M2 macrophage-derived exosomal miR-25-3p improves high glucose-induced podocytes injury through activation autophagy via inhibiting DUSP1 expression.

Diabetic nephropathy (DN) is the primary reason of chronic kidney disease. The aim of our study is to explore the role and action mechanism of M2 macrophage-derived exosomes in high glucose (HG)-induced podocytes injury. Here, 30 mmol/L of HG was used to induce podocytes injury. Annexin V-FITC/PI double staining was performed to measure podocytes apoptosis, and western blot was carried out to ensure proteins expression. The shape of exosomes was identified using TEM. Besides, the expression of miR-25-3p was determined by qRT-PCR, FAM-labeled miR-25-5p combined with DiI-labeled exosomes were utilized to explore the uptake of podocytes to exosomes. Relationship between miR-25-3p and DUSP family members was ensued by luciferase activity assay. In the beginning, we found that M2 macrophage ameliorated HG-induced podocytes apoptosis and epithelial-mesenchymal transition through secreting exosomes. Subsequently, highly expressed miR-25-3p was found in M2 macrophage-derived exosomes that effectively improved HG-induced podocytes injury. Furthermore, inhibition of miR-25-3p in M2 macrophage inefficiently repressed HG-induced podocytes injury, thus we proposed that M2 macrophage attenuated podocytes injury through secreting exosomal miR-25-3p. Then, we used an autophagy inhibitor to stimulate podocytes, and demonstrated that M2 macrophage-derived exosomal miR-25-3p improved HG-induced podocytes injury through activating autophagy. Finally, DUSP1 was proved to be a downstream target and mediated the inhibition of exosomal miR-25-3p to HG-induced podocytes injury. Our results indicated that M2 macrophage could improve HG-induced podocytes injury via secreting exosomal miR-25-3p to activate autophagy of the cells through suppressing DUSP1 expression. We proved a newly potential therapy strategy for DN treatment.

Metformin improves survival in lung cancer patients with type 2 diabetes mellitus: A meta-analysis.

BACKGROUND AND OBJECTIVE: In recent years, many studies have investigated metformin and its effects on lung cancer. However, since previous studies have shown that the relationship between metformin and lung cancer is complicated, we performed a meta-analysis to analyze this relationship. MATERIAL AND METHODS: An electronic database search was conducted using PubMed, Embase, and Cochrane library. Outcomes were quantified with hazard ratios and 95% confidence intervals to compare lung cancer survival in patients treated with or without metformin. RESULTS: Ten studies, involving 4397 participants, were included. In the pooled analysis, we found that metformin treatment significantly improved the survival of lung cancer patients (hazard ratio=0.75, 95% confidence interval: 0.70-0.80; P<0.001). Subgroup analysis showed that when stratified by geographic region, the hazard ratios for overall survival were 0.76 (95% confidence interval: 0.71-0.81, P<0.001) and 0.51 (95% confidence interval: 0.25-0.78, P<0.001) for Western and Asian countries, respectively. When stratified by lung cancer subtype, the hazard ratios for overall survival were 0.78 (95% confidence interval: 0.71-0.84, P<0.001), 0.73 (95% confidence interval: 0.66-0.81, P<0.001), and 0.51 (95% confidence interval: 0.25-0.78, P<0.001) for non-divided, non-small cell, and small-cell lung cancer subtypes, respectively. When stratified by study design, the hazard ratios for overall survival were 0.77 (95% confidence interval: 0.71-0.83, P<0.001) and 0.71 (95% confidence interval: 0.63-0.80, P<0.001) for cohort-based and case-controlled studies, respectively.

Metformin improves survival in lung cancer patients with type 2 diabetes mellitus: A meta-analysis / La metformina mejora la supervivencia en pacientes con cáncer de pulmón y diabetes mellitus tipo 2: metaanálisis

Background and objective: In recent years, many studies have investigated metformin and its effects on lung cancer. However, since previous studies have shown that the relationship between metformin and lung cancer is complicated, we performed a meta-analysis to analyze this relationship. Material and methods: An electronic database search was conducted using PubMed, Embase, and Cochrane library. Outcomes were quantified with hazard ratios and 95% confidence intervals to compare lung cancer survival in patients treated with or without metformin. Results: Ten studies, involving 4397 participants, were included. In the pooled analysis, we found that metformin treatment significantly improved the survival of lung cancer patients (hazard ratio = 0.75, 95% confidence interval: 0.70-0.80; P<0.001). Subgroup analysis showed that when stratified by geographic region, the hazard ratios for overall survival were 0.76 (95% confidence interval: 0.71-0.81, P<0.001) and 0.51 (95% confidence interval: 0.25-0.78, P<0.001) for Western and Asian countries, respectively. When stratified by lung cancer subtype, the hazard ratios for overall survival were 0.78 (95% confidence interval: 0.71-0.84, P<0.001), 0.73 (95% confidence interval: 0.66-0.81, P<0.001), and 0.51 (95% confidence interval: 0.25-0.78, P<0.001) for non-divided, non-small cell, and small-cell lung cancer subtypes, respectively. When stratified by study design, the hazard ratios for overall survival were 0.77 (95% confidence interval: 0.71-0.83, P<0.001) and 0.71 (95% confidence interval: 0.63-0.80, P<0.001) for cohort-based and case-controlled studies, respectively

Antecedentes y objetivo: En los últimos años, muchos estudios han investigado los efectos de la metformina sobre el cáncer de pulmón. Sin embargo, dado que estudios previos habían demostrado que la relación entre la metformina y el cáncer de pulmón era complicada, realizamos un metaanálisis para estudiar esta relación. Materiales y métodos: Se realizó una búsqueda en las bases de datos electrónicas PubMed, Embase y Cochrane Library. Los resultados se cuantificaron con cociente de riesgos instantáneos e intervalos de confianza del 95% para comparar la supervivencia del cáncer de pulmón en pacientes tratados con o sin metformina. Resultados: Se incluyeron 10 estudios con un total de 4.397 participantes. En el análisis combinado, el tratamiento con metformina mejoró significativamente la supervivencia de los pacientes con cáncer de pulmón (cociente de riesgos instantáneos=0,75; intervalo de confianza del 95%: 0,70-0,80; p<0,001). El análisis de subgrupos mostró que cuando se estratificó por región geográfica, los cocientes de riesgos para la supervivencia global fueron de 0,76 (intervalo de confianza del 95%: 0,71-0,81; p<0,001) y 0,51 (intervalo de confianza del 95%: 0,25-0,78; p<0,001) para los países occidentales y asiáticos, respectivamente. Cuando se estratificó por subtipo de cáncer de pulmón, los cocientes de riesgo para la supervivencia global fueron de 0,78 (intervalo de confianza del 95%: 0,71-0,84; p<0,001), de 0,73 (intervalo de confianza del 95%: 0,66-0,81; p<0,001) y de 0,51 (intervalo de confianza del 95%: 0,25-0,78; p<0,001) para subtipos de cáncer de pulmón no microcítico, de células no pequeñas y de células pequeñas, respectivamente. Cuando se estratificó según el diseño del estudio, los cocientes de riesgo para la supervivencia global fueron de 0,77 (intervalo de confianza del 95%: 0,71-0,83; p<0,001) y de 0,71 (intervalo de confianza del 95%: 0,63-0,80; p<0,001) para estudios de cohortes y de casos-controles, respectivamente