Interleukin‐35 (IL‐35), a recently discovered heterodimeric cytokine with anti‐inflammatory/immunosuppressive properties, has a central role in limiting the immune response in various disease models including colitis, arthritis and asthma. However, it remains unknown whether IL‐35 is different from other anti‐inflammatory cytokines such as IL‐10 and transforming growth factor (TGF)‐β in terms of inhibition of inflammation initiation or suppression of full‐blown inflammation. In this study, we examined the tissue expression profiles and regulatory mechanisms of IL‐35 in comparison to other anti‐inflammatory cytokines. Our results suggest that in contrast to TGF‐β, IL‐35 is not constitutively expressed in human tissues but is inducible in response to inflammatory stimuli. We also provide structural evidence suggesting that AU‐rich element (ARE) binding proteins and microRNAs target IL‐35 subunit transcripts, which are responsible for quick degradation of IL‐35. Furthermore, we propose a new system to categorize anti‐inflammatory cytokines into two groups: (1) the housekeeping cytokines, such as TGF‐β, inhibit the initiation of inflammation whereas (2) the responsive cytokines including IL‐35 suppress inflammation in full‐blown stage. Our in‐depth analysis of molecular events that regulate the production of IL‐35 and new categorization system of anti‐inflammatory cytokines are important for the design of new strategies of immune intervention. This work was partially supported by the National Institutes of Health Grants HL094451 and HL108910 (XFY), HL67033, HL82774 and HL77288 (HW).

Caspase-1 activation senses metabolic danger-associated molecular patterns (DAMPs) and mediates the initiation of inflammation in endothelial cells. Here, we examined whether the caspase-1 pathway is responsible for sensing hyperlipidemia as a DAMP in bone marrow (BM)-derived Stem cell antigen-1 positive (Sca-1+) stem/progenitor cells and weakening their angiogenic ability. Using biochemical methods, gene knockout, cell therapy and myocardial infarction (MI) models, we had the following findings: 1) Hyperlipidemia induces caspase-1 activity in mouse Sca-1+ progenitor cells in vivo; 2) Caspase-1 contributes to hyperlipidemia-induced modulation of vascular cell death-related gene expression in vivo; 3) Injection of Sca-1+ progenitor cells from caspase-1−/− mice improves endothelial capillary density in heart and decreases cardiomyocyte death in a mouse model of MI; and 4) Caspase-1−/− Sca-1+ progenitor cell therapy improves mouse cardiac function after MI. Our results provide insight on how hyperlipidemia activates caspase-1 in Sca-1+ progenitor cells, which subsequently weakens Sca-1+ progenitor cell repair of vasculature injury. These results demonstrate the therapeutic potential of caspase-1 inhibition in improving progenitor cell therapy for MI.

Background: Thirty-eight NF-B-signaling genes are analyzed for tissue expression profile and pretranscriptional mechanisms. Results: NF-B-signaling genes are differentially expressed and can be regulated by specific transcription factors, multiple alternative promoters/spliced isoforms, DNA methylation, and microRNAs. Conclusion: Pretranslational regulatory mechanisms contribute to NF-B activation and inflammatory diseases. Significance: Pretranslational regulatory mechanisms can be used as therapeutic targets.

HIV and T. gondii infection markers were measured among 383 Intravenous Drug Users (IDU). And cytokine concentrations (IL-4, IL-6, IL-10, IL-12, IFN-gamma and TNF-alpha) were determined. The results showed IDU with HIV infection or HIV/T. gondii co-infection could disturb Th regulatory mechanism.

Objective The aim was to investigate the role and potential mechanism of geranylgeranylacetone (GGA) in the development of atherosclerosis, and to explore the role of heat shock protein 22 (HSP22) in mediating GGA effect. Methods Human coronary artery endothelial cell (HCAEC) was used for in vitro study. RNA interference was applied to suppress HSP22 in the cells. Cellular apoptosis and intracellular level of reactive oxygen species (ROS) were detected by flow cytometer, and proteins of HSP22, NF-κB, eNOS, and ICAM-1 were assessed by immunoblotting. HSP22 -/- //ApoE -/- , and HSP22 +/+ //ApoE -/- mice were used to investigate the effect of GGA in the animal model of atherosclerosis. Atherosclerotic lesion of the mice aortas was evaluated by Oil Red O staining and H&E staining. Results GGA significantly inhibited HCAEC apoptosis in response to oxidized-LDL (ox-LDL), but stimulated HSP22 synthesis in the cells. Transfection of HSP22-siRNA in the cells resulted in complete blockage of the GGA effect on apoptosis. GGA also significantly inhibited ROS, NF-κB, and ICAM-1 in the cells transfected control siRNA, but not in the cells transfected with HSP22-siRNA. Atherosclerotic plaque in the aorta was significantly less in the wild type (WT) animals treated with GGA as stained either by Oil Red O or by H&E staining, but not in the HSP22-KO mice. GGA significantly inhibited expression of NF-κB and ICAM-1 in the WT mice, but not in the HSP22-KO mice. Conclusion GGA-induced HSP22, and inhibited ox-LDL-induced apoptosis as well as expression of NF-κB and ICAM-1 in the HCAECs. GGA also attenuated formation of atherosclerotic plaques in mice aorta. Suppression of HSP22 by siRNA resulted in blockage of the GGA inhibition on apoptosis or stimulation on NF-κB and ICAM-1. These findings suggested that GGA protects endothelial cells from injury in response to ox-LDL and block atherosclerotic development in mice aorta through induction of HSP22.

