The CRK14 gene encoding a cysteine-rich receptor-like kinase is implicated in the regulation of global proliferative arrest in Arabidopsis thaliana.

Global proliferative arrest (GPA) is a phenomenon in monocarpic plants in which the activity of all aboveground meristems generally ceases in a nearly coordinated manner after the formation of a certain number of fruits. Despite the fact that GPA is a biologically and agriculturally important event, the underlying molecular mechanisms are not well understood. In this study, we attempted to elucidate the molecular mechanism of GPA regulation by identifying the gene responsible for the Arabidopsis mutant fireworks (fiw), causing an early GPA phenotype.

Lit-LAMP-DNA-vaccine for shrimp allergy prevents anaphylactic symptoms in a murine model.

Allergen-specific immunotherapy (AIT) is a promising therapeutic approach to food allergy but requires optimization in terms of both efficacy and safety due to the risk of undesired anaphylactic reactions. Here, we investigated the potential of a single DNA plasmid vaccine (Lit-LAMP-DNA-vaccine) encoding multivalent shrimp antigens (Lit v (Litopenaeus vannamei; Whiteleg shrimp) 1, Lit v4, and Lit v3) and a lysosomal-associated membrane protein (LAMP) as the next generation of AIT for patients with allergy. We first confirmed the expression of the LAMP-1-Lit v1-Lit v4-Lit v3 fusion protein in human cells transfected with the Lit-LAMP-DNA-vaccine, and the induction of anti-Lit v1, Lit v3, and Lit v4 IgG2a antibody production as well as Th1 response in Lit-LAMP-DNA-vaccine-treated mice.

PGE-EP2/EP4 signaling elicits immunosuppression by driving the mregDC-Treg axis in inflammatory tumor microenvironment.

Active inflammation generally promotes immune activation. However, in the tumor microenvironment (TME), active inflammation occurs in parallel with immunosuppression, and both contribute to tumor growth. Why inflammation does not lead to immune activation in TME remains unclear.

Peficitinib improves bone fragility by recovering bone turnover imbalance in arthritic mice.

Peficitinib, a pan-JAK inhibitor, is known to suppress the activation of fibroblast-like synoviocytes (FLSs) and thereby reduces joint inflammation associated with rheumatoid arthritis (RA). However, the effect on osteoporosis in RA remains to be elucidated. In this study, the effect of peficitinib or etanercept on joint inflammation, and consequently decreased bone mineral density (BMD) was evaluated in mice with collagen-induced arthritis (CIA).

Characterization of ASP8374, a fully-human, antagonistic anti-TIGIT monoclonal antibody.

The T-cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT) is a validated immune checkpoint protein expressed on memory CD4T-cellls, Tregs, CD8T-cell and natural killer (NK) cells. ASP8374 is a fully human monoclonal immunoglobulin (Ig) G4 antibody designed to block the interaction of TIGIT with its ligands and inhibit TIGIT signaling. ASP8374 exhibited high affinity binding to TIGIT and increased interferon (IFN)-γ production of cultured peripheral blood mononuclear cells (PBMCs) in a titratable manner.

Role of JAK-STAT signaling in the pathogenic behavior of fibroblast-like synoviocytes in rheumatoid arthritis: Effect of the novel JAK inhibitor peficitinib.

Rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLS) play a crucial role in the pathogenesis of RA. RA-FLS display passive pro-inflammatory responses and self-directed aggressive responses, such as pro-inflammatory mediator production, reduced apoptosis and formation of a thickened synovial lining. Evidence suggests a role for Janus kinase (JAK)-signal transducer and transcriptional activator (STAT) signaling in the passive response but the aggressive behavior of RA-FLS is poorly understood.

Integrin, alpha9 subunit blockade suppresses collagen-induced arthritis with minimal systemic immunomodulation.

Integrin, alpha9 subunit (hereinafter, alpha9) has been identified as a novel putative therapeutic target for rheumatoid arthritis (RA). Support for this target comes from the observations that alpha9 is overexpressed both in the joints of RA patients and in animal models of arthritis. In the experimental models, the increase in alpha9 expression precedes the onset of arthritic symptoms.

Constitutive Activation of Integrin α9 Augments Self-Directed Hyperplastic and Proinflammatory Properties of Fibroblast-like Synoviocytes of Rheumatoid Arthritis.

Despite advances in the treatment of rheumatoid arthritis (RA), currently approved medications can have significant side effects due to their direct immunosuppressive activities. Additionally, current therapies do not address residual synovial inflammation. In this study, we evaluated the role of integrin α9 and its ligand, tenascin-C (Tn-C), on the proliferative and inflammatory response of fibroblast-like synoviocytes (FLSs) from RA patients grown in three-dimensional (3D)-micromass culture.

Amelioration of collagen-induced arthritis in mice by a novel phosphodiesterase 7 and 4 dual inhibitor, YM-393059.

YM-393059 is a novel phosphodiesterase (PDE) 7 and PDE4 dual inhibitor that inhibits PDE7A with high potency (IC50=14 nM) and PDE4 with moderate potency (IC50=630 nM). It inhibits lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha production in mice with an ED50 value of 2.1 mg/kg [Yamamoto, S.

Pharmacological profile of a novel phosphodiesterase 7A and -4 dual inhibitor, YM-393059, on acute and chronic inflammation models.

YM-393059 is a novel phosphodiesterase (PDE) 7A and PDE4 dual inhibitor that inhibits both Th1 [interleukin (IL)-2 and interferon-gamma] and Th2 (IL-4) cytokines in vitro [Yamamoto, S., Sugahara, S., Naito, R.

The effects of a novel phosphodiesterase 7A and -4 dual inhibitor, YM-393059, on T-cell-related cytokine production in vitro and in vivo.

YM-393059, (+/-)-N-(4,6-dimethylpyrimidin-2-yl)-4-[2-(4-methoxy-3-methylphenyl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-1H-indol-1-yl]benzenesulfonamide difumarate, is a novel phosphodiesterase (PDE) inhibitor that inhibited the PDE7A isoenzyme with a high potency (IC50=14 nM) and PDE4 with a moderate potency (IC50=630 nM). In a cell-based assay, YM-393059 was found to inhibit anti-CD3 antibody, Staphylococcal enterotoxin B, and phytohaemagglutinin-induced interleukin (IL)-2 production in mouse splenocytes with IC50 values ranging from 0.48 to 1.

Kinins are involved in the development of allergic nasal hyperresponsiveness in guinea pigs.

We evaluated roles of kinins in allergen-induced nasal blockage and sneezing, and development of nasal hyperresponsiveness to leukotriene D4 in a Japanese cedar pollen-induced allergic rhinitis model of guinea pigs. Sensitised guinea pigs were repeatedly challenged by pollen inhalation once every week. Neither a bradykinin B1 receptor antagonist, des-Arg9-[Leu8]bradykinin nor a bradykinin B2 receptor antagonist, icatibant suppressed allergen-induced sneezing and nasal blockage.