Macrophage polarization toward M1 phenotype in T cell transfer colitis model.

Background: T cell transfer colitis model is often used to study the CD4 T cell functions in the intestine. However, the specific roles of macrophages in colitis remain unclear. In this study, we aimed to evaluate the phenotype and functions of macrophages in the colonic lamina propria (LP) in a colitis model.

Application of Piezoelectric PLLA Braided Cord as Wearable Sensor to Realize Monitoring System for Indoor Dogs with Less Physical or Mental Stress.

We attempted to realize a prototype system that monitors the living condition of indoor dogs without physical or mental burden by using a piezoelectric poly--lactic acid (PLLA) braided cord as a wearable sensor. First, to achieve flexibility and durability of the piezoelectric PLLA braided cord used as a sensor for indoor dogs, the process of manufacturing the piezoelectric PLLA fiber for the piezoelectric braided cord was studied in detail and improved to achieve the required performance. Piezoelectric PLLA braided cords were fabricated from the developed PLLA fibers, and the finite element method was used to realize an e-textile that can effectively function as a monitoring sensor.

Pituitary adenylate cyclase-activating polypeptide promotes cutaneous dendritic cell functions in contact hypersensitivity.

Background: Sensory nerves regulate cutaneous local inflammation indirectly through induction of pruritus and directly by acting on local immune cells. The underlying mechanisms for how sensory nerves influence cutaneous acquired immune responses remain to be clarified.

Objective: This study aimed to explore the effect of peripheral nerves on cutaneous immune cells in cutaneous acquired immune responses.

A novel JAK inhibitor JTE-052 reduces skin inflammation and ameliorates chronic dermatitis in rodent models: Comparison with conventional therapeutic agents.

Janus kinases (JAKs) are required for several inflammatory cytokine signalling pathways and are implicated in the pathogenesis of chronic dermatitis, including atopic dermatitis and psoriasis. JAK inhibitors are therefore promising therapeutic candidates for chronic dermatitis. In this study, we evaluated the effects of the novel JAK inhibitor JTE-052 on inflammatory responses associated with chronic dermatitis, and compared its profile with those of conventional therapeutic agents in rodent models of chronic dermatitis.

JAK inhibitor JTE-052 regulates contact hypersensitivity by downmodulating T cell activation and differentiation.

Background: Using JAK inhibitors to inhibit cytokine signaling is presumed to be a possible means of treating skin inflammatory disorders such as contact dermatitis.

Objective: To clarify the action site of JAK inhibitors in skin inflammatory disorders.

Methods: We analyzed the mechanism of action of the JAK inhibitor JTE-052 using murine skin inflammation models, including contact hypersensitivity (CHS) and irritant contact dermatitis.

Improvement of spontaneous locomotor activity with JAK inhibition by JTE-052 in rat adjuvant-induced arthritis.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to joint destruction, disability, and decreased quality of life (QOL). Inhibition of Janus kinase (JAK) signaling ameliorates articular inflammation and joint destruction in animal models of RA, but its effects on behaviors indicating well-being are poorly understood. In this study, we evaluated the effect of JAK inhibition on spontaneous locomotor activity in rats with adjuvant-induced arthritis, a rodent model of RA.

Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses.

Resolvin E1 (RvE1) is a lipid mediator derived from ω3 polyunsaturated fatty acids that exerts potent antiinflammatory roles in several murine models. The antiinflammatory mechanism of RvE1 in acquired immune responses has been attributed to attenuation of cytokine production by dendritic cells (DCs). In this study, we newly investigated the effect of RvE1 on DC motility using two-photon microscopy in a contact hypersensitivity (CHS) model and found that RvE1 impaired DC motility in the skin.

The Janus kinase inhibitor JTE-052 improves skin barrier function through suppressing signal transducer and activator of transcription 3 signaling.

Background: Barrier disruption and the resulting continuous exposure to allergens are presumed to be responsible for the development of atopic dermatitis (AD). However, the mechanism through which skin barrier function is disrupted in patients with AD remains unclear.

Objectives: Taking into account the fact that the TH2 milieu impairs keratinocyte terminal differentiation, we sought to clarify our hypothesis that the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays a critical role in skin barrier function and can be a therapeutic target for AD.

Pharmacological properties of JTE-052: a novel potent JAK inhibitor that suppresses various inflammatory responses in vitro and in vivo.

Objective: To evaluate the pharmacological properties of JTE-052, a novel Janus kinase (JAK) inhibitor.

Methods: The JAK inhibitory activity of JTE-052 was evaluated using recombinant human enzymes. The inhibitory effects on cytokine signaling pathways were evaluated using primary human inflammatory cells.

IL-17A as an inducer for Th2 immune responses in murine atopic dermatitis models.

Atopic dermatitis (AD) is generally regarded as a type 2 helper T (Th2)-mediated inflammatory skin disease. Although the number of IL-17A-producing cells is increased in the peripheral blood and in acute skin lesion of AD patients, the role of IL-17A in the pathogenesis of AD remains unclear. To clarify this issue, we used murine AD models in an IL-17A-deficient condition.

An aggregate-prone mutant of human glyceraldehyde-3-phosphate dehydrogenase augments oxidative stress-induced cell death in SH-SY5Y cells.

Glycerladehyde-3-phosphate dehydrogenase (GAPDH), a classic glycolytic enzyme, also has a role in mediating cell death under oxidative stress. Our previous reports suggest that oxidative stress-induced GAPDH aggregate formation is, at least in part, a mechanism to account for the death signaling. Here we show that substitution of cysteine for serine-284 of human GAPDH (S284C-GAPDH) leads to aggregate-prone GAPDH, and that its expression in SH-SY5Y human neuroblastoma results in greater dopamine-induced cell death than expression of wild type-GAPDH.

Glyceraldehyde-3-phosphate dehydrogenase aggregate formation participates in oxidative stress-induced cell death.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)(2) is a classic glycolytic enzyme that also mediates cell death by its nuclear translocation under oxidative stress. Meanwhile, we previously presented that oxidative stress induced disulfide-bonded GAPDH aggregation in vitro. Here, we propose that GAPDH aggregate formation might participate in oxidative stress-induced cell death both in vitro and in vivo.

The active site cysteine of the proapoptotic protein glyceraldehyde-3-phosphate dehydrogenase is essential in oxidative stress-induced aggregation and cell death.

Recent studies have revealed that the redox-sensitive glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), is involved in neuronal cell death that is triggered by oxidative stress. GAPDH is locally deposited in disulfide-bonded aggregates at lesion sites in certain neurodegenerative diseases. In this study, we investigated the molecular mechanism that underlies oxidative stress-induced aggregation of GAPDH and the relationship between structural abnormalities in GAPDH and cell death.

[Coronary risk factor management in primary practice in Shibuya, Tokyo].

Objectives: Many large-scale clinical trials have confirmed that coronary risk factors such as hypertension, hyperlipidemia and diabetes mellitus predict a higher incidence of cardiovascular events and that control of these risk factors reduces the incidence. However, the actual management of such risk factors and the resultant improvement of the cardiovascular events in primary practice remains unclear. The Heart Care Network Shibuya, a voluntary study group of regional primary physicians, surveyed the management of coronary risk factors and the clinical outcomes.