Importance of PLD2 in an IL-23 driven psoriasiform dermatitis model and potential link to human psoriasis.

Phospholipase D2 (PLD2), a major isoform of the PLD family, has been reported to regulate inflammatory responses. Thus far, the relevance of PLD2 in psoriasis, an inflammatory skin disease, has not been explored. In the current study, we examined PLD2 expression in the skin of psoriasis patients and the role of PLD2 in an interleukin (IL)-23-induced mouse model of psoriasiform dermatitis.

A non-clinical comparative study of IL-23 antibodies in psoriasis.

Four antibodies that inhibit interleukin (IL)-23 are approved for the treatment of moderate-to-severe plaque psoriasis. Here, we present non-clinical data comparing ustekinumab, guselkumab, tildrakizumab and risankizumab with regard to thermostability, IL-23 binding affinity, inhibitory-binding mode, potency and efficacy. Risankizumab and guselkumab exhibited 5-fold higher affinity for IL-23 and showed more potent inhibition of IL-23 signaling than ustekinumab and tildrakizumab.

ACT1 Is Required for Murine IL-23-Induced Psoriasiform Inflammation Potentially Independent of E3 Ligase Activity.

Psoriasis is a debilitating skin disease characterized by epidermal thickening, abnormal keratinocyte differentiation, and proinflammatory immune cell infiltrate into the affected skin. IL-17A plays a critical role in the etiology of psoriasis. ACT1, an intracellular adaptor protein and a putative ubiquitin E3 ligase, is essential for signal transduction downstream of the IL-17A receptor.

CD40/anti-CD40 antibody complexes which illustrate agonist and antagonist structural switches.

Background: CD40 is a 48 kDa type I transmembrane protein that is constitutively expressed on hematopoietic cells such as dendritic cells, macrophages, and B cells. Engagement of CD40 by CD40L expressed on T cells results in the production of proinflammatory cytokines, induces T helper cell function, and promotes macrophage activation. The involvement of CD40 in chronic immune activation has resulted in CD40 being proposed as a therapeutic target for a range of chronic inflammatory diseases.

Hit-to-lead evaluation of a novel class of sphingosine 1-phosphate lyase inhibitors.

Inhibition of sphingosine-1-phosphate lyase has recently been proposed as a potential treatment option for inflammatory disorders such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. In this report we describe our hit-to-lead evaluation of the isoxazolecarboxamide 6, a high-throughput screening hit (in vitro IC50=1.0 μM, cell IC50=1.

2,4-Diaminopyrimidine MK2 inhibitors. Part II: Structure-based inhibitor optimization.

We describe structure-based optimization of a series of novel 2,4-diaminopyrimidine MK2 inhibitors. Co-crystal structures (see accompanying Letter) demonstrated a unique inhibitor binding mode. Resulting inhibitors had IC(50) values as low as 19nM and moderate selectivity against a kinase panel.

Upright static pelvic posture as rotations and translations in 3-dimensional from three 2-dimensional digital images: validation of a computerized analysis.

Purpose: The aim of this study was to determine the accuracy in measuring the pelvic orientations of a phantom model using the PosturePrint method.

Methods: In the Université du Québec à Trois-Rivières biomechanics laboratory, Trois-Rivières, Quebec, Canada, a mannequin was fixed on a rotating platform. For a set of 3 photographs (left lateral, anterior to posterior, right lateral) of each position, the mannequin pelvis was placed in 68 different postures on a stand, 61 cm from a wall, in front of a digital camera.

Three dimensional evaluation of posture in standing with the PosturePrint: an intra- and inter-examiner reliability study.

Background: Few digitizers can measure the complexity of upright human postural displacements in six degrees of freedom of the head, rib cage, and pelvis.

Methods: In a University laboratory, three examiners performed delayed repeated postural measurements on forty subjects over two days. Three digital photographs (left lateral, AP, right lateral) of each of 40 volunteer participants were obtained, twice, by three examiners.

Validity of a computer postural analysis to estimate 3-dimensional rotations and translations of the head from three 2-dimensional digital images.

Objective: The purpose of this study is to describe and evaluate the validity/accuracy of the computerized system PosturePrint for measuring head posture.

Methods: Computer analysis was compared with 125 measured positions of a mannequin head in 5 degrees of freedom. For each mannequin position, 3 digital photographs were obtained (left lateral, anteroposterior, and right lateral) and were processed through the PosturePrint computer system.

Validation of a computer analysis to determine 3-D rotations and translations of the rib cage in upright posture from three 2-D digital images.

Since thoracic cage posture affects lumbar spine coupling and loads on the spinal tissues and extremities, a scientific analysis of upright posture is needed. Common posture analyzers measure human posture as displacements from a plumb line, while the PosturePrint claims to measure head, rib cage, and pelvic postures as rotations and translations. In this study, it was decided to evaluate the validity of the PosturePrint Internet computer system's analysis of thoracic cage postures.