2-Deoxy-D-Glucose Downregulates Fatty Acid Synthase Gene Expression Via an Endoplasmic Reticulum Stress-Dependent Pathway in HeLa Cells.

Fatty acid synthase (FASN) catalyzes the rate-limiting step of cellular lipogenesis. FASN expression is upregulated in various types of cancer cells, implying that FASN is a potential target for cancer therapy. 2-Deoxy-D-glucose (2-DG) specifically targets cancer cells by inhibiting glycolysis and glucose metabolism, resulting in multiple anticancer effects.

Differential regulation of Actn2 and Actn3 expression during unfolded protein response in C2C12 myotubes.

ACTN2 and ACTN3 encode sarcomeric α-actinin-2 and α-actinin-3 proteins, respectively, that constitute the Z-line in mammalian skeletal muscle fibers. In human ACTN3, a nonsense mutation at codon 577 that encodes arginine (R) produces the R577X polymorphism. Individuals having a homozygous 577XX genotype do not produce α-actinin-3 protein.

Readthrough of ACTN3 577X nonsense mutation produces full-length α-actinin-3 protein.

The ACTN3 gene encodes α-actinin-3 protein, which stabilizes the contractile apparatus at the Z-line in skeletal muscle cell fast fibers. A nonsense mutation of the arginine (R) at the codon for amino acid 577 of the ACTN3 gene generates a premature termination codon (PTC) and produces the R577X polymorphism in humans (X specifies translational termination). The ACTN3 577X genotype abolishes α-actinin-3 protein production due to targeted degradation of the mutant transcript by the cellular nonsense-mediated mRNA decay (NMD) system, which requires mRNA splicing.

Predictors for the Treatment Effect of Sodium Glucose Co-transporter 2 Inhibitors in Patients with Type 2 Diabetes Mellitus.

Introduction: Predictors for the effect of sodium glucose co-transporter 2 (SGLT2) inhibitors at lowering hemoglobin A1c (HbA1c) levels in type 2 diabetes mellitus patients remain unclear. We therefore aimed to elucidate these predictors in type 2 diabetes patients after 3 months of SGLT2 treatment.

Methods: A total of 302 consecutive type 2 diabetes patients who had been treated with SGLT2 inhibitors as monotherapy or add-on therapy to existing antidiabetic treatments were enrolled retrospectively.

Efficacy and safety of rivaroxaban in extreme elderly patients with atrial fibrillation: Analysis of the Shikoku Rivaroxaban Registry Trial (SRRT).

Background: The Shikoku Rivaroxaban Registry Trial (SRRT) is a retrospective survey of the use of rivaroxaban for stroke prevention in elderly patients in Shikoku, Japan.

Methods: The SRRT enrolled 1339 patients from 8 hospitals. Patients were divided into two groups according to their age, the extreme elderly group (453 patients aged ≧80 years) and the control group (886 patients aged <80 years).

Endoplasmic Reticulum Stress in Mice Increases Hepatic Expression of Genes Carrying a Premature Termination Codon via a Nutritional Status-Independent GRP78-Dependent Mechanism.

Nonsense-mediated mRNA decay (NMD) degrades mRNAs carrying a premature termination codon (PTC) in eukaryotes. Cellular stresses, including endoplasmic reticulum (ER) stress, inhibit NMD, and up-regulate PTC-containing mRNA (PTC-mRNA) levels in several cell lines. However, whether similar effects exist under in vivo conditions that involve systemic nutritional status is unclear.

A novel lipoprotein (a) lowering drug, D-47, decreases neointima thickening after vascular injury.

Although Lp(a) have been thought to be a cardiovascular risk factor, it is unclear whether lowering Lp(a) levels reduces the risk of cardiovascular diseases. No pharmacological agents which selectively reduce serum Lp(a) levels, and Lp(a) is present in primate but absent in common laboratory animals such as mice and pigs. In the present study we used transgenic mice of human Lp(a) and tested effect a novel Lp(a) lowering drug D-47 on neointima formation after vascular injury.

Intracerebroventricular injection of ghrelin decreases wheel running activity in rats.

There is an increasing interest in elucidating the molecular mechanisms by which voluntary exercise is regulated. In this study, we examined how the central nervous system regulates exercise. We used SPORTS rats, which were established in our laboratory as a highly voluntary murine exercise model.

DNA Methylation Suppresses Leptin Gene in 3T3-L1 Adipocytes.

Leptin is a key regulator of energy intake and expenditure. This peptide hormone is expressed in mouse white adipose tissue, but hardly expressed in 3T3-L1 adipocytes. Using bisulfite sequencing, we found that CpG islands in the leptin promoter are highly methylated in 3T3-L1cells.

Long-term dietary supplementation with saury oil attenuates metabolic abnormalities in mice fed a high-fat diet: combined beneficial effect of omega-3 fatty acids and long-chain monounsaturated fatty acids.

Background: Pacific saury is a common dietary component in East Asia. Saury oil contains considerable levels of n-3 unsaturated fatty acids (PUFA) and long-chain monounsaturated fatty acids (LCMUFA) with aliphatic tails longer than 18 carbons. In our previous study, consumption of saury oil for 4 to 6 wk improved insulin sensitivity and the plasma lipid profile in mice.

Intracerebroventricular injection of adiponectin regulates locomotor activity in rats.

Enhancing exercise motivation is the best way to prevent obesity and diabetes. In this study, we examined whether adiponectin affects locomotion activity in Wister and Spontaneously-Running Tokushima-Shikoku (SPORTS) rats using two types of behavioral assays: home cage and wheel running activity. SPORTS rats were established from an original line from Wister strain that had shown high level of wheel running activity in our laboratory.

Efficacy of percutaneous endoscopic gastrostomy on unplanned treatment interruption and nutritional status in patients undergoing chemoradiotherapy for advanced head and neck cancer.

