WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects.

Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a constellation of adult onset phenotypes consistent with an acceleration of intrinsic biological aging. It is caused by pathogenic variants in the WRN gene, which encodes a multifunctional nuclear protein with exonuclease and helicase activities. WRN protein is thought to be involved in optimization of various aspects of DNA metabolism, including DNA repair, recombination, replication, and transcription.

[Molecular mechanism of pathogenesis of the progeria].

Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome (WS) exhibit accelerated aging phenotypes, which are caused by mutations in the LMNA or WRN genes, respectively. Accumulating evidence suggested that the mutations commonly caused senes- cent phenotypes such as DNA damage, cell cycle arrest, nuclear enlargement and nuclear shape abnormality. Furthermore, both mutations showed significant loss of nuclear lamina -binding proteins, a heterochromatin protein, and an epigenetic H3K9me3 mark in hetero- chromatin loci.

Real-world evidence for the safety of ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus (STELLA-ELDER): final results of a post-marketing surveillance study.

Objective: To investigate the real-world safety of ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus (T2DM).

Research Design And Methods: Japanese patients (≥65 years old) who were first prescribed ipragliflozin within 3 months after its launch in April 2014 were registered in this post-marketing surveillance (PMS). Final data collection was in July 2015.

A novel podocyte gene, semaphorin 3G, protects glomerular podocyte from lipopolysaccharide-induced inflammation.

Kidney diseases including diabetic nephropathy have become huge medical problems, although its precise mechanisms are still far from understood. In order to increase our knowledge about the patho-physiology of kidney, we have previously identified >300 kidney glomerulus-enriched transcripts through large-scale sequencing and microarray profiling of the mouse glomerular transcriptome. One of the glomerulus-specific transcripts identified was semaphorin 3G (Sema3G) which belongs to the semaphorin family.

Effects of K-877, a novel selective PPARα modulator (SPPARMα), in dyslipidaemic patients: A randomized, double blind, active- and placebo-controlled, phase 2 trial.

Background And Aims: To assess the efficacy and safety of K-877 (Pemafibrate), a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα) that possesses unique PPARα activity and selectivity, compared with placebo and fenofibrate in dyslipidaemic patients with high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels.

Methods And Results: This study was a double blind, placebo-controlled, parallel-group 12-week clinical trial. The study randomized 224 patients to K-877 0.

Elevated Adiponectin Antibody Levels in Sera of Patients with Atherosclerosis-Related Coronary Artery Disease, Cerebral Infarction and Diabetes Mellitus.

Adiponectin secreted from the adipocytes plays pleiotropic, anti-atherosclerotic roles, such as enhancement of insulin secretion and an increase in energy expenditure. The measurement of levels of circulating adiponectin is useful to evaluate the progression of atherosclerosis-related diseases, such as coronary artery disease (CAD), cerebral infarction (CI) and diabetes mellitus (DM). We examined the serum antibody levels against recombinant adiponectin protein via the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) method.

Matricellular protein CCN3 mitigates abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a major cause of morbidity and mortality; however, the mechanisms that are involved in disease initiation and progression are incompletely understood. Extracellular matrix proteins play an integral role in modulating vascular homeostasis in health and disease. Here, we determined that the expression of the matricellular protein CCN3 is strongly reduced in rodent AAA models, including angiotensin II-induced AAA and elastase perfusion-stimulated AAA.

Safety of ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus (STELLA-ELDER): Interim results of a post-marketing surveillance study.

Objective: To determine the incidence of adverse drug reactions (ADRs) associated with ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus.

Research Design And Methods: We report interim results of a postmarketing surveillance survey. Japanese physicians recorded ADRs in elderly patients (≥ 65 years old) who were first prescribed with ipragliflozin within 3 months of its launch (April 2014).

Early-Onset Severe Diffuse Alveolar Hemorrhage after Bortezomib Administration Suggestive of Pulmonary Involvement of Myeloma Cells.

Severe acute lung injury is a rare but life-threatening complication associated with bortezomib. We report a patient with multiple myeloma who developed a severe diffuse alveolar hemorrhage (DAH) immediately after the first bortezomib administration. The patient was suspected to have pulmonary involvement of myeloma, which caused DAH after rapidly eradicating myeloma cells in the lungs with bortezomib.

