cancer (PCa) is to understand the mechanism by which the disease acquires the castration-resistant phenotype and progresses to a fatal disease. PCa has a high genetic heterogeneity, and cannot be separated into well-defined molecular subtypes. Despite this, there is consensus about the role of the androgen receptor (AR) in all stages of the disease, including the transition to the castration-resistant phenotype. Since AR is a transcription factor, we investigated the possibility of PCa presenting a pattern of global gene expression during disease progression. By analyzing the TCGA and CCLE datasets, we were able to find a pattern of waves of genes being expressed during each stage of disease progression. This phenomenon suggests the existence of a mechanism that globally regulates gene expression, being AR, telomeres, and zinc finger proteins (ZNF), three important players. The AR modulates the telomere biology, and its transcription is regulated by ZNF. Recently, a study suggested that the telomere length might influence the expression of ZNF. Thus, we hypothesized that changes in the triad AR, telomeres, and ZNF control gene expression during the progression of PCa.

Introduction Mobile applications (“apps”) developed for smartphones and tablets are increasingly used in healthcare, allowing remote patient support or promoting self-health care. Prostate cancer (PC) screening allows for early-stage PC diagnosis, resulting in high rates of curative procedures such as radical prostatectomy. The main complications following surgery are urinary incontinence and erectile dysfunction. However, the exact numbers related to these morbidities are often missing due to brief interviews during consultations in the medical office. Therefore, the aim of this study was to create an app to determine whether response rates to pre- and post-surgical PC questionnaires will increase. Methods The app was built using the IONIC framework system and provided to patients through a prospective randomized study. We included 100 patients divided into two groups: 1. first group used the app (n = 50); and 2. second group responded via validated printed questionnaires (control group) (n = 50). All patients received discharge counseling to respond to the questionnaires 1, 3, 6 and 12 months after the procedure. The app group received verbal guidance on how monitoring would occur, received an SMS containing a username and password providing access to the system and received reminder alerts to respond to the questionnaires. Results The new app is called UroHealth and is available for download in the Apple App Store or at www.urohealth.com.br . When we evaluated the response rates, we found that 42.9% of the patients answered the preoperative questionnaire in the app group, while 16% responded in the control group (p = 0.003). By the end of the follow-up, we found that 24.5% of the patients answered the questionnaire in the app group, while 4% responded in the control group (p = 0.003). Conclusion This app enabled almost 6 times more patients to answer long-term follow-up questions after surgical procedures, providing high-quality information regarding morbidity related to treatment. Although our initial results indicate that this app may become a useful tool in obtaining more frequent and realistic answers, thus helping to improve surgical techniques, other ways of reaching the patient should be tested to achieve higher response rates.

IntroductionInterstitial Cystitis (IC) is a chronic condition diagnosed based on the presence of symptoms, such as suprapubic/ pelvic pain, pressure or discomfort in association with urgency and increased urinary frequency. Confusable diseases must be excluded. However, there is no objective test or marker to establish the presence of the disease. Diagnosis and patient management is often difficult, given the poor understanding of IC pathogenesis and its unknown etiology and genetics. As an attempt to find biomarkers related to IC, we assessed the association between 20 selected single nucleotide polymorphism (SNPs) with IC and pain severity.ObjectivesTo assess the presence of SNPs in IC patients' blood samples and correlate them with the disease and chronic pain condition.MethodsA case-control study was conducted. We selected 34 female patients with IC diagnosed according to NIDDK criteria and 23 patients in the control group (previously healthy women with only stress urinary incontinence). IC patients were allocated into two groups according to reported chronic pain severity. We selected the following SNPs for analysis: rs1800871, rs1800872, rs1800896, rs1800471, rs1800629, rs361525, rs1800497, rs6311, rs6277, rs6276, rs6313, rs2835859, rs11127292, rs2243248, rs6887695, rs3212227, rs1799971, rs12579350, rs3813034, and rs6746030. Genotyping was performed by real-time PCR (q-PCR).ResultsThe polymorphic allele of SNP rs11127292 exhibited a higher frequency in subjects with IC than in controls (p:0.01). The polymorphic allele of SNP rs6311 was more frequent in patients with severe pain (p:0.03). The frequency of the wild-type allele of SNP rs1799971 was higher in patients with mild to moderate pain (p:0.04).ConclusionThe results indicated differences in SNP frequency among subjects, suggesting that SNPs could serve either as a marker of IC or as a marker of pain severity in IC patients. The study showed promising results regarding IC and polymorphism associations. These associations have not been previously reported.