Objective: Efficacy of percutaneous endoscopic gastrostomy (PEG) on unplanned treatment interruption and nutritional status was examined in patients undergoing chemoradiotherapy (CRT) for advanced head and neck cancer.

Methods: We retrospectively reviewed hospital charts of 44 patients with advanced head and neck cancer who were treated with CRT.

Results: CRT-induced mucositis of grade 3 or worse and inadequate oral intake of less than one third of their usual intake developed in 33 patients who were recommended PEG placement, but not in 11 patients.

C-terminal region of GADD34 regulates eIF2α dephosphorylation and cell proliferation in CHO-K1 cells.

GADD34 is a member of a growth arrest and DNA damage (GADD)-inducible gene family. Here, we established a novel Chinese hamster ovary (CHO)-K1-derived cell line, CHO-K1-G34M, which carries a nonsense mutation (termed the Q525X mutation) in the GADD34 gene. The Q525X mutant protein lacks the C-terminal 66 amino acids required for GADD34 to bind to and activate protein phosphatase 1 (PP1).

Correlations among obesity-associated gene polymorphisms, body composition, and physical activity in patients with type 2 diabetes mellitus.

Context: Various studies have focused on the correlation between β2-adrenergic receptor (β2AR), the β3-adrenergic receptor (β3AR), and the uncoupling protein 1 (UCP1) polymorphisms and obesity in patients with type 2 diabetes mellitus (T2DM).

Aims: We examined the correlation between these polymorphisms and body composition variables and between body composition and lifestyle variables in Japanese T2DM patients.

Materials And Methods: Of the 48, T2DM outpatients in Kanagawa prefecture recruited for participation, 32 (6 men and 26 women) met the study criteria and were enrolled.

Serum albumin levels correlate with inflammation rather than nutrition supply in burns patients: a retrospective study.

The aim of this retrospective study was to examine whether serum albumin levels offer a good marker of nutritional status in patients with burns. Serum albumin levels have been used to evaluate nutritional status in burns patients, even though these levels are affected by various factors and are not specific to malnutrition. To clarify whether provision of nutrition or presence of inflammation affects serum albumin levels, we studied serum albumin levels, C-reactive protein (CRP) levels and caloric intake over time in 30 patients with burns.

Swallowing rehabilitation with nutrition therapy improves clinical outcome in patients with dysphagia at an acute care hospital.

Dysphagia is associated with nutritional deficits and increased risk of aspiration pneumonia. The aim of the present study was to evaluate the impact of nutrition therapy for the patients with dysphagia at an acute care hospital. We also tried to clarify the factors which improve swallowing function in these patients.

A novel peptide of endothelin family, 31 amino-acid length endothelin in patients with acute myocardial infarction.

Human chymase converts big endothelin (ET)-1 to 31-amino acid length ET-1 {ET-1(1-31)} that also possesses a potent vasoconstrictive action. In addition, ET-1(1-31) is an intermediate peptide, which is then readily transformed to mature ET-1 by the neutral endopeptidase 24-11. To investigate the relevance of pathophysiology of ET-1(1-31) in vivo, we have developed specific sandwich-type, enzyme-linked immunosorbent assay to measure the plasma concentration of ET-1(1-31) in healthy volunteers and patients with myocardial infarction.

Propofol-induced relaxation of rat aorta is altered by aging.

Background: Propofol causes vasodilation via endothelium-dependent and -independent mechanisms. Because endothelial function is impaired with aging, the effects of propofol on endothelium-dependent vasodilation might be altered by aging. The aim of this study was thus to determine the effects of aging on vascular responses to propofol.

Enhancement of endothelial function inhibits left atrial thrombi development in an animal model of spontaneous left atrial thrombosis.

Background: Left atrial (LA) thrombosis is an important cause of systemic embolization. The SPORTS rat model of LA thrombi (Spontaneously-Running Tokushima-Shikoku), which have a unique characteristic of high voluntary wheel running, was previously established. The aim of the present study was to investigate how SPORTS rats develop LA thrombi.

Establishment of a model of spontaneously-running-Tokushima-shikoku rats with left atrial thrombosis.

Studies that investigate the underlying mechanisms of disease and treatment options typically require the use of a suitable animal model. Few suitable animal models exist for left atrial thrombosis. Here, we demonstrated that the Spontaneously-Running-Tokushima-Shikoku (SPORTS) rat - a Wistar strain known for its running ability-is predisposed to the development of thrombi in the left atrium.

Glutamine protects the small intestinal mucosa in anticancer drug-induced rat enteritis model.

Supportive therapy during chemotherapy has become essential, but effective preventive therapies to gastrointestinal mucosal injury are few. We investigated the efficacy of glutamine in rat anticancer drug-induced enteritis model. In this study, we used twenty male SD rats.

Albumin-normalized serum zinc: a clinically useful parameter for detecting taste impairment in patients undergoing dialysis.

Patients with renal failure often experience decreased serum zinc that remains uncorrected after dialysis. A complication of this depletion is taste impairment, which can detrimentally influence diet and nutrition. However, because more than half of all serum zinc is bound to albumin, we hypothesized that normalizing serum zinc to albumin levels may be associated with taste impairment.

Islet infiltration, cytokine expression and beta cell death in the NOD mouse, BB rat, Komeda rat, LEW.1AR1-iddm rat and humans with type 1 diabetes.

Aims/hypothesis: Research on the pathogenesis of type 1 diabetes relies heavily on good animal models. The aim of this work was to study the translational value of animal models of type 1 diabetes to the human situation.

Methods: We compared the four major animal models of spontaneous type 1 diabetes, namely the NOD mouse, BioBreeding (BB) rat, Komeda rat and LEW.