Research progress of virus-mediated gene therapy in type 2 diabetes mellitu / 中国临床药理学与治疗学

Type 2 diabetes mellitus results from a combination of genetic and lifestyle factors, and the prevalence of T2DM is increasing worldwide. At present, there are many drawbacks in the clinical treatment of T2DM, so there is an urgent need for a new treatment method for improvement. In recent years, gene therapy has been proved to reverse T2DM related symptoms such as insulin resistance at the animal level, and no obvious side effects such as hypoglycemia have been found. Therefore, gene therapy may be the main development direction of T2DM therapy in the future. This article reviews the role of fibroblast growth factor related genes such as fibroblast growth factor 21, glucagon like peptide-1, peroxisome proliferator activated receptor and insulin in glucose and lipid metabolism and the development of T2DM, and summarized the application of various viral vectors in gene therapy of T2DM. The significance and existing problems of gene therapy in T2DM are discussed, and the possible development direction of gene therapy T2DM in the future is prospected.

Ambient particulate matter-associated autophagy alleviates pulmonary inflammation induced by Platanus pollen protein 3 (Pla3).

Subpollen particles (SPPs) with diameter less than 1 mm released from allergenic pollen grains contain allergens could trigger asthma and lung inflammation after being inhaled. In the meaning time, ambient fine particles attached on the pollen grains could have further effects on the inflammation. However, the mechanisms underlying these phenomena have not been fully elucidated. In this study, the effects of autophagy triggered by PM2.5 and Platanus SPPs were evaluated by using the A549 cell lines and a pollen sensitized rat model. First, autophagy in A549 cells was analyzed after exposure to PM2.5 using acridine orange staining, real-time quantitative PCR (qRT-PCR), and western blot (WB) assays. The increased levels of ROS, superoxide dismutase, and malonaldehyde in the lung homogenates of rats exposed to SPPs indicated that inflammatory response was triggered in the lungs. Treatment with autophagy-inhibiting drugs showed that autophagy suppressed ROS formation and decreased the production of thymic stromal lymphopoietin (TSLP), a critical pathway altering the inflammatory response. Although the effect was indirect, autophagy appeared to negatively regulate TSLP levels, resulting in a compromised immune response. These results suggested that SPPs promote ROS generation and increase TSLP levels, triggering downstream inflammation reactions. However, ambient PM2.5 could aggravate autophagy, which in turn effectively suppressed ROS and TSLP levels, leading to the alleviation of the immune response and pulmonary inflammation.

Subpollens delivery of Platanus acerifolia pollen allergen Pla a3 and nucleic acid into lungs and cells.

Pollen allergy is a very serious seasonal respiratory disease. However, there has been a lack of understanding how pollen allergens enter the body and act on cells. This study focused on the release, transport and characteristic of Pla a3 allergen of the Platanus acerifolia pollen. Pla a3 protein was purified by prokaryotic expression system for preparation of polyclonal antibody. The distribution and release of Pla a3 protein in pollen were observed by immunohistochemistry. Mice were immunized with purified Pla a3 protein and SPPs, respectively. The pathological examination of mouse lung tissue proved that SPPs, as a fine particle in the range of 0.1-1µm, can enter the deep part of the lung directly through the respiratory tract and led to inflammation. Furthermore, DAPI staining confirmed a certain amount of nucleic acids in SPPs. After incubation with SPPs for 6 h, the Pla a3 mRNA could be detected in A549 cells by PCR. This suggests that nucleic acid wrapped in SPPs could be delivered into A549 cells. These results could provide a new clue and experimental data accumulation for further study on the mechanism of pollen sensitization.

Chemical elements and their source apportionment of PM(10) in Beijing urban atmosphere.

Monitoring of Beijing PM(10) was undertaken, data collected in a period of one year showed seasonal variation of the mass level of Beijing PM(10) being highest in winter and spring, lower in summer and lowest in autumn. PIXE was used to investigate the chemical elements in PM(10). Results showed the chemical concentration also varied seasonally. Percentage of the masses of the crustal elements such as Al, Si, Mg, K, Ca, Fe, Mn and Ti, reached highest in spring and S, Cl, Pb, As, Cu, Ni and Zn which originated from anthropogenic sources reached highest in winter. The monitoring data showed gradual increase of the abundance of the elements from spring to winter in Beijing air and especially strong correlation of Si, Ca, Al, Fe, Mg and Ti from the factor analysis indicating these elements coming from the earth crust or soil, S, Zn and Pb probably from industrial pollution and Cl and As from combustion.