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How functional genetics research can be applied to improving crop yields is a timely challenge. One of the most direct methods is to produce larger inflorescences with higher productivity, which should be accompanied by a balance between stem cell proliferation and lateral organ initiation in meristems. Unbalanced proliferation of stem cells causes the fasciated inflorescences, which reflect the abnormal proliferation of meristems, derived from the Latin word 'fascis', meaning 'bundle'. Maize, a model system for grain crops, has shown tremendous yield improvements through the mysterious transformation of the female inflorescence during domestication. In this review, we focus on maize inflorescence architecture and highlight the patterns of fasciation, including recent progress. [ABSTRACT FROM AUTHOR]

Objectives: The hemoglobin glycation index (HGI) quantifies interindividual variations in glycated hemoglobin (HbA1c) and is associated with diabetic complications and metabolic diseases. However, information on the association between HGI and non‐alcoholic fatty liver disease (NAFLD) in healthy subjects is limited, particularly in Asian populations. This study aimed to investigate the association between HGI and NAFLD in a healthy Korean cohort. Design: Subjects were stratified in quartiles according to their HGI level. NAFLD was diagnosed by hepatic ultrasonography, hepatic steatosis index and fatty liver index. Multiple logistic regression analysis was performed to evaluate the association between HGI quartiles and the risk of NAFLD. Patients: Data from subjects without diabetes who underwent liver ultrasonography during routine health examinations were retrospectively reviewed. Results: Data from 14 465 subjects were included in the analysis. The prevalence of NAFLD increased significantly with each HGI quartile (24.8%, 29.7%, 32.6% and 40.6% in quartiles 1‐4, respectively; P < 0.001). In comparison with the lowest HGI quartile group, the highest quartile exhibited worse metabolic parameters, including body weight, waist circumference, body mass index and lipid profiles. Multiple logistic regression analysis adjusted for multiple factors showed that the odds ratio of having NAFLD was 1.564 (95% CI: 1.350‐1.813, P < 0.001) in the highest HGI quartile. Conclusions: Elevated HGI levels are independently associated with NAFLD in a healthy Asian population. [ABSTRACT FROM AUTHOR]

We aimed to investigate the clinical factors affecting the therapeutic effectiveness of the sodium–glucose cotransporter-2 inhibitor empagliflozin in patients with type 2 diabetes mellitus (T2DM). We reviewed the medical records of 374 T2DM patients aged between 20 and 75 years who were prescribed empagliflozin 10 mg or 25 mg as add-on therapy for more than 90 consecutive days. Changes in hemoglobin A1c (HbA1c) from baseline levels and the reduction in body weights of the study participants were assessed. We found that younger patients (≤ 50 years), patients with the highest levels of HbA1c (>9%) at baseline, patients with an estimated glomerular filtration rate (eGFR) of >90 mL/min/1.73 m2, and patients with a shorter duration of T2DM (< 10 years) were more likely to exhibit a better glycemic response. Multivariate linear regression analysis revealed that a shorter duration of T2DM, higher baseline levels of HbA1c, and higher eGFR were positively associated with HbA1c reduction. Higher BMI and lower HbA1c levels were predictors of a more significant reduction in body weight among patients taking empagliflozin. The glucose-lowering effect of empagliflozin was more evident in T2DM patients with higher baseline HbA1c levels, better renal function, and shorter duration of T2DM. [ABSTRACT FROM AUTHOR]

