Efficient strategy for the molecular diagnosis of intractable early-onset epilepsy using targeted gene sequencing.

Background: We intended to evaluate diagnostic utility of a targeted gene sequencing by using next generation sequencing (NGS) panel in patients with intractable early-onset epilepsy (EOE) and find the efficient analytical step for increasing the diagnosis rate.

Methods: We assessed 74 patients with EOE whose seizures started before 3 years of age using a customized NGS panel that included 172 genes. Single nucleotide variants (SNVs) and exonic and chromosomal copy number variations (CNVs) were intensively examined with our customized pipeline and crosschecked with commercial or pre-built software.

Whole genome and transcriptome analysis reveal MALDI-TOF MS and SDS-PAGE have limited performance for the detection of the key outer membrane protein in carbapenem-resistant isolates.

To detect the outer membrane protein (OMP), which plays a key role in carbapenem resistance, whole-genome and transcriptome analysis of the clinical carbapenem-resistant was carried out. The index strain lacked both OmpK35 and OmpK36, whereas the other strains lacked only OmpK35. After SDS-PAGE, the putative OMP bands were excised and identified as OmpA and OmpK36.

Diagnostic application of clinical exome sequencing in Leber congenital amaurosis.

Purpose: Leber congenital amaurosis (LCA) is a hereditary retinal dystrophy with wide genetic heterogeneity. Next-generation sequencing (NGS) targeting multiple genes can be a good option for the diagnosis of LCA, and we tested a clinical exome panel in patients with LCA.

Methods: A total of nine unrelated Korean patients with LCA were sequenced using the Illumina TruSight One panel, which targets 4,813 clinically associated genes, followed by confirmation using Sanger sequencing.

The effect of trauma and PTSD on telomere length: An exploratory study in people exposed to combat trauma.

Telomere length has been suggested to be a cellular marker for age-related diseases as well as psychosocial stress. The present study investigated whether telomere length is associated with post-traumatic stress disorder (PTSD) among veterans exposed to combat trauma in the Vietnam War. The potentially associated factors on cellular aging were considered.

Telomere length in alcohol dependence: A role for impulsive choice and childhood maltreatment.

Telomere shortening, a marker of cellular aging, has been considered to be linked with psychosocial stress as well as with chronic alcohol consumption, possibly mediated by oxidative stress and inflammatory response. Recent findings suggested that early life adversity on telomere dynamics may be related to impulsive choice. To further our understanding of the association of impulsive choice and childhood trauma on telomere length, we examined whether delayed discounting and childhood trauma or their interaction is related to leukocyte telomere length, while controlling for multiple potential confounding variables, in patients with alcohol dependence who are considered to have higher impulsive choice and shorter telomere length.

Next-generation sequencing of in breast cancer patients: potential effects on clinical decision-making using rapid, high-accuracy genetic results.

Purpose: We evaluated the clinical role of rapid next-generation sequencing (NGS) for identifying mutations compared to traditional Sanger sequencing.

Methods: Twenty-four paired samples from 12 patients were analyzed in this prospective study to compare the performance of NGS to the Sanger method. Both NGS and Sanger sequencing were performed in 2 different laboratories using blood samples from patients with breast cancer.

Detection of Immunoglobulin Heavy Chain Gene Clonality by Next-Generation Sequencing for Minimal Residual Disease Monitoring in B-Lymphoblastic Leukemia.

Minimal residual disease (MRD) following B-lymphoblastic leukemia (B-ALL) treatment has gained prognostic importance. Clonal immunoglobulin heavy chain (IGH) gene rearrangement is a useful follow-up marker in B-ALL owing to its high positivity rate. We evaluated the performance and clinical applicability of a next-generation sequencing (NGS) assay for IGH rearrangement in B-ALL MRD monitoring.

Effects of Neutralization by Soluble ABH Antigens Produced by Transplanted Kidneys From ABO-Incompatible Secretor Donors.

Background: Grafts survive despite blood group antigens on the transplant being continuously exposed to antibodies in the blood of recipients in ABO-incompatible kidney transplantation (ABOi KT), owing to the mechanism of accommodation. We analyzed the immunodynamics of soluble ABH antigens in allografts from secretor donors and the influence of such immunodynamics on accommodation and subsequent graft survival in ABOi KT.

