Leptin-mediated ERK Signaling Pathway Promotes the Transformation of Rat Alveolar Type II Epithelial Cells Induced by Yunnan Tin Mine Dust / 中国肺癌杂志

BACKGROUND@#Currently, a significant number of miners are involved in mining operations at the Gejiu tin mine in Yunnan. This occupational setting is associated with exposure to dust particles, heavy metals, polycyclic aromatic hydrocarbons, and radioactive radon, thereby significantly elevating the risk of lung cancer. This study aims to investigate the involvement of leptin-mediated extracellular regulated protein kinase (ERK) signaling pathway in the malignant transformation of rat alveolar type II epithelial cells induced by Yunnan tin mine dust.@*METHODS@#Immortalized rat alveolar cells type II (RLE-6TN) cells were infected with Yunnan tin mine dust at a concentration of 200 μg/mL for nine consecutive generations to establish the infected cell model, which was named R₂₀₀ cells. The cells were cultured normally, named as R cells. The expression of leptin receptor in both cell groups was detected using the Western blot method. The optimal concentration of leptin and mitogen-activated protein kinase kinase (MEK) inhibitor (U0126) on R₂₀₀ cells was determined using the MTT method. Starting from the 20th generation, the cells in the R group were co-cultured with leptin, while the cells in the R₂₀₀ group were co-cultured with the MEK inhibitor U0126. The morphological alterations of the cells in each group were visualized utilizing hematoxylin-eosin staining. Additionally, concanavalin A (ConA) was utilized to detect any morphological differences, and an anchorage-independent growth assay was conducted to assess the malignant transformation of the cells. The changes in the ERK signaling pathway in epithelial cells after the action of leptin were detected using the Western blot method.@*RESULTS@#Both the cells in the R group and R₂₀₀ group express leptin receptor OB-R. Compared to the R₂₀₀ group, the concentration of leptin at 100 ng/mL shows the most significant pro-proliferation effect. The proliferation of R₂₀₀ cells infected with the virus is inhibited by 30 μmol/L U0126, and a statistically significant divergence was seen when compared to the control group (P<0.05). Starting from the 25th generation, the cell morphology of the leptin-induced R₂₀₀ group (R₂₀₀L group) underwent changes, leading to malignant transformation observed at the 30th generation. The characteristics of malignant transformation became evident by the 40th generation in the R₂₀₀L group. In contrast, the other groups showed agglutination of P40 cells, and the speed of cell aggregation increased with an increase in ConA concentration. Notably, the R₂₀₀L group exhibited faster cell aggregation compared to the U0126-induced R₂₀₀ (R₂₀₀LU) group. Additionally, the cells in the R₂₀₀L group were capable of forming clones starting from P30, with a colony formation rate of 2.25‰±0.5‰. However, no clonal colonies were observed in the R₂₀₀LU group and R₂₀₀ group. The expression of phosphorylated extracellular signal-regulated kinase (pERK) was enhanced in cells of the R₂₀₀L group. However, when the cells in the R₂₀₀L group were treated with U0126, a blocking agent, the phosphorylation level of pERK decreased.@*CONCLUSIONS@#Leptin can promote the malignant transformation of lung epithelial cells infected by mine dust, and the ERK signaling pathway may be necessary for the transformation of alveolar type II epithelial cells induced by Yunnan tin mine dust.

Disfunção cardíaca induzida por obesidade genética e dietética: modulação pelo trânsito de cálcio / Cardiac dysfunction induced by genetic and dietetic obesity: modulation by calcium handling

