Sabrina Thalita Reis

Bladder cancer (BC) is the 10th most common cancer worldwide, accounting for approximately 5% of new cases. Several factors contribute to tumor progression, including increased MMP9. Recently, CRISPR‐Cas9 and immunotherapy have offered high specificity for treatments; therefore, we edited MMP9 using CRISPR‐Cas9 methodology to inhibit metastatic mechanisms and evaluated potential synergy with BCG and anti‐PD‐L1 therapy. We performed CRISPR‐Cas9 gene editing using an RNP complex in the MB49 murine BC cell line. Gene expression of MMPs, integrins, and BAX was analyzed, along with protein expression. Cells were divided into a Scramble control group and CRISPR‐Cas9 for the MMP9 edited group (MMP9−/−). Female C57BL/6 mice received orthotopic BC cells (scramble and MMP9−/− groups) treated with BCG and anti‐PD‐L1. Statistical analyses were performed using t test or ANOVA. MMP9 gene and protein expression were reduced in the MMP9−/− group compared with the scramble group. No differences were observed in other MMPs. Decreased ITGB3, increased BAX gene expression, as well as reduced migration and adhesion to ECM were observed in the MMP9−/− group. Animals in the scramble group showed greater weight loss and lower survival than treated groups. Overall, MMP9 modulated key cellular mechanisms, but did not show synergistic effects with BCG and anti‐PD‐L1 in vivo.

Introduction: Cystinuria is an inherited disorder characterized by impaired proximal tubular reabsorption of cystine, resulting in recurrent cystine stone formation. Mutations in the SLC3A1 and SLC7A9 genes are the main genetic causes of the disease, while variants in PBX1 have also been associated with cystinuria in specific populations. Despite advances in understanding its molecular basis, cystinuria remains clinically heterogeneous, making disease progression and prognosis difficult to predict. This study aimed to investigate circulating microRNAs (miRNAs) as potential molecular biomarkers, characterize their expression profile in patients with cystinuria, and evaluate their association with clinical indicators of disease severity. Methods: The study group included 16 patients with a clinically established diagnosis of cystinuria, while the control group consisted of 11 healthy individuals without a history of nephrolithiasis. Candidate miRNAs were selected based on their predicted regulatory interactions with genes implicated in cystinuria pathogenesis. Eight microRNAs (miR-29a-3p, miR-29b-3p, miR-29c-3p, miR-1207-3p, miR-10a-3p, miR-3658, miR-141-3p, and miR-200a-3p) were analyzed by quantitative real-time PCR (qPCR). Results: Among the eight miRNAs evaluated, miR-10a, miR-141, miR-200a, and miR-3658 were significantly downregulated in patients with cystinuria compared with healthy controls. Higher expression levels of miR-10a, miR-141, and miR-200a were significantly associated with a greater number of previous surgical procedures (p < 0.05). Additionally, increased miR-10a expression was associated with impaired renal function, defined as serum creatinine levels above 1.2 mg/dL. Conclusions: miR-10a, miR-141, miR-200a, and miR-3658 were significantly downregulated in patients with cystinuria compared with healthy controls. Within the cystinuria cohort, higher expression of miR-10a was associated with impaired renal function, whereas increased expression of miR-10a, miR-141, and miR-200a correlated with a greater number of surgical interventions, suggesting a potential relationship with disease severity. Further studies in larger, genetically characterized cohorts are warranted to clarify the biological role and clinical utility of these miRNAs as biomarkers of cystinuria.