Objective: This systematic review was designed to evaluate the overall efficacy of optical coherence tomography (OCT)-guided implantation versus angiography-guided for percutaneous coronary intervention. Methods: The following electronic databases, such as CENTRAL, PubMed, Cochrane, and EMBASE were searched for systematic reviews to investigate OCT-guided and angiography-guided implantation. We measured the following 7 parameters in each patient: stent thrombosis, cardiovascular death, myocardial infarction, major adverse cardiac events (MACE), target lesion revascularization (TLR), target vessel revascularization (TVR), all-cause death. Results: In all, 11 studies (6 RCTs and 5 observational studies) involving 4026 subjects were included, with 1903 receiving intravascular ultrasound-guided drug-eluting stent (DES) implantation and 2123 using angiography-guided DES implantation. With regard to MACE, MT, TLR, TVR, stent thrombosis and all-cause death, the group of OCT-guided implantation had no significant statistical association with remarkably improved clinical outcomes. However, its effect on cardiovascular death has a significant statistical difference in angiography-guided implantation group. Conclusion: In the present pool analysis, OCT-guided DES implantation showed a tendency toward improved clinical outcomes compared to angiography-guided implantation. More eligible randomized clinical trials are warranted to verify the findings and to determine the beneficial effect of OCT-guidance for patients.

ObjectiveThis systematic review was designed to evaluate the efficacy of remote ischemic conditioning (RIC) with primary percutaneous coronary intervention (PCI) versus primary PCI alone for ST-segment elevation myocardial infarction (STEMI).Search strategyComputerized search for trials from PubMed, EMBASE, CENTRAL and Cochrane Database of Systematic Reviews databases.Selection criteriaTrials investigating RIC plus primary PCI (group A) versus primary PCI alone (group B).Outcome measuresMyocardial enzyme levels; left ventricular ejection fraction (LVEF); major adverse cardiac and cerebrovascular events (MACCEs); TIMI flow grade III; myocardial salvage index or infarct size per patients.ResultsIn all, 14 studies involving 3165 subjects were included. There was a significant association of myocardial edema levels, myocardial salvage index and incidence of MACCEs in group A compared with group B (myocardial edema levels: SMD = − 0.36, 95% CI (− 0.59, − 0.13); myocardial salvage index: MD = 0.06, 95% CI (0.02, 0.10); MACCE: OR = 0.70, 95% CI (0.57, 0.85)). With regard to infarct size, TIMI flow grade III and LVEF, group A appeared to be equivalent with group B (infarct size: MD = − 1.67, 95% CI (− 3.46, 0.11); TIMI flow grade III: OR = 1.04, 95% CI (0.71, 1.52); LVEF: MD = 0.74, 95% CI (− 0.80, 2.28)).ConclusionRIC was associated with lower myocardial edema levels, myocardial salvage index and incidence of MACCE, while non-significant beneficial effect on infarct size, TIMI flow grade III or LVEF. These findings suggest that RIC is a promising adjunctive treatment to PCI for the prevention of reperfusion injury in STEMI patients.

One of the pathological functions of heat shock protein 22 (HSP22) is the association with inflammatory diseases and atherosclerosis. However, the effects of a high-fat diet (HFD) or oxidized low-density lipoprotein (ox-LDL) combined with atorvastatin (ATV) on HSP22 expression are entirely unknown. The present study investigated the effects of ATV on HSP22 expression in HFD-induced atherosclerotic apolipoprotein E-deficient (ApoE−/−) mice and in ox-LDL-induced human umbilical vein endothelial cells (HUVECs). Furthermore, the influence of HSP22-knockdown on the HFD- or ox-LDL-induced atherosclerotic model was also examined. It was found that HFD or ox-LDL treatment significantly increased HSP22 expression in the serum and aorta, accompanied by decreased phosphorylated (p)-endothelial nitric oxide synthase (p-eNOS) activity and activated p38 mitogen-activated protein kinase (MAPK). However, these effects were suppressed by treatment with ATV. Furthermore, HSP22-knockdown showed reduced ox-LDL-induced lesions, evidenced by increased p-eNOS activity and inactivated p38 MAPK, while suppression of cell proliferation inhibition and cell cycle arrest were also observed. Taken together, the results of this study suggest that HFD or ox-LDL increased the expression of HSP22 and p-p38 MAPK, and decreased the p-eNOS activity in vitro and in vivo, and ATV could reduce the effects by downregulating HSP22 expression.