Inhibition of RIPK3 Pathway Attenuates Intestinal Inflammation and Cell Death of Inflammatory Bowel Disease and Suppresses Necroptosis in Peripheral Mononuclear Cells of Ulcerative Colitis Patients

Receptor-interacting serine/threonine-protein kinase (RIPK) 3 is a member of the TNF receptor-I signaling complex and mediates necroptosis, an inflammatory cell death. Ulcerative colitis (UC) is an excessive inflammatory disease caused by uncontrolled T cell activation. The current study is aimed to determine whether RIPK3 inhibitor attenuates UC development inhibiting inflammation and necroptosis using experimental colitis mice model. Dextran sulfate sodium-induced colitis mice were administered RIPK3 inhibitor (3 mg/ml) 3 times and their tissues were analyzed by immunohistochemistry. RIPK3, mixed lineage kinase domain-like (MLKL), phosphorylated MLKL, IL-17, and CD4 in colitis patient colon tissues were detected using confocal microscopy. Protein levels were measured using immunohistochemistry and ELISA. The differentiation of Th17 cells was evaluated using flow cytometry. The expression of proinflammatory cytokines and necroptosis in peripheral blood mononuclear cells from UC patients was decreased markedly by RIPK3 inhibitor treatment. We also observed that the injection of RIPK3 inhibitor improves colitis severity and protects intestinal destruction. RIPK3 inhibitor reduced necroptosis factors and proinflammatory cytokines in the colon and consequently protected colon devastation. The expression of inflammatory mediators in experimental colitis mice splenocytes was decreased significantly by RIPK3 inhibitor treatment. These results suggest that RIPK3 inhibitor ameliorates severity of experimental colitis and reduces inflammation through the inhibition of inflammatory response and necroptosis and support RIPK3-targeting substances for treatment of UC.

STX0119 Ameliorates Arthritis in SKG Mice via Inhibiting T Helper 17

Rheumatoid arthritis (RA) is an autoimmune disease with chronic and excessive inflammation. Upregulation of interleukin (IL)-17 is involved in the pathogenesis of RA. STX0119 is a specific inhibitor of signal transducer and activator of transcription 3 (STAT3) as a potential target for the treatment of RA. STAT3 is a member of DNA-binding molecules that regulates the expression of proinflammatory cytokines involved in the pathogenesis of RA. The objective of this study was to determine whether STX0119 could inhibit STAT3 and IL-17. We demonstrated that STX0119 decreased T helper (Th) 17 differentiation and IL-17 expression in vitro. STX0119 also improved the severity of zymosan induced arthritis and reduced joint inflammation. STX0119 reduced the proliferation of Th17 and phosphorylated STAT3 expression while increasing Treg differentiation and phosphorylated STAT5 expression. Moreover, STX0119 decreased the expression of IL-6 and -17 but not IL-10. These findings suggest that STX0119 can be used to treat autoimmune RA through inhibiting the activation of STAT3.

The Effect of Dietary Intervention Through the Modification of Fatty Acids Composition and Antioxidant Vitamin Intake on Plasma TXB2 Level in Korean Postmenopausal Women with Hypercholesterolemia

The purpose of this study was to observe the effects of dietary intervention, through the modification of dietary fatty acids composition and antioxidant vitamins, on plasma thromboxane B2 (TXB2) levels in postmenopausal women with hypercholesterolemia. The subjects were treated for 12 weeks with one of three methods: hormone replacement therapy (HRT group, n=8), dietary intervention (DIET group, n=8), or HRT combined with dietary intervention (HRT +DIET group, n=8). Changes in serum phospholipid fatty acids composition, serum peroxides, and plasma TXB2 levels were measured at weeks 0, 4 and 12. The P/S ratio increased and the n-6/ n-3 ratio decreased in the DIET and the HRT +DIET group at week 4 (p<0.05). The ratio of C20:5/C20:4 in serum phospholipid increased in the DIET (p<0.05) and the HRT +DIET groups (NS) at week 4. Plasma TXB2 levels decreased in the DIET (-35%, p<0.05) and the HRT +DIET groups (-18.8%, NS) at week 4. Serum lipid peroxides levels significantly decreased by 10.5% and 15.2% in the DIET group at weeks 4 and 12, and by 10.8% in the HRT +DIET group only at week 12 (p<0.05). Dietary intervention may lower thrombotic risks in Korean postmenopausal women by changing the serum fatty acid composition, serum lipid peroxides levels and plasma thromboxane B2 levels.

