Inhibitory effects of triarylpyrazole derivatives on LPS-induced nitric oxide and PGE2 productions in murine RAW 264.7 macrophages.

In this article, a series of 22 triarylpyrazole derivatives were evaluated for in vitro antiinflammatory activity as inhibitors of nitric oxide (NO) and prostaglandin E2 (PGE2) release induced by lipopolysaccharide (LPS) in murine RAW 264.7 macrophages. The synthesized compounds 1a-h, 2a-f and 3a-h were first examined for their cytotoxicity for determination of the non-toxic concentration for antiinflammatory screening, so that the inhibitory effects against NO and PGE2 production were not caused by non-specific cytotoxicity. Compounds 1h and 2f were the most active PGE2 inhibitors with IC50 values of 2.94 µM and 4.21 µM, respectively. Western blotting and cell-free COX-2 screening revealed that their effects were due to inhibition of COX-2 protein expression. Moreover, compound 1h exerted strong inhibitory effect on the expression of COX-2 mRNA in LPS-induced murine RAW 264.7 macrophages.

Relationship between Handgrip Strength and Incident Diabetes in Korean Adults According to Gender: A Population-Based Prospective Cohort Study.

(1) Background: Diabetes mellitus (DM) is a well-known disease that causes comorbidities such as chronic kidney disease (CKD) and cardiovascular disease. Therefore, it is necessary to develop diagnostic tools to prevent DM. Handgrip strength, a known diagnostic tool for sarcopenia, is a predictor of several diseases. However, the value of handgrip strength as an indicator of incident DM in Asian populations remains unknown. This study aimed to identify the relationship between handgrip strength and incidence of DM in Korean adults according to sex. (2) Methods: A total of 173,195 participants registered in a nationwide cohort were included in this study. After applying the exclusion criteria, 33,326 participants remained. DM occurred in 1473 individuals during the follow-up period (mean follow-up period, 4.1 years). To reduce the impact of body size, the study population was subdivided into quartiles of relative handgrip strength, defined as absolute handgrip strength divided by body mass index. Multivariate Cox regression analysis revealed that the relative handgrip strength was inversely associated with new-onset DM. (3) Results: Compared with the lowest quartile (Q1), the hazard ratios (HRs) [95% confidence intervals (CIs)] for new-onset DM for the highest quartiles (Q4) was 0.60 (0.43-0.84) in men and 0.72 (0.52-0.99) in women after adjusting for confounding factors. The incidence of DM decreased with the increase in the relative handgrip strength. These inverse relationships were statistically more significant in men than in women. (4) Conclusions: This novel study revealed that relative handgrip strength is related to incident DM in both men and women. Relative handgrip strength can be used as a practical tool to prevent DM. Regular measurement of handgrip strength can be used to detect DM.

Association of handgrip strength with new-onset CKD in Korean adults according to gender.

Introduction: Handgrip strength (HGS) is an indicator of many diseases such as pneumonia, cardiovascular disease and cancer. HGS can also predict renal function in chronic kidney disease (CKD) patients, but the value of HGS as a predictor of new-onset CKD is unknown. Methods: 173,195 subjects were recruited from a nationwide cohort and were followed for 4.1 years. After exclusions, 35,757 participants remained in the final study, and CKD developed in 1063 individuals during the follow-up period. Lifestyle, anthropometric and laboratory data were evaluated in relation to the risk of CKD. Results: The participants were subdivided into quartiles according to relative handgrip strength (RGS). Multivariate Cox regression demonstrated that RGS was inversely associated with incident CKD. Compared with the lowest quartile, the hazard ratios (HRs) [95% confidence intervals (CIs)] for incident CKD for the highest quartile (Q4) was 0.55 (0.34-0.88) after adjusting for covariates in men and 0.51 (0.31-0.85) in women. The incidence of CKD decreased as RGS increased. These negative associations were more significant in men than in women. The receiver operating characteristic (ROC) curve showed that baseline RGS had predictive power for new-onset CKD. Area under the curve (AUC) (95% CIs) was 0.739 (0.707-0.770) in men and 0.765 (0.729-0.801) in women. Conclusion: This is the novel study demonstrating that RGS is associated with incident CKD in both men and women. The relationship between RGS and incident CKD is more significant in women than in men. RGS can be used in clinical practice to evaluate renal prognosis. Regular measurement of handgrip strength is essential to CKD detection.

Elevated Uric Acid Levels with Early Chronic Kidney Disease as an Indicator of New-Onset Ischemic Heart Disease: A Cohort of Koreans without Diabetes.

