Macrophages play essential roles in the generation and resolution of inflammation. Ischemia-reperfusion injury (IRI) triggers a systemic inflammatory response and leads to cellular injury and organ failure.During surgical procedures of the liver, such as hepatic resection and liver transplantation, IRI leads to the dysfunction of the liver. Rho-associated protein kinase (ROCK) inhibitors were reported protecting the liver from IRI. However, the systematic administration of ROCK inhibitors causes severe hypotension.Here, using Fasudil carried liposomes, we specifically inhibited the ROCK-II expression in Kupffer cells and blood monocytes. Through this macrophage/monocyte specific treatment of Fasudil, we successfully protected the liver from IRI by shifting Kupffer cells/monocytes from M1/classical to M2/patrolling phenotype in the liver and peripheral blood. Our finding provides novel insights into the macrophage/monocyte-specific drug delivery and the treatment of liver IRI.
Background
Whether antisense noncoding RNA in the INK4 locus (ANRIL) polymorphisms are associated with the likelihood of coronary artery disease (CAD) remains controversial. Therefore, we performed this study to explore correlation between ANRIL polymorphisms and CAD.
Methods
Literature retrieve was conducted in PubMed, Medline and Embase. Odds ratios and 95% confidence intervals were calculated.
Results
Nineteen studies were enrolled for analyses. Pooled overall analyses showed that rs1333040 (dominant model: P < 0.0001; recessive model: P < 0.0001; allele model: P < 0.0001), rs1333049 (dominant model: P = 0.02; allele model: P = 0.02) and rs2383207 (additive model: P = 0.004; allele model: P = 0.03) polymorphisms were significantly associated with the likelihood of CAD. Further subgroup analyses revealed that rs1333040, rs1333049, rs2383206, rs2383207, rs10757274, and rs10757278 polymorphisms were all significantly correlated with the likelihood of CAD in East Asians. Additionally, rs2383206, rs10757274, and rs10757278 polymorphisms were also significantly correlated with the likelihood of CAD in Caucasians and West Asians.
Conclusions
Our findings indicated that rs1333040, rs1333049, rs2383206, rs2383207, rs10757274, and rs10757278 polymorphisms may serve as genetic biomarkers of CAD in East Asians. Moreover, rs2383206, rs10757274, and rs10757278 polymorphisms may also serve as genetic biomarkers of CAD in Caucasians and West Asians.
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