Research advances in abnormal activation and secretion of pancreatic enzymes in acute pancreatitis / 临床肝胆病杂志

Abnormal activation and secretion of pancreatic enzymes in pancreatic acinar cells is one of the important pathogeneses of acute pancreatitis (AP) and can directly damage the pancreatic tissue to accelerate disease progression and induce severe AP. At present, the drugs inhibiting the abnormal activation and secretion of pancreatic enzymes tend to have an unsatisfactory effect in clinical practice, and therefore, it is of great importance to search for new therapeutic targets. This article summarizes the pathological events of abnormal activation and secretion of pancreatic enzymes (cytoplasmic calcium overload, colocalization of lysosomes and zymogen granules, organelle injury, obstructed apical secretion of trypsin, and increased basal secretion of trypsin), collects the molecular mechanisms of related events, and discusses the role of abnormal activation and secretion of pancreatic enzymes in the early stage of AP, so as to provide ideas for the development of targeted drugs in the future.

EFFECTS OF AEROBIC TRAINING ON THE CARDIOMYOCYTES OF THE RIGHT ATRIUM OF MICE / EFEITOS DO TREINAMENTO AERÓBICO EM CARDIOMIÓCITOS DO ÁTRIO DIREITO DE CAMUNDONGOS / EFECTOS DEL ENTRENAMIENTO AERÓBICO EN CARDIOMIOCITOS DEL ATRIO DERECHO DE RATONES

ABSTRACT Introduction: Polypeptide hormones (natriuretic peptides, NPs) are secreted by the cardiac atria and play an important role in the regulation of blood pressure. Objective: To evaluate the effects of aerobic training on the secretory apparatus of NPs in cardiomyocytes of the right atrium. Methods: Nine-month-old mice were divided in two groups (n=10): control group (CG) and trained group (TG). The training protocol was performed on a motor treadmill for 8 weeks. Systolic blood pressure was measured at the beginning of the experiment (9 months of age) and at moment of the sacrifice (11 months of age). Electron micrographs were used to quantify the following variables: the quantitative density and area of NP granules, the relative volumes of the mitochondria, endoplasmic reticulum, and Golgi complex and the relative volume of euchromatin in the nucleus and the number of pores per 10 µm of the nuclear membrane. The results were compared by Student's t test (p< 0.05). Results: The cardiomyocytes obtained from TG mice showed increased density and sectional area of secretory granules of NP, higher relative volume of endoplasmic reticulum, mitochondria, and Golgi complex compared with the CG mice. Furthermore, the quantitative density of nuclear pores and the relative volume of euchromatin in the nucleus were significantly higher compared with the CG mice. Conclusion: Aerobic training caused hypertrophy of the secretory apparatus in the cardiomyocytes of right atrium, which could explain the intense synthesis of natriuretic peptides in trained mice with respect to the untrained mice.

RESUMO Introdução: Os hormônios polipeptídicos (peptídeos natriuréticos, PN) são secretados pelos átrios cardíacos e desempenham um papel importante na regulação da pressão arterial. Objetivo: Avaliar os efeitos do treinamento aeróbico sobre o aparelho secretor de PN nos cardiomiócitos do átrio direito. Métodos: Camundongos com nove meses de idade foram divididos em dois grupos (n = 10): grupo controle (GC) e grupo treinado (GT). O protocolo de treinamento foi realizado em esteira motorizada durante 8 semanas. A pressão sistólica dos animais foi medida no início do experimento (9 meses de idade) e no momento do sacrifício (11 meses). Foram usadas eletromicrografias para quantificar as seguintes variáveis densidade quantitativa e área dos grânulos de PN; volumes relativos (%) de mitocôndrias, retículo endoplasmático e aparelho de Golgi e o volume relativo de eucromatina no núcleo e o número de poros por 10 µm de membrana nuclear. Os resultados foram comparados pelo teste t de Student (p < 0,05). Resultados: Os cardiomiócitos obtidos dos camundongos GT apresentaram maior densidade e área seccional de grânulos secretórios de PN, aumento do volume relativo do retículo endoplasmático, das mitocôndrias e do complexo de Golgi, em comparação com os camundongos GC. Além disso, a densidade quantitativa dos poros nucleares e o volume relativo da eucromatina nuclear foram significantemente superiores em comparação com os camundongos GC. Conclusão: O treinamento aeróbico causou hipertrofia do aparelho secretor dos cardiomiócitos do átrio direito, o que poderia explicar a síntese intensa de peptídeos natriuréticos em camundongos treinados, quando comparados aos não treinados.