Methods: The genotype of a known human β-galactoside α-1,2-fucosyltransferase gene (FUT2), which determines soluble ABH antigen secretor status, was established in 32 donors for ABOi KT at the Severance Hospital, from June 2010 to July 2015.

Panel strain of for beta-lactam antibiotic evaluation: their phenotypic and genotypic characterization.

is responsible for numerous infections caused in hospitals, leading to mortality and morbidity. It has been evolving as a multi-drug resistant pathogen, acquiring multiple resistances such as such as horizontal gene transfer, transposon-mediated insertions or change in outer membrane permeability. Therefore, constant efforts are being carried out to control the infections using various antibiotic therapies.

Evaluation of an amplicon-based next-generation sequencing panel for detection of BRCA1 and BRCA2 genetic variants.

The recent advances in the next-generation sequencing (NGS) technology have enabled fast, accurate, and cost-effective genetic testing. Here, we evaluated the performance of a targeted NGS panel for BRCA1/2 sequencing and confirmed its applicability in routine clinical diagnostics. We tested samples from 88 patients using the TruSeq custom panel (Illumina Inc, USA) and a MiSeq sequencer (Illumina) and compared the results to the outcomes of conventional Sanger sequencing.

Affinity Maturation of Monoclonal Antibody 1E11 by Targeted Randomization in CDR3 Regions Optimizes Therapeutic Antibody Targeting of HER2-Positive Gastric Cancer.

Anti-HER2 murine monoclonal antibody 1E11 has strong and synergistic anti-tumor activity in HER2-overexpressing gastric cancer cells when used in combination with trastuzumab. We presently optimized this antibody for human therapeutics. First, the complementarity determining regions (CDRs) of the murine antibody were grafted onto human germline immunoglobulin variable genes.

Combination of novel HER2-targeting antibody 1E11 with trastuzumab shows synergistic antitumor activity in HER2-positive gastric cancer.

The synergistic interaction of two antibodies targeting the same protein could be developed as an effective anti-cancer therapy. Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-25% of breast and gastric cancer patients, and HER2-targeted antibody therapy using trastuzumab is effective in many of these patients. Nonetheless, improving therapeutic efficacy and patient survival is important, particularly in patients with HER2-positive gastric cancer.

Fermented soybean product (Cheonggukjang) improved some attributes of protein and growth hormone measurements in Sprague-Dawley rats.

We hypothesized that the administration of Cheonggukjang (CKJ) would exert positive effects on factors implicated with growth in Sprague-Dawley (SD) rats. To test this hypothesis, we measured specific aspects of bone and organ growth in male SD rats that were treated for 6 weeks with 3 concentrations of CKJ. Although the CKJ extract contained high concentrations of flavonoids and phenolic compounds, no significant differences in body length, organ weights, or femur weight were detected between the CKJ- and vehicle-treated groups.

Growth sensitivity in the epiphyseal growth plate, liver and muscle of SD rats is significantly enhanced by treatment with a fermented soybean product (cheonggukjang) through stimulation of growth hormone secretion.

Cheonggukjang (CKJ), a fermented soybean product, has been reported to have beneficial effects on various chronic diseases, including cardiovascular disease, cancer and immune diseases. To investigate whether CKJ induces growth sensitivity in mammals, alterations of key parameters related to their growth were analyzed. Sprague‑Dawley (SD) rats were treated with a high concentration of CKJ (H‑CKJ) or a low concentration of CKJ (L‑CKJ) for 10 days, and compared with vehicle-treated rats.

Proteomic analysis of kidneys from selenoprotein M transgenic rats in response to increased bioability of selenium.

Background: To characterize changes in global protein expression in kidneys of transgenic rats overexpressing human selenoprotein M (SelM) in response to increased bioabivility of selenium (Sel), total proteins extracted from kidneys of 10-week-old CMV/hSelM Tg and wild-type rats were separated by 2-dimensional gel electrophoresis and measured for changes in expression.

