Improving the hERG model fitting using a deep learning-based method.

The hERG channel is one of the essential ion channels composing the cardiac action potential and the toxicity assay for new drug. Recently, the comprehensive proarrhythmia assay (CiPA) was adopted for cardiac toxicity evaluation. One of the hurdles for this protocol is identifying the kinetic effect of the new drug on the hERG channel.

Cell-cell contacts via N-cadherin induce a regulatory renin secretory phenotype in As4.1 cells.

The lack of a clonal renin-secreting cell line has greatly hindered the investigation of the regulatory mechanisms of renin secretion at the cellular, biochemical, and molecular levels. In the present study, we investigated whether it was possible to induce phenotypic switching of the renin-expressing clonal cell line As4.1 from constitutive inactive renin secretion to regulated active renin secretion.

Variability, Mean, and Baseline Values of Metabolic Parameters in Predicting Risk of Type 2 Diabetes.

Context: The effect of baseline (B) and alteration of metabolic parameters (MPs), including plasma glucose (PG) testing, insulin resistance surrogates, and lipid profile and their mutual interactions on the development of type 2 diabetes mellitus (T2DM), has not been investigated systematically.

Objective: To access the association of the past variability (V), past mean (M), and B values of various MPs and their mutual interaction with the risk of T2DM.

Methods: A community-based, longitudinal analysis was conducted using the Korean Genome and Epidemiology Study comprising 3829 nondiabetic participants with completed MPs measurements during 3 biannually visits who were followed over the next 10 years.

Development of a Portable Respiratory Gas Analyzer for Measuring Indirect Resting Energy Expenditure (REE).

Objective: A rapidly growing home healthcare market has resulted in the development of many portable or wearable products. Most of these products measure, estimate, or calculate physiologic signals or parameters, such as step counts, blood pressure, or electrocardiogram. One of the most important applications in home healthcare is monitoring one's metabolic state since the change of metabolic state could reveal minor or major changes in one's health condition.

Teaching cardiac excitation-contraction coupling using a mathematical computer simulation model of human ventricular myocytes.

To understand the excitation-contraction (E-C) coupling of cardiomyocytes, including the electrophysiological mechanism of their characteristically long action potential duration, is one of the major learning goals in medical physiology. However, the integrative interpretation of the responses occurring during the contraction-relaxation cycle is challenging due to the dynamic interaction of underlying factors. Starting in 2017, we adopted the mathematical computer simulation model of human ventricular myocyte (Cardiac E-C_Sim), hypothesizing that this educational technology may facilitate students' learning of cardiac physiology.

models for evaluating proarrhythmic risk of drugs.

Safety evaluation of drugs requires examination of the risk of generating Torsade de Pointes (TdP) because it can lead to sudden cardiac death. Until recently, the QT interval in the electrocardiogram (ECG) has been used in the evaluation of TdP risk because the QT interval is known to be associated with the development of TdP. Although TdP risk evaluation based on QT interval has been successful in removing drugs with TdP risk from the market, some safe drugs may have also been affected due to the low specificity of QT interval-based evaluation.

A Novel Nicotinamide Adenine Dinucleotide Correction Method for Intracellular Ca2+ Measurement with Fura-2-Analog in Live Cells.

To measure [Ca] quantitatively, fura-2 analogs, which are ratiometric fluoroprobes, are frequently used. However, dye usage is intrinsically limited in live cells because of autofluorescence interference, mainly from nicotinamide adenine dinucleotide (NADH). More specifically, this is a major obstacle when measuring the mitochondrial [Ca] quantitatively using fura-2 analogs because the majority of NADH is in the mitochondria.

Koreans Do Not Have Higher Percent Body Fat than Australians: Implication for the Diagnosis of Obesity in Asians.

Objective: It has been assumed that, for a given BMI, Asians have higher percent body fat (PBF) than Caucasians. As a result, it has been suggested that the BMI threshold for diagnosing obesity in Asians be lowered to less than  30 kg/m . This study sought to compare PBF between Koreans and Australians.

Three-Dimensional Heart Model-Based Screening of Proarrhythmic Potential by Simulation of Action Potential and Electrocardiograms.

The proarrhythmic risk is a major concern in drug development. The Comprehensive Proarrhythmia Assay (CiPA) initiative has proposed the JTpeak interval on electrocardiograms (ECGs) and qNet, an metric, as new biomarkers that may overcome the limitations of the hERG assay and QT interval. In this study, we simulated body-surface ECGs from patch-clamp data using realistic models of the ventricles and torso to explore their suitability as new biomarkers for cardiac safety.

Toward a grey box approach for cardiovascular physiome.

The physiomic approach is now widely used in the diagnosis of cardiovascular diseases. There are two possible methods for cardiovascular physiome: the traditional mathematical model and the machine learning (ML) algorithm. ML is used in almost every area of society for various tasks formerly performed by humans.

Seasonal effects on resting energy expenditure are dependent on age and percent body fat.

Seasonal variation in resting energy expenditure (REE) is still under debate. This study investigated seasonal changes in REE and relevant factors among Korean adults. A total of 867 healthy volunteers (385 men and 482 women) aged 20-69 years were divided into four seasonal groups and subgroups based on age, body mass index (BMI), and percent body fat (PBF) quartiles.

