Association between Variations in Body Mass Index and Cognitive Function in Older Korean Adults.

BACKGROUND: Although several studies have assessed obesity and cognitive impairment, most of these studies focus on body mass index (BMI) and cognitive impairment. Therefore to better understand the importance of weight maintenance with aging, this study investigated the relationship between variations in weight and cognitive impairment using the Korean version of the Mini-Mental State Examination (K-MMSE) in individuals aged 45 years or older in Korea. METHODS: Data on 3,477 adults with normal cognitive function (K-MMSE ≥24) at baseline were acquired from the Korean Longitudinal Study of Aging (KLoSA) 2006-2016. The association between weight variability and risk of cognitive impairment was assessed using multiple logistic regression models. We also assessed weight variability and change in cognitive function over the 6-year follow-up using multiple linear regression. RESULTS: Overall, higher variations in BMI were associated with cognitive impairment. Patients in the quintile with the highest variation (Q5) in BMI (mean of BMI changes, 2.69) showed the greatest degree of cognitive impairments (adjusted odds ratio, 1.52; 95% confidence interval [CI], 1.08-2.14; P for trend=0.016). Furthermore, a higher frequency in the number of times (3 times) the patient's body weight changed was associated with a lower cognitive function (adjusted odds ratio, 3.42; 95% CI, 1.67-7.03; P for trend<0.001). CONCLUSION: In this nationally representative study, weight variability was associated with a higher risk of cognitive decline during mid- and late-life stages.

Association between Consumption of Sugar-Sweetened Beverages and Risk of Cardiovascular Disease in Korean Men: Analysis Based on the Korea National Health and Nutrition Examination Survey 2014-2016.

BACKGROUND: This study aimed to evaluate the association between the high risk of cardiovascular disease (CVD) and the consumption of sugar-sweetened beverages (SSBs) in Korean men. METHODS: This cross-sectional study analyzed the data of 3,705 men (age 30-64 years) who participated in the 2014-2016 Korea National Health and Nutrition Examination Survey (KNHANES). SSB intake was defined as the sum of the intakes of carbonated beverages and fruit juices. Participants were categorized into study groups depending on their intake of SSBs: ≤2, 3-4, or ≥5 times per week. High CVD risk was defined as a 10-year risk of more than 10%, based on the Framingham Heart Study 10-year CVD Risk Calculator. The association between high CVD risk and SSB intake was evaluated using a multivariable-adjusted logistic regression model. RESULTS: Korean men who consumed SSBs 3-4 and ≥5 times a week showed a multivariate-adjusted odds ratio of 1.49 (95% confidence interval [CI], 1.05-2.11) and 1.61 (95% CI, 0.97-2.67) for high CVD risk, respectively, compared with those who consumed SSBs ≤2 times per week. Additionally, the risk of CVD increased with the increase in the intake of SSBs (P-trend=0.01). In subgroup analysis, no association was observed between SSB intake and high CVD risk in the group with regular physical activity (P for interaction=0.01). CONCLUSION: In Korean men, except those with regular physical activity, SSB intake ≥3 times a week is associated with a high risk for CVD (10-year CVD risk ≥10%).

Risk Factors of Cardiovascular Disease according to Alcohol Behavioral Change after Cancer Diagnosis.

BACKGROUND: Problem drinking increases the incidence of all-cause mortality and specific cancers, and persistent drinking is associated with cardiovascular disease in certain cancer survivors. This study analyzed the cardiovascular risk factors before and after diagnosis in Korean cancer survivors. METHODS: Data for the period between 2002 and 2013 were collected from the National Health Insurance Service Health-Examinee Cohort Database. Among the 27,835 patients included, those with moderate alcohol consumption before and after cancer diagnosis were excluded. Problem drinking was defined as males under 65 years consuming over 14 glasses a week, and males over 65 years or females consuming over seven glasses a week. A t-test, chi-square test, and linear regression analysis were performed for differences in cardiovascular risk factors and differences according to cancer types. RESULTS: There was a difference in the body mass index, systolic and diastolic blood pressure, and total cholesterol among patients who became moderate drinkers after diagnosis, but fasting blood glucose did not show any significant changes. Risk factors for cardiovascular disease were analyzed in patients with liver, stomach, rectal, and breast cancer with improved drinking behavior, and there were significant differences in body mass index, systolic and diastolic blood pressure, fasting blood glucose, and total cholesterol in stomach cancer patients. CONCLUSION: Moderate drinking can lower cardiovascular risk in cancer survivors, and among the many drinking-related cancers, stomach cancer patients demonstrated significantly reduced cardiovascular risk factors.

Suppression of the lipopolysaccharide-induced expression of MARCKS-related protein (MRP) affects transmigration in activated RAW264.7 cells.

The molecular action mechanism of MRP, one of the protein kinase C (PKC) substrates, has been under intense investigation, but reports on its role in macrophage function remain controversial. The treatment of macrophage cell lines with bacterial lipopolysaccharide (LPS) induced a high level of MRP expression suggesting that MRP plays a role in the function of activated macrophages. In order to investigate the role of MRP in activated RAW264.7 cells, we stably transfected MRP-specific shRNA expression constructs and tested for alterations in macrophage-related functions. The down-regulation of MRP expression resulted in a marked reduction in chemotaxis toward MCP-1 or extracellular matrix proteins. Furthermore, pharmacological inhibitors of PKC significantly inhibited the chemotaxis in RAW264.7 cells. These data reveals the pivotal role of MRP in the transmigration of activated RAW264.7 cells.