Cushing Syndrome Due to ACTH-Secreting Pheochromocytoma, Aggravated by Glucocorticoid-Driven Positive-Feedback Loop.

Context: Pheochromocytoma is a catecholamine-producing tumor that originates from adrenal chromaffin cells and is capable of secreting various hormones, including ACTH.

Case Description: A 56-year-old female presented with Cushingoid appearance and diabetic ketoacidosis. Endocrinological examinations demonstrated ectopic ACTH production with hypercortisolemia and excess urinary cortisol accompanied by elevated plasma and urine catecholamines.

Successful Allogeneic Stem Cell Transplantation for Severe Aplastic Anemia after Treatment of Lymphoproliferative Disorder Caused by Rabbit Antithymocyte Globulin.

Immunosuppressive therapy (IST) with a combination of antithymocyte globulin (ATG) and cyclosporine (CsA) is an effective therapeutic modality for patients with aplastic anemia (AA) who are not eligible for allogeneic stem cell transplantation (Allo-SCT) from a human leukocyte antigen-identical sibling donor. However, there have been reports of some patients developing lymphoproliferative disorder (LPD) after IST for AA. We herein report a case of a 26-year-old man with severe AA (SAA) complicated by LPD after a single course of IST, who was successfully treated with Allo-SCT from an unrelated donor.

Urinary podocalyxin levels were associated with urinary albumin levels among patients with diabetes.

Diabetic nephropathy has dramatically increased worldwide. In this study, we measured urinary podocalyxin in 240 patients with diabetes. The relationship between urinary podocalyxin and clinical parameters and the effects of dipeptidyl peptidase-4 inhibitors (DPP4i) and alpha-glucosidase inhibitor (a-GI) on urinary podocalyxin levels were examined.

Unsuppressed lipolysis in adipocytes is linked with enhanced gluconeogenesis and altered bile acid physiology in Insr(P1195L/+) mice fed high-fat-diet.

High-fat diet (HFD) triggers insulin resistance and diabetes mellitus, but their link remains unclear. Characterization of overt hyperglycemia in insulin receptor mutant (Insr(P1195L/+)) mice exposed to HFD (Insr(P1195L/+)/HFD mice) revealed increased glucose-6-phosphatase (G6pc) expression in liver and increased gluconeogenesis from glycerol. Lipolysis in white adipose tissues (WAT) and lipolysis-induced blood glucose rise were increased in Insr(P1195L/+)/HFD mice, while wild-type WAT transplantation ameliorated the hyperglycemia and the increased G6pc expression.

Obesity Drives Th17 Cell Differentiation by Inducing the Lipid Metabolic Kinase, ACC1.

Chronic inflammation due to obesity contributes to the development of metabolic diseases, autoimmune diseases, and cancer. Reciprocal interactions between metabolic systems and immune cells have pivotal roles in the pathogenesis of obesity-associated diseases, although the mechanisms regulating obesity-associated inflammatory diseases are still unclear. In the present study, we performed transcriptional profiling of memory phenotype CD4 T cells in high-fat-fed mice and identified acetyl-CoA carboxylase 1 (ACC1, the gene product of Acaca) as an essential regulator of Th17 cell differentiation in vitro and of the pathogenicity of Th17 cells in vivo.

GERMLINE DELETION OF ARMC5 IN FAMILIAL PRIMARY MACRONODULAR ADRENAL HYPERPLASIA.

Objective: Primary macronodular adrenal hyperplasia (PMAH) is considered a predominantly sporadic disease, but familial forms are well recognized. Genetic studies revealed germline mutations in the armadillo repeat containing 5 gene (ARMC5) in the majority of PMAH cases. Furthermore, somatic ARMC5 mutations, as different types of second-hit mutations and loss of heterozygosity have been reported in each adrenal nodule in PMAH.

Mechanical overloading causes mitochondrial superoxide and SOD2 imbalance in chondrocytes resulting in cartilage degeneration.

Mechanical stress and aging are major risk factors of cartilage degeneration. Human studies have previously reported that oxidative damage increased, while SOD2 protein was reciprocally downregulated in osteoarthritic degenerated cartilage. However, it remains unclear whether mitochondrial superoxide imbalance in chondrocytes causes cartilage degeneration.