RESUMEN Introducción: Las hormonas polipeptídicas (péptidos natriuréticos, PN) son secretadas por las aurículas cardíacas y juegan un papel importante en la regulación de la presión arterial. Objetivo: Evaluar los efectos del entrenamiento aeróbico sobre el aparato secretor de PN en cardiomiocitos de la aurícula derecha. Métodos: Ratones de nueve meses de edad fueron divididos en dos grupos (n = 10): grupo control (GC) y grupo entrenado (GE). El protocolo de entrenamiento se realizó en cinta caminadora durante 8 semanas. La presión arterial sistólica se midió al inicio del experimento (9 meses de edad) y en el momento del sacrificio (11 meses de edad). Las electromicrografías se utilizaron para cuantificar las siguientes variables: la densidad cuantitativa y el área de gránulos de PN; los volúmenes relativos (%) de mitocondrias, del retículo endoplásmico y del aparato de Golgi y el volumen relativo de eucromatina en el núcleo y el número de poros por 10 µm de la membrana nuclear. Los resultados se compararon mediante la prueba t de Student (p < 0,05). Resultados: Los cardiomiocitos obtenidos de los ratones GE mostraron aumento de la densidad y del área seccional de gránulos secretorios de PN, aumento del volumen relativo de retículo endoplásmico, mitocondrias y aparato de Golgi en comparación con los ratones GC. Además, la densidad cuantitativa de los poros nucleares y el volumen relativo de la eucromatina nuclear fueron significativamente mayores en comparación con los ratones CG. Conclusión: El entrenamiento aeróbico causó hipertrofia del aparato secretor en los cardiomiocitos de la aurícula derecha, lo que podría explicar la intensa síntesis de péptidos natriuréticos en ratones entrenados con respecto a los ratones no entrenados.

Research progression on relationship between angiosteosis and matrix vesicle / 中华老年医学杂志

Angiosteosis is associated with increased vascular stiffness and leads to clinical manifestations such as high blood pressure and heart failure,which increases the risk of cardiovascular morbidity and mortality.Angiosteosis is considered to be ectopic deposits of calcium phosphate crystallization in the form of hydroxyapatite in cardiovascular tissue.However,the mechanism of angiosteosis is not yet clear.The pathophysiologic process of angiosteosis is similar to normal bone mineralization.Matrix vesicles (MV) play an important role in bone mineralization.Researches confirmed the existence of MV in the calcified arteries under the microscope.Angiosteosis is widely found in clinical diseases,so the studies of the mechanism of angiosteosis and the role of MV in angiosteosis are of great significance.

Insulin replacement restores the vesicular secretory apparatus in the diabetic rat lacrimal gland / Reposição de insulina restaura o mecanismo secretório da glândula lacrimal de ratos diabéticos

ABSTRACT Purpose: In the lacrimal gland (LG) acinar cells, signaling regulates the release of secretory vesicles through specific Rab and SNARE exocytotic proteins. In diabetes mellitus (DM), the LGs are dysfunctional. The aim of this work was to determine if secretory apparatus changes were associated with any effects on the secretory vesicles (SV) in diabetic rats as well as the expression levels of constituent Rab and members of the SNARE family, and if insulin supplementation reversed those changes. Methods: DM was induced in male Wistar rats with an intravenous dose of streptozotocin (60 mg/kg). One of the two diabetic groups was then treated every other day with insulin (1 IU). A third control group was injected with vehicle. After 10 weeks, Western blotting and RT-PCR were used to compared the Rab and SNARE secretory factor levels in the LGs. Transmission electron microscopy evaluated acinar cell SV density and integrity. Results: In the diabetes mellitus group, there were fewer and enlarged SV. The Rab 27b, Rab 3d, and syntaxin-1 protein expression declined in the rats with diabetes mellitus. Insulin treatment restored the SV density and the Rab 27b and syntaxin expression to their control protein levels, whereas the Vamp 2 mRNA expression increased above the control levels. Conclusions: Diabetes mellitus LG changes were associated with the declines in protein expression levels that were involved in supporting exocytosis and vesicular formation. They were partially reversed by insulin replacement therapy. These findings may help to improve therapeutic management of dry eye in diabetes mellitus. .

