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Objective To explore the effect and underlying mechanism of transcription factor activator protein-1 (AP-1) in cholestatic liver injury. Methods ICR mice were randomly divided into control group, cholestatic liver injury model group and AP-1 inhibitor(T-5244) intervention model group(5 in each group). α-naphthyl isothiocyanate(ANIT) and T-5224 were dissolved in corn oil respectively. The mice were fasted for 12 h overnight before the experiment. The control group was treated with corn oil by oral gavage. The cholestatic liver injury model group and the T-5244 intervention model group were treated with ANIT 120 mg/kg(a single dose). The T-5244 intervention group was intraperitoneally injected with T-5224 inhibitor AP-1 100 mg/kg 0.5~1 h before ANIT treatment. The T-5224 treatment was repeated 24 h later. After 48 hrs, all mice were sacrificed to collect serum, liver and gallbladder. The biochemical markers, histopathological changes and liver injury among different groups were analyzed and compared. Results Compared with the control group, the biomarker of liver injury, aspartate alanine aminotransferase (ALT), and aminotransferase (AST), increased from (7.2±1.6)μmol/L and (2.5±0.5) μmol/L to (132.0±48.4)μmol/L and (94.2±22.2)μmol/L in cholestatic liver injury group. It confirmed a successful development of cholestatic model. In contrast with the cholestatic liver injury group, the two biomarkers in the T-5224 intervention group were reduced to (48.4±12.8)μmol/L and (23.1±2.6)μmol/L respectively. At the protein level, activation of AP-1 was inhibited. Expression of CXCL10, CCL2 were inhibited by 90% and 79% respectively in the T-5224 intervention group, and liver injury was significantly reversed. Conclusions AP-1 mediated chemotaxis plays an important role in ANIT-induced cholestatic liver injury.

White matter asymmetries of the human brain have been well documented using diffusion tensor imaging. The purpose of this study was to investigate white matter asymmetry across the whole brain in cerebral small vessel disease patients and evaluate the relation between the factors which often represent disease existence and white matter asymmetry. A total of 105 nondemented elderly subjects with cerebral small vessel disease aged between 60 and 85 years were included in this study. All subjects underwent T1 MPRAGE, fluid-attenuated inversion recovery, and diffusion tensor imaging scanning. With tract-based spatial statistics in diffusion tensor imaging, this study examined the white matter asymmetries and the correlations between white matter asymmetries and four distinct factors such as deep white matter hyperintensities score, periventricular hyperintensities score, cerebral microbleed number and lacune number. The study suggested the asymmetric microstructural change in small vessel disease patients involving the right side being more injured than the left. The four factors jointly affect right brain anisotropy decrease in the middle cerebellar peduncle, the cerebral peduncle, the pontine crossing tract, the corticospinal tract, the medial lemniscus, the posterior limb of internal capsule, and the frontal pattern of white matter. Results of the study demonstrated the lost right white matter may be the main origin of dysfunction in small vessel disease patients. This asymmetry should help with the evaluation of prognostic indicators of disease progression in lesion-based neuropathology.

Objective To study the role and mechanism of platelet-derived growth factor BB (PDGF-BB) on platelet production in Kawasaki disease (KD) mice and human megakaryocytic Dami cells through in vitro and in vivo experiments. Methods ELISA was used to measure the expression of PDGF in the serum of 40 children with KD and 40 healthy children. C57BL/6 mice were used to establish a model of KD and were then randomly divided into a normal group, a KD group, and an imatinib group (30 mice in each group). Routine blood test was performed for each group, and the expression of PDGF-BB, megakaryocyte colony forming unit (CFU-MK), and the megakaryocyte marker CD41 were measured. CCK-8, flow cytometry, quantitative real-time PCR, and Western blot were used to analyze the role and mechanism of PDGF-BB in platelet production in Dami cells. Results PDGF-BB was highly expressed in the serum of KD children (P<0.001). The KD group had a higher expression level of PDGF-BB in serum (P<0.05) and significant increases in the expression of CFU-MK and CD41 (P<0.001), and the imatinib group had significant reductions in the expression of CFU-MK and CD41 (P<0.001). In vitro experiments showed that PDGF-BB promoted Dami cell proliferation, platelet production, mRNA expression of PDGFR-β, and protein expression of p-Akt (P<0.05). Compared with the PDGF-BB group, the combination group (PDGF-BB 25 ng/mL + imatinib 20 p,mol/L) had significantly lower levels of platelet production, mRNA expression of PDGFR-β, and protein expression of p-Akt (P<0.05). Conclusions PDGF-BB may promote megakaryocyte proliferation, differentiation, and platelet production by binding to PDGFR-β and activating the PI3K/Akt pathway, and the PDGFR-β inhibitor imatinib can reduce platelet production, which provides a new strategy for the treatment of thrombocytosis in KD. [ABSTRACT FROM AUTHOR]