Serum and salivary inflammatory biomarkers in juvenile idiopathic arthritis-an explorative cross-sectional study.

Background: Biomarkers may be useful in monitoring disease activity in juvenile idiopathic arthritis (JIA). With new treatment options and treatment goals in JIA, there is an urgent need for more sensitive and responsive biomarkers.

Objective: We aimed to investigate the patterns of 92 inflammation-related biomarkers in serum and saliva in a group of Norwegian children and adolescents with JIA and controls and in active and inactive JIA.

Oral health problems are associated with malnutrition in hospitalised adult patients.

Background & Aims: Hospitalised patients are especially vulnerable to malnutrition, which is associated with an increased risk of complications, leading to longer hospital stays, increased healthcare costs, and with a potentially negative effect on the prognosis. Poor oral health may make food intake difficult and contribute to poor nutritional status. The aim of the present cross-sectional study was to assess the occurrence of poor oral health and malnutrition in adult hospitalised patients, and further to investigate associations between oral health problems and malnutrition.

The Copenhagen Actinic Keratosis Study (COAKS). A decentralised clinical trial to evaluate tolerability, safety and efficacy of daily field-directed topical treatment with cytosolic phospholipase A inhibitor, AVX001, in participants with actinic keratosis: protocol for a randomised controlled phase I/IIa trial.

Introduction: Actinic keratosis (AK) is the most common precancerous skin condition caused by long-term UV exposure. Given the high recurrence rate of 15%-53%, identifying safe and effective treatment options is warranted. AVX001, a cytosolic phospholipase Aα (cPLAα) enzyme inhibitor, is a novel anti-inflammatory drug for field-directed, self-administered, topical therapy of AK.

A study of socio-economic inequalities in self-reported oral and general health in South-East Norway.

This study assesses the association between socioeconomic determinants and self-reported health using data from a regional Norwegian health survey. We included 9,068 participants ≥ 25 years. Survey data were linked to registry data on education and income.

Vitamin D, oral health, and disease characteristics in juvenile idiopathic arthritis: a multicenter cross-sectional study.

Background: Vitamin D deficiency has been associated with autoimmune diseases and oral health. Knowledge about the association between vitamin D status and oral conditions in JIA is limited. We aimed to investigate vitamin D status in a cohort of Norwegian children and adolescents with JIA and possible associations between serum vitamin D levels, clinical indicators of oral health, and JIA disease characteristics.

Inhibition of Cytosolic Phospholipase A2α Induces Apoptosis in Multiple Myeloma Cells.

Cytosolic phospholipase A2α (cPLA2α) is the rate-limiting enzyme in releasing arachidonic acid and biosynthesis of its derivative eicosanoids. Thus, the catalytic activity of cPLA2α plays an important role in cellular metabolism in healthy as well as cancer cells. There is mounting evidence suggesting that cPLA2α is an interesting target for cancer treatment; however, it is unclear which cancers are most relevant for further investigation.

Systematic assessment of salivary inflammatory markers and dental caries in children: an exploratory study.

Objective: To investigate associations between a wide panel of salivary inflammatory markers and the presence of dental caries among children.

Material And Methods: In this exploratory, cross-sectional study, 176 children, aged 7-9, underwent a dental examination. Information on the children's oral health habits and lifestyles was collected from their mothers.

Oral health in children and adolescents with juvenile idiopathic arthritis - a systematic review and meta-analysis.

Background: Observational studies examining the association between oral health and juvenile idiopathic arthritis (JIA) among children and adolescents have reported inconsistent findings. The aims of this systematic review and meta-analysis were to ascertain a potential difference in oral health and oral health-related quality of life (OHRQoL) among children and adolescents with JIA and healthy peers, and to assess the association of prevalence of oral diseases/conditions, temporomandibular disorders (TMD), including temporomandibular joint (TMJ) diseases, in relation to activity and severity of JIA.

Method: Medline Ovid, Embase, CINAHL, SweMed+ and Cochrane Library were searched up to 25 November 2018.

Cytosolic Phospholipase A2 Alpha Regulates TLR Signaling and Migration in Metastatic 4T1 Cells.

Metastatic disease is the leading cause of death in breast cancer patients. Disrupting the cancer cell's ability to migrate may be a strategy for hindering metastasis. Cytosolic phospholipase A2 α (cPLA2α), along with downstream proinflammatory and promigratory metabolites, has been implicated in several aspects of tumorigenesis, as well as metastasis, in various types of cancer.