Abstract: Aims/Introduction: We aimed to evaluate the efficacy and safety of pioglitazone (PIO) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) as additions to insulin therapy for the management of type 2 diabetes mellitus. Materials and Methods: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov through December 2016. Randomized controlled trials published in English that compared SGLT2i plus insulin (SGLT2i/INS) or PIO plus insulin (PIO/INS) with placebo plus insulin (PCB/INS) in type 2 diabetes mellitus patients were included. We compared the efficacy and safety between SGLT2i/INS and PIO/INS indirectly. Results: A total of 14 randomized controlled trials comparing 7,226 participants were included (8 SGLT2i and 6 PIO studies). SGLT2i/INS achieved similar reductions in hemoglobin A1c (weighted mean difference [WMD] −0.01% [−0.1 mmol/mol], 95% confidence interval [CI] −0.25 to 0.22% [−2.7 to −2.4 mmol/mol]; P = 0.896) and fasting plasma glucose (WMD −0.90 mg/dL, 95% CI: −15.50 to 13.71 mg/dL; P = 0.904), and a similar proportion of participants achieved hemoglobin A1c <7.0% (<53.0 mmol/mol; relative risk 0.98, 95% CI: 0.73 to 1.33; P = 0.917) as compared with the PIO/INS group, with greater weight reduction (WMD −4.54 kg, 95% CI: −5.67 to −3.41 kg; P < 0.001). PIO/INS showed non‐significant trends toward a higher risk of hypoglycemia (relative risk 1.15, 95% CI: 0.97 to 1.35; P = 0.102) and higher reduction of total daily insulin doses (WMD −2.45 IU/day, 95% CI: −7.30 to 2.40 IU/day; P = 0.438). Conclusions: Both PIO and SGLT2i are feasible adjunctive oral agents to pre‐existing insulin therapy in individuals with inadequately controlled type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: The prevalence of metabolic syndrome has markedly increased worldwide. However, studies in the United States show that it has remained stable or slightly declined in recent years. Whether this applies to other countries is presently unclear. Objectives: We examined the trends in the prevalence of metabolic syndrome and its components in Korea. Methods: The prevalence of metabolic syndrome and its components was estimated in adults aged >30 years from the Korean National Health Insurance Service data from 2009 to 2013. The revised National Cholesterol Education Program criteria were used to define metabolic syndrome. Results: Approximately 10 million individuals were analyzed annually. The age-adjusted prevalence of metabolic syndrome increased from 28.84% to 30.52%, and the increasing trend was more prominent in men. Prevalence of hypertriglyceridemia, low HDL-cholesterol, and impaired fasting plasma glucose significantly increased. However, the prevalence of hypertension decreased in both genders. The prevalence of abdominal obesity decreased in women over 50 years-of-age but significantly increased in young women and men (<50 years). Conclusions: The prevalence of metabolic syndrome is still increasing in Korea. Trends in each component of metabolic syndrome are disparate according to the gender, or age groups. Notably, abdominal obesity among young adults increased significantly; thus, interventional strategies should be implemented particularly for this age group. [ABSTRACT FROM AUTHOR]

Objective: Some individuals with metabolically healthy obesity (MHO) convert to metabolically unhealthy obesity (MUO) phenotype, and visceral adiposity is one of proposed mechanisms underlying such conversion. Visceral adipose index (VAI) is a novel mathematical model which estimates visceral adiposity based on anthropometric and lipid profiles. We aimed to determine the association of VAI-estimated visceral adiposity with the MHO-to-MUO conversion and the predictive value of VAI in estimating such unfavorable outcomes. Methods: A total of 2,204 Korean subjects with the MHO phenotype were enrolled and stratified by body mass index and metabolic health state according to Wildman criteria at baseline and last follow-up examinations. VAI was calculated at baseline. Results: Over a median follow-up period of 41.1 months, 46.0% of subjects converted to MUO phenotype. Higher VAI quartiles were associated with a greater proportion of subjects who underwent MHO-to-MUO conversion, and also with increased odds ratios for such conversion even after multivariate analyses. The optimal VAI cut off value was around 1.00, and VAI had a greater power in the prediction of MHO-to MUO conversion than waist circumference in both genders. Conclusion: MHO phenotypes with high VAI values are associated with poor future metabolic outcomes. VAI-estimated visceral adiposity is well correlated with the prognosis of MHO subjects, and VAI has a good predictive value in determining the MHO-to-MUO conversion. [ABSTRACT FROM AUTHOR]

