Metformin improves insulin sensitivity in insulin sensitive tissues such as liver, muscle and fat. However, the functional roles and the underlying mechanism of metformin action in pancreatic β cells remain elusive. Here we show that, under normal growth condition, metformin suppresses MIN6 β cell proliferation and promotes apoptosis via an AMPK-dependent and autophagy-mediated mechanism. On the other hand, metformin protects MIN6 cells against palmitic acid (PA)-induced apoptosis. Our findings indicate that metformin plays a dual role in β cell survival and overdose of this anti-diabetic drug itself may lead to potential β cell toxicity.
Cell-derived small extracellular vesicles have been exploited as potent drug vehicles. However, significant challenges hamper their clinical translation, including inefficient cytosolic delivery, poor target-specificity, low yield, and inconsistency in production. Here, we report a bioinspired material, engineered fusogen and targeting moiety co-functionalized cell-derived nanovesicle (CNV) called eFT-CNV, as a drug vehicle. We show that universal eFT-CNVs can be produced by extrusion of genetically modified donor cells with high yield and consistency. We demonstrate that bioinspired eFT-CNVs can efficiently and selectively bind to targets and trigger membrane fusion, fulfilling endo-lysosomal escape and cytosolic drug delivery. We find that, compared to counterparts, eFT-CNVs significantly improve the treatment efficacy of drugs acting on cytosolic targets. We believe that our bioinspired eFT-CNVs will be promising and powerful tools for nanomedicine and precision medicine.
23 January 2022 in Therapeutic Advances in Hematology
Background: Primary central nervous system lymphoma (PCNSL) has received more attention because of an inferior prognosis. Less is known about the incidence rate, histological type, and survival rate of PCNSL, especially in the 2010s. Methods: Data of PCNSL from the Surveillance, Epidemiology, and End Results (SEER) registry database (SEER 9 registries and SEER 18 registries) were used. Incidence was estimated by age, gender, race, site, and histological type. Trends were analyzed using joinpoint regression and described as annual percent change (APC) and average annual percent change (AAPC). Five-year overall survival estimates were compared using log-rank tests. Results: Most PCNSL occurred in the brain, followed by the spinal cord. The most frequent histological type of PCNSL was diffuse large B-cell lymphoma, followed by marginal zone lymphoma. Incidence rate increased from 0.1/100,000 to 0.5/100,000 with an AAPC of 5.3% from 1975 to 2017. Incidence rates varied greatly between the younger and older age population. The 5-year overall survival rates in SEER 9 registries and SEER 18 registries were 30.5% and 37.4%, respectively. Even though the 5-year overall survival rate significantly increased from 27.9% for the 1975–1979 time period to 44.8% for the 2010–2017 time period, survival benefit could not be expected for patients ⩾60 years. The 5-year survival rate for elderly patients was about 30% in the 2010s. Conclusion: With aging, the incidence of PCNSL in the elderly is increased. Over the past decade, no advances have been made in the treatment of elderly PCNSL. Prospective trials with PCNSL are warranted to improve the survival of elderly patients.
Background. In this day and age, 17% of children less than 5 years of age died of pneumonia; it is the common cause of children death. It is one of the main children respiratory infectious diseases, i.e., mycoplasma pneumonia (MP). The imaging examination can be adopted to quickly observe the morphology and scope of the pulmonary lesions and know the effect of disease treatment and subsequent changes in the disease in order to provide a basis for treatment. Therefore, the most commonly applied technology for detecting pneumonia in children is imaging technology, including chest X-ray and CT. Objectives. The main objective of the work is to investigate the chest computed tomography (CT) findings of children patients with Mycoplasma pneumoniae pneumonia (MPP) and MP combined with streptococcal pneumonia (SP). The mixed infection of MP and SP is very common clinically, and the diagnosis of this type of mixed pneumonia is a critical research topic faced by pediatric respiratory physicians. The comparison is done on the incidence of bronchial and pulmonary interstitial lesions, the degree of lymph node enlargement, the volume and depth of pleural effusion, and the location and morphology of the pulmonary lesions in the chest CT images of children patients from the two groups. Methods. There were comparisons on the incidence of bronchial and pulmonary interstitial lesions, the degree of lymph node enlargement, the volume and depth of pleural effusion, and the location and morphology of the pulmonary lesions in the chest CT images of children patients from the two groups. All the experiments are done in the MATLAB. Results. The results showed that the proportions of reticular shadow, ground glass shadow, bronchial inflation phase, tube wall thickening, and vascular bundle thickening on the CT images of children patients from the MPP group were dramatically higher than those of the MP + SP group ( ). The maximum transverse diameter of enlarged lymph node in children patients from the MPP group was obviously larger than the diameter of the MP + SP group ( ). The number of children patients with pleural effusion was 22 in the MP + SP group, which was greatly higher than the MPP group ( ). Conclusion. In conclusion, the chest CT images of children patients from the MPP group were mainly pulmonary interstitial changes. Furthermore, the alveolar inflammation could be observed on the CT images shown when children patients were combined with SP infection. The more obvious manifestations were that the flaky shadows appeared in the lungs, the pleural effusion became thicker, and the transverse diameters of enlarged lymph nodes were bigger.