Anti-vascular effects of the cytosolic phospholipase A2 inhibitor AVX235 in a patient-derived basal-like breast cancer model.

Background: Group IVA cytosolic phospholipase A2 (cPLA2α) plays an important role in tumorigenesis and angiogenesis. It is overexpressed in basal-like breast cancer (BLBC), which is aggressive and usually triple-negative, making it unresponsive to current targeted therapies. Here, we evaluated the anti-angiogenic effects of a specific cPLA2α inhibitor, AVX235, in a patient-derived triple-negative BLBC model.

Cytosolic phospholipase A2 modulates TLR2 signaling in synoviocytes.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis leading to destruction of cartilage and bone. PLA2 enzymes are key players in inflammation regulating the release of unsaturated fatty acids such as arachidonic acid (AA), a precursor of pro-inflammatory eicosanoids. Several lines of evidence point to toll-like receptors (TLRs) as drivers of synovitis and joint destruction in RA.

Inhibition of group IVA cytosolic phospholipase A2 by thiazolyl ketones in vitro, ex vivo, and in vivo.

Group IVA cytosolic phospholipase A2 (GIVA cPLA2) is the rate-limiting provider of pro-inflammatory mediators in many tissues and is thus an attractive target for the development of novel anti-inflammatory agents. In this work, we present the synthesis of new thiazolyl ketones and the study of their activities in vitro, in cells, and in vivo. Within this series of compounds, methyl 2-(2-(4-octylphenoxy)acetyl)thiazole-4-carboxylate (GK470) was found to be the most potent inhibitor of GIVA cPLA2, exhibiting an XI(50) value of 0.

Cytosolic phospholipase A2 regulates TNF-induced production of joint destructive effectors in synoviocytes.

Introduction: Rheumatoid arthritis (RA) is an inflammatory disease of the joint characterized by chronic synovitis causing pain, swelling and loss of function due to destruction of cartilage and bone. The complex series of pathological events occurring in RA is largely regulated via excessive production of pro-inflammatory cytokines, the most prominent being tumor necrosis factor (TNF). The objective of this work was to elucidate possible involvement of group IVA cytosolic phospholipase A2 (cPLA2α) in TNF-induced regulation of synovitis and joint destructive effectors in RA, to evaluate the potential of cPLA2α as a future therapeutic target.

Platelet-activating factor induces proliferation in differentiated keratinocytes.

Increased levels of platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) are found in several inflammatory dermatoses, but PAF's exact role in epidermis is uncertain. In order to better understand the physiological consequences of excess PAF production in epidermis, we examined the gene regulatory effects of PAF short-term stimulation in differentiated HaCaT keratinocytes by transcriptional profiling. Even though PAF induces COX2 expression, we found that PAF regulates only few genes associated with inflammation in differentiated keratinocytes.

The ω3-polyunsaturated fatty acid derivatives AVX001 and AVX002 directly inhibit cytosolic phospholipase A(2) and suppress PGE(2) formation in mesangial cells.

Background And Purpose: ω3-polyunsaturated fatty acids (ω3-PUFAs) are known to exert anti-inflammatory effects in various disease models although their direct targets are only poorly characterized.

Experimental Approach: Here we report on two new cPLA(2) inhibitors, the ω3-derivatives AVX001 and AVX002, and their effects on inflammatory PGE(2) production in cultures of renal mesangial cells.

Key Results: AVX001 and AVX002 dose-dependently inhibited the group IVA cytosolic phospholipase A(2) (cPLA(2) ) in an in vitro activity assay with similar IC(50) values for AVX001 and AVX002, whereas the known cPLA(2) inhibitor AACOCF(3) was less potent and docosahexaenoic acid (DHA) was inactive.

Presence of secretory group IIa and V phospholipase A2 and cytosolic group IValpha phospholipase A2 in chondrocytes from patients with rheumatoid arthritis.

Both secretory and cytosolic phospholipase A2 enzymes have been implicated in the pathogenesis of arthritis in animal models, but the exact expression patterns of the enzymes in diseased human joint tissue are uncertain. We investigated the messenger RNA expression of group IIa, IValpha and V phospholipase A2 and localized the presence of group IIa and IValpha phospholipase A2 at protein levels in articular cartilage from patients with rheumatoid arthritis, osteoarthritis and patients with non-arthritic joints. Both group IIa phospholipase A2 messenger RNA and protein were detected in all samples independent of diagnosis, but were far more prominent in cartilage from rheumatoid arthritis samples.