Introduction: Nipple sparing mastectomy (NSM) can improve domains of body image and sexuality, but preservation of the nipple-areola complex (NAC) does not guarantee sensory maintenance. NAC neurotization/reinnervation techniques have been proposed to restore sensitivity and optimize quality of life. The aim was to synthesize evidence on ACN reinnervation after NSM with immediate reconstruction, including techniques, objective measures, PROs, and complications. Methods: This is a systematic review according to PRISMA (CRD420261331412). We searched PubMed/MEDLINE, Embase, and Cochrane, without date restriction, for terms related to NSM, NAC, neurotization/cooptation/neural grafts, and sensory evaluation. Included were studies on NSM with immediate reconstruction that described reinnervation/preservation directed at the NAC and reported objective sensory outcomes and/or BREAST-Q. Results: Overall, 411 records were identified and 12 studies were included. There was a predominance of series and cohorts in implant-based reconstruction, often pre-pectoral. The techniques were convergent, with intercostal branches (mainly 4th; 3rd–5th) and, in the majority, processed allografts (∼7 cm) directed to the subareolar plexus/areolar dermis; there were variations with autologous graft and delayed neurotization. Objective measures (PSSD, monofilaments, and two-point discrimination) suggested improvement throughout follow-up, with gains in the first 6–12 months. In a comparative prospective cohort, neurotization was associated with better psychosocial and sexual well-being scores and greater perception of nipple sensation. Major complications were uncommon and no persistent neuromas or dysesthesias were reported; oncological outcomes were poorly reported. Conclusion: NAC reinnervation after NSM is feasible and demonstrates progressive sensory recovery, with emerging evidence suggesting benefits in patient-centered outcomes, including psychosocial and sexual well-being. Current evidence also highlights the clinical relevance of sensory preservation as part of a more functional and humanized reconstructive approach. However, important gaps remain due to heterogeneous methodologies, non-randomized designs, and limited oncological reporting, reinforcing the need for standardized prospective studies.

Introduction Elevated BMI, including overweight and obesity, is increasingly recognized as a potential risk factor for the development and progression of prostate cancer (PCa). However, its influence on perioperative, pathological, and postoperative outcomes following radical prostatectomy remains a subject of debate. This study sought to evaluate the association between elevated BMI and the clinical, surgical, pathological, and postoperative outcomes in patients undergoing robot-assisted radical prostatectomy. Methods This retrospective observational study included patients with histologically confirmed PCa who underwent robot-assisted radical prostatectomy at a private tertiary care hospital in Brazil between September 2017 and August 2025. Patients were stratified into two groups according to BMI: normal weight (BMI < 25 kg/m²) and elevated BMI (BMI ≥ 25 kg/m²), the latter comprising both overweight and obese individuals based on the World Health Organization (WHO) criteria. Demographic, clinical, intraoperative, pathological, laboratory, and postoperative variables were analyzed and compared between the groups. Missing data were addressed through an available-case analysis. Statistical analyses were performed using appropriate parametric and non-parametric tests, with a p-value < 0.05 considered statistically significant. Results A total of 1,366 patients were included in the analysis. Elevated BMI was significantly associated with a higher prevalence of systemic arterial hypertension (SAH) and diabetes mellitus (both p < 0.001). No significant associations were identified between BMI category and pathological characteristics, including pathological stage, extraprostatic extension, lymph node involvement, International Society of Urological Pathology (ISUP) grade group, seminal vesicle invasion, surgical margin status, tumor volume, or postoperative prostate-specific antigen (PSA) levels. Likewise, no significant differences were observed in intraoperative variables or in most postoperative outcomes. However, patients with elevated BMI were more likely to experience absence of spontaneous postoperative diuresis (p = 0.017). The incidence of postoperative complications did not differ significantly between the groups. Conclusions Elevated BMI was associated with a higher prevalence of metabolic comorbidities but was not linked to significant differences in pathological, intraoperative, or most postoperative outcomes following robot-assisted radical prostatectomy. These findings indicate that excess body weight alone may not negatively affect short-term surgical or pathological outcomes in this population. Further prospective multicenter studies are warranted to elucidate the impact of elevated BMI on PCa prognosis.

Bladder cancer (BC) is the sixth most common cancer among men worldwide and represents a significant cause of morbidity and mortality. High-grade BC is associated with an increased risk of progression to muscle-invasive and metastatic disease, negatively impacting patient prognosis. Despite advances in molecular characterization, therapeutic strategies remain limited, and the identification of novel molecular targets is essential. MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation and play critical roles in tumor development and progression. Among them, miRNA-23b and miRNA-27b have been implicated in several malignancies; however, their functional role in high-grade BC remains incompletely understood. This study aimed to evaluate the expression levels of miRNAs-23b and 27b in a high-grade BC cell line and to investigate their effects on cell migration, invasion, and proliferation, exploring their potential therapeutic relevance. The high-grade BC T24 cell line was used. Cells were divided into four groups: Control (no transfection), negative control (Scramble), miRNA-23b mimic, and miRNA-27b mimic. Relative miRNA expression levels were determined by quantitative polymerase chain reaction (qPCR). Functional assays included wound healing (migration), Matrigel invasion assay, and colony formation assay (proliferation). Statistical analyses were performed to compare groups, and p-values < 0.05 were considered statistically significant. Transfection resulted in significant overexpression of miRNA-23b and miRNA-27b compared to both Scramble (p = 0.0344 and p = 0.0386, respectively) and Control groups (p = 0.0343 and p = 0.0390, respectively). Both miRNA-23b and miRNA-27b significantly reduced cell migration compared to Scramble (p = 0.0286). Additionally, miRNA-23b significantly decreased invasion compared to Scramble and Control (p < 0.0001), with similar findings observed for miRNA-27b (p < 0.0001). No statistically significant differences were observed in colony formation among groups. Overexpression of miRNA-23b and miRNA-27b significantly reduced migration and invasion in a high-grade BC cell line, without affecting proliferation. These findings suggest that both miRNAs may act as tumor suppressors in high-grade BC and represent promising candidates for future therapeutic development in bladder cancer.