Introdução: A obesidade é considerada importante problema de saúde pública e fator de risco para o desenvolvimento de doenças cardiovasculares. Estudos apontam que o trânsito de cálcio (Ca+2) intracelular e extracelular, mecanismo essencial no acoplamento excitação-contração-relaxamento cardíaco, está envolvido nesse processo patológico. Enquanto o influxo de Ca+2 promove aumento da concentração de Ca+2 livre no citosol na fase de contração, a recaptura e a extrusão do Ca+2 são importantes para a diminuição do Ca+2 intracelular durante o relaxamento. Objetivo: Identificar, baseado na literatura científica, a modulação da disfunção cardíaca pelo trânsito de cálcio em modelos de obesidade genética e dietética. Métodos: A busca de artigos em bases de dados eletrônicas foi realizada com palavras-chaves e seus correspondentes em inglês. Resultados: Inicialmente os artigos que apresentassem uma das palavras-chaves no título foram selecionados. Após processo de triagem, foram identificados 23 artigos para leitura na íntegra. Foram selecionados ao debate na seção "Discussão" apenas 18 artigos, visto que apresentaram conteúdo satisfatório sobre o tema abordado. Conclusão: A literatura mostra que a obesidade, genética ou dietética, promove disfunções cardíacas moduladas por diversas alterações no trânsito de Ca+2 intracelular e em suas proteínas regulatórias.

Introduction: Obesity is considered an important public that presents increasing prevalence on a global scene. Obese individuals have greater susceptibility to the development of cardiac disease. Studies show that calcium (Ca2+) handling, essential mechanism in the process contraction-relaxation of the cardiac muscle, is associated with cardiac dysfunction in obesity models. While Ca2+ influx promotes elevation of free Ca2 + concentration in the cytosol in the contraction period, the recapture and extrusion Ca2 + are important to Ca2+ reduction during the relaxation. Objective: To identify, based on scientific literature, modulation of cardiac function by calcium handling impairments in models of genetic and dietetic obesity. Methods: The search for articles in electronic databases was performed with key words. Results: Initially studies that showed in title one of the key words were selected for analysis. 23 articles were obtained for reading in full. Then, 18 relevant articles were identified on cardiac dysfunction in obesity, both genetic and dietary and participation of the intracellular calcium handling. Conclusion: The literature presents that both genetic and dietetic obesity promotes cardiac dysfunction modulated by various changes in traffic intracellular Ca2+ and its regulators protein.

Obesidade, adipocitocinas e gravidez: uma atualização da literatura / Obesity, adipocytokines and pregnancy: an update of the literature

Atualmente, a obesidade é considerada um dos maiores e mais visíveis, porém mais negligenciados, problemas de saúde pública em todo o mundo. A adiposidade visceral, mais do que a subcutânea, é determinante para o aparecimento de doenças como o diabetes mellitus, a hipertensão arterial e a doença vascular coronariana. Fisiologicamente, as alterações no metabolismo dos carboidratos e dos lipídios ocorrem na gravidez para garantir um fornecimento contínuo de nutrientes para feto em crescimento promovendo um estado de resistência à insulina (RI). Além dos hormônios placentários, citocinas pró-inflamatórias, as adipocitocinas, secretadas por células do tecido adiposo e pela placenta, desempenham um papel significativo na instalação e manutenção desta RI na gravidez. Nesta revisão, procuramos atualizar o conhecimento sobre as alterações promovidas pelas adipocitocinas e pela obesidade central no organismo da gestante, ressaltando o diagnóstico da adiposidade visceral na gravidez e o risco que envolve este tipo de obesidade para a gestante.

Currently, obesity is considered one of the largest and most visible, but most neglected, public health problems worldwide. The visceral adiposity, rather than subcutaneously, is crucial to the emergence of diseases such as diabetes mellitus, hypertension and coronary vascular disease. Physiologically, changes in the metabolism of carbohydrates and lipids occur in pregnancy to ensure a continuous supply of nutrients to the growing fetus by promoting a state of insulin resistance (IR). In addition to the placental hormones, proinflammatory cytokines, the adipocytokines, secreted by fat tissue and the placenta, play a significant role in the installation and maintenance of IR in pregnancy. In this review, we present the knowledge of the changes promoted by adipocytokines and obesity in the central body of the mother, emphasizing the diagnosis of visceral fat in pregnancy and the risks surrounding this type of obesity in pregnant women.