Objectives: Metabolically healthy obese (MHO) phenotype describes an obese state with a favorable metabolic profile. However, the prognosis of this subpopulation remains controversial. We aimed to examine whether MHO phenotype is associated with progression of atherosclerotic activity, reflected as the changes in coronary artery calcification (CAC) over time. If so, we sought to determine the role of fatty liver disease (FLD), the hallmark of hepatic steatosis, in this progression. Methods: We enrolled 1,240 asymptomatic subjects who underwent repeated CAC score measurement during routine health examinations. CAC score progression was defined as either incident CAC in a population free of CAC at baseline, or an increase by ≥2.5 units between the baseline and final square root of CAC scores in participants with detectable CAC at baseline. Subjects were stratified by body mass index (cut-off, 25.0 kg/m2) and metabolic health state using Adult Treatment Panel-III criteria. FLD was assessed via ultrasonography. Results: Over 2.9 years of follow-up, 25.2% of total subjects exhibited CAC score progression. The MHO phenotype was not significantly associated with CAC score progression (multivariate adjusted-odds ratio [OR], 1.45; 95% confidence interval [CI], 0.93–2.25), as compared to the metabolically healthy non-obese (MHNO) phenotype. However, subgroup analysis indicated that the MHO/FLD phenotype was significantly associated with CAC score progression (multivariate adjusted-OR, 2.37; 95% CI, 1.34–4.16), as compared to the MHNO/no FLD phenotype, whereas the MHO/no FLD phenotype was not (multivariate adjusted OR, 1.25; 95% CI, 0.71–2.24). Conclusions: Obese individuals with FLD have an increased risk of atherosclerosis progression, despite their healthy metabolic profile. Preventive interventions targeting cardiometabolic risk factors should be considered in such individuals, regardless of the weight status. [ABSTRACT FROM AUTHOR]

Objective Metabolically healthy obese (MHO) phenotype refers to obese individuals with a favourable metabolic profile. Its prognostic value remains controversial and may partly depend on differences in how the phenotype is defined. We aimed to investigate whether the MHO phenotype is associated with future development of incident hypertension in a Korean population according to various definitions of metabolic health. Subjects and Methods The study population comprised 31 033 Koreans without hypertension. Participants were stratified into metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) by body mass index (cut-off value, 25·0 kg/m2) and metabolic health state, using four different definitions: Adult Treatment Panel (ATP)-III, Wildman, Karelis and the homoeostasis model assessment (HOMA) criteria. Results Over the median follow-up period of 35·0 months (range, 4·5-81·4 months), 4589 of the 31 033 individuals (14·8%) developed incident hypertension. Compared with the MHNO group, the MHO group showed increased association with incident hypertension with multivariate-adjusted odds ratios of 1·56 (95% confidence interval [CI], 1·41-1·72), 1·58 (95% CI 1·42-1·75), 1·52 (95% CI 1·35-1·71) and 1·46 (95% CI 1·33-1·61), when defined by ATP-III, Wildman, Karelis and HOMA criteria, respectively. Conclusion MUO individuals showed the highest association with the incident hypertension (adjusted odds ratios up to 2·00). MHO subjects showed an approximately 1·5-fold higher association with incident hypertension than their nonobese counterpart regardless of the definition of metabolic health used. Thus, considering both metabolic health and obesity is important for the assessment of potential cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the effect of fatty liver disease (FLD) on the risk of incident type 2 diabetes in a population with metabolically healthy obesity (MHO).Methods: The study population comprised 34,258 Koreans without type 2 diabetes. Participants were stratified by BMI (cutoff value, 25.0 kg/m(2) ) and metabolic health state (using Wildman criteria). FLD was defined by the fatty liver index (FLI), a predictive algorithm to detect FLD. Subjects were classified into low and high FLI groups based on tertile.Results: At baseline, there were significant differences in FLI between four study groups. During a median follow-up of 36.5 months, 1.7% individuals developed type 2 diabetes. The risk of incident type 2 diabetes varied for the MHO group according to the level of FLI. The risk of type 2 diabetes in the MHO with low FLI was not significantly elevated compared with the metabolically healthy individuals without obesity (MHNO) with low FLI (multivariate-adjusted HR, 1.19 [95% CI 0.66-2.14]). However, the MHO with high FLI had an elevated risk of incident type 2 diabetes (multivariate-adjusted HR, 1.99 [95% CI 1.36-2.92]).Conclusions: MHO subjects have a substantially higher risk of incident type 2 diabetes than MHNO subjects. The presence of FLD assessed by FLI partially explains this increased risk. [ABSTRACT FROM AUTHOR]