Background: Urothelial carcinoma, the predominant form of bladder cancer, represents a global public health challenge due to its high rates of recurrence and progression. At the molecular level, microRNA-21 (miR-21) has been characterized as an “oncomir” because of its ability to negatively regulate tumor suppressor genes, thereby promoting tumor survival and progression. In this context, the CRISPR/Cas9 system has emerged as a precise genome-editing tool. Objective: To investigate the biological effects of miR-21 modulation using CRISPR/Cas9-mediated genome editing in the T24 high-grade invasive urothelial carcinoma cell line. Methods: The CRISPR/Cas9 system was delivered as a ribonucleoprotein (RNP) complex. Editing efficiency was assessed using quantitative reverse transcription PCR (RT-qPCR). Functional effects were evaluated through gene expression assays, cell migration assays, as well as Matrigel invasion assays. The presence of the Cas9 protein was confirmed by immunofluorescence. Results: CRISPR/Cas9 treatment targeting miR-21 showed a trend toward reduced miR-21 expression (p = 0.0563), although this did not reach statistical significance. A statistically significant increase in MASPIN (p < 0.0001) and PDCD4 (p = 0.0239), as well as a trend toward increased PTEN expression (p = 0.055), was observed following treatment. Functionally, a significant reduction in the migratory capacity of edited cells was observed after 48 h (p = 0.0334). The presence of Cas9 was successfully confirmed in transfected cells. Conclusion: These findings suggest that CRISPR/Cas9-mediated modulation of miR-21 may influence tumor suppressor pathways and reduce the migratory potential of urothelial carcinoma cells.

Autologous fat grafting enriched with mesenchymal stem cells is a promising minimally invasive regenerative therapy for post‐traumatic anal incontinence. This approach may restore continence and quality of life, even when structural sphincter defects persist.

Introduction: Cholangiocarcinoma (CHOL) is a malignant neoplasm of the biliary epithelium and represents the second most usual form of liver cancer. Its high aggressiveness and late diagnosis hinder the implementation of effective therapies. The lack of reliable prognostic biomarkers also impairs proper clinical management. In this context, microRNAs (miRNAs) emerge as post-transcriptional regulators of gene expression, with diagnostic and prognostic potential in various tumors. Objective: Identify key miRNAs associated with the diagnosis and prognosis of CHOL, with a particular focus on lymph node metastasis, through bioinformatic analysis of data from The Cancer Genome Atlas (TCGA). Method: A cross-sectional, descriptive, and exploratory study based on bioinformatics was conducted. A total of 45 samples (36 tumoral and 9 normal) were analyzed from TCGA. The CancerMIRNome, OncomiR, and UALCAN platforms were used for screening, filtering, and differential expression analysis of miRNAs in relation to clinical and demographic variables. Results: Two hundred forty-five miRNAs with statistical significance were identified, of which nine were associated with lymph node metastasis: let-7c-5p, miR-1258, miR-182-5p, miR-183-5p, miR-194-3p, miR-301a-3p, miR-378a-3p, miR-92b-3p, and miR-96-5p. Notably, miR-194-3p was associated with all clinical variables analyzed. No significant correlation was found between miRNA expression and overall survival. Conclusion: The identified miRNAs demonstrate potential prognostic value in CHOL, particularly for stratifying patients with lymph node metastasis. Further studies involving experimental validation and functional analyses are necessary to confirm their role in CHOL tumor progression.