The ion channel activator CyPPA inhibits melanogenesis via the GSK3β/β-catenin pathway.

Research into materials that inhibit melanogenesis in skin has gained interest. Screening for such compounds in B16F10 cells revealed that cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA), a positive modulator of small-conductance Ca-activated K channels, is a strong inhibitor of melanogenesis. We investigated the anti-melanogenic activity of CyPPA and the molecular mechanism by which CyPPA reduced melanin production in normal human melanocytes (NHM).

Pulmonary Function Difference in Sasang Constitutional Types.

The purpose of this study was to determine the differences in pulmonary function among Sasang constitutional types in young adults. The Sasang Constitutional Analysis Tool (SCAT), pulmonary function tests (PFTs), and cardiopulmonary exercise tests were conducted in 417 participants from 2009 to 2015. Subjects with the Tae-Eum (TE) type had significantly higher inspiratory capacity (IC) and inspiratory reserve volume (IRV) values than those with the So-Yang (SY) and So-Eum (SE) types ( < 0.

Body weight difference between dual-energy X-ray absorptiometry and multi-frequency bioelectrical impedance analysis attenuates the equivalence of body-composition assessment.

Background/objectives: Low agreement of body-composition analysis (BCA) using dual-energy X-ray absorptiometry (DXA) and multi-frequency bioelectrical impedance analysis (MF-BIA) has been reported. We examined whether this discrepancy is influenced by the precision of body weight (BW) measurement using DXA.

Subjects/methods: This cross-sectional study enrolled 1353 participants aged 53-83 years.

Anthropometry-based estimation of body heat capacity in individuals aged 7-69 years: the Size Korea Survey 2010.

Although our previously developed anthropometry-based calculation of heat capacity (HC) for adults appeared to be precise and valid, its use in children and adolescents may be associated with bias. This study investigated a large dataset from the Size Korea survey, a national anthropometric survey conducted in 2010, to revalidate our previous HC equation and to develop another one that is appropriate for children and adolescents. We enrolled 12,766 participants aged 7-69 years with body composition data measured by multi-frequency bioelectrical impedance analysis.

Lower cellular metabolic power can be an explanation for obesity trend in Tae-Eum type: hypothesis and clinical observation.

Background: Those classified as Tae-Eum (TE)-type people in Sasang constitutional medicine (SCM) are prone to obesity. Although extensive clinical observations have confirmed this tendency, the underlying physiological mechanisms are unknown. Here, we propose a novel hypothesis using integrative physiology to explain this phenomenon.

Body composition and personality traits in so-Yang type males.

Background: The purpose of the present study was to examine the body composition of So-Yang type males according to Sasang constitutional medicine, which is popular in Korea. Different Sasang constitutional types are associated with different muscle distributions, body shapes, and disease susceptibilities. We used the Sasang Personality Questionnaire (SPQ) as a measure of the temperament of each Sasang type.

Neuronal nitric oxide synthase modulation of intracellular Ca handling overrides fatty acid potentiation of cardiac inotropy in hypertensive rats.

Cardiac neuronal nitric oxide synthase (nNOS) is an important molecule that regulates intracellular Ca homeostasis and contractility of healthy and diseased hearts. Here, we examined the effects of nNOS on fatty acid (FA) regulation of left ventricular (LV) myocyte contraction in sham and angiotensin II (Ang II)-induced hypertensive (HTN) rats. Our results showed that palmitic acid (PA, 100 μM) increased the amplitudes of sarcomere shortening and intracellular ATP in sham but not in HTN despite oxygen consumption rate (OCR) was increased by PA in both groups.

Relationship of the Cold-Heat Sensation of the Limbs and Abdomen with Physiological Biomarkers.

The present study explored the relationship between the regional Cold-Heat sensation, the key indicator of the Cold-Heat patterns in traditional East Asian medicine (TEAM), and various biomarkers in Korean population. 734 apparently healthy volunteers aged 20 years and older were enrolled. Three scale self-report questions on the general thermal feel in hands, legs, and abdomen were examined.

Cardiac inotropy, lusitropy, and Ca handling with major metabolic substrates in rat heart.

Fatty acid (FA)-dependent oxidation is the predominant process for energy supply in normal heart. Impaired FA metabolism and metabolic insufficiency underlie the failing of the myocardium. So far, FA metabolism in normal cardiac physiology and heart failure remains undetermined.

Impaired Inactivation of L-Type Ca2+ Current as a Potential Mechanism for Variable Arrhythmogenic Liability of HERG K+ Channel Blocking Drugs.

The proarrhythmic effects of new drugs have been assessed by measuring rapidly activating delayed-rectifier K+ current (IKr) antagonist potency. However, recent data suggest that even drugs thought to be highly specific IKr blockers can be arrhythmogenic via a separate, time-dependent pathway such as late Na+ current augmentation. Here, we report a mechanism for a quinolone antibiotic, sparfloxacin-induced action potential duration (APD) prolongation that involves increase in late L-type Ca2+ current (ICaL) caused by a decrease in Ca2+-dependent inactivation (CDI).

Perspectives of physiome research.

Physiome is an area of physiology to generate a whole system by analyzing and integrating scattered and discrete information. The term "physiome" was first introduced by James B. Bassingthwaight in 1993, and officially announced by the International Union of Physiological Societies as the new field to be accomplished in the 21st century.