Abstract Objective: With the increasing incidence and mortality of laryngeal squamous cell carcinoma worldwide, researchers continue to search for novel prognostic factors and treatment methods for preventing early laryngeal squamous cell carcinoma from becoming advanced laryngeal squamous cell carcinoma. This study aims to determine if tumor budding is an independent risk factor associated with the survival of patients with laryngeal squamous cell carcinoma. Methods: 268 cases of laryngeal squamous cell carcinoma were studied, and tumor budding was analyzed for associations with clinicopathological features and clinical outcomes. Results: Tumor budding was divided into low-grade tumor budding (0-6/0.785mm2) and high-grade tumor budding (≥7/0.785 mm2) based on the results of the receiver operating characteristics curve analysis. Logistic regression analysis showed that smaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were the risk factors for high-grade tumor budding (p < 0.05). In the low-grade tumor budding group, there was no statistic difference in survival between patients without tumor budding and those with 1 -6/0.785 mm2 tumor budding. Multivariate survival analysis showed high-grade tumor budding (p < 0.001) was independent prognostic factors for disease-free survival and overall survival in laryngeal squamous cell carcinoma. High-grade tumor budding was also an independent prognostic factor for disease-free survival (p = 0.037) and overall survival (p = 0.009) in T1-2N0 laryngeal squamous cell carcinoma. Conclusions: Smaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were closely associated with high-grade tumor budding in laryngeal squamous cell carcinoma. High-grade tumor budding may be an adverse risk factor that affects not only the disease-free survival and overall survival of laryngeal squamous cell carcinoma patients but also the survival of T1-2N0 laryngeal squamous cell carcinoma patients. Level of Evidence: Level 4.

Altered expression of miR-182 has been observed in various types of human cancer. The purpose of this study was to investigate the expression of miR-182 and its role in prostate cancer (PCa). Expression of miR-182 and ST6GALNAC5 in tumor tissues and the Du145 PCa cell line was analyzed. Cell proliferation assay, colony formation assay, transwell assay, and wound healing assay were performed. The impact of miR-182 on tumor growth was investigated using a xenograft model. The results indicated that expression of miR-182 was higher in PCa tissues and cell lines, while ST6GALNAC5 was decreased. Downregulating miR-182 significantly inhibited the capacities of proliferation and invasion of PC3 and Du145 cells. ST6GALNAC5 was demonstrated to be a target of miR-182 by luciferase assay, and western blot results indicated PI3K/Akt pathway was involved in miR-182 associated effects on PC3 and Du145 cells. The animal experiment suggested that knockdown of miR-182 inhibited tumor growth. Our study proved that miR-182 participated in the proliferation and invasion of PCa cells via mediating expression of ST6GALNAC5 and established a miR-182/ST6GALNAC5/PI3K/AKT axis in regulation of tumor progression. Our investigation provided a basis for further exploration of the application of miR-182 or ST6GALNAC5-associated therapies for PCa patients.

Resumo Objetivo: A melatonina possui um papel protetor em adultos com doença cardiovascular, porém os efeitos da melatonina em crianças com disfunção cardíaca não são bem entendidos. O estudo foi projetado para explorar a variação nos níveis de melatonina, mieloperoxidase e caspase 3 em crianças que sofrem de insuficiência cardíaca. Métodos: 72 pacientes pediátricos com insuficiência cardíaca e 12 crianças saudáveis foram inscritos no estudo. Um sistema de classificação de Ross modificada foi utilizado para avaliar a função cardíaca clínica. Os pacientes com escore de > 2 pontos foram incluídas no estudo e foram divididos em três grupos de acordo com a gravidade da insuficiência cardíaca: leve (escore: 3-6), moderada (escore: 7-9) e grave (escore: 10-12). Os parâmetros ecocardiográficos, dados laboratoriais e níveis séricos de melatonina, mieloperoxidase e caspase 3 foram medidos e analisados em todos os pacientes. Resultados: Em comparação com os pacientes com insuficiência cardíaca de gravidade leve e moderada, os pacientes no grupo de insuficiência cardíaca grave apresentaram redução significativa da fração de ejeção do ventrículo esquerdo (p < 0,001) e aumento significativo nos níveis séricos de melatonina (p = 0,013) e níveis de mieloperoxidase (p < 0,001). Os níveis séricos de melatonina foram positivamente correlacionados com os níveis séricos de caspase 3 (p < 0,001). Os valores de corte ideais dos níveis séricos de melatonina para diagnóstico de IC e cardiomiopatia primária em pacientes pediátricos com insuficiência cardíaca foram 54,14 pg/mL e 32,88 pg/mL, respectivamente. Conclusões: Os níveis séricos de melatonina e mieloperoxidase mostraram aumento em crianças com insuficiência cardíaca grave. Especulamos se o aumento nos níveis de melatonina pode agir como um mecanismo compensatório em crianças pediátricas com insuficiência cardíaca.

