Structural analysis of the FERM domain of human protein tyrosine phosphatase non-receptor type 21.

Protein tyrosine phosphatase non-receptor type 21 (PTPN21) is a cytosolic protein tyrosine phosphatase that regulates cell growth and invasion. Due to its oncogenic properties, PTPN21 has recently emerged as a potential therapeutic target for cancer. In this study, the three-dimensional structure of the PTPN21 FERM domain was determined at 2.

Novel Small-Molecule Inhibitor of NLRP3 Inflammasome Reverses Cognitive Impairment in an Alzheimer's Disease Model.

Aberrant activation of the Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome plays an essential role in multiple diseases, including Alzheimer's disease (AD) and psoriasis. We report a novel small-molecule inhibitor, NLRP3-inhibitory compound 7 (NIC7), and its derivative, which inhibit NLRP3-mediated activation of caspase 1 along with the secretion of interleukin (IL)-1β, IL-18, and lactate dehydrogenase. We examined the therapeutic potential of NIC7 in a disease model of AD by analyzing its effect on cognitive impairment as well as the expression of dopamine receptors and neuronal markers.

Quantum Artificial Neural Network Approach to Derive a Highly Predictive 3D-QSAR Model for Blood-Brain Barrier Passage.

A successful passage of the blood-brain barrier (BBB) is an essential prerequisite for the drug molecules designed to act on the central nervous system. The logarithm of blood-brain partitioning (LogBB) has served as an effective index of molecular BBB permeability. Using the three-dimensional (3D) distribution of the molecular electrostatic potential (ESP) as the numerical descriptor, a quantitative structure-activity relationship (QSAR) model termed AlphaQ was derived to predict the molecular LogBB values.

Long-Term Particulate Matter Exposure and Incidence of Arrhythmias: A Cohort Study.

Background Studies have shown that short-term exposure to air pollution is associated with cardiac arrhythmia hospitalization and mortality. However, the relationship between long-term particulate matter air pollution and arrhythmias is still unclear. We evaluate the prospective association between particulate matter (PM) air pollution and the risk of incident arrhythmia and its subtypes.

Detection of SARS-CoV-2 in Fecal Samples From Patients With Asymptomatic and Mild COVID-19 in Korea.

Background & Aims: Although coronavirus disease 2019 (COVID-19) is characterized by fever and respiratory symptoms, some patients have no or mild symptoms. Severe acute respiratory syndrome-coronavirus (SARS-CoV-2) has been detected in feces of patients. We investigated gastrointestinal symptoms and shedding of virus into feces of patients with asymptomatic or mild COVID-19.

Long-Term Particulate Matter Exposure and Onset of Depression in Middle-Aged Men and Women.

Background: Long-term exposure to particulate matter (PM) air pollution is associated with all-cause mortality and adverse cognitive outcomes, but the association with developing depression remains inconsistent.

Objective: Our goal was to evaluate the prospective association between PM air pollution and developing depression assessed using the Center for Epidemiological Studies Depression (CES-D) scale.

Methods: Subjects were drawn from a prospective cohort study of 123,045 men and women free of depressive symptoms at baseline who attended regular screening exams in Seoul and Suwon, South Korea, from 2011 to 2015.

Comparison of Clinical Outcomes between Plastic Stent and Novel Lumen-apposing Metal Stent for Endoscopic Ultrasound-Guided Drainage of Peripancreatic Fluid Collections.

Background/aims: Endoscopic ultrasound (EUS)-guided transmural drainage for peripancreatic fluid collections (PFCs) has gained wide acceptance as a nonsurgical intervention. Although a lumen-apposing metal stent (LAMS) was recently introduced, there are few data comparing the clinical outcomes between LAMS and plastic stent (PS) drainage.

Methods: Endoscopy databases of all patients who had undergone EUS-guided drainage for PFCs were searched and the clinical outcomes of EUS-guided drainage according to stent-type used were compared.

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).

Human Placental Extract as a Subcutaneous Injection Is Effective in Chronic Fatigue Syndrome: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study.

Chronic fatigue (CF) is a common reason for consulting a physician due to affecting quality of life, but only a few effective treatments are available. The aim of this study was to examine the effectiveness of subcutaneous injection of the human placental extract (HPE) on medically indescribable cases of CF and safety in a randomized, double-blind, placebo-controlled clinical trial. A total of 78 subjects with CF were randomly assigned to either a HPE group or a placebo group.

