Molecular diagnosis of McArdle disease using whole-exome sequencing.

Whole-exome sequencing (WES) analysis has been used recently as a diagnostic tool for finding molecular defects. In the present study, researchers attempted to analyze molecular defects through WES in a 13-year-old female patient who had not been diagnosed through a conventional genetic approach. DNA was extracted and subjected to WES analysis to identify the genetic defect.

Melatonin modulates adiponectin expression on murine colitis with sleep deprivation.

Aim: To determine adiponectin expression in colonic tissue of murine colitis and systemic cytokine expression after melatonin treatments and sleep deprivation.

Methods: The following five groups of C57BL/6 mice were used in this study: (1) group I, control; (2) group II, 2% DSS induced colitis for 7 d; (3) group III, 2% DSS induced colitis and melatonin treatment; (4) group IV, 2% DSS induced colitis with sleep deprivation (SD) using specially designed and modified multiple platform water baths; and (5) group V, 2% DSS induced colitis with SD and melatonin treatment. Melatonin (10 mg/kg) or saline was intraperitoneally injected daily to mice for 4 d.

Aliskiren Regulates Neonatal Fc Receptor and IgG Metabolism with Attenuation of Anti-GBM Glomerulonephritis in Mice.

Background: Renin, in addition to its activation of the renin-angiotensin system, binds to the (pro)renin receptor (PRR) and triggers inflammatory and fibrogenic signaling in tissue. In addition, aliskiren, a direct renin inhibitor, has been shown to affect IgG metabolism by altering PRR and neonatal Fc receptors (FcRns).

Methods: We investigated the effect of aliskiren on proteinuria, glomerular extracellular matrix, expressions of fibronectin, transforming growth factor β1 (TGF-β1), PRR, FcRn and renal metabolism of IgG in a mice model of anti-glomerular basement membrane glomerulonephritis (anti-GBM GN).

Melatonin improves experimental colitis with sleep deprivation.

Sleep deprivation (SD) is an epidemic phenomenon in modern countries, and its harmful effects are well known. SD acts as an aggravating factor in inflammatory bowel disease. Melatonin is a sleep-related neurohormone, also known to have antioxidant and anti-inflammatory effects in the gastrointestinal tract; however, the effects of melatonin on colitis have been poorly characterized.

Congenital nephrogenic diabetes insipidus with a novel mutation in the aquaporin 2 gene.

Congenital nephrogenic diabetes insipidus (CNDI) is a rare disorder caused by mutations of the arginine vasopressin (AVP) V2 receptor or aquaporin 2 () genes. The current study presented the case of CNDI in a 1-month-old male with a novel mutation in the gene. The patient was referred due to the occurrence of hypernatremia and mild-intermittent fever since birth.

17β-estradiol induces an interaction between adenosine monophosphate-activated protein kinase and the insulin signaling pathway in 3T3-L1 adipocytes.

Estrogen (17β-estradiol) has been implicated in maintaining insulin sensitivity. It is thought to act predominantly through genomic pathways and regulate the expression of various genes via binding to estrogen receptors (ERs)-α and -β. 17β-estradiol has been reported to simultaneously stimulate protein kinase B (Akt) and adenosine monophosphate-activated protein kinase (AMPK) in ex vivo skeletal muscle.

A novel mutation of exon 7 in growth hormone receptor mRNA in a patient with growth hormone insensitivity syndrome and neurofibromatosis type I.

Growth hormone insensitivity syndrome (GHIS), a genetic disease characterized by growth retardation combined with high serum concentration of growth hormone (GH) and low insulin-like growth factor 1 (IGF-1) levels, can be caused by mutations in the GH receptor (GHR) gene. We investigated the molecular defects in the GHR gene in a patient with neurofibromatosis type 1 (NF-1). The patient, a 2-year-old boy with NF-1, was assessed on his short stature by auxological, biochemical and molecular studies.

Melatonin improves inflammatory cytokine profiles in lung inflammation associated with sleep deprivation.

Sleep disturbance has become an endemic behavior in modern countries, and its prevalence has also increased. Even a subtle sleep deficiency is related to health problems. Particularly, patients with pulmonary disease often complain of insomnia.

Exendin-4 Protects Against Sulfonylurea-Induced β-Cell Apoptosis.

Sulfonylurea is one of the commonly used anti-diabetic drugs that stimulate insulin secretion from β-cells. Despite their glucose lowering effects in type 2 diabetes mellitus, long-term treatment brought on secondary failure characterized by β-cell exhaustion and apoptosis. ER stress induced by Ca depletion in endoplasmic reticulum (ER) is speculated be one of the causes of secondary failure, but it remains unclear.

Exendin-4 protects against sulfonylurea-induced β-cell apoptosis.

Sulfonylurea is one of the commonly used anti-diabetic drugs that stimulate insulin secretion from β-cells. Despite their glucose lowering effects in type 2 diabetes mellitus, long-term treatment brought on secondary failure characterized by β-cell exhaustion and apoptosis. ER stress induced by Ca(2+) depletion in endoplasmic reticulum (ER) is speculated be one of the causes of secondary failure, but it remains unclear.

Exendin-4 protects oxidative stress-induced β-cell apoptosis through reduced JNK and GSK3β activity.

Oxidative stress induced by chronic hyperglycemia in type 2 diabetes plays a crucial role in progressive loss of β-cell mass through β-cell apoptosis. Glucagon like peptide-1 (GLP-1) has effects on preservation of β-cell mass and its insulin secretory function. GLP-1 possibly increases islet cell mass through stimulated proliferation from β-cell and differentiation to β-cell from progenitor cells.

Vascular endothelial growth factor, fms-like tyrosine kinase-1 (Flt-1) and soluble Flt-1 gene expressions in Korean pre-eclamptic placentas.