Comparisons of Nutrients Intake of Normocholesterolemia and Hypercholesterolemia in the Postmenopausal Women / 대한지역사회영양학회지

The purpose of this study was to explore the difference in nutrient intakes between normocholesterolemia and hypercholesterolemia. The subjects were classified as normocholesterolemia and hypercholesterolemia based on The Guideline for Korean Hyperlipidemia. A semiquantitative food frequency questionnaire was used to measure the dietary intakes of the subjects. The results obtained are summarized as follows. Intakes of nutrients such as energy, carbohydrate, protein, fat, minerals, and antioxidant vitamins were not significantly different between the normocholesterolemia group and hypercholesterolemia group. However, antioxidant vitamins and folate intakes in the hypercholesterolemia group tended to be lower than those in the normocholesterolmia group. Intakes of vitamin A, vitamin E, and Ca in normocholesterolemia was much less than the RDA for those nutrients in normocholesterolemia. Cholesterol intake in the hypercholesterolemia group was significantly higher than that in the normochoesterolemia group. However, mean cholesterol intake(240 mg/day) of the hypercholesterolemia group was much less than that of Americans whose cholesterol intake was 400 - 500 me/day. Fatty acid intakes were not significantly different between normocholesterolemia and hypercholesterolemia groups but the hypercholesterolemia group tended to consume omega3 fatty acids less than the normocholesterolemia group. Out data indicate that cholesterol intake is man important determinant of serum cholesterol levels in postmenopausal women. The results of this study provide information that is important in designing appropriate dietary guidelines for hypercholesterolemia in postmenopausal women.

Comparisons of Nutrients Intake of Normocholesterolemia and Hypercholesterolemia in the Postmenopausal Women / 대한지역사회영양학회지

The purpose of this study was to explore the difference in nutrient intakes between normocholesterolemia and hypercholesterolemia. The subjects were classified as normocholesterolemia and hypercholesterolemia based on The Guideline for Korean Hyperlipidemia. A semiquantitative food frequency questionnaire was used to measure the dietary intakes of the subjects. The results obtained are summarized as follows. Intakes of nutrients such as energy, carbohydrate, protein, fat, minerals, and antioxidant vitamins were not significantly different between the normocholesterolemia group and hypercholesterolemia group. However, antioxidant vitamins and folate intakes in the hypercholesterolemia group tended to be lower than those in the normocholesterolmia group. Intakes of vitamin A, vitamin E, and Ca in normocholesterolemia was much less than the RDA for those nutrients in normocholesterolemia. Cholesterol intake in the hypercholesterolemia group was significantly higher than that in the normochoesterolemia group. However, mean cholesterol intake(240 mg/day) of the hypercholesterolemia group was much less than that of Americans whose cholesterol intake was 400 - 500 me/day. Fatty acid intakes were not significantly different between normocholesterolemia and hypercholesterolemia groups but the hypercholesterolemia group tended to consume omega3 fatty acids less than the normocholesterolemia group. Out data indicate that cholesterol intake is man important determinant of serum cholesterol levels in postmenopausal women. The results of this study provide information that is important in designing appropriate dietary guidelines for hypercholesterolemia in postmenopausal women.

A Study of the Dietary Intake Status and One Portion Size of Commonly Consumed Food and Dishes in Korean Elderly Women / 대한지역사회영양학회지

The use of semiquantitative food frequency to estimate dietary intake has become widespread in nutritional epidemiologic studies. It had been suggested that knowledge about a person's usual portion size of each meal in addition to consumption frequency will improve the accuracy of this method. This study was performed to investigate the dietary intake status(nutrient, food, and dish intake) and one portion size of commonly consumed food and dishes to develop a semiquantitative food frequency questionnaire that will be used to expore the relationship between the incidence of cardiovascular disease and diet in Korean women after menopause. Intake of food or dish in 123 elderly women were measured by 3-day food records in March to May, 1996. The results obtained in this study were summarized as follow : 1) Calcium, vitamin A, and vitamin E intakes were less adequate than Recommended dietary allowances(RDA). 2) The subjects who consumed more than 20% of the energy from fat were 35% and the subjects consumed dietary cholesterol more than 300mg were 18%. 3) The most frequently consumed foods or dishes by the subjects were Korean cabbage kimchi