Lysyl oxidase like 4, a novel target gene of TGF-beta1 signaling, can negatively regulate TGF-beta1-induced cell motility in PLC/PRF/5 hepatoma cells.

Transforming growth factor-beta1 (TGF-beta1) is a multi-functional cytokine involved in the regulation of cell proliferation, differentiation and extracellular matrix formation. In search for novel genes mediating the TGF-beta1 function at downstream signaling, we performed a cDNA microarray analysis and identified 60 genes whose expression is regulated by TGF-beta1 in the liver cancer cell line PLC/PRF/5. Among them, we report here lysyl oxidase like 4 (LOXL4) as a novel target of TGF-beta1 signaling, and provide experimental evidence for its expression regulation and function. LOXL4 was found to be the only member of LOX family whose expression is induced by TGF-beta1 in hepatoma cells. Deletion mapping of the LOXL4 promoter indicated that the TGF-beta1 regulation of LOXL4 expression is mediated through the binding of AP1 transcription factor to a conserved region of the promoter. This was confirmed by the chromatin immunoprecipitation assay that captured c-Fos-bound chromatin from TGF-beta1-treated cells. Forced expression of LOXL4 in PLC/PRF/5 cells resulted in inhibition of cell motility through Matrigel in the presence of TGF-beta1 treatment. In parallel, LOXL4 suppressed the expression of laminins and alpha3 integrin and the activity of MMP2. These results suggest that LOXL4 may function as a negative feedback regulator of TGF-beta1 in cell invasion by inhibiting the metabolism of extracellular matrix (ECM) components.

Reverse signaling initiated from GITRL induces NF-kappaB activation through ERK in the inflammatory activation of macrophages.

Glucocorticoid-induced TNF receptor family related protein ligand (GITRL) is known to interact with its cognate receptor GITR. In order to investigate the potential role of GITRL in the pro-inflammatory activation of macrophages and the signaling pathway induced by GITRL, we stimulated the macrophage cell line, THP-1, and primary macrophages with an anti-GITRL monoclonal antibody or a GITR:Fc fusion protein and analyzed the cellular responses. The stimulation of GITRL induced the expression of pro-inflammatory cytokines and matrix metalloproteinase (MMP)-9 and up-regulated ICAM-1 expression levels, which was responsible for enhanced cellular aggregation and adhesion to extracellular matrix proteins. The activation of these pro-inflammatory mediators required the activation of ERK1/2 mitogen-activated protein kinase (MAPK) and negatively regulated by p38 MAPK and JNK. Immunofluorescence analysis detected nuclear translocation of the NF-kappaB p50 subunit and this was blocked by ERK inhibitor, indicating that GITRL stimulation induced ERK1/2 phosphorylation and subsequent activation of NF-kappaB. Furthermore, the expression of GITRL and GITR was detected in macrophages in inflammatory disease specimens such as atherosclerotic plaques and synovial tissues of rheumatoid arthritis. These observations raise the possibility that the GITRL-mediated inflammatory activation of macrophages is involved in the pathogenesis of inflammatory diseases.

Glucocorticoid-induced tumour necrosis factor receptor family related protein (GITR) mediates inflammatory activation of macrophages that can destabilize atherosclerotic plaques.

Glucocorticoid-induced tumour necrosis factor receptor family related protein (GITR) is the 18th member of the tumour necrosis factor receptor superfamily (TNFRSF18) and is known to interact with its cognate ligand GITRL (TNFSF18). We investigated the potential role of GITR in the pro-inflammatory activation of macrophages. Immunohistochemistry and in situ hybridization analyses of human atherosclerotic plaques demonstrated that GITR and its ligand are expressed mainly in lipid-rich macrophages. We then investigated the role of GITR in human and mouse monocyte/macrophage functions. Stimulation of GITR caused nuclear factor (NF)-kappaB-dependent activation of matrix metalloproteinase-9 (MMP-9) and pro-inflammatory cytokine expression in both the human and mouse monocytic/macrophage cell lines, THP-1 and RAW264.7, respectively. These cellular responses were also observed when the THP-1 cells were treated with phorbol-12 myristate-13 acetate (PMA), which is known to induce macrophage differentiation. To demonstrate that these responses are not restricted to cultured cell lines, we tested primary macrophages. Both peritoneal and bone marrow-derived macrophages responded to GITR stimulation with induction of MMP-9 and tumour necrosis factor-alpha (TNF-alpha). Furthermore, the GITR staining pattern overlapped with those of MMP-9 and TNF-alpha in atherosclerotic plaques. These data indicate that GITR-mediated macrophage activation may promote atherogenesis via the induction of pro-atherogenic cytokines/chemokines, and destabilize the atherosclerotic plaques via the induction of the matrix-degrading enzyme, MMP-9.