Several studies have showed that hyperuricemia is related to the development of ischemic heart disease (IHD). There is also growing evidence indicating that hyperuricemia may contribute to the progression of IHD as a pathogenic factor. Ironically, uric acid can be an antioxidant agent, as shown in experimental studies. The aim of our study is to analyse the association between uric acid and IHD with early-stage chronic kidney disease (CKD). Data were assessed from 17,492 participants without cardiovascular disease from the Korean Genome and Epidemiology Study (KoGES) and Korea Health Insurance Review and Assessment (HIRA) data. The subjects were categorized as four groups according to CKD and uric acid levels. We retrospectively evaluated hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD by using multivariate Cox regression analysis over a 4-year period from the baseline survey. During the follow-up, 335 individuals (3.4%; 236 men and 99 women) developed IHD. Compared to the participants without elevated uric acid and early CKD HRs for incident IHD according to uric acid levels and early CKD, the uric acid level was 1.13 (95% CI, 0.86-1.48) in participants with elevated uric acid and without early CKD, 0.99 (95% CI, 0.55-1.77) in participants without elevated uric acid and with early CKD, and 1.65 (95% CI, 1.03-2.66) in participants with elevated uric acid and early CKD after adjusting for confounding metabolic factors. Early CKD and high uric acid levels increased the risk of new-onset IHD (HR, 1.65; 95% CI, 1.03-2.66). Elevated uric acid levels were related to an increased risk of incident IHD in early-stage CKD patients. It is expected that uric acid can be a reliable predictor for IHD, even in early-stage CKD patients; thus, in those with CKD, proactively managing uric acid levels can play a significant role in reducing the risk of cardiovascular disease.

The Combination of Uric Acid and Hemoglobin Levels Predicts the Incident Risk of Ischemic Heart Disease More Than Uric Acid Alone in Non-Diabetic Koreans: A Longitudinal Study Using National Health Insurance Data.

Uric acid has been related to cardiovascular disease (CVD). Recently, slightly elevated hemoglobin (Hb) was also shown to be associated with CVD. We retrospectively investigated the joint effect of uric acid and elevated Hb by comparing normal-range uric acid alone on incident ischemic heart disease (IHD) risk in a large cohort of non-diabetic Korean adults using National Health Insurance data. We assessed 16,786 participants without diabetes (8595 men and 8191 women) using extensive cohort data. High Hb was defined as ≥16.4 g/dL in men and 13.8 g/dL in women (>75th percentile). We analyzed the data using two different methods. First, the participants were divided into quartiles according to uric acid levels. Second, subjects were also divided into quartiles: reference (group 1), high uric acid and normal Hb (group 2), normal uric acid and high Hb (group 3), and normal uric acid and high Hb (group 4). We evaluated hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox regression analysis over a 50-month follow-up. During the follow-up, 345 (1.9%) participants developed IHD. In the analysis using both uric acid and Hb, compared with the reference group, the HRs for IHD were 1.37 (95% CI, 1.01-1.86) in the second group, 1.63 (95% CI, 1.21-2.21) in the third group, and 1.86 (95% CI, 1.30-2.67) in the fourth group after adjusting for IHD risk factors. Subsequently, patients with high uric acid are more likely to develop incident IHD than control patients. Moreover, we confirmed the joint effects of high uric acid and high hemoglobin on incident IHD. Awareness of these interactions is essential for clinicians. Risk factor management and screening for IHD are part of the routine management of patients with high uric acid and Hb.

Development of a simple method for protein conjugation by copper-free click reaction and its application to antibody-free Western blot analysis.

There are currently many methods available for labeling proteins in order to study their structure and function. However, the utility of these methods is hampered by low efficiency, slow reaction rates, nonbiocompatible reaction conditions, large-sized labeling groups, and the requirement of specific side chains such as cysteine or lysine. In this study, a simple and efficient method for protein labeling was developed, in which an azide-containing amino acid was introduced into a protein and conjugated to a labeling reagent by strain-promoted azide-alkyne cycloaddition (SPAAC). This method allowed us to label proteins by simply mixing a protein and a labeling reagent in physiological conditions with a labeling yield of approximately 80% in 120 min. In addition, the specificity of SPAAC made it possible to analyze the expression level of a protein quantitatively by simple mixing and SDS-PAGE analysis with no need for antibodies or multistep incubations. Because the genetic incorporation of the azide-containing amino acid can be generally applied to any protein and the SPAAC reaction is highly specific, this method should prove useful for labeling and analyzing proteins.