Vaccine Therapy for Heart Failure Targeting the Inflammatory Cytokine Igfbp7.

Background: The heart comprises many types of cells such as cardiomyocytes, endothelial cells (ECs), fibroblasts, smooth muscle cells, pericytes, and blood cells. Every cell type responds to various stressors (eg, hemodynamic overload and ischemia) and changes its properties and interrelationships among cells. To date, heart failure research has focused mainly on cardiomyocytes; however, other types of cells and their cell-to-cell interactions might also be important in the pathogenesis of heart failure.

Acidic extracellular pH drives accumulation of N1-acetylspermidine and recruitment of protumor neutrophils.

An acidic tumor microenvironment plays a critical role in tumor progression. However, understanding of metabolic reprogramming of tumors in response to acidic extracellular pH has remained elusive. Using comprehensive metabolomic analyses, we demonstrated that acidic extracellular pH (pH 6.

Hypoxia activates SREBP2 through Golgi disassembly in bone marrow-derived monocytes for enhanced tumor growth.

Bone marrow-derived cells (BMDCs) infiltrate hypoxic tumors at a pre-angiogenic state and differentiate into mature macrophages, thereby inducing pro-tumorigenic immunity. A critical factor regulating this differentiation is activation of SREBP2-a well-known transcription factor participating in tumorigenesis progression-through unknown cellular mechanisms. Here, we show that hypoxia-induced Golgi disassembly and Golgi-ER fusion in monocytic myeloid cells result in nuclear translocation and activation of SREBP2 in a SCAP-independent manner.

Glutamine deficiency in solid tumor cells confers resistance to ribosomal RNA synthesis inhibitors.

Ribosome biogenesis is an energetically expensive program that is dictated by nutrient availability. Here we report that nutrient deprivation severely impairs precursor ribosomal RNA (pre-rRNA) processing and leads to the accumulation of unprocessed rRNAs. Upon nutrient restoration, pre-rRNAs stored under starvation are processed into mature rRNAs that are utilized for ribosome biogenesis.

Distribution of Severe Fever with Thrombocytopenia Syndrome Virus and Antiviral Antibodies in Wild and Domestic Animals in Oita Prefecture, Japan.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging life-threatening infectious disease caused by the tickborne SFTS virus (SFTSV), first identified in China in 2009 and then in Japan in 2013. Human SFTS cases were reported to be concentrated in western Japan, but the epidemiological conditions of SFTSV infection in a specific region are still obscure. We performed an epidemiological study of SFTSV in Oita Prefecture on the island of Kyushu, located in western Japan.

Gold(I) Complexation of Phosphanoxy-Substituted Phosphaalkenes for Activation-Free LAuCl Catalysis.

The phosphanoxy-substituted phosphaalkene bearing the P=C-O-P skeleton can be prepared from diphosphene Mes*P=PMes* (Mes*=2,4,6-tBu C H ), and their use for catalysis is of interest. In this paper, complexation of the phosphanoxy-substituted phosphaalkenes with gold are investigated, and the catalytic activity of the mono- and bis(chlorogold) complexes are subsequently evaluated. Reaction of the P=C-O-P compound with (tht)AuCl (tht=tetrahydrothiophene) showed dominant coordination on the sp phosphorus, and complete coordination on the sp phosphorus required removal of tetrahydrothiophene.

Advances in Artificial Cell Membrane Systems as a Platform for Reconstituting Ion Channels.

An artificial cell membrane that is composed of bilayer lipid membranes (BLMs) with transmembrane proteins incorporated within them represents a well-defined system for the analysis of membrane proteins, especially ion channel proteins that are major targets for drug design. Because the BLM system has a high compatibility with recently developed cell-free expression systems, it has attracted attention as a next-generation drug screening system. However, three issues associated with BLM systems, i.

Influence of seasonal variations on physical activity in older people living in mountainous agricultural areas.

