Objective To explore the impact of change in oxygen concentration on the expression of angiopoietin-like protein 8(ANGPTL8)by endothelial cells(HPAECs)of human pulmonary artery,and the role and mecha-nism of ANGPTL8 in pulmonary hypertension(PH).Methods HPAECs were treated under hypoxic and hyperoxic conditions,and the expression level of ANGPTL8 was detected using Western blot and PCR.The changes in endo-thelial-mesenchymal transition(EndMT)and ERK signaling pathway activity were analyzed.Simultaneously,new-born rats were exposed to hyperoxia to develop a bronchopulmonary dysplasia(BPD)model.The expression of ANGPTL8 protein and changes in the ERK signaling pathway in lung tissue were observed.Results Under hypoxic condition,the protein expression of ANGPTL8 in HPAECs was significantly increased accompanied by inhibition of the ERK signaling pathway.ANGPTL8 promoted the EndMT process induced by hypoxia(P<0.05)and silencing the expression of ANGPTL8 resulted in a partial reversal of EndMT.The protein expression of ANGPTL8 was decreased in hyperoxia-exposed HPAECs and rat lung tissues accompanied by the activation of the ERK signaling pathway(P<0.05).Conclusions ANGPTL8 is highly sensitive to the change of oxygen concentration in HPAECs and closely correlated to its expression level and to the activity of ERK signaling pathway.This result suggests that ANGPTL8 may have potential regulatory effects on the development of PH.

Purpose To investigating the pathological characteristics of the heart and spleen in a Kawasaki disease(KD)model induced by candida albicans watersoluble fraction(CAWS)and to provide a research basis for the pathological mechanisms of KD.Methods Intraperitoneal injection of CAWS was used to establish a KD model in C57BL/6 mice.Specimens of the heart,aorta,and spleen were collected to measure body weight and the weights of the heart and spleen.HE staining was utilized to examine the morphological alterations in the heart,aorta,and spleen.The expression levels of the ma-ture macrophage marker(F4/80),TNF-α,and IL-1β in the spleen were measured using qRT-PCR and immunofluorescence.its clinical pathological characteristics were analyze and relevant literatures were reviewed.Results Compared to the control group,there were no significant differences in the heart and body mass of the model group mice,but their spleen mass signif-icantly increased(P＜0.05).In the myocardial interstitium of model group mice,there was infiltration of mononuclear cells,disorder of the elastic fibers in the aortic wall along with mucoid degeneration,disruption of the splenic red and white pulp struc-ture,and significant macrophage infiltration.In the model group mice,the mRNA levels and immunofluorescence staining inten-sity of spleen F4/80(2.58-fold,P＜0.000 1),TNF-α(1.43-fold,P＜0.001),and IL-1β(3.62-fold,P＜0.000 1)were significantly higher than those in the control group.Conclusion Mice with KD models induced by CAWS can exhibit patholog-ical alterations akin to KD in the heart and aorta,significant en-largement of the spleen,infiltration by macrophages,with ele-vated expressions of TNF-α and IL-1β.

Increased intestinal barrier permeability, leaky gut, has been reported in patients with autism. However, its contribution to the development of autism has not been determined. We selected dextran sulfate sodium (DSS) to disrupt and metformin to repair the intestinal barrier in BTBR T⁺tf/J autistic mice to test this hypothesis. DSS treatment resulted in a decreased affinity for social proximity; however, autistic behaviors in mice were improved after the administration of metformin. We found an increased affinity for social proximity/social memory and decreased repetitive and anxiety-related behaviors. The concentration of lipopolysaccharides in blood decreased after the administration of metformin. The expression levels of the key molecules in the toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-nuclear factor kappa B (NF-κB) pathway and their downstream inflammatory cytokines in the cerebral cortex were both repressed. Thus, "leaky gut" could be a trigger for the development of autism via activation of the lipopolysaccharide-mediated TLR4-MyD88-NF-κB pathway.
Mice ; Animals ; NF-kappa B ; Myeloid Differentiation Factor 88/metabolism* ; Lipopolysaccharides/pharmacology* ; Toll-Like Receptor 4/metabolism* ; Autistic Disorder/metabolism* ; Signal Transduction/physiology*