Effects of Marital Status and Income on Hypertension: The Korean Genome and Epidemiology Study (KoGES)

Objectives:This study aimed to analyze the associations of income, marital status, and health behaviors with hypertension in male and female over 40 years of age in the Korea.Methods:The data were derived from the Korean Genome and Epidemiology Study (KoGES; 4851-302) which included 211 576 participants. To analyze the relationships of income, marital status, and health behaviors with hypertension in male and female over 40 years of age, multiple logistic regression was conducted with adjustments for these variables.Results:The prevalence of hypertension increased linearly as income decreased. The odds ratio for developing hypertension in people with an income of <0.5 million Korean won (KRW) compared to ≥6.0 million KRW was 1.55 (95% confidence interval [CI], 1.25 to 1.93) in the total population, 1.58 (95% CI, 1.27 to 1.98) in male, and 1.07 (95% CI, 0.35 to 3.28) in female. The combined effect of income level and marital status on hypertension was significant. According to income level and marital status, in male, low income and divorce were most associated with hypertension (1.76 times; 95% CI, 1.01 to 3.08). However, in female, the low-income, married group was most associated with hypertension (1.83 times; 95% CI, 1.71 to 1.97).Conclusions:The results of this study show that it is necessary to approach male and female marital status separately according to income in health policies to address inequalities in the prevalence of hypertension.     

Relative Effectiveness of COVID-19 Vaccination in Healthcare Workers: 3-Dose Versus 2-Dose Vaccination

The omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to have high infectivity and is more likely to evade vaccine immunity. However, booster vaccination is expected to strengthen cross-reactive immunity, thereby increasing the vaccine effectiveness (VE). This study aimed to evaluate the relative VE of the 3-dose (booster) vaccination compared with the 2-dose primary series vaccination in healthcare workers during omicron variant-dominant periods. During the omicron-dominant period from February 1, 2022 to February 28, 2022, a 1:1 matched case-control study was conducted. Healthcare workers with positive SARS-CoV-2 test results were classified as positive cases, whereas those with negative results served as controls. Compared with the 2-dose primary series vaccination, booster vaccination with mRNA vaccine showed moderate VE (53.1%). However, in multivariate analysis including the time elapsed after vaccination, the significant VE disappeared, reflecting the impact of recent vaccination rather than the third dose itself.     

Validation of the Korean Version of the Delirium Diagnostic Tool-Provisional (K-DDT-Pro)

Objective The Delirium Diagnostic Tool-Provisional (DDT-Pro) was designed to detect the presence and severity of delirium briefly and objectively regardless of psychiatric expertise. We translated the DDT-Pro into Korean and validated it in elderly Korean patients. Methods To validate the translation and evaluate inter-rater reliability, a psychiatric trainee and a research nurse independently assessed the same patients referred to the Department of Psychiatry. The results were compared with the reference evaluations performed by a psychiatrist using the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). Results We enrolled 42 elderly patients. The Cronbach’s alpha coefficient were 0.839 (the trainee), 0.822 (the nurse). The Cohen’s weighted κ between the trainee and nurse, ranged from 0.555±0.102 to 0.776±0.062. The Pearson correlation coefficients (Korean version of the DDT-Pro [K-DDT-Pro] and Korean version of the Delirium Rating Scale-Revised-98 [DRS-R98-K] total score) were γ=-0.850 (the trainee), and γ=-0.821 (the nurse). The areas under the ROC curves (AUCs) were 0.974 (the trainee) and 0.893 (the nurse). Conclusion The K-DDT-Pro exhibited high internal consistency and relatively substantial inter-rater reliability. The correlation with the DRS-R98-K was strongly negative. The accuracy of the K-DDT-Pro was excellent, regardless of expertise. In conclusion, the K-DDT-Pro is a brief and simple tool that usefully screens for delirium in elderly patients.     

Emphysematous gastritis: Impressive radiological findings

Emphysematous gastritis is a rare form of phlegmonous gastritis, characterized by the formation of air in the gastric wall by gas-forming microorganisms. Early diagnosis and treatment are important because of its fatal consequences (high morbidity and mortality). A 64-year-old woman presented to our emergency department with abdominal discomfort, nausea, and general weakness. An abdominal examination revealed severe epigastric tenderness, and laboratory findings revealed elevated inflammatory markers. A computed tomography scan revealed gas within the gastric wall and marked gastric wall thickening. Herein, we present a case of early diagnosed emphysematous gastritis, which was successfully treated conservatively without surgery.     