Results: Ten and three proteins showing high antioxidant enzymatic activity were up- and down-regulated, respectively, in SelM-overexpressing CMV/hSelM Tg rats compared to controls based on an arbitrary 2-fold difference. Up-regulated proteins included LAP3, BAIAP2L1, CRP2, CD73 antigen, PDGF D, KIAA143 homolog, PRPPS-AP2, ZFP313, HSP-60, and N-WASP, whereas down-regulated proteins included ALKDH3, rMCP-3, and STC-1.

Quantitative evaluation of therapeutic effect of Liriope platyphylla on phthalic anhydride-induced atopic dermatitis in IL-4/Luc/CNS-1 Tg mice.

Ethnopharmacological Relevance: A variety of previous pharmacological studies have suggested that Liriope platyphylla may exert beneficial biological effects on inflammation, diabetes, neurodegenerative disorder, obesity, and atopic dermatitis (AD).

Aim Of The Study: The therapeutic effect of aqueous extract of Liriope platyphylla (AEtLP) on AD was quantified using the luciferase report system in IL-4/Luc/CNS-1 transgenic (Tg) mice.

Materials And Methods: Alteration of the luciferase signal was quantified in IL-4/Luc/CNS-1 Tg mice co-treated with phthalic anhydride (PA) and AEtLP for 2 weeks using the IVIS imaging system.

Nicastrin overexpression in transgenic mice induces aberrant behavior and APP processing.

Nicastrin (NCT) is a component of the presenilin protein complex, which is involved in the cleavage of β-amyloid precursor protein (βAPP) and Notch. The aim of this study was to determine the manner in which overexpression of wild-type human nicastrin (hNCTw) or mutant human nicastrin (hNCTm, D336A/Y337A) regulates brain functions and amyloid precusor protein (APP) processing. For this, we created transgenic (Tg) mice expressing neuron-specific enolase (NSE)-controlled hNCTw or hNCTm and measured their phenotypes as time passed.

Alzheimer's phenotypes induced by overexpression of human presenilin 2 mutant proteins stimulate significant changes in key factors of glucose metabolism.

Alzheimer's disease (AD) is closely associated with significant defects in glucose metabolism. To investigate whether AD pathology induced by overexpression of human mutant presenilin 2 (PS2) protein induces changes in glucose metabolism, glucose‑related factors were analyzed in the brain of 12‑month‑old neuron‑specific enolase (NSE)/hPS2m transgenic (Tg) mice. NSE/hPS2m Tg mice used in this study showed AD‑like phenotypes such as the accumulation of Aβ‑42, the increase of γ‑secretase activity and Tau hyperphosphorylation.

Protective effects of gomisin A isolated from Schisandra chinensis against CCl(4)-induced hepatic and renal injury.

The aim of the present study was to investigate the protective effects of gomisin A, a lignan compound isolated from Schisandra chinensis, against liver and kidney damage induced by CCl(4) exposure. We assessed alterations in organ weights, levels of serum biochemical indicators, and activation of the caspase-3 and MAPK signaling pathways and carried out histological analysis of liver and kidney tissue in rats pretreated with gomisin A for four days. In the gomisin A/CCl(4)-treated group, only the liver experienced a significant increase in weight, whereas the other organs did not undergo any changes.

Toxicity of red Liriope platyphylla manufactured by steaming process on liver and kidney organs of ICR mice.

Red Liriope platyphylla (RLP) produced by steaming process has been reported to enhance the secretion of insulin and nerve growth factor (NGF). However, there has been no report on the toxicity of RLP in the specific organs of mice. To investigate the toxic effect of RLP, we tried to observe a significant alteration on body weight, food/water intake, organ weight, liver pathology and kidney pathology in female ICR mice received 12.

Aqueous extract of Liriope platyphylla, a traditional Chinese medicine, significantly inhibits abdominal fat accumulation and improves glucose regulation in OLETF type II diabetes model rats.

Liriope platyphylla is a medical herb that has long been used in Korea and China to treat cough, sputum, neurodegenerative disorders, obesity, and diabetes. The aims of this study were to determine the antidiabetic and antiobesity effects of aqueous extract of L. platyphylla (AEtLP) through glucose and lipid regulation in both pre-diabetes and obesity stage of type II diabetes model.