Abstract Objective: Melatonin has a protective role in adults with cardiovascular disease, but the effects of melatonin in children with cardiac dysfunction are not well understood. This study was designed to explore the variations in melatonin, myeloperoxidase, and caspase-3 levels in children suffering from heart failure. Methods: Seventy-two pediatric patients with heart failure and twelve healthy children were enrolled in this study. A modified Ross scoring system was used to evaluate clinical cardiac function. Patients with a score of >2 points were included in the study and were divided into three groups according to severity of heart failure: mild (score: 3-6), moderate (score: 7-9), and severe (score: 10-12). Echocardiographic parameters, laboratory data, and serum levels of melatonin, myeloperoxidase, and caspase-3 were measured and analyzed in all patients. Results: Compared with patients with mild and moderate heart failure, patients in the severe heart failure group had significantly decreased left ventricular ejection fraction (p < 0.001), and significantly increased serum melatonin levels (p = 0.013) and myeloperoxidase levels (p < 0.001). Serum melatonin levels were positively correlated with serum caspase-3 levels (p < 0.001). The optimal cutoff values of serum melatonin levels for the diagnosis of severe heart failure and primary cardiomyopathy in pediatric patients with heart failure were 54.14 pg/mL and 32.88 pg/mL, respectively. Conclusions: Serum melatonin and myeloperoxidase levels were increased in children with severe heart failure. It is likely that increasing melatonin levels may act as a compensatory mechanism in pediatric children with heart failure.

Objetivo : A visfatina é uma adipocina recentemente descoberta que contribui com as condições relacionadas à glicose e à obesidade. Até hoje, pouco se sabe da sua resposta à metformina, um agente sensibilizador de insulina, e ao exercício. Nosso objetivo foi investigar o impacto do tratamento com metformina e/ou da natação sobre a visfatina no soro e no tecido adiposo subcutâneo (TAS), tecido adiposo perirrenal (TAP) e músculo esquelético (ME) em ratos com obesidade induzida por dieta com alto teor de gordura. Materiais e métodos : Ratos Sprague-Dawley foram alimentados com uma dieta normal ou com alto teor de gordura por 16 semanas para o desenvolvimento de um modelo de obesidade. Os ratos do modelo de obesidade foram, então, randomizados para a metformina, natação ou terapia de combinação com metformina e natação, além do grupo controle de obesidade induzida por alto teor de gordura e do grupo controle normal. Cada grupo apresentava 10 ratos. Parâmetros zoométricos e glicêmicos, perfil lipídico e níveis de visfatina sérica foram avaliados no momento inicial e após seis semanas de tratamento. Os níveis de visfatina em TAS, TAP e ME foram determinados por Western Blot. Resultados : A metformina e a natação melhoraram o perfil lipídico e aumentaram a sensibilidade à insulina, com redução do peso corporal. Tanto a metformina quanto a natação levaram à regulação para baixo dos níveis de visfatina no TAS e TAP, enquanto a terapia de combinação apresentou os maiores benefícios, mas não foram observadas alterações nos níveis de visfatina no ME. Conclusão : Nossos resultados indicam que a regulação para baixo da visfatina no TAS e TAP pode ser um dos mecanismos pelos quais a metformina e a natação inibem a obesidade.

Objective : Visfatin is a recently discovered adipocytokine that contributes to glucose and obesity-related conditions. Until now, its responses to the insulin-sensitizing agent metformin and to exercise are largely unknown. We aim to investigate the impact of metformin treatment and/or swimming exercise on serum visfatin and visfatin levels in subcutaneous adipose tissue (SAT), peri-renal adipose tissue (PAT) and skeletal muscle (SM) of high-fat-induced obesity rats. Materials and methods : Sprague-Dawley rats were fed a normal diet or a high-fat diet for 16 weeks to develop obesity model. The high-fat-induced obesity model rats were then randomized to metformin (MET), swimming exercise (SWI), or adjunctive therapy of metformin and swimming exercise (MAS), besides high-fat obesity control group and a normal control group, all with 10 rats per group. Zoometric and glycemic parameters, lipid profile, and serum visfatin levels were assessed at baseline and after 6 weeks of therapy. Visfatin levels in SAT, PAT and SM were determined by Western Blot. Results : Metformin and swimming exercise improved lipid profile, and increased insulin sensitivity and body weight reduction were observed. Both metformin and swimming exercise down-regulated visfatin levels in SAT and PAT, while the adjunctive therapy conferred greater benefits, but no changes of visfatin levels were observed in SM. Conclusion : Our results indicate that visfatin down-regulation in SAT and PAT may be one of the mechanisms by which metformin and swimming exercise inhibit obesity.