Aim: To assess the expressions of vascular endothelial growth factor (VEGF), fms-like tyrosine kinase-1 (Flt-1), and soluble Flt-1 (sFlt-1) genes in healthy normotensive and pre-eclamptic placentas of Korean women.

Methods: We investigated 12 healthy normotensive pregnant women and 10 pre-eclamptic pregnant women at Eulji University Hospital. The obtained placental tissues were analyzed using reverse transcription polymerase chain reaction and real-time quantitative polymerase chain reaction.

Parenteral 17beta-estradiol decreases fasting blood glucose levels in non-obese mice with short-term ovariectomy.

Aims: long-term ovariectomy-induced metabolic changes such as insulin resistance and glucose intolerance might be caused directly by estrogen deficiency and may occur partly as secondary effects of obesity arising due to the orexigenic effects of estrogen deficiency. Long-term estrogen treatment prevented those by exerting anorexigenic and metabolic actions in ovariectomized mice. However, the effect of short-term estrogen treatment on glucose metabolism in mice with short-term ovariectomy, during which ovariectomy-induced obesity does not develop, is not yet clear.

Mutation analysis of factor VIII in Korean patients with severe hemophilia A.

Hemophilia A is an X-linked recessive disorder caused by mutations of the factor VIII gene. The mutation spectrum has been reported in various populations, but not in Koreans. Mutation analysis of the factor VIII gene was performed in 22 unrelated Korean patients with severe hemophilia A.

Circulating concentrations of monocyte chemoattractant protein-1 are associated with menopause status in Korean women.

Background: Monocyte chemoattractant protein-1 (MCP-1) plays a role in adipose tissue inflammation and insulin resistance. Human circulating MCP-1 concentrations reportedly increase or remain unchanged according to obesity or insulin resistance in various ethnic populations; whether or not circulating MCP-1 concentrations increase after menopause has remained unclear.

Methods: We investigated the relationship between circulating MCP-1 concentrations and obesity or insulin resistance, and the relationship between circulating MCP-1 and menopause status in premenopausal (n=111) and postmenopausal (n=64) Korean women.

A novel germline mutation of hMLH1 in a Korean hereditary non-polyposis colorectal cancer family.

Hereditary non-polyposis colorectal cancer (HNPCC) is an inherited disease caused by a germline mutation of the mismatch repair (MMR) genes, and the distinctive feature is that colorectal and extracolonic malignancies occur early in life. We report on the case of a Korean HNPCC family with endometrial cancer, with the goal of elucidating the involvement of an MMR deficiency. Although the family history did not fulfill the Amsterdam criteria II, blood samples were subjected to genetic testing by the revised Bethesda guidelines.

Melatonin attenuates lipopolysaccharide-induced acute lung inflammation in sleep-deprived mice.

Sleep disorders are great problems in modern society. Even minimal changes of sleep can affect health. Especially, patients with pulmonary diseases complain of sleep problems such as sleep disturbance and insomnia.

Body mass index is associated with USF1 haplotype in Korean premenopausal women.

The upstream stimulatory factor 1 (USF1) gene has been shown to play an essential role as the cause of familial combined hyperlipidemia, and there are several association studies on the relationship between USF1 and metabolic disorders. In this study, we analyzed two single nucleotide polymorphisms in USF1 rs2073653 (306A>G) and rs2516840 (1748C>T) between the case (dyslipidemia or obesity) group and the control group in premenopausal females, postmenopausal females, and males among 275 Korean subjects. We observed a statistically significant difference in the GC haplotype between body mass index (BMI) > or =25 kg/m2) and BMI <25 kg/m2 groups in premenopausal females ( chi2=4.

High prevalence of RET, RAS, and ERK expression in Hashimoto's thyroiditis and in papillary thyroid carcinoma in the Korean population.

Background: The RET/PTC-RAS-BRAF cascade is associated with papillary thyroid carcinoma (PTC).

Objective: The relationship between PTC and Hashimoto's thyroiditis (HT) is still elusive. To determine whether thyrocytes showing oxyphil cell metaplasia in HT also express RET, RAS, and ERK proteins, which are associated with PTC.

Selenium regulates cyclooxygenase-2 and extracellular signal-regulated kinase signaling pathways by activating AMP-activated protein kinase in colon cancer cells.

Epidemiologic and experimental evidences indicate that selenium, an essential trace element, can reduce the risk of a variety of cancers. Protection against certain types of cancers, particularly colorectal cancers, is closely associated with pathways involving cyclooxygenase-2 (COX-2). We found that AMP-activated protein kinase (AMPK), which functions as a cellular energy sensor, mediates critical anticancer effects of selenium via a COX-2/prostaglandin E(2) signaling pathway.

Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway.

EGCG [(-)epigallocatechin-3-gallate], a green tea-derived polyphenol, has been shown to suppress cancer cell proliferation, and interfere with the several signaling pathways and induce apoptosis. Practically, there is emerging evidence that EGCG has a potential to increase the efficacy of chemotherapy in patients. We hypothesized that EGCG may exert cell cytotoxicity through modulating AMPK (AMP-activated protein kinase) followed by the decrease in COX-2 expression.

Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP-activated protein kinase.

Phytochemicals such as soy isoflavone genistein have been reported to possess therapeutic effects for obesity, diabetes, and cardiovascular diseases. In the present study, the molecular basis of selective phytochemicals with emphasis on their ability to control intracellular signaling cascades of AMP-activated kinase (AMPK) responsible for the inhibition of adipogenesis was investigated. Recently, the evolutionarily conserved serine/threonine kinase, AMPK, emerges as a possible target molecule of anti-obesity.