Background: The usefulness of the 2013 ACC/AHA guidelines for the management of blood cholesterol in the Asian population remains controversial. In this study, we investigated whether eligibility for statin therapy determined by the 2013 ACC/AHA guidelines is better aligned with the presence of subclinical coronary atherosclerosis detected by CCTA (coronary computed tomography angiography) compared to the previously recommended 2004 NCEP ATP III guidelines. Methods: We collected the data from 5,837 asymptomatic subjects who underwent CCTA using MDCT during routine health examinations. Based on risk factor assessment and lipid data, we determined guideline-based eligibility for statin therapy according to the 2013 ACC/AHA and 2004 NCEP ATP III guidelines. We defined the presence and severity of subclinical coronary atherosclerosis detected in CCTA according to the presence of significant coronary artery stenosis (defined as >50% stenosis), plaques, and the degree of coronary calcification. Results: As compared to the 2004 ATP III guidelines, a significantly higher proportion of subjects with significant coronary stenosis (61.8% vs. 33.8%), plaques (52.3% vs. 24.7%), and higher CACS (CACS >100, 63.6% vs. 26.5%) was assigned to statin therapy using the 2013 ACC/AHA guidelines (P < .001 for all variables). The area under the curves of the pooled cohort equation of the new guidelines in detecting significant stenosis, plaques, and higher CACS were significantly higher than those of the Framingham risk calculator. Conclusions: Compared to the previous ATP III guidelines, the 2013 ACC/AHA guidelines were more sensitive in identifying subjects with subclinical coronary atherosclerosis detected by CCTA in an Asian population. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Bilirubin, a natural product of heme catabolism by heme oxygenase, one of key antioxidant enzymes, has been recognized as a substance with potent antioxidant and cytoprotective properties. Several studies have shown a significant negative relationship between serum bilirubin levels and the risk of metabolic disorders, including type 2 diabetes. However, longitudinal studies investigating the association of elevated serum bilirubin levels and type 2 diabetes are lacking. In the present study, we aimed to investigate the longitudinal effects of baseline serum bilirubin concentrations on the development of type 2 diabetes in healthy Korean men. Materials and Methods: This 4year retrospective longitudinal observational study was conducted at the Asan Medical Center, Seoul, Republic of Korea. The study population consisted of 5960 men without type 2 diabetes who underwent routine health examinations in 2007 (baseline) and 2011 (follow-up). Baseline serum bilirubin concentrations were determined by the vanadate oxidation method. Results: During a 4year period, 409 incident cases of diabetes (6.9 %) were identified. Incident type 2 diabetes decreased across the baseline bilirubin quartile categories (P for trend <0.001). In multivariable-adjusted model, the relative risk (RR) for the development of type 2 diabetes was significantly lower in the highest (i.e., 1.30–2.00mg/dl) than in the lowest bilirubin quartile category (i.e., ≤0.90mg/dl), even after adjustment for confounding variables (RR=0.69, 95% confidence interval 0.48–0.99, P for trend=0.041). Conclusions: The results indicate that serum total bilirubin level may provide additional information for predicting future development of type 2 diabetes in healthy subjects. [Copyright &y& Elsevier]

We have investigated radiation-sensitive expressed genes (EGs), their signal pathways, and the effects of ionizing radiation in the thymus of ICR and AKR/J mice. Whole-body and relative thymus weights were taken and microarray analyses were done on the thymuses of high-dose-rate (HDR, 137Cs, 0.8 Gy/min, a single dose of 4.5 Gy) and low-dose-rate (LDR, 137Cs, 0.7 mGy/h, a cumulative dose of 1.7 Gy) irradiated ICR and AKR/J mice. Gene expression patterns were validated by quantitative polymerase chain reaction (qPCR). The effect of ionizing radiation on thymus cell apoptosis was measured terminal deoxynucleotidyltransferase- mediated dUTP-end labeling (TUNEL). LDR-irradiation increased the mean whole-body weight, but decreased the relative thymus weight of AKR/J mice. Radiation-sensitive EGs were found by comparing HDR- and LDR-irradiated ICR and AKR/J mice. qPCR analysis showed that 12 EGs had dose and dose-rate dependent expression patterns. Gene-network analysis indicated that Ighg, Igh-VJ558, Defb6, Reg3g, and Saa2 may be involved in the immune response, leukocyte migration, and apoptosis. Our data suggest that expression of the HDR (Glut1, Glut4, and PKLR) and LDR radiation-response genes (Ighg and Igh-VJ558) can be dose or dose-rate dependent. There was an increased number of apoptotic cells in HDR-irradiated ICR mice and LDR-irradiated AKR/J mice. Thus, changes of the mean whole-body weight and relative thymus weight, EGs, signal pathways, and the effects of ionizing radiation on the thymus of ICR and AKR/J mice are described. [ABSTRACT FROM AUTHOR]