The acquisition of a castration-resistant prostate cancer phenotype by prostate cancer cells is the alteration that has the worst prognosis for patients. The aim of this study was to evaluate the role of the microRNAs-23b/-27b as well as the possible CCNG1 target gene in tissue samples from patients with localized prostate cancer that progressed to castration-resistant prostate cancer and in a castration-resistant prostate cancer cell line (PC-3). The microRNAs and target gene expression levels of the surgical specimens were analyzed by quantitative real-time polymerase chain reaction. The prostate cancer cell line, PC-3, was transfected with pre-miR-23b, pre-miR-27b, and their respective controls using Lipofectamine RNAiMAX and exposed or not to flutamide. After transfections, expression levels of both the microRNAs and the gene, CCNG1, were analyzed by quantitative real-time polymerase chain reaction. The apoptosis and cell cycle assays were performed on the mini MUSE cytometer. MicroRNAs-23b/-27b were underexpressed in surgical specimens of prostate cancer; however, their target gene, CCNG1, was overexpressed in 69% of the cases. After transfection with the microRNAs-23b/-27b and flutamide, we observed a reduction in gene expression compared with cells that were treated only with microRNAs or only with flutamide. In the apoptosis assay, we demonstrated cell sensitization following transfection with microRNAs-23b/-27b and potentiation when co-administered with flutamide. The number of cells in apoptosis was almost three times higher with the simultaneous treatments (miR + flutamide) compared with the control (p < 0.05). In the cell cycle assay, only flutamide treatment showed better results; a higher number of cells were found in the G0-G1 phase, and a lower percentage of cells completed the final phase of the cycle (p < 0.05). We conclude that microRNAs-23b/-27b are downexpressed in prostate cancer, and their target gene, CCNG1, is overexpressed. We postulated that microRNAs-23b/-27b sensitize the PC-3 cell line and that after the addition of flutamide in the apoptosis assay, we would observe synergism in the treatments between miR and flutamide. In the cell cycle assay, the use of flutamide was sufficient to decrease the number of cells in mitosis. Therefore, we postulate that microRNAs, along with other drugs, may become very useful therapeutic tools in the treatment of castration-resistant prostate cancer.

The aim of our study was to determine regions of loss of heterozygosity, copy number variation analysis, and single nucleotide polymorphisms (SNPs) in Brazilian patients with cystinuria. A linkage study was performed using DNA samples from six patients with cystinuria and six healthy individuals. Genotyping was done with the Genome‐Wide Human SNP 6.0 arrays (Affymetrix, Inc., Santa Clara, CA, USA). For validation, SNPs were genotyped using a TaqMan® SNP Genotyping Assay Kit. The homozygote polymorphic genotype of SNP rs17383719 in the gene PBX1 was more frequent (P = 0.015) in cystinuric patients. The presence of the polymorphic allele for this SNP increased the chance of cystinuria by 3.0‐fold (P = 0.036). Pre‐B‐cell leukaemia transcription factor 1 (PBX1) was overexpressed 3.3‐fold in patients with cystinuria. However, when we compared the gene expression findings with the genotyping, patients with a polymorphic homozygote genotype had underexpression of PBX1, while patients with a heterozygote or wild‐type homozygote genotype had overexpression of PBX1. There is a 3‐fold increase in the risk of the development of cystinuria among individuals with this particular SNP in the PBX1 gene. We postulate that the presence of this SNP alters the expression of PBX1, thus affecting the renal absorption of cystine and other amino acids, predisposing to nephrolithiasis.

Objective: To test the performance of a new fixative for pap smear collection for liquid-based cervical cytology, CellPreserv® and compare it with the commercially available, PreservCyt® used in the diagnosis and detection of human papillomavirus (HPV). Methods: Seven hundred twenty five women participated in this study after signing an informed consent. The specimens were collected using a traditional device, agitated in PBS, and equally divided in both fixatives. The slides were prepared routinely, stained by Papanicolaou, examined blindly by 2 cytologists, and reviewed by one cytopathologist. To search for HPV, 1,000 μL from each fixative was taken and processed by polymerase chain reaction. Results: Considering the adequacy of samples, both fixatives had similar results – 0.33 and 0.32% of the cases unsatisfactory for PreservCyt® and CellPreserv®, respectively. Considering the 701 satisfactory cases and comparing the new fixative to the traditional fixative, there was 99.3% concordance between both. The results regarding the HPV detection was 100% concordant between the 2 fixatives. Conclusion: The new methanol-based fixative, CellPreserv®, is cheaper and equally efficient for treating cervical cancer screening and for HPV detection, and can be safely used by the health system prevailing in low-income countries.