IL-1β–dependent extravasation of preexisting lung-restricted autoantibodies during lung transplantation activates complement and mediates primary graft dysfunction

Preexisting lung-restricted autoantibodies (LRAs) are associated with a higher incidence of primary graft dysfunction (PGD), although it remains unclear whether LRAs can drive its pathogenesis. In syngeneic murine left lung transplant recipients, preexisting LRAs worsened graft dysfunction, which was evident by impaired gas exchange, increased pulmonary edema, and activation of damage-associated pathways in lung epithelial cells. LRA-mediated injury was distinct from ischemia-reperfusion injury since deletion of donor nonclassical monocytes and host neutrophils could not prevent graft dysfunction in LRA-pretreated recipients. Whole LRA IgG molecules were necessary for lung injury, which was mediated by the classical and alternative complement pathways and reversed by complement inhibition. However, deletion of Fc receptors in donor macrophages or mannose-binding lectin in recipient mice failed to rescue lung function. LRA-mediated injury was localized to the transplanted lung and dependent on IL-1β–mediated permeabilization of pulmonary vascular endothelium, which allowed extravasation of antibodies. Genetic deletion or pharmacological inhibition of IL-1R in the donor lungs prevented LRA-induced graft injury. In humans, preexisting LRAs were an independent risk factor for severe PGD and could be treated with plasmapheresis and complement blockade. We conclude that preexisting LRAs can compound ischemia-reperfusion injury to worsen PGD for which complement inhibition may be effective.     

The chloroform fraction of Solanum nigrum suppresses nitric oxide and tumor necrosis factor-α in LPS-stimulated mouse peritoneal macrophages through inhibition of p38, JNK and ERK1/2

Solanum nigrum L., commonly known as black nightshade, is used worldwide for the treatment of skin and mucosal ulcers, liver cirrhosis and edema. We aimed to determine the anti-inflammatory active fraction of S. nigrum by serial extractions. S. nigrum was first extracted with methanol, then fractionated with chloroform and water. The effects of S. nigrum fractions, diosgenin and α-solanine on LPS/interferon-gamma-induced nitric oxide (NO) and inducible NO synthase (iNOS), or LPS-induced tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, in mouse peritoneal macrophages were determined. Western blotting analysis was used to detect LPS-induced phosphorylation of p38, JNK and ERK1/2. The chloroform fraction of S. nigrum was cytotoxic in a time and concentration dependent manner; however, the methanol and water fractions were not. The chloroform fraction reduced NO through inhibition of iNOS synthesis and inhibited TNF-α and IL-6 at the level of protein secretion; the methanol and water fractions showed a weak or no effect. The chloroform fraction also suppressed p38, JNK and ERK1/2. Diosgenin and α-solanine were cytotoxic at a high concentration. In particular, diosgenin was able to inhibit TNF-α and IL-6, but both compounds did not affect LPS-induced iNOS expression. These results indicate that the anti-inflammatory compounds of S. nigrum exist preferentially in the nonpolar fraction, ruling out the possibility that diosgenin and α-solanine are the likely candidates. The inhibition of iNOS, TNF-α and IL-6 by the chloroform fraction may be partly due to the suppression of p38, JNK and ERK1/2. Further study is required to identify the active compounds of S. nigrum.     

Antiproliferative triterpenes from the leaves and twigs of Juglans sinensis on HSC-T6 cells

Bioassay-guided fractionation of an 80% MeOH extract of leaves and twigs of Juglan sinensis has resulted in the isolation of four new triterpenes (1-4) and 17 known triterpenes (5-21). The new compounds were determined to be 1-oxo-3β,23-dihydroxyolean-12-en-28-oic acid 28-O-β-D-glucopyranoside (1), 1-oxo-3β-hydroxyolean-18-ene (2), 3β,23-dihydroxyurs-12-en-28-oic acid 28-O-β-D-glucopyranoside (3), and 3β,22α-dihydroxyurs-12-en-28-oic acid 28-O-β-D-glucopyranoside (4) by spectroscopic analysis. Compounds 2, 13, 15, and 21 showed antiproliferative activities (14.2, 14.8, 15.6, and 11.0% at 100 μM, respectively) in HSC-T6 cells. Flow cytometry assays revealed that these compounds inhibited HSC-T6 proliferation by inducing apoptosis.     