Development of the Perceived Stress Inventory: A New Questionnaire for Korean Population Surveys.

Background: Given emerging evidence of the association between stress and disease, practitioners need a tool for measuring stress. Several instruments exist to measure perceived stress; however, none of them are applicable for population surveys because stress conceptualization can differ by population. The aim of this study was to develop and validate the Perceived Stress Inventory (PSI) and its short version for use in population surveys and clinical practice in Korea.

Clinical significance of nuclear factor κB and chemokine receptor CXCR4 expression in patients with diffuse large B-cell lymphoma who received rituximab-based therapy.

Background/aims: This study investigated the expression of nuclear factor κB (NF-κB) and the chemokine receptor (CXCR4) in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy.

Methods: Seventy patients with DLBCL and treated with rituximab-CHOP (R-CHOP) were included, and immunohistochemistry was performed to determine the expression of NF-κB (IκB kinase α, p50, and p100/p52) and CXCR4. To classify DLBCL cases as germinal center B-cell-like (GCB) and non-GCB, additional immunohistochemical expression of CD10, bcl-6, or MUM1 was used in this study.

Clinical association between non-alcoholic fatty liver disease and the development of hypertension.

Background And Aim: Non-alcoholic fatty liver disease (NAFLD) is getting an increasing attention for its clinical implications on cardiovascular disease (CVD). However, epidemiologic data are not so evident to sustain the causative association between NAFLD and hypertension, the major cause of CVD. Accordingly, we designed this study to investigate the clinical association between NAFLD and the development of hypertension.

Two CML patients who subsequently developed features of essential thrombocythemia with JAK2-V617F mutation while in complete cytogenetic remission after treatment with imatinib mesylate.

The present report describes two chronic myelogenous leukemia (CML) patients with the JAK2-V617F mutation who were in complete hematologic and cytogenetic remission and subsequently developed clinical features of essential thrombocythemia under treatment with tyrosine kinase inhibitors. In light of the findings from previous reports, screening for the JAK2-V617F mutation should be considered for any Ph(+) CML patients with thrombocytosis, leukocytosis, or erythrocytosis at diagnosis and for patients who subsequently develop thrombocytosis, leukocytosis, or erythrocytosis during follow-up, even for CML patients in complete cytogenetic response and major molecular response.

The clinical availability of non alcoholic fatty liver disease as an early predictor of the metabolic syndrome in Korean men: 5-year's prospective cohort study.

Objectives: There were many studies for the clinical association between non alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS). However, while most of studies have focused on the unilateral effects of MetS on NAFLD, studies for reverse association were comparatively rare. Therefore, we carried out a prospective cohort study to evaluate the longitudinal effects of NAFLD on the development of MetS according to the degree of NAFLD.

Clinical availability of nonalcoholic fatty liver disease as an early predictor of type 2 diabetes mellitus in Korean men: 5-year prospective cohort study.

Unlabelled: There have been several reports about the clinical association between type 2 diabetes mellitus (DM) and nonalcoholic fatty liver disease (NAFLD). However, most of the studies were about the unilateral effects of type 2 DM on NAFLD, and studies on the reverse relation are rare. Thus, this study was designed to investigate the effect of NAFLD on type 2 DM.

Blockade of K+ and Ca2+ channels by azole antifungal agents in neonatal rat ventricular myocytes.

Some azole antifungal agents induce long QT syndrome and arrhythmias. Although composite functions of ion channels in cardiomyocytes contribute to the shaping of action potentials, information on the effects of azole antifungal agents on ion currents, except human-ether-a-go-go-related gene (HERG) K+ currents, is largely lacking. Using the whole cell patch-clamp technique, we investigated the effects of four azole agents (miconazole, ketoconazole, fluconazole, and itraconazole) on inward rectifying K+ currents (IKir), voltage-gated L-type Ca2+ currents (ICaL), and delayed rectifier K+ currents (IKdr) in rat neonate ventricular myocytes.

N-3 polyunsaturated fatty acid attenuates cholesterol gallstones by suppressing mucin production with a high cholesterol diet in mice.