We sought to determine the associations between hemoglobin A1c (A1c) and admission glucose with in-hospital mortality among patients with diabetes mellitus (DM) hospitalized with COVID-19. Adults hospitalized between 3/5/20 and 12/1/20 in a Connecticut health care system were included if they had prior DM diagnosis, an in-hospital A1c, and a positive RT-PCR nasopharyngeal swab for SARS-CoV-2. A1c was stratified into <7%, 7-<9%, and ≥9%. Both bivariate and multi-variable adjusted logistic regression analyses were performed to determine the association of A1c categories and admission glucose >200 mg/dL with mortality (in-hospital death or transition to hospice) and with intensive care unit (ICU) use. Models were adjusted for demographics and 8 relevant comorbidities. Among 733 patients (median age 67 years [interquartile range, 56-77], 48.3% female, 43.11% White, 35.47% Black, 24.97% Hispanic, 1.64% Asian), 31.7% had A1c <7%, 40.5% 7-<9%, 27.8% ≥9%, and 38.1% admission glucose >200 mg/dL. During hospitalization, 111 (15.1%) patients died or transitioned to hospice and 230 (31.4%) required ICU care. In 2 multi-variable adjusted analyses, neither A1c category nor high admission glucose were significantly associated with mortality (A1c 7-<9%: OR 0.89, 95% CI 0.53-1.49; A1c >9% OR 1.3, CI 0.72-2.35 compared with A1c <7%; glucose >200 OR 1.34, CI 0.72-2.35) or ICU care (A1c 7-<9% OR 1.30, 95% CI 0.88-1.93; A1c ≥9% OR 1.35, CI 0.86-2.1 compared with A1c <7%; glucose >200 OR 1.26, CI 0.9-1.78). Age (per year OR 1.06, CI 1.04-1.08), male sex (OR 1.78, CI 1.14-2.81), obesity (OR 1.85, CI 1.16-2.96) and CKD (OR 1.90, CI 1.19-3.03) were significantly associated with mortality. Only female sex (OR 0.67, CI 0.48-0.93) was significantly associated with ICU care. In our retrospective study of hospitalized patients with DM, neither A1c nor admission glucose were prognostic of COVID-19 mortality or ICU care. In those with DM, male sex, obesity and CKD predicted worse outcomes. Disclosure: J. Brancale: None. A. M. Jastreboff: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk, Other Relationship; Spouse/Partner; Elucidata. K. J. Lipska: None. D. Athonvarangkul: None. M. Simonov: None. J. Alausa: None. L. K. Subair: None. A. M. Hajduk: None. Y. Kang: None. T. Arora: None. F. P. Wilson: Other Relationship; Self; Efference LLC, Medscape. Funding: National Institutes of Health (1T32GM136651-01) [ABSTRACT FROM AUTHOR]

To evaluate the in vivo effects of low-dose-rate (0.7 mGy h–1) gamma radiation, abnormal shapes of sperm in the caudal epidydimus of Apodemus agrarius coreae (A. a. coreae) were used. The six categories of abnormal forms (amorphous heads, blunt hooks, excessive hooks, two heads and tails, folded tails and short tails) of sperm were observed eight days after gamma irradiation (0, 0.5, 1 and 2 Gy) with a high dose rate (0.8 Gy min–1) and a low dose rate. The frequency of total abnormal sperm gradually increased starting from 0.5 Gy after high-dose-rate radiation. Blunt hooks and short tails shaped sperm, in particular, were gradually increasing in the high-dose-rate irradiated mice. Dose rate reduction effects for the frequency of abnormal sperms in low-dose-rate irradiated mice to high-dose-rate irradiated mice were 1 at 0.5 Gy, 0.7 at 1 Gy and 0.5 at 2 Gy. Our results indicate that low-dose-rate radiation is not detrimental to spermatogenic cells. [ABSTRACT FROM PUBLISHER]

