The Food Nutritional And Pathologic Mechanism Studies Based On Tissue Remodeling In Inflammatory Diseases

In the pathogenesis of chronic inflammatory diseases, such as obesity and varicose veins, extensive tissue remodeling events are involved. Based on these events, such as angiogenesis, adipogenesis and proteolysis, preforming pathological and food nutritional studies will help the development of new related diagnostic and therapeutic approaches. Aimed on the important scientific problems in the field of agricultural products processing and storage engineering, this paper study of the functional food factor-luteolin action on obesity and related metabolic diseases; in addition, research on cysteinyl cathepsin role in obesity-related varicose veins pathogenesis.Part One:mechanism studies of luteolin on ameliorating diet-induced obesity and insulin resistance in miceMast cells play important roles in diet-induced obesity and diabetes, and some synthetic mast cell stabilizers such as DSCG and ketotifen can improve related metabolic disturbances in mice. As a potent natural mast cells stabilizer, luteolin possess multiple biological activities benefit for human healthy and more effective than DSCG and ketotifen in blocking mast cells degranulation and cytokine release.The male C57BL/6mice were fed low fat diet, high fat diet (HFD), HFD with0.002%and0.01%luteolin for12weeks, respectively. Dietary luteolin suppressed HFD-induced body weight gain, fat deposition and adipocyte hypertrophy. Meanwhile, glucose intolerance and insulin sensitivity was also improved. Interestingly, dietary luteolin ameliorated angiogenesis and associated cell apoptosis and cathepsin activity in epididymis adipose tissues (EAT), which is a critical mechanism that mast cells are involved in diet-induced obesity and diabetes. Further, we showed dietary luteolin reduced macrophage infiltrations in EAT and inflammatory cytokine levels in EAT and serum. Finally, luteolin inhibited mast cell infiltrations and mast cell specific protease expression in EAT.As a natural flavonoid, low-dose diet supplement of luteolin ameliorates diet-induced obesity and insulin resistance in mice, suggesting a new therapeutic and nutrition interventional approach for these diseases. Part Two:functions of lysosomal cysteinyl cathepsins in human varicose veins:a histology studyVaricose veins (VVs) are a major chronic venous disease characterized by extensive remodeling of the extracellular matrix (ECM) architecture and proteolytic events in the vascular wall, which may be important in VVs development—though direct evidence is still missing. Primary VVs formation is a complex and multicentric pathological process. Although the aetiology and pathogenesis of varicose vein remain unclear, obesity is one of the risk factors for varicose vein development. Among proteolysis events, matrix metalloproteinases and their tissue inhibitors have garnered the most attention and been linked with the pathological events of VVs, but little is known about the functional relevance of other protease family members. Whether a cysteinyl cathepsin expression regulatory profile similar to that in arteries occurs in veins, however, remains unknown.Here, we studied the distribution of lysosomal cysteine proteases, cathepsin B, L, K, and S, and their endogenous inhibitor, cystatin C, in long saphenous vein specimens from9normal donors and18patients with Ws. Immunohistochemical analysis demonstrated increased levels of cathepsin L, K, B, and S and reduced levels of cystatin C in Ws. This imbalance between cathepsins and cystatin C may favor Ws remodeling. To investigate the inflammatory mechanism of their expression, we examined a detailed inflammatory cell profile in Ws, including macrophages, T lymphocytes, and mast cells. Increased numbers of CD3-positive T cells and tryptase-positive mast cells were found in Ws, and enhanced levels of cathepsins were detected from lesion T cells、 mast cells、 endothelial cells、 macrophage and smooth-muscle cells. In varicose vein wall, lymphatic vasa significantly hyperplasia aggravated inflammatory cell infiltration into vascular wall.Elevated cathepsins, and their co-localization to infiltrated inflammatory cells and to vascular cells, suggest that these proteases participate in ECM degradation in response to inflammation during W pathogenesis.