Tongji University

About: Tongji University is a education organization based out in Shanghai, China. It is known for research contribution in the topics: Computer science & Population. The organization has 76116 authors who have published 81176 publications receiving 1248911 citations. The organization is also known as: Tongji & Tóngjì Dàxué.

Inhibitor of apoptosis-stimulating protein of p53 inhibits ferroptosis and alleviates intestinal ischemia/reperfusion-induced acute lung injury

Abstract: Acute lung injury (ALI) is a life-threatening disorder with high rates of morbidity and mortality. Reactive oxygen species and epithelial apoptosis are involved in the pathogenesis of acute lung injury. Ferroptosis, an iron-dependent non-apoptotic form of cell death, mediates its effects in part by promoting the accumulation of reactive oxygen species. The inhibition of ferroptosis decreases clinical symptoms in experimental models of ischemia/reperfusion-induced renal failure and heart injury. This study investigated the roles of inhibitor of apoptosis-stimulating protein of p53 (iASPP) and Nrf2 in ferroptosis and their potential therapeutic effects in intestinal ischemia/reperfusion-induced acute lung injury. Intestinal ischemia/reperfusion-induced ALI was induced in wild-type and Nrf2-/- mice. The mice were treated with erastin followed by liproxstatin-1. Ferroptosis-related factors in mice with ischemia/reperfusion-induced acute lung injury or in mouse lung epithelial-2 cells with hypoxia/regeneration (HR)-induced ALI were measured by western blotting, real-time PCR, and immunofluorescence. Ferroptosis contributed to intestinal ischemia/reperfusion-induced ALI in vivo. iASPP inhibited ferroptosis and alleviated intestinal ischemia/reperfusion-induced acute lung injury, and iASPP-mediated protection against ischemia/reperfusion-induced ALI was dependent on Nrf2 signaling. HR-induced acute lung injury enhanced ferroptosis in vitro in mouse lung epithelial-2 cells, and ferroptosis was modulated after the enhancement of intestinal ischemia/reperfusion in Nrf2-/- mice. iASPP mediated its protective effects against acute lung injury through the Nrf2/HIF-1/TF signaling pathway. Ferroptosis contributes to intestinal ischemia/reperfusion-induced ALI, and iASPP treatment inhibits ferroptosis in part via Nrf2. These findings indicate the therapeutic potential of iASPP for treating ischemia/reperfusion-induced ALI.

PfSETvs methylation of histone H3K36 represses virulence genes in Plasmodium falciparum

Abstract: The variant antigen Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), which is expressed on the surface of P. falciparum-infected red blood cells, is a critical virulence factor for malaria. Each parasite has 60 antigenically distinct var genes that each code for a different PfEMP1 protein. During infection the clonal parasite population expresses only one gene at a time before switching to the expression of a new variant antigen as an immune-evasion mechanism to avoid the host antibody response. The mechanism by which 59 of the 60 var genes are silenced remains largely unknown. Here we show that knocking out the P. falciparum variant-silencing SET gene (here termed PfSETvs), which encodes an orthologue of Drosophila melanogaster ASH1 and controls histone H3 lysine 36 trimethylation (H3K36me3) on var genes, results in the transcription of virtually all var genes in the single parasite nuclei and their expression as proteins on the surface of individual infected red blood cells. PfSETvs-dependent H3K36me3 is present along the entire gene body, including the transcription start site, to silence var genes. With low occupancy of PfSETvs at both the transcription start site of var genes and the intronic promoter, expression of var genes coincides with transcription of their corresponding antisense long noncoding RNA. These results uncover a previously unknown role of PfSETvs-dependent H3K36me3 in silencing var genes in P. falciparum that might provide a general mechanism by which orthologues of PfSETvs repress gene expression in other eukaryotes. PfSETvs knockout parasites expressing all PfEMP1 proteins may also be applied to the development of a malaria vaccine.

Spreading and vanishing in nonlinear diffusion problems with free boundaries

Abstract: We study nonlinear diffusion problems of the form ut = uxx+f(u) with free boundaries. Such problems may be used to describe the spreading of a biological or chemical species, with the free boundary representing the expanding front. For special f(u) of the Fisher-KPP type, the problem was investigated by Du and Lin [8]. Here we consider much more general nonlinear terms. For any f(u) which is C and satisfies f(0) = 0, we show that the omega limit set ω(u) of every bounded positive solution is determined by a stationary solution. For monostable, bistable and combustion types of nonlinearities, we obtain a rather complete description of the long-time dynamical behavior of the problem; moreover, by introducing a parameter σ in the initial data, we reveal a threshold value σ∗ such that spreading (limt→∞ u = 1) happens when σ > σ∗, vanishing (limt→∞ u = 0) happens when σ < σ ∗, and at the threshold value σ∗, ω(u) is different for the three different types of nonlinearities. When spreading happens, we make use of “semi-waves” to determine the asymptotic spreading speed of the front.