Luminal surface of vascular endothelium is decorated with a variety of polysaccharide-protein complexes,which constitute the glycocalyx.It has been demonstrated that vascular endothelial glycocalyx plays an important role in modulation of selective permeability of vessels,mediation of the blood cell-endothelial cell interactions and the release of nitric oxide induced by fluid shear stress under physiological condition.In inflammation condition,sheding of glycocalyx due to inflammation mediator leads to its functional weakening in vessel protection.At the same time,heparan sulfate as a major constituent of vascular endothelial glycocalyx could be involved in regulating the evolution of inflammation.Heparan sulfate interacts with L-selectin to mediating leukocyte rolling,presents chemokines on luminal surfaces of endothelial cells to mediate leukocyte crawling and firm adhesion,participates in transcytosis of chemokines from tissue to luminal side of endothelial cells during inflammation.Various risk factors of atherosclerosis,as an inflammatory disease,are closely associated with vascular endothelial glycocalyx.This paper is aimed to review the role of vascular endothelial glycocalyx in inflammation and atherosclerosis.

To investigate the effects of curcumin on mitochondrial dysfunction induced by high glucose(40 mmol/L glucose, 24 h)in L6 cells, curcumin(10, 20, 40 μmol/L)was administered for 24 h after high glucose culture. The effects of curcumin on the mitochondrial dysfunction were evaluated by mitochondrial membrane potential, reactive oxygen species(ROS), ATP content and mtDNA copy number. The mRNA and protein expression of uncoupling protein 2(UCP2), PPARγ coactivator 1α(PGC-1α)and sirtuin-1(Sirt3)were also determined. As improvement of high glucose damage, curcumin significantly raised mitochondrial membrane potential and ATP content, and decreased ROS level. Curcumin significantly ameliorated the down regulation of UCP2 yet with little effect on mtDNA copy number and PGC-1α and Sirt3 expression. In conclusion, curcumin could significantly ameliorate mitochondrial dysfunction in L6 cells induced by high glucose, which involved the mechanism of multiple antioxidants.

Objective:To investigate the effects of Resolvin D1 (RvD1) on the inflammatory response and the expression of Nod-like receptor protein 3(NLRP3) inflammasomes in mice with acute lung injury.Methods:The 30 male BALB/c mice weighing 25-30 g were divided into 3 groups(each group with 10 mice). Mice in the normal control group were given normal saline by tail vein injection.Mice in the lipopolysaccharide (LPS) group were given the same volume of LPS (10 mg/kg) via tail vein injection.Mice in the RvD1 group were injected with RvD1 (5 μg/kg) through the tail vein 30 minutes prior to LPS administration.Mice were humanely sacrificed after 6 hours.Histopatholo-gical changes of lung tissue, the levels of pro-inflammatory cytokines interleukin(IL)-18 and IL-1β, and the expression of NLRP3 inflammasomes in lung tissue were measured.Results:After LPS administration, the lung of mice showed pathological damage.The levels of pro-inflammatory factors IL-18 and IL-1β as well as the expression of NLRP3, apoptosis-associated speck-like protein containing a card(ASC)and Caspase-1 in the LPS group were significantly higher than those in the normal control group (all P<0.05). After pretreatment with RvD1, the pathological damage of lung tissue was alleviated.The levels of pro-inflammatory factors IL-18 and IL-1β as well as the expression of NLRP3, ASC and Caspase-1 in the RvD1 group were significantly lower than those in the LPS group (all P<0.05). Conclusions:RvD1 can attenuate the pulmonary inflammation in acute lung injury and inhibit the release of pro-inflammatory factors, which is possibly related to the suppression of NLRP3.

Disrupted redox status primarily contributes to myocardial ischemia/reperfusion injury (MIRI). NRF2, the endogenous antioxidant regulator, might provide therapeutic benefits. Dihydrotanshinone-I (DT) is an active component in Salvia miltiorrhiza with NRF2 induction potency. This study seeks to validate functional links between NRF2 and cardioprotection of DT and to investigate the molecular mechanism particularly emphasizing on NRF2 cytoplasmic/nuclear translocation. DT potently induced NRF2 nuclear accumulation, ameliorating post-reperfusion injuries via redox alterations. Abrogated cardioprotection in NRF2-deficient mice and cardiomyocytes strongly supports NRF2-dependent cardioprotection of DT. Mechanistically, DT phosphorylated NRF2 at Ser40, rendering its nuclear-import by dissociating from KEAP1 and inhibiting degradation. Importantly, we identified PKC-δ-(Thr505) phosphorylation as primary upstream event triggering NRF2-(Ser40) phosphorylation. Knockdown of PKC-δ dramatically retained NRF2 in cytoplasm, convincing its pivotal role in mediating NRF2 nuclear-import. NRF2 activity was further enhanced by activated PKB/GSK-3β signaling via nuclear-export signal blockage independent of PKC-δ activation. By demonstrating independent modulation of PKC-δ and PKB/GSK-3β/Fyn signaling, we highlight the ability of DT to exploit both nuclear import and export regulation of NRF2 in treating reperfusion injury harboring redox homeostasis alterations. Coactivation of PKC and PKB phenocopied cardioprotection of DT in vitro and in vivo, further supporting the potential applicability of this rationale. Graphical abstract