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1.
Am J Transplant ; 23(3): 336-352, 2023 03.
Article in English | MEDLINE | ID: mdl-36695693

ABSTRACT

Acute rejection (AR) is an important factor that leads to poor prognosis after liver transplantation (LT). Macrophage M1-polarization is an important mechanism in AR development. MicroRNAs play vital roles in disease regulation; however, their effects on macrophages and AR remain unclear. In this study, rat models of AR were established following LT, and macrophages and peripheral blood mononuclear cells were isolated from rats and humans, respectively. We found miR-449a expression to be significantly reduced in macrophages and peripheral blood mononuclear cells. Overexpression of miR-449a not only inhibited the M1-polarization of macrophages in vitro but also improved the AR of transplant in vivo. The mechanism involved inhibiting the noncanonical nuclear factor-kappaB (NF-κB) pathway. We identified procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 (PLOD1) as a target gene of miR-449a, which could reverse miR-449a's inhibition of macrophage M1-polarization, amelioration of AR, and inhibition of the NF-κB pathway. Overall, miR-449a inhibited the NF-κB pathway in macrophages through PLOD1 and also inhibited the M1-polarization of macrophages, thus attenuating AR after LT. In conclusion, miR-449a and PLOD1 may be new targets for the prevention and mitigation of AR.


Subject(s)
Liver Transplantation , MicroRNAs , Animals , Humans , Rats , Leukocytes, Mononuclear/metabolism , Macrophages/metabolism , MicroRNAs/genetics , NF-kappa B/metabolism , Procollagen/metabolism , Procollagen/pharmacology
2.
Int J Ophthalmol ; 12(3): 457-463, 2019.
Article in English | MEDLINE | ID: mdl-30918816

ABSTRACT

AIM: To investigate serum levels of soluble CD146 (sCD146) and vascular endothelial growth factor receptor 2 (VEGFR2) in patients with age-related macular degeneration (AMD). METHODS: Eighty-eight patients with exudative AMD and 45 sex- and age-matched healthy controls were enrolled in this study conducted in China. Serum samples was obtained from the patients with exudative AMD and from the controls. Serum sCD146 and VEGFR2 protein levels were measured using an enzyme-linked immunosorbent assay. RESULTS: We found that serum sCD146 and VEGFR2 protein levels were significantly higher in the patients with exudative AMD group than in the controls (t=3.859, P<0.001 and t=3.829, P<0.001, respectively). Serum sCD146 levels were significantly higher in patients with classic choroidal neovascularization (CNV) than in those with occult CNV (t=9.899, P<0.001). There was a significant difference in the trend for exudative AMD in the highest versus lowest quartile of circulating sCD146 levels (χ 2=10.29, P=0.001). The receiver operating characteristic curve analysis showed that the area under the curve was 0.696 for sCD146 (95%CI: 0.601-0.791) with an optimum diagnostic cut-off value of 157.16 ng/mL, a sensitivity of 55.7%, and a specificity of 82.2%. CONCLUSION: The serum sCD146 level increases and may be a biomarker for exudative AMD.

3.
Angew Chem Int Ed Engl ; 55(21): 6315-8, 2016 05 17.
Article in English | MEDLINE | ID: mdl-27072872

ABSTRACT

An FeBr3 -catalyzed reductive coupling of various aldehydes with alkenes that proceeds through a direct hydride transfer pathway has been developed. With (i) PrOH as the hydrogen donor under mild conditions, previously challenging coupling reactions of unactivated alkyl and aryl aldehydes with simple alkenes, such as styrene derivatives and α-olefins, proceeded smoothly to furnish a diverse range of functionalized alcohols with complete linear regioselectivity.

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