Background: Nonalcoholic fatty liver disease (NAFLD) and prediabetes are well-known risk factors for diabetes. However, few studies have been performed about the risk of diabetes in subjects with prediabetes in the presence of NAFLD. In addition, little information was known about the impact of waist circumference (WC) and body mass index (BMI) changes on the development of diabetes. In this study, we examined the association of NAFLD with diabetes and the impact of WC and BMI changes in subjects with prediabetes. Methods: We enrolled 6,240 subjects with prediabetes who underwent general routine health evaluations in 2007 and returned for follow-up examinations in 2008 -2013 at least one time. Subjects were stratified by WC and BMI changes into three groups. The relative ratios (RRs) of NAFLD for diabetes was evaluated. Results: The prevalence of NAFLD in study participants was 45.4% (2,830/6,240). Subjects with NAFLD had higher BMI, WC, HbA1c levels, blood pressure levels, blood lipid levels, and also higher ALT levels (P < 0.001). During the follow-up, the total incidence of diabetes was 8.093%. Subjects with NAFLD at baseline had a higher incidence of diabetes and the adjusted RRs were 2.181 [95% confidence interval (CI), 1.778 to 2.674]. Furthermore, the RRs were closely related to WC changes. The adjusted RRs for diabetes according to WC change (≤ 0.0 cm, 0 cm to 3.0 cm, and > 3.0 cm) were 1.953 (95% CI, 1.365 to 2.794), 1.996 (95% CI, 1.407 to 2.833), and 2.302 (95% CI, 1.598 to 3.314), respectively. Furthermore, the RRs were also closely related to BMI changes and the adjusted RRs for diabetes according to BMI change (< -0.35 kg/m2, -0.35 kg/m2 to 0.35 kg/m2, and > 0.35 kg/m2) were 1.633 (95% CI, 1.121 to 2.380), 1.995 (95% CI, 1.415 to 2.811), and 2.924 (95% CI, 2.053 to 4.165), respectively. Conclusion: There was a strong and independent association between NAFLD and diabetes in Korean subjects with prediabetes, and this relationship was closely related to WC and BMI changes. Disclosure: J. Lee: None. Y. Kang: None. J. Park: None. W. Lee: None. [ABSTRACT FROM AUTHOR]

Aims: Hemoglobin glycation index (HGI), which quantifies interindividual variations in glycated hemoglobin (HbA1c), is known to be associated with diabetic complications and metabolic diseases. However, information on the association between HGI and nonalcoholic fatty liver disease (NAFLD) in healthy population, especially in Asian population is limited. Methods: A total of 14,465 subjects without diabetes who underwent liver ultrasonography during routine health examination were enrolled and stratified in quartiles according to HGI levels. Results: The prevalence of NAFLD significantly increased with HGI quartiles (24.8%, 29.7%, 32.6% and 40.6% in the 1st, 2nd, 3rd, and 4th HGI quartiles, respectively; p-value<0.001). As compared with the lowest HGI quartile group, the highest HGI quartile group had worse metabolic parameters including body weight, waist circumference, body mass index and lipid profiles. In the multiple logistic regression analysis adjusted for multiple factors, the odds ratio of having NAFLD was 1.564 (95% CI: 1.350-1.813, p <0.001) in the highest HGI quartile group. Conclusions: Elevated HGI levels are independently associated with prevalence of NAFLD in a healthy Asian population. Disclosure: J. Yoo: None. W. Lee: None. J. Park: None. J. Lee: None. Y. Kang: None. C. Jung: None. Y. Cho: None. C. Park: None. [ABSTRACT FROM AUTHOR]

Although recent studies have reported cardioprotective effects of C1q/TNF-related protein 9 (CTRP9), the closet adiponectin paralog, its role on cytokine-induced endothelial inflammation is unknown. We investigated whether CTRP9 prevented inflammatory cytokine-induced nuclear factor-kappa B (NF-κB) activation and inhibited the expression of adhesion molecules and a chemokine in the vascular endothelial cell. We used human aortic endothelial cells (HAECs) to examine the effects of CTRP9 on NF-κB activation and the expression of NF-κB-mediated genes, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1). Tumor necrosis factor alpha (TNFα) was used as a representative proinflammatory cytokine. In an adhesion assay using THP-1 cells, CTRP9 reduced TNFα-induced adhesion of monocytes to HAECs. Treatment with CTRP9 significantly decreased TNFα-induced activation of NF-κB, as well as the expression of ICAM-1, VCAM-1, and MCP-1. In addition, treatment with CTRP9 significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), the downstream target of AMPK. The inhibitory effect of CTRP9 on the expression of ICAM-1, VCAM-1, and MCP-1 and monocyte adhesion to HAECs was abolished after transfection with an AMPKα1-specific siRNA. Our study is the first to demonstrate that CTRP9 attenuates cytokine-induced vascular inflammation in endothelial cells mediated by AMPK activation. [ABSTRACT FROM AUTHOR]

