A pan-cancer analysis of prognostic significance and immunological role of lysosomal-associated membrane protein 3.

Lysosomal dysfunction can drive carcinogenesis. Lysosomal-associated membrane protein 3 (LAMP3), is a member of the Lysosome Associated Membrane Proteins and is involved in the malignant phenotype such as tumour metastasis and drug resistance, while the mechanisms that regulate the malignant progression of tumour remain vague. Our study aims to provide a more systematic and comprehensive understanding of the role of LAMP3 in the progression of various cancers by various databases.We explored the role of LAMP3 in pan-cancer using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. Multiple online web platforms and software were used for data analysis, including HPA, TIMER, TISIDB, GEPIA, UALCAN, Kaplan-Meier plotter, DAVID and TIGER. The immunohistochemistry was used to quantify the LAMP3 and PD-L1 expression levels in cancer.High LAMP3 expression was found in most cancers and differentially expressed across molecular and immune subtypes. The expression of LAMP3 was involved in the immune-associated processes of Antigen processing and presentation, Th17 cell differentiation, Th1 and Th2 cell differentiation, and the immune-associated pathways of T cell receptor and B cell receptor signalling pathways in most cancers. It also correlated with genetic markers of immunomodulators in various cancers. LAMP3 and PD-L1 expression in BRCA and HNSC tissues was higher than that in corresponding adjacent normal tissues by immunohistochemistry. There is a significant correlation between the expression of LAMP3 and PD-L1.Our study elucidates that LAMP3 has different expression patterns and genetic alteration patterns in different tumours. It is a potential biomarker for immune-related cancer diagnosis, prognosis and efficacy prediction.

TSTA3 overexpression promotes malignant characteristics in LUSC by regulating LAMP2-mediated autophagy and tumor microenvironment.

BACKGROUND: TSTA3 gene encoding GDP-L-fucose synthase has recently been proved to be closely related to the prognosis of patients with various tumors. However, its role in lung cancer is still unclear. The purpose of this study is to explore the expression level, prognostic effect, potential function and mechanism of TSTA3 in lung cancer. METHODS: Based on TCGA database, Kaplan-Meier and COX regression was used to analyze the relationship between TSTA3 expression and prognosis of lung cancer patients. Immunohistochemistry was used to determine the TSTA3 protein expression in lung cancer and normal tissues. The function of TSTA3 in lung squamous cell carcinoma (LUSC) cell was determined by CCK8, colony formation, transwell assay in vitro and subcutaneous xenografts in vivo. Transcriptome analysis, Lyso-Tracker Red staining and rescue experiment were used to explore the possible underlying mechanism. RESULTS: The expression of TSTA3 was significantly increased in lung cancer, especially in LUSC, and was significantly correlated with the malignant characteristics of LUSC. COX regression analysis showed that the high expression of TSTA3 was an independent prognostic factor in LUSC patients. This was also confirmed by immunohistochemical staining. Compared with the control group, the proliferation, colony formation, invasion and migration ability of LUSC cells with TSTA3 overexpression was enhanced. Similarly, the ability of cell proliferation, colony formation, invasion and migration were weakened after transient knockdown of TSTA3. In vivo experiment showed that compared with control group, TSTA3 overexpression significantly promoted the growth of tumor and shortened survival time. In addition, transcriptome sequencing analysis showed that the differentially expressed genes between TSTA3 overexpression and control group was mainly concentrated in the lysosome pathway. Further study found that TSTA3 might affect the proliferation, invasion and migration of LUSC by regulating the expression of lysosome-associated membrane protein 2 (LAMP2) in LUSC. CONCLUSION: The expression level of TSTA3 in LUSC is significantly higher than that in normal tissues. High expression of TSTA3 is associated with poor prognosis of LUSC patients. TSTA3 may affect the proliferation, invasion and migration of LUSC by regulating LAMP2.

Effect of sports training on the rehabilitation of hypertensive patients / Efeitos de treino esportivo na reabilitação de pacientes hipertensos / Efectos de entrenamiento deportivo en la rehabilitación de pacientes hipertensos

ABSTRACT Introduction: Hypertension is one of the most common cardiovascular and cerebrovascular diseases and a major public health problem. Although, through the rational use of drugs, the blood pressure of hypertensive patients can be better controlled, a series of side effects of drugs and expensive medical expenses limit the ability of patients to comply with the demands of hypertension. Objective: To explore the effect of long-term exercise training on the rehabilitation of hypertensive patients. Methods: The patients were divided into a control group and an exercise group, and we used multiple measurements of blood pressure, a questionnaire, and registered the situation of each patient, after what results were compared and analyzed. Results: After 12 weeks of training, the subject's blood pressure has dropped significantly. The systolic blood pressure dropped by an average of 15.5mmHg compared to before the exercise prescription was implemented, diastolic blood pressure dropped by an average of 10.6mmHg. Conclusions: Continuous physical exercise in hypertensive patients has medium- and long-term effect on blood pressure control. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: A hipertensão é uma das doenças cardiovasculares e cerebrovasculares mais comuns e um importante problema de saúde. Embora a pressão de pacientes hipertensos possa ser melhor controlada através do uso racional de medicamentos, seus efeitos colaterais e os elevados custos médicos limitam a habilidade dos pacientes de atender às demandas da hipertensão. Objetivo: Explorar o efeito a longo prazo de exercícios na reabilitação de pacientes hipertensos. Métodos: Dividiram-se os pacientes em um grupo controle e um grupo de exercícios e realizaram-se múltiplas avaliações de sua pressão sanguínea. Além disso, foi aplicado um questionário e a situação de cada paciente foi registrada. Em seguida, os resultados foram comparados e analisados. Resultados: Depois de 12 dias de treino, a pressão sanguínea dos pacientes caiu significativamente. A pressão sanguínea sistólica após a implementação dos exercícios caiu em média 15.5mmHg, e a pressão diastólica caiu em média 10.6mmHg. Conclusões: Atividade física continua em pacientes hipertensos tem efeitos de médio e longo prazo no controle da pressão sanguínea. Nível de evidência II; Estudos terapêuticos - investigação de resultados de tratamento.

RESUMEN Introducción: La hipertensión es una de las enfermedades cardiovasculares y cerebrovasculares más comunes y un importante problema de salud. Aunque la presión de pacientes hipertensos pueda ser mejor controlada a través del uso racional de medicamentos, sus efectos colaterales y los elevados costos médicos limitan la habilidad de los pacientes de atender a las demandas de la hipertensión. Objetivo: Explorar el efecto a largo plazo de ejercicios en la rehabilitación de pacientes hipertensos. Métodos: Los pacientes fueron divididos en un grupo control y un grupo de ejercicios y realizaron múltiples evaluaciones de su presión sanguínea. Además, fue aplicado un cuestionario y la situación de cada paciente fue registrada. Luego, los resultados fueron comparados y analizados. Resultados: Después de 12 días de entrenamiento, la presión sanguínea de los pacientes disminuyó significativamente. La presión sanguínea sistólica, después de la implementación de los ejercicios, descendió en promedio 15.5mmHg, y la presión diastólica descendió en promedio 10.6mmHg. Conclusiones: La actividad física continua en pacientes hipertensos tiene efectos de medio y largo plazo en el control de la presión sanguínea. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados de tratamiento.