Background And Aim: The increasing prevalence of cholesterol gallstone (CG) disease has become an economic burden to the healthcare system. Ursodeoxycholic acid (UDCA) is the only established medical agent used to dissolve gallstones. In investigating novel therapeutics for CG, we assessed the preventive effects of n-3 polyunsaturated fatty acids (n-3PUFA) on the formation of CG induced by feeding a lithogenic diet (LD) containing high cholesterol levels to mice.

Clinical characteristics of patients with medically unexplained chronic widespread pain: a primary care center study.

Background: Chronic widespread pain (CWP) is known as a common symptom of several organic and psychological disorders. Although medically unexplained CWP (MUE) has lots of clinical distress symptoms, there were no distinct symptoms or signs. Therefore, we conducted this study to investigate clinical distress symptoms of MUE distinct from those of medically explained CWP (ME).

Feasibility of non-TBI conditioning with busulfan and fludarabine for allogeneic stem cell transplantation in lymphoid malignancy.

Background/aims: This retrospective study evaluated the transplantation outcomes of patients with adult lymphoid malignancies who received chemotherapy-based conditioning with busulfan and fludarabine (BuFlu) and busulfan and cyclophosphamide (BuCy2).

Methods: Thirty-eight patients (34 with acute lymphoblastic leukemia and 4 with lymphoblastic lymphoma) were included in the current study. The conditioning regimen was BuCy2 for 14 patients and BuFlu for the remaining 24 patients.

Prospective Randomization Trial of G-CSF-Primed Induction Regimen versus Standard Regimen in Patients with AML.

The sensitization of leukemia cells with hematopoietic growth factors can enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML). Therefore, the current trial attempted to evaluate the efficacy of granulocyte colony-stimulating factor (G-CSF) priming in remission induction chemotherapy with an intensified dose of Ara-C for newly diagnosed AML. Patients with newly diagnosed AML were randomly assigned to receive idarubicin (12 mg/m(2)/24 hr, days 1-3) plus Ara-C (500 mg/m(2)/12 hr, days 4-8) with G-CSF (250 µg/m(2)/d, days 3-7) (IAG group) or standard idarubicin (12 mg/m(2)/24 hr, days 1-3) plus Ara-C (100 mg/m(2)/12 hr, days 1-7) without G-CSF (IA group).

Anticancer activity and differentially expressed genes in head and neck cancer cells treated with a novel cyclin-dependent kinase inhibitor.

Background: Cyclin-dependent kinases (CDKs) are involved in the regulation of the cell cycle and the growth of tumor cells. In this study, we investigated the antitumor effect and differentially expressed genes (DEGs) in head and neck cancer cells treated by a novel CDK inhibitor, 2-[1,1'-biphenyl]- 4-yl-N-[5-(1,1-dioxo-1lambda(6)-isothiazolidin-2-yl)-1H-indazol-3-yl] acetamide (BAI).

Methods: Cell growth was measured by XTT assay.

Bioavailability of the amino acid-attached prodrug as a new anti-HIV agent in rats.

The primary objective of this study was to compare the pharmacokinetics of a new anti-human immunodeficiency virus agent 1-(2-amino-pyridin-4-ylmethyl)-6-(3,5-dimethylbenzoyl)-5-isopropyl-1H-pyrimidine-2,4-dione (VP-0502) with its amino acid prodrug alanine amide of VP-0502 (VP-0502AL), following intravenous and oral administrations to rats. The plasma concentrations of both analytes were analyzed via high-performance liquid chromatography coupled with photodiode-array detection (HPLC-DAD). When VP-0502 was intravenously administered at 20 mg/kg, the analyte appeared in low levels with an AUC of 0.

Prevalence of chronic fatigue and chronic fatigue syndrome in Korea: community-based primary care study.

There have been many epidemiological and clinical researches on chronic fatigue (CF) and chronic fatigue syndrome (CFS) since the 1990s, but such studies have been quite limited in Korea. The aim of this study was to investigate the point prevalence of CF and CFS in patients who visited community-based eight primary care clinics in Korea. The study subjects were 1,648 patients aged 18 yr and over who visited one of eight primary care clinics in Korea between the 7th and 17th of May 2001.