Macrophage cholesterol efflux is a central step in reverse cholesterol transport, which helps to maintain cholesterol homeostasis and to reduce atherosclerosis. Lipophagy has recently been identified as a new step in cholesterol ester hydrolysis that regulates cholesterol efflux, since it mobilizes cholesterol from lipid droplets of macrophages via autophagy and lysosomes. In this review, we briefly discuss recent advances regarding the mechanisms of the cholesterol efflux pathway in macrophage foam cells, and present lipophagy as a therapeutic target in the treatment of atherosclerosis.
Atherosclerosis ; Autophagy ; Cholesterol* ; Foam Cells ; Homeostasis ; Hydrolysis ; Lipid Droplets ; Lysosomes ; Macrophages*

We investigated the effect of tilianin upon inducible nitric oxide synthesis in the plasma of low-density lipoprotein receptor knock-out (Ldlr-/-) mice fed with high cholesterol diet and in primary peritoneal macrophages of Ldlr-/- mice. High cholesterol diet induced nitric oxide production in the plasma of Ldlr-/- mice. Tilianin reduced the level of nitric oxide (NO) in plasma from Ldlr-/- mice induced by the high cholesterol diet. Tilianin also inhibited the NO production from the primary culture of peritoneal macrophages treated with lipopolysaccharide. The inhibition of NO production was caused by the suppression of inducible nitric oxide synthase (iNOS) gene expression in peritoneal macrophages isolated from Ldlr-/- mice. Moreover, tilianin inhibited the transcriptional activation of iNOS promoter that has NF-kappa B binding element. Thus, these results provide the first evidence that tilianin inhibit iNOS expression and production of NO and may act as a potential anti-inflammatory agent.
Tyrosine/analogs & derivatives/metabolism ; Tissue Distribution ; Sinus of Valsalva/metabolism/pathology/ultrastructure ; Receptors, LDL/*genetics ; Promoter Regions (Genetics)/drug effects ; Nitric Oxide Synthase Type II/*metabolism ; Nitric Oxide/biosynthesis/blood ; NF-kappa B/metabolism ; Mice, Knockout ; Mice ; Male ; Inflammation/metabolism ; Glycosides/*pharmacology ; Flavonoids/*pharmacology ; Down-Regulation/drug effects ; Atherosclerosis/metabolism ; Animals

A variety of benzylidenethiazole analogs have been demonstrated to inhibit 5-lipoxygenase (5-LOX). Here we report the anti-atherogenic potential of 5-(4-hydroxy-2,3,5-trimethylbenzylidene) thiazolidin-2,4-dione (HMB-TZD), a benzylidenethiazole analog, and its potential mechanism of action in LDL receptor-deficient (Ldlr-/-) mice. HMB-TZD Treatment reduced leukotriene B4 (LTB4) production significantly in RAW264.7 macrophages and SVEC4-10 endothelial cells. Macrophages or endothelial cells pre-incubated with HMB-TZD for 2 h and then stimulated with lipopolysaccharide or tumor necrosis factor-alpha (TNF-alpha) displayed reduced cytokine production. Also, HMB-TZD reduced cell migration and adhesion in accordance with decreased proinflammatory molecule production in vitro and ex vivo. HMB-TZD treatment of 8-week-old male Ldlr-/- mice resulted in significantly reduced atherosclerotic lesions without a change to plasma lipid profiles. Moreover, aortic expression of pro-atherogenic molecules involved in the recruitment of monocytes to the aortic wall, including TNF-alpha , MCP-1, and VCAM-1, was downregulated. HMB-TZD also reduced macrophage infiltration into atherosclerotic lesions. In conclusion, HMB-TZD ameliorates atherosclerotic lesion formation possibly by reducing the expression of proinflammatory molecules and monocyte/macrophage recruitment to the lesion. These results suggest that HMB-TZD, and benzylidenethiazole analogs in general, may have therapeutic potential as treatments for atherosclerosis.
Animals ; Atherosclerosis/*drug therapy ; Cell Adhesion/drug effects ; Cell Line ; Cell Movement/drug effects ; Chemokine CCL2/metabolism ; Dinoprostone/metabolism ; Enzyme-Linked Immunosorbent Assay ; Humans ; Leukotriene B4/metabolism ; Macrophages/cytology/drug effects ; Male ; Mice ; Monocytes/cytology/*drug effects ; Random Allocation ; Receptors, LDL/deficiency/genetics ; Thiazolidinediones/*therapeutic use ; Tumor Necrosis Factor-alpha/pharmacology

BACKGROUND: The worldwide prevalence of obesity and allergic diseases has increased. We aimed to explore the relation of overweight to asthma, atopic dermatitis, allergic rhinitis and conjunctivitis in a sample of Korean adolescents. METHODS: We investigated the prevalence of symptoms of asthma and other allergic diseases by using a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. The survey was conducted among 1,499 high school students in 3 regions of Korea. RESULTS: The lifetime prevalence of wheezing (21.2% vs. 15.7%, P = 0.04), the 12 months-prevalence of wheezing (4.5% vs. 2.0%, P = 0.04), exercise induced wheezing (13.8% vs. 9.3%, P = 0.04), treatment of asthma (3.3% vs. 1.1%, P = 0.01) and the prevalence of symptoms of allergic rhinitis (11.0% vs. 5.1%, P = 0.001) were signifi cantly higher in overweight boys than normal weight boys, but not in girls. However, there were no signifi cant differences of the prevalence of symptoms and past history of atopic dermatitis and allergic conjunctivitis between overweight and normal weight groups. In boys, overweight increased the risk of the lifetime prevalence of wheezing (OR 1.54, 95% CI: 1.05-2.24) and 12 months-prevalence of exercise induced wheezing (OR 1.64, 95% CI: 1.05-2.55) after adjusting for confounding variables. CONCLUSION: Overweight could be a risk factor for the development of symptoms of asthma and allergic rhinitis in adolescent boys, whereas it was not a signifi cant risk factor for allergic diseases in girls.
Adolescent ; Asthma ; Confounding Factors (Epidemiology) ; Conjunctivitis ; Conjunctivitis, Allergic ; Dermatitis, Atopic ; Humans ; Hypersensitivity ; Korea ; Obesity ; Overweight ; Prevalence ; Respiratory Sounds ; Rhinitis ; Rhinitis, Allergic, Perennial ; Risk Factors

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients’ values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.