Korean Circulation Journal 대한심장학회지 순환기 Kim I, et al. Korean Circ J. 2022 Dec;53:e2. https://doi.org/10.4070/kcj.2022.0210

Kim I, et al. Korean Circ J. 2018 Aug;49:e47. https://doi.org/10.4070/kcj.2018.0379

We investigated the diagnostic value and pathophysiological role of circulating microRNA (miR) in vasospastic angina (VA). We enrolled patients who underwent coronary angiography for chest pain to explore the miR’s diagnostic utility. In addition, we investigated the role of miRs in regulating endothelial nitric oxide synthase (eNOS) expression in human coronary artery endothelial cells (hCAECs). Among the 121 patients, 46 were diagnosed with VA (VA group), 26 with insignificant coronary lesions (ICL group), and 49 with atherothrombotic angina (AA group). The VA group showed a significantly higher expression of miR-17-5p, miR-92a-3p, and miR-126-3p than the ICL group. In contrast, miR-221-3p and miR-222-3p were upregulated in the AA group compared to the VA group, and all levels of miR-17-5p, miR-92a-3p, miR-126-3p, miR-145-5p, miR-221-3p, and miR-222-3p differed between the AA group and the ICL group. In the hCAECs, transfection with mimics (pre-miR) of miR-17-5p, miR-92a-3p, and miR-126-3p was associated with eNOS suppression. Additionally, transfection with inhibitors (anti-miR) of miR-92a-3p significantly rescued the eNOS suppression induced by lipopolysaccharide. In conclusion, the circulating miRs not only proved to have diagnostic utility, but also contributed to pathogenesis by eNOS regulation.

A packed-bed chromatographic model developed in this study includes adsorption isotherms considering steric mass action (SMA) as well as non-linearity in liquid/solid phases, adsorption kinetics and mass transport. For solving the nonlinear and nonequilibrium adsorption model described by a partial differential algebraic equation (PDAE) system, a fast and accurate numerical method (i.e., conservation element/solution element (CE/SE) method), is proposed. Sensitivity and elasticity of the model parameters (e.g., steric/shape factors, adsorption heat coefficient, effective protein charge, equilibrium constant, mass transfer coefficient, axial dispersion coefficient and bed voidage) are analyzed for a BSA–salt system in a low protein concentration range. Within a low concentration range of bovine serum albumin (BSA) where linear adsorption isotherms are shown, the adsorption heat coefficient, shape and steric factors have little effect on adsorption isotherms and the retention time. However, the effective protein charge which is related to pH and ionic strength affects the retention time significantly even if the change is slight. The mass transfer coefficient (i.e., adsorption rate coefficient) has an effect on the peak height of the elution curve at the same retention time. Sensitivity of the retention time to the bed voidage is relatively large, since the bed voidage changes the fluid velocity of the mobile phase. Comparing the proposed model with experimental elution curves obtained at different salt concentrations, it is proposed that the effective protein charge could depend upon the salt concentration (or ionic strength). The reason for this dependence may be a steric hindrance of protein binding sites combined with a salt shielding effect neutralizing the surface charges of the protein.

Sim JY, et al. J Gastric Cancer. 2024 Sep;24:e36. https://doi.org/10.5230/jgc.2024.24.e36

Dinotefuran, a widely used neonicotinoid insecticide, is environmentally persistent and frequently detected in aquatic systems, raising concerns for non-target organisms. However, its cardiotoxic effects remain unclear. Here, we provide the first comprehensive evidence of its cardiotoxicity in normal and heart failure zebrafish model. Dinotefuran exposure increased the incidence of uninflated swim bladders, reduced survival and locomotor activity in a dose-dependent manner. Cardiac structure was altered, with looping defects more frequent, as the incidence of no-loop formations increased from 13 % to 37 %, and the atrium-ventricle ratio rose from 0.9 to 1.4. Cardiac function was impaired, with contractile performance declining as ejection fraction decreased from 43 % to 29 % and relative cardiac output from 0.3 to 0.1. Rhythm stability was also reduced, with reduced heart rate and increased beat-to-beat variability by 43 %. At the cellular level, dinotefuran markedly promoted apoptosis and upregulated reactive-oxygen species (ROS)-related genes without antioxidant compensation. In parallel, the cardiac stress marker was induced by two-folds, and maladaptive shifts in chamber-specific gene. In conclusion, dinotefuran exerted impaired cardiotoxicity through oxidative stress, highlighting its environmental and human health risks. Future studies should validate these mechanisms in mammalian and human-relevant systems and assess the effects of chronic exposures to better define long-term health and environmental risks.