AMPK activation by prolonged stimulation with interleukin-1β contributes to the promotion of GLUT4 translocation in skeletal muscle cells.

Impaired insulin signaling in skeletal muscle cells causes insulin resistance associated with the onset of type 2 diabetes. Although interleukin (IL)-1β has been considered to be implicated in the pathogenesis of type 2 diabetes, the action of prolonged stimulation with IL-1β on the insulin signaling pathway in skeletal muscle cells remains poorly understood. In the current study, we investigated the effect of IL-1β stimulation on insulin signal transduction from the insulin receptor (IR), resulting in glucose transporter 4 (GLUT4) translocation in skeletal muscle cells.

Inhibitory Effects of Eight Green Tea Catechins on Cytochrome P450 1A2, 2C9, 2D6, and 3A4 Activities.

Purpose: Green tea is a traditional beverage that has been enjoyed by the Japanese to this day. Recently, there has been an increase in the consumption of green tea beverage having high concentrations of catechins, such as (-)-epigallocatechin-3-O-gallate (EGCG). Many people tend to ingest large amounts of catechins through the frequent consumption of green tea beverage, and this dietary habit may lead to unwanted interactions between the catechins in green tea and medicinal drug.

Active hexose correlated compound modulates LPS-induced hypotension and gut injury in rats.

We hypothesized that AHCC; (Amino UP Chemical Co., Ltd., Sapporo, Japan), a mushroom mycelium extract obtained from liquid culture of Lentinula edodes, restores immune function in LPS-induced inflammation in the gut, especially when the nitric oxide signaling pathway is impaired.

Epalrestat Upregulates Heme Oxygenase-1, Superoxide Dismutase, and Catalase in Cells of the Nervous System.

Heme oxygenase (HO)-1 has potent antioxidant and anti-inflammatory functions. Recent studies have shown that the upregulation of HO-1 is beneficial to counteract neuroinflammation, making HO-1 a new therapeutic target for neurological diseases. We have reported that epalrestat (EPS), which is currently used for the treatment of diabetic neuropathy, increases HO-1 levels through the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) in bovine aortic endothelial cells.

Immunopotentiator from Pantoea agglomerans 1 (IP-PA1) Promotes Murine Hair Growth and Human Dermal Papilla Cell Gene Expression.

Background/aim: The lipopolysaccharide (LPS)-like compound derived from Pantoea agglomerans (immunopotentiator from Pantoea agglomerans 1 (IP-PA1)) has been used not only as dietary supplement or cosmetic for humans, but also by Japanese veterinarians as an anti-tumor, anti-allergy, "keep a fine coat of fur" and hair growth-promoting functional food for dogs and cats. In the present study, we focused on the hair growth-promoting effects of IP-PA1 on a hair-shaved animal model and its mechanism of action. We also investigated its potential on gene expression after stimulating human dermal papilla cells with IP-PA1.

Sustained distribution of aerosolized PEGylated liposomes in epithelial lining fluids on alveolar surfaces.

The distribution characteristics of aerosolized PEGylated liposomes in alveolar epithelial lining fluid (ELF) were examined in rats, and the ensuing mechanisms were investigated in the in vitro uptake and protein adsorption experiments. Nonmodified or PEGylated liposomes (particle size 100 nm) were aerosolized into rat lungs. PEGylated liposomes were distributed more sustainably in ELFs than nonmodified liposomes.

Perilla leaf extract prevents atopic dermatitis induced by an extract of Dermatophagoides farinae in NC/Nga mice.

Background: Perilla (Perilla frutescens Britton) leaf comprises many types of active components, mainly flavonoids, and acts as an anti-inflammatory agent in in vitro and in vivo atopic dermatitis (AD) models.

Objective: We investigated the effects of orally administered perilla leaf extract (PLE) on the symptoms of AD induced by Dermatophagoides farinae extract (DFE) in NC/Nga AD model mice.

Methods: The mice were allowed free intake of 0.

Influence of the polymorphism of the DUSP14 gene on the expression of immune-related genes and development of pulmonary tuberculosis.

Recently, a genome-wide screening identified a functional single-nucleotide polymorphism in dual-specificity phosphatase 14 gene (DUSP14), which was associated with pulmonary tuberculosis (TB) in a West African study. DUSP14 regulates T-cell proliferation and cytokine production in a negative way via dephosphorylation and inactivation of key signaling molecules. The aim of this study is to further explore the possible significance of the DUSP14 polymorphism.

Involvement of Monocarboxylate Transporter 4 Expression in Statin-Induced Cytotoxicity.

Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are the most widely used cholesterol-lowering agents for prevention of obstructive cardiovascular events. However, statins can cause a variety of skeletal muscle problems, and exercise leads to an increase in statin-induced muscle injury. Exercise induces the protein content of monocarboxylate transporter 4 (MCT4), which is expressed strongly in skeletal muscle and is thought to play a major role in the transport of metabolically important monocarboxylates such as l-lactate.

[Introduction and Evaluation of an Integrated Program to Develop Pharmacotherapeutic Management Skills].

Pharmacists must be able to select and collect important information for patient care, to accurately assess and monitor the status of patients, to develop care plans, propose optimal formulations, and provide advice to patients about pharmacotherapy. The core curriculum of Japan's pharmacy education model was revised in 2013 based on the "Basic competencies required of a pharmacist" that should be developed by the time of a student's graduation. Specific behavioral objectives to be acquired include competency in "The ability to implement pharmacotherapeutic management", which involves gaining the ability to understand patient information, to design and propose prescriptions, and to conduct pharmacotherapeutic assessments.

Alteration in Intrapulmonary Pharmacokinetics of Aerosolized Model Compounds Due to Disruption of the Alveolar Epithelial Barriers Following Bleomycin-Induced Pulmonary Fibrosis in Rats.

Idiopathic pulmonary fibrosis is a lethal lung disease that is characterized by the accumulation of extracellular matrix and a change in lung structure. In this study, intrapulmonary pharmacokinetics of aerosolized model compounds were evaluated using rats with bleomycin-induced pulmonary fibrosis. Aerosol formulations of indocyanine green, 6-carboxyfluorescein (6-CF), and fluorescein isothiocyanate dextrans (FD; 4.

Effects of Angiotensin II Receptor Blockers on Metabolism of Arachidonic Acid via CYP2C8.

Arachidonic acid (AA) is metabolized to epoxyeicosatrienoic acids (EETs) via cytochrome enzymes such as CYP 2C9, 2C8 and 2J2. EETs play a role in cardioprotection and regulation of blood pressure. Recently, adverse reactions such as sudden heart attack and fatal myocardial infarction were reported among patients taking angiotensin II receptor blockers (ARBs).

Glycolaldehyde induces endoplasmic reticulum stress and apoptosis in Schwann cells.

Schwann cell injury is caused by diabetic neuropathy. The apoptosis of Schwann cells plays a pivotal role in diabetic nerve dysfunction. Glycolaldehyde is a precursor of advanced glycation end products that contribute to the pathogenesis of diabetic neuropathy.

The Role of CYP2C8 and CYP2C9 Genotypes in Losartan-Dependent Inhibition of Paclitaxel Metabolism in Human Liver Microsomes.

The aim of the present study was to further investigate a previously identified metabolic interaction between losartan and paclitaxel, which is one of the marker substrates of CYP2C8, by using human liver microsomes (HLMs) from donors with different CYP2C8 and CYP2C9 genotypes. Although CYP2C8 and CYP2C9 exhibit genetic linkage, previous studies have yet to determine whether losartan or its active metabolite, EXP-3174 which is specifically generated by CYP2C9, is responsible for CYP2C8 inhibition. Concentrations of 6α-hydroxypaclitaxel and EXP-3174 were measured by high-performance liquid chromatography after incubations with paclitaxel, losartan or EXP-3174 in HLMs from seven donors with different CYP2C8 and CYP2C9 genotypes.

Cilostazol inhibits interleukin-1-induced ADAM17 expression through cAMP independent signaling in vascular smooth muscle cells.

Increased A disintegrin and metalloprotease 17 (ADAM17) expression in vascular smooth muscle cells (VSMC) is implicated in the development of cardiovascular diseases including atherosclerosis and hypertension. Although cilostazol, type III phosphodiesterase (PDE III) inhibitor, has recently been found to inhibit VSMC proliferation, the mechanisms remain largely unclear. Here, we hypothesized that cilostazol regulates the ADAM17 expression in VSMC.

Simultaneous Determination Method of Epoxyeicosatrienoic Acids and Dihydroxyeicosatrienoic Acids by LC-MS/MS System.

Epoxyeicosatrienoic acids (EETs) are produced primarily by CYPs from arachidonic acid (AA) and then further metabolized to the corresponding dihydroxyeicosatrienoic acids (DHETs). EETs play important roles in physiological processes such as regulating vasodilation and inflammation. Thus, the drug inhibition of CYP-mediated AA metabolism could reduce production of EETs, potentially resulting in adverse cardiovascular events.

EFFECT OF SEASONAL CHANGES ON TESTICULAR MORPHOLOGY AND THE EXPRESSION OF CIRCADIAN CLOCK GENES IN JAPANESE WOOD MICE (APODEMUS SPECIOSUS).