Obesity has become an important risk factor for chronic kidney disease (CKD). The metabolically healthy obese (MHO) phenotype refers to obese individuals with a favorable metabolic profile. However, its prognostic value remains controversial and may depend on the health outcome being investigated. To assess this, we examined the risk of MHO phenotype with incident CKD in a Korean population of 41,194 people without CKD. Individuals were stratified by body mass index (cutoff value, 25.0 kg/m(2)) and metabolic health state (assessed using Adult Treatment Panel-III criteria). Incident CKD was defined as a glomerular filtration rate of <60 ml/min per 1.73 m(2) calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Over the median follow-up period of 38.7 months, 356 of the individuals developed incident CKD. Compared with the metabolically healthy nonobese (MHNO) group, the MHO group showed increased risk of incident CKD with a multivariate-adjusted hazard ratio of 1.38 (95% CI, 1.01-1.87). Nonobese but metabolically unhealthy individuals were at an increased risk of incident CKD (multivariate-adjusted hazard ratio, 1.37 (95% CI, 1.02-1.93)) than the MHNO group. Metabolically unhealthy obese individuals were at the highest risk of incident CKD. Thus, a healthy metabolic profile does not protect obese adults from incident CKD. Hence, it is important to consider metabolic health along with obesity when evaluating CKD risk. [ABSTRACT FROM AUTHOR]

Abstract: AKR/J mice carrying leukemia viral inserts develop thymic lymphoma. Recently, we demonstrated that the incidence of thymic lymphoma was decreased when these mice were raised in a low-dose-rate γ-irradiation facility. In contrast, mice irradiated at a high-dose rate developed severe thymic lymphoma and died much earlier. To understand the genetic changes occurred by low- versus high-dose-rate γ-irradiation whole genome microarray was performed. Both groups of mice demonstrated up-regulation of Ifng, Igbp1, and IL7 in their thymuses, however, mice exposed to high-dose-rate γ-irradiation exhibited marked down-regulation of Sp3, Il15, Traf6, IL2ra, Pik3r1, and Hells. In contrast, low-dose-rate irradiated mice demonstrated up-regulation of Il15 and Jag2. These gene expression profiles imply the impaired immune signaling pathways by high-dose-rate γ-irradiation while the facilitation of anti-tumor immune responses by low-dose-rate γ-irradiation. Therefore, our data delineate common and distinct immune-associated pathways downstream of low- versus high-dose-rate irradiation in the process of cancer progression in AKR/J mice. [Copyright &y& Elsevier]

Abstract: While a high-dose of ionizing radiation is generally harmful and causes damage to living organisms, a low-dose of radiation has been shown to be beneficial in a variety of animal models. To understand the basis for the effect of low-dose radiation in vivo, we examined the cellular and immunological changes evoked in mice exposed to low-dose radiation at very low (0.7mGy/h) and low (3.95mGy/h) dose rate for the total dose of 0.2 and 2Gy, respectively. Mice exposed to low-dose radiation, either at very low- or low-dose rate, demonstrated normal range of body weight and complete blood counts. Likewise, the number and percentage of peripheral lymphocyte populations, CD4+ T, CD8+ T, B, or NK cells, stayed unchanged following irradiation. Nonetheless, the sera from these mice exhibited elevated levels of IL-3, IL-4, leptin, MCP-1, MCP-5, MIP-1α, thrombopoietin, and VEGF along with slight reduction of IL-12p70, IL-13, IL-17, and IFN-γ. This pattern of cytokine release suggests the stimulation of innate immunity facilitating myeloid differentiation and activation while suppressing pro-inflammatory responses and promoting differentiation of naïve T cells into T-helper 2, not T-helper 1, types. Collectively, our data highlight the subtle changes of cytokine milieu by chronic low-dose γ-radiation, which may be associated with the functional benefits observed in various experimental models. [Copyright &y& Elsevier]