Impact of leptin levels upon cardiac systoloc; diastolic global myocardial and autonomic function in patients with non insulin dependent diabetes

The increased cardiovascular burden associated with diabetes mellitus [DM], is due to structural or functional abnormalities induced by DM only or by hyperinsulinemia and insulin resistance associated with metabolic disorders. Recent studies have shown that leptin increases in insulin-resistant states, such as obesity and hypertension. On the basis of evidence of plasma leptin effect on cardiovascular system, we assessed possible Impact of leptin upon cardiac function whether systolic or diastolic, also the impact upon global myocardial function assessed by a Doppler-derived myocardial performance index [Tei index] as well as cardiac autonomic function [CAN] in type 2 diabetic patients. Twenty four type 2 diabetic patients aged 51.1 +/- 7.2 years with LV functional changes defined as fasting plasma glucose >/= 126mg/dl without hypertension. Twenty four type 2 diabetic patients without LV functional changes, aged 47.6 +/- 9.0 years, were the control. ESG was performed and QTc dispersion [QTcd] was calculated for detection of CAN Ejection fraction [EF], fractional shortening [FS], E velocity, E/A ratio, isovolumetric relaxation time [IRT], isovolumetric contraction time [ICT], ejection time [ET], and the combined index of myocardial performance [Tei index = IRT + ICT/ET], were calculated by echocardiography Doppler. Fasting serum leptin and insulin were assessed. Fasting blood sugar [FBS] and glycosylated of hemoglobin [HbAlc] were also assessed. The correlations of leptin to QTcd, EF, FS, E/A ratio and Tei index were statistically analyzed. BMI, FBS, fasting serum leptin and insulin were significantly greater in the cases than in the control. QTcd, EF and FS showed non-significant difference between groups. There were statistically significant differences between groups in E/A ratio and Tei index. In the case group, leptin was significantly correlated with FBS and fasting serum inslin. Leptin was not significantly correlated with QTcd. Leptin was negatively correlated with E/A ratio and positively correlated with Tei index in the case group. It can be concluded that in conjunction with hyperglycemia, increased free fatly acids, insulin resistance and cardiac autonomic neuropathy, serum leptin is another risk factor associated with the development of diabetic cardiomyopathy

Angiogenic effects of leptin in patients with nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis [NASH] is characterized by morphological features indistinguishable from alcoholic hepatitis in individuals who do not consume excess alcohol. The role of leptin in the development of NASH is claimed to be through its inflammatory, fibrogenic and angiogenic effects. to evaluate the leptin status in patients with NASH with the emphasis on its angiogenic effects and its relation to basic fibroblast growth [BFGF]. This study was conducted on twenty-five patients with NASH and twenty normal persons of matched age and sex as control. For both groups, lipid profile, fasting and postprandial blood glucose, Serum leptin and BFGF were determined. All the results were tabulated and statistically evaluated. Obesity, hyperlipidaemia and diabetes mellitus were prevalent among patients with NASH. There were significant increase of leptin and basic fibroblast growth factor in patients with NASH, as compared to control. Leptin plays an important role in the pathogenesis of NASH through its metabolic, fibrogenic and angiogenic effects. It may also have a role in the development of complications

O processo puberal normal / Normal puberty

Definido como o período de transição entre a infância e a vida adulta, o processo puberal objetiva a aquisição damaturidade sexual completa. Esse processo caracteriza-se pelo desenvolvimento dos caracteres sexuais secundáriose pelo estirão de crescimento, que ocorrem sob a regulação principal dos esteróides sexuais e do hormônio do crescimento. A ativação do eixo hipotálamo-hipófise-gonadal consiste no principal evento neuroendócrino associado ao desencadeamento da puberdade, porém os mecanismos que levam a essa ativação permanecem desconhecidos. Dentre as teorias propostas, a mais recente delas relaciona o início do processo puberal à ação da leptina, um hormônio secretado pelos adipócitos, que foi recentemente descoberto