Identification and characterization of antioxidants from Sophora flavescens

The objectives of this study were to investigate the radical-scavenging activity and protective potential of Sophora flavescens from oxidative damage by the radical generator 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH) in renal epithelial LLC-PK(1) cells and to identify the active components using the bioassay-linked fractionation method. The MeOH extract and fractions of CH(2)Cl(2), BuOH, and H(2)O from S. flavescens showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging effects in a dose-dependent manner (p<0.01),whereas only the BuOH and CH(2)Cl(2) fractions showed protective effects against LLC-PK(1) cellular damage induced by AAPH in a dose-dependent manner (p<0.01). In particular, the BuOH fraction had the most effective (p<0.05) antioxidative capacity. Employing a bioassay-linked HPLC/MS method, the active constituents from the BuOH fraction of S. flavescens were isolated and characterized as sophoraflavanone G and kurarinone with potent antioxidant effects against the DPPH radical, with IC(50) values of 5.26 and 7.73 microg/ml, respectively. Moreover, the compounds dose dependently recovered cell viability decreased by AAPH treatment (p<0.01), suggesting their protective roles against cellular oxidative damage. The results of this study suggest that S. flavescens has excellent antioxidative and kidney-protective potential and that flavonoids from S. flavescens, i.e., sophoraflavanone G and kurarinone, are the active constituents.     

Puerarin activates endothelial nitric oxide synthase through estrogen receptor-dependent PI3-kinase and calcium-dependent AMP-activated protein kinase

The cardioprotective properties of puerarin, a natural product, have been attributed to the endothelial nitric oxide synthase (eNOS)-mediated production of nitric oxide (NO) in EA.hy926 endothelial cells. However, the mechanism by which puerarin activates eNOS remains unclear. In this study, we sought to identify the intracellular pathways underlying eNOS activation by puerarin. Puerarin induced the activating phosphorylation of eNOS on Ser1177 and the production of NO in EA.hy926 cells. Puerarin-induced eNOS phosphorylation required estrogen receptor (ER)-mediated phosphatidylinositol 3-kinase (PI3K)/Akt signaling and was reversed by AMP-activated protein kinase (AMPK) and calcium/calmodulin-dependent kinase II (CaMKII) inhibition. Importantly, puerarin inhibited the adhesion of tumor necrosis factor (TNF)-α-stimulated monocytes to endothelial cells and suppressed the TNF-α induced expression of intercellular cell adhesion molecule-1. Puerarin also inhibited the TNF-α-induced nuclear factor-κB activation, which was attenuated by pretreatment with N^G-nitro-l-arginine methyl ester, a NOS inhibitor. These results indicate that puerarin stimulates eNOS phosphorylation and NO production via activation of an estrogen receptor-mediated PI3K/Akt- and CaMKII/AMPK-dependent pathway. Puerarin may be useful for the treatment or prevention of endothelial dysfunction associated with diabetes and cardiovascular disease.     

Water extract of Korean red ginseng stimulates angiogenesis by activating the PI3K/Akt-dependent ERK1/2 and eNOS pathways in human umbilical vein endothelial cells

Angiogenesis is important for promoting cardiovascular disease, wound healing, and tissue regeneration. We investigated the effects of Korean red ginseng water extract (KRGE) on angiogenesis and its underlying signal mechanism. KRGE increased in vitro proliferation, migration, and tube formation of human umbilical vein endothelial cells, as well as stimulated in vivo angiogenesis without increasing VEGF expression. KRGE-induced angiogenesis was accompanied by phosphorylation of ERK1/2, phosphatidylinositol 3-kinase (Akt), and endothelial nitric oxide synthase (eNOS) as well as an increase in NO production. Inhibition of PI3K activity by wortmannin completely inhibited KRGE-induced angiogenesis and phosphorylation of Akt, ERK1/2, and eNOS, indicating that PI3K/Akt activation is an upstream event of the KRGE-mediated angiogenic pathway. The MEK inhibitor PD98059 blocked KRGE-induced ERK1/2 phosphorylation without affecting Akt and eNOS activation. However, the eNOS inhibitor N(G)-monomethyl-L-arginine effectively inhibited tube formation, but partially blocked proliferation and migration as well as ERK phosphorylation, without altering Akt and eNOS activation, revealing that the eNOS/NO pathway is partially involved in ERK1/2 activation. This study demonstrated that KRGE stimulates in vitro and in vivo angiogenesis through the activation of the PI3K/Akt-dependent ERK1/2 and eNOS signal pathways and their cross talk.