RESUMO Objetivo: Células acinares da glândula lacrimal (GL) sinalizam a regulação da liberação através de vesículas secretórias específicas Rab proteínas exocitóticas SNARE. No diabetes mellitus (DM), as glândulas lacrimais são disfuncionais. O objetivo deste trabalho foi determinar se em ratos diabéticos, alterações dos aparatos secretórios estão associados a efeitos sobre vesículas secretoras (VS) e sobre os níveis de expressão do constituinte Rab, bem como membros da família SNARE, e se a suplementação de insulina reverte as alterações. Métodos: DM foi induzido em ratos Wistar machos com uma dose intravenosa de estreptozotocina (60 mg/kg). Um dos dois grupos diabéticos foi então tratado a cada dois dias com insulina (1 UI). Um terceiro grupo controle foi injetado com o veículo. Após 10 semanas, western blot e RT-PCR comparou níveis de fatores secretórios de Rab e SNARE na glândula lacrimal. Microscopia eletrônica de transmissão (MET) avaliaram a densidade e integridade de VS de célula acinar. Resultados: No grupo diabetes mellitus , houve poucas e alargadas VS. Rab27b, Rab 3d e Sintaxina-1 diminuiu a expressão da proteína em ratos com Diabetes Mellitus. O tratamento com insulina restaurou a densidade das VS e expressão de Rab 27b e Sintaxina para seus níveis de proteína controle, enquanto a expressão de Vamp 2 RNAm aumentou em relação aos controles. Conclusões: Alterações na glândula lacrimal de diabetes mellitus estão associadas a reduções nos níveis de expressão de proteínas envolvidas no apoio a exocitose e formação vesicular. Eles são, em parte, revertida por terapia de reposição de insulina. Estes resultados podem ajudar a melhorar a conduta terapêutica do olho seco no diabetes mellitus. .

The Transcription Factor Mist1 Regulates the Cellular Polarity in Mouse Pancreatic Acinar Cells

Pancreatic acinar cells exhibit a polarity that is characterized by the localization of secretory granules at the apical membrane. However, the factors that regulate cellular polarity in these cells are not well understood. In this study, we investigated the effect of Mist1, a basic helix-loop-helix transcription factor, on the cellular architecture of pancreatic acinar cells. Mist1-null mice displayed secretory granules that were diffuse throughout the pancreatic acinar cells, from the apical to basolateral membranes, whereas Mist1 heterozygote mice showed apical localization of secretory granules. Deletion of the Mist1 gene decreased the expression of type 3 inositol 1,4,5-triphosphate receptors (IP3R) but did not affect apical localization and expression of IP3R2. Mist1-null mice also displayed an increase in luminal areas and an increase in the expression of zymogen granules in pancreatic acinar cells. These results suggest that Mist1 plays a critical role in polar localization of cellular organelles and in maintaining cellular architecture in mouse pancreatic acinar cells.

Acinic Cell Carcinoma of the Palatine Tonsil: A Brief Case Report

Acinic cell carcinoma (ACC) is a rare, low-grade malignancy of the salivary glands. Most cases occur in the major salivary glands, especially the parotid gland, with only a few cases involving the minor salivary gland previously described. A 67-year-old male patient was admitted complaining of an obstructive feeling in the throat. On examination, a lobulated mass in the tonsillar surface was noticed. Tonsillectomy was performed under general anesthesia. Histopathological examination of the mass revealed sheets of large, polygonal acinar cells with granular, slightly basophilic cytoplasm, which led to the diagnosis of ACC. Here, we present a case of low-grade ACC of the palatine tonsil, which we believe to be the first reported case of ACC in this location.