This study aimed to determine the seasonality of reproduction throughout the year in Japanese wood mice (Apodemus speciosus). The effect of seasonal changes on testicular morphology and the periodic expression of circadian clock genes in the hypothalamus and testes of male individuals was evaluated. We also examined the morphology of the testes and caudae epididymides of male mice.

TACR1 gene polymorphism and sex differences in postoperative nausea and vomiting.

We hypothesised that the genetic effect of single nucleotide polymorphisms in the TACR1 gene, which encodes NK1 receptors, could influence the sex difference in postoperative nausea and vomiting. Thirty-two selected single nucleotide polymorphisms were genotyped by the Sanger sequencing method in 200 patients who underwent lower abdominal surgery. The incidence and severity of postoperative nausea and vomiting were evaluated after surgery.

DDX60 Is Involved in RIG-I-Dependent and Independent Antiviral Responses, and Its Function Is Attenuated by Virus-Induced EGFR Activation.

RIG-I-mediated type I interferon (IFN) production and nuclease-mediated viral RNA degradation are essential for antiviral innate immune responses. DDX60 is an IFN-inducible cytoplasmic helicase. Here, we report that DDX60 is a sentinel for both RIG-I activation and viral RNA degradation.

The peroxidase activity of ADM-Fe(3+) cooperates with lipid peroxidation: The participation of hydroperoxide and hydroxyl radicals in the damage to proteins and DNA.

To investigate the mechanisms of cardiotoxicity induced by adriamycin (ADM), the enzymatic activities of ADM-Fe(3+), including the peroxidase and lipoxygenase (LOX) activity, and participation of active oxygen species in the damage to biological components were examined. ADM-Fe(3+), but not ADM, steadily oxidized tetramethyl-p-phenylenediamine in the presence of peroxides, indicating that ADM-Fe(3+) acts as a peroxidase. However, the activity of ADM-Fe(3+) as peroxidase was very low compared with that of heme peroxidase, but was similar to that of LOX, which has a known peroxidase activity.

Effect of alteration of caveolin-1 expression on doxorubicin-induced apoptosis in H9c2 cardiac cells.

Doxorubicin is an anthracycline antibiotic widely used in cancer treatment. Although its antitumor efficacy appears to be dose dependent, its clinical use is greatly restricted by the development of cardiotoxicity associated with apoptosis. Although caveolin-1, the major structural protein in caveolae, can positively or negatively regulate apoptosis depending on the stimulus or cell types, the contribution of caveolin-1 to doxorubicin-induced apoptosis remains unknown.

MMP-9/ANC score as a predictive biomarker for efficacy of bevacizumab plus platinum doublet chemotherapy in patients with advanced or recurrent non-squamous non-small cell lung cancer.

Background: Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), which is a key regulator of tumor angiogenesis.

Objective: To evaluate biomarkers to predict the benefit of paclitaxel and carboplatin plus bevacizumab (PCB) therapy in patients with advanced or recurrent non-squamous non-small cell lung cancer.

Methods: Among 21 patients treated with PCB, 10 were included in the good responder group and 11 in the non-responder group.

Administration of olanzapine as an antiemetic agent changes glucose homeostasis in cisplatin-treated rats.

We investigated the effects of olanzapine on cisplatin-induced pica (the consumption of non-nutrient materials such as kaolin) and glucose homeostasis in rats to clarify the effects of olanzapine when used as an anti-emetic drug. Rats were injected intraperitoneally (i.p.

Efficient delivery to human lung fibroblasts (WI-38) of pirfenidone incorporated into liposomes modified with truncated basic fibroblast growth factor and its inhibitory effect on collagen synthesis in idiopathic pulmonary fibrosis.

In the present in vitro study, we assessed the delivery of pirfenidone incorporated into liposomes modified with truncated basic fibroblast growth factor (tbFGF) to lung fibroblasts and investigated the anti-fibrotic effect of the drug. The tbFGF peptide, KRTGQYKLC, was used to modify the surface of liposomes (tbFGF-liposomes). We used the thin-layer evaporation method, followed by sonication, to prepare tbFGF-liposomes containing pirfenidone.

Epalrestat increases glutathione, thioredoxin, and heme oxygenase-1 by stimulating Nrf2 pathway in endothelial cells.

Epalrestat (EPS) is the only aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Recently, we found that EPS at near-plasma concentration increases the intracellular levels of glutathione (GSH) in rat Schwann cells. GSH plays a crucial role in protecting endothelial cells from oxidative stress, thereby preventing vascular diseases.