Increasing activity levels in older people is important for maintaining quality of life and ameliorating the risks of morbidity related to falls, depression, and dementia. This study aimed to clarify the seasonal variation effects on total energy expenditure, number of steps, time spent in low- and moderate- or high-intensity physical activities, and daily activities performed. This was a cross-sectional study of 22 community-dwelling older individuals (3 men, 19 women; mean age, 75.

Ligand-Less Iron-Catalyzed Aromatic Cross-Coupling Difluoromethylation of Grignard Reagents with Difluoroiodomethane.

Iron-catalyzed cross-coupling difluoromethylations of the Grignard reagents with difluoroiodomethane provide various aromatic difluoromethyl products in good yields, not employing sterically demanding ligands. Difluoromethylations proceed within 30 min at -20 °C with 2.0 equiv of the Grignard reagents and FeCl or Fe(acac) (2.

An optimized protocol for the analysis of house dust mite (Dermatophagoides farinae)-induced neutrophil-dominant airway inflammation.

House dust mites (HDMs), Dermatophagoides sp., are one of the most widespread aeroallergens worldwide and cause various allergic diseases, including asthma. The pathophysiology of asthma has been intensively investigated using murine models of allergic airway inflammation induced by exposure to D.

Separation of glycosphingolipids with titanium dioxide.

We introduce the principle of a new technique to isolate glycosphingolipids (GSLs) from phospholipids. Neutral and acidic GSLs in organic solvent bind to titanium dioxide under neutral pH and can be eluted with 5 mg/ml of 2,5-dihydroxybenzoic acid in methanol. This special property is applicable for eliminating phospholipids, including sphingomyelin, which cannot be eliminated by a typical mild alkaline treatment.

Amphiphobic Septa Enhance the Mechanical Stability of Free-Standing Bilayer Lipid Membranes.

Artificial bilayer lipid membranes (BLMs) provide well-defined systems for investigating the fundamental properties of membrane proteins, including ion channels, and for screening the effect of drugs that act on them. However, the application of this technique is limited due to the low stability and low reconstitution efficiency of the process. We previously reported on improving the stability of BLM based on the fabrication of microapertures having a tapered edge in SiO/SiN septa and efficient ion channel incorporation based on vesicle fusion accelerated by a centrifugal force.

[Evaluation of Dissolution Profiles of Famotidine from OTC Drugs].

　In recent years, self-medication has started to receive more attention in Japan owing to increasing medical costs and health awareness among people. One of the main roles of pharmacists in self-medication is to provide appropriate information regarding OTC drugs. However, pharmacists promoting the proper use of OTC drugs have little information on their formulation properties.

Mechanically stable solvent-free lipid bilayers in nano- and micro-tapered apertures for reconstitution of cell-free synthesized hERG channels.

The self-assembled bilayer lipid membrane (BLM) is the basic component of the cell membrane. The reconstitution of ion channel proteins in artificially formed BLMs represents a well-defined system for the functional analysis of ion channels and screening the effects of drugs that act on them. However, because BLMs are unstable, this limits the experimental throughput of BLM reconstitution systems.

Menin Controls the Memory Th2 Cell Function by Maintaining the Epigenetic Integrity of Th2 Cells.

Posttranslational modifications of histones are well-established epigenetic modifications that play an important role in gene expression and regulation. These modifications are partly mediated by the Trithorax group (TrxG) complex, which regulates the induction or maintenance of gene transcription. We investigated the role of Menin, a component of the TrxG complex, in the acquisition and maintenance of Th2 cell identity using T cell-specific Menin-deficient mice.

Importance of prevention in pneumonia in elderly -Attempted use of macrolide therapy.

Pneumonia ranks as the third leading cause of death in Japan. About 97% of patients who die because of pneumonia are elderly, with aspiration generally thought to be involved in the majority of cases of pneumonia in elderly. Once an elderly individual contracts pneumonia, their physical function often declines and their activities of daily living diminish with hospital admission, even in individuals with no underlying disorders.

Akt1-mediated Gata3 phosphorylation controls the repression of IFNγ in memory-type Th2 cells.

Th2 cells produce Th2 cytokines such as IL-4, IL-5 and IL-13, but repress Th1 cytokine IFNγ. Recent studies have revealed various distinct memory-type Th2 cell subsets, one of which produces a substantial amount of IFNγ in addition to Th2 cytokines, however it remains unclear precisely how these Th2 cells produce IFNγ. We herein show that phosphorylation of Gata3 at Ser308, Thr315 and Ser316 induces dissociation of a histone deacetylase Hdac2 from the Gata3/Chd4 repressive complex in Th2 cells.

Methylation of Gata3 protein at Arg-261 regulates transactivation of the Il5 gene in T helper 2 cells.

Gata3 acts as a master regulator for T helper 2 (Th2) cell differentiation by inducing chromatin remodeling of the Th2 cytokine loci, accelerating Th2 cell proliferation, and repressing Th1 cell differentiation. Gata3 also directly transactivates the interleukin-5 (Il5) gene via additional mechanisms that have not been fully elucidated. We herein identified a mechanism whereby the methylation of Gata3 at Arg-261 regulates the transcriptional activation of the Il5 gene in Th2 cells.

Gata3/Ruvbl2 complex regulates T helper 2 cell proliferation via repression of Cdkn2c expression.

GATA-binding protein 3 (Gata3) controls the differentiation of naive CD4 T cells into T helper 2 (Th2) cells by induction of chromatin remodeling of the Th2 cytokine gene loci, direct transactivation of Il5 and Il13 genes, and inhibition of Ifng. Gata3 also facilitates Th2 cell proliferation via additional mechanisms that are far less well understood. We herein found that Gata3 associates with RuvB-like protein 2 (Ruvbl2) and represses the expression of a CDK inhibitor, cyclin-dependent kinase inhibitor 2c (Cdkn2c) to facilitate the proliferation of Th2 cells.

Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity.

GATA binding protein 3 (Gata3) is a GATA family transcription factor that controls differentiation of naïve CD4 T cells into T helper 2 (Th2) cells. However, it is unknown how Gata3 simultaneously activates Th2-specific genes while repressing those of other Th lineages. Here we show that chromodomain helicase DNA-binding protein 4 (Chd4) forms a complex with Gata3 in Th2 cells that both activates Th2 cytokine transcription and represses the Th1 cytokine IFN-γ.

Recombinant human soluble thrombomodulin administration improves sepsis-induced disseminated intravascular coagulation and mortality: a retrospective cohort study.

Background: Early treatment of disseminated intravascular coagulation (DIC) can be associated with improved patient outcomes. The Japanese Ministry of Health and Welfare (JMHW) and the International Society on Thrombosis and Haemostasis (ISTH) criteria are the most specific for diagnosis of septic DIC. The revised Japanese Association for Acute Medicine (JAAM) criteria are able to diagnose sepsis-induced DIC in the early stage.

A fluorescent-based high-throughput screening assay for small molecules that inhibit the interaction of MdmX with p53.

A fluorescent-based high-throughput screening (HTS) assay for small molecules that inhibit the interaction of MdmX with p53 was developed and applied to identify new inhibitors. The assay evaluated the MdmX-p53 interaction by detecting the quenching of the fluorescence of green fluorescent protein (GFP) fused to the MdmX protein, after its interaction with a p53 peptide labeled with a fluorescence quencher. In this report, the developed HTS assay was applied to about 40 000 compounds, and 255 hit compounds that abrogated the GFP quenching were selected.

Comparison of the effects of cilnidipine and amlodipine on cardiac remodeling and diastolic dysfunction in Dahl salt-sensitive rats.

Objective: The L/N-type calcium channel blocker (CCB) cilnidipine suppresses sympathetic nerve activity and has a superior renoprotective effect compared with L-type CCBs such as amlodipine. The cardioprotective action of cilnidipine has remained largely uncharacterized, however. We have now investigated the effects of cilnidipine, in comparison with amlodipine, on cardiac pathophysiology in rats with salt-sensitive hypertension.