c-Jun N-Terminal Kinase in Inflammation and Rheumatic Diseases.

The c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinase (MAPK) family and are activated by environmental stress. JNK is also activated by proinflammatory cytokines, such as TNF and IL-1, and Toll-like receptor ligands. This pathway, therefore, can act as a critical convergence point in immune system signaling for both adaptive and innate responses. Like other MAPKs, the JNKs are activated via the sequential activation of protein kinases that includes two dual-specificity MAP kinase kinases (MKK4 and MKK7) and multiple MAP kinase kinase kinases. MAPKs, including JNKs, can be deactivated by a specialized group of phosphatases, called MAP kinase phosphatases. JNK phosphorylates and regulates the activity of transcription factors other than c-Jun, including ATF2, Elk-1, p53 and c-Myc and non-transcription factors, such as members of the Bcl-2 family. The pathway plays a critical role in cell proliferation, apoptosis, angiogenesis and migration. In this review, an overview of the functions that are related to rheumatic diseases is presented. In addition, some diseases in which JNK participates will be highlighted

An In Vitro Evaluation of the Effects of Air-Polishing Powders on Sound and Demineralised Enamel.

AIM To evaluate the effects of two air-polishing powders, during orthodontic treatment, on the surface roughness of sound and demineralised enamel. MATERIALS AND METHODS Forty-two caries-free human molars were collected, and the enamel surfaces were flattened and polished. Teeth were assigned to two groups (n = 21 each), a sound- and a demineralised-enamel group (subjected to pH-cycling over 2 weeks to create artificially induced white spot-like lesions). Within each group, teeth were further assigned to three groups (n = 7 each), air polished with either sodium bicarbonate, erythritol, or a negative control (water). Each sample was treated for 5 and 150 s. The average surface roughness (Ra) for each sample was measured using white-light-sensor profilometry. RESULTS On sound enamel, the Ra was roughly 0.17 ± 0.07 μm. After 150 s of air polishing, the Ra increased with erythritol (by 0.28 μm), and even more so with bicarbonate treatment (by 0.68 μm) (p < 0.01). On demineralised enamel, the Ra was roughly 0.79 ± 0.56 μm. The Ra increased after 5 s of air-polishing treatment similarly with erythritol and bicarbonate powders (by 1.03 μm and 1.04 μm, respectively) (p = 0.025), and even more after 150 s (by 2.48 μm and 2.49 μm, respectively) (p < 0.001). CONCLUSIONS On white spot lesions, one should be aware that enamel surface roughness will increase with both erythritol and bicarbonate air-polishing powders, especially with longer exposure times

Synovial cell metabolism and chronic inflammation in rheumatoid arthritis

Metabolomic studies of body fluids show that immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) are associated with metabolic disruption. This is likely to reflect the increased bioenergetic and biosynthetic demands of sustained inflammation and changes to nutrient and oxygen availability in damaged tissue. The synovial membrane lining layer is the principle site of inflammation in RA. Here the resident cells are the fibroblast-like synoviocytes (FLS) and the synovial tissue macrophages (STM), which are transformed toward overproduction of enzymes which degrade cartilage and bone, and cytokines which promote immune cell infiltration. Recent studies have shown metabolic changes in both FLS and macrophages from RA patients and these may be therapeutically targetable. However, as the origins and subset specific functions of synoviocytes are poorly understood and the signaling modules which control metabolic deviation in RA synovial cells are yet to be explored, significant additional research is needed to translate these findings toward clinical application. Furthermore, in many inflamed tissues, different cell types can forge metabolic collaborations through solute carriers (SLC) in their membranes, to meet a high demand for energy or biomolecules. Such relationships are likely to exist in the synovium and are yet to be explored. Finally, it is not yet known whether metabolic change is a consequence of disease or if primary changes to cellular metabolism might underlie or contribute to early stage disease pathogenesis. This article collates what is known about metabolism in synovial tissue cells and highlights future research directions in this area

Sodium Benzoate and Bitumen Coatings as Inhibitors of Corrosion Deterioration of Mechanical Properties of Low Carbon Steel

ABSTRAC

PHENOMENOLOGICAL STUDY ON BIRACIALISM AMONG FILIPINO ADOLESCENTS

Biracials are individuals from parents of two different races. They have difficulty in adjustment. As there are limited studies on Filipino adolescents&nbsp; who are biracials, the present research determined the challenges experienced by biracials studying in the Philippines. The participants of the study were chosen according to the following&nbsp; criteria: 1) either mother’s or father’s nationality is Filipino and the other parent has another nationality; 2) currently staying in the Philippines for not over five years; 3) born and raised in a foreign country other than the Philippines. &nbsp; A qualitative approach using phenomenological design was used in the study. There were six biracials who participated in the study. The interviews were audio-recorded, transcribed, and analyzed. The results of the study revealed that the dominant challenges experienced by biracials include language barrier, difficulty in adjusting with other students, and difficulty in balancing two cultures.&nbsp; Positive experiences were also encountered by biracials. They also felt privileged being biracials as they were accepted by the community. However, the respondents of the study experienced being bullied and discriminated by other students

Role of mitochondria-bound HK2 in rheumatoid arthritis fibroblast-like synoviocytes

BackgroundGlucose metabolism, specifically, hexokinase 2 (HK2), has a critical role in rheumatoid arthritis (RA) fibroblast-like synoviocyte (FLS) phenotype. HK2 localizes not only in the cytosol but also in the mitochondria, where it protects mitochondria against stress. We hypothesize that mitochondria-bound HK2 is a key regulator of RA FLS phenotype.MethodsHK2 localization was evaluated by confocal microscopy after FLS stimulation. RA FLSs were infected with Green fluorescent protein (GFP), full-length (FL)-HK2, or HK2 lacking its mitochondrial binding motif (HK2ΔN) expressing adenovirus (Ad). RA FLS was also incubated with methyl jasmonate (MJ; 2.5 mM), tofacitinib (1 µM), or methotrexate (1 µM). RA FLS was tested for migration and invasion and gene expression. Gene associations with HK2 expression were identified by examining single-cell RNA sequencing (scRNA-seq) data from murine models of arthritis. Mice were injected with K/BxN serum and given MJ. Ad-FLHK2 or Ad-HK2ΔN was injected into the knee of wild-type mice.ResultsCobalt chloride (CoCl2) and platelet-derived growth factor (PDGF) stimulation induced HK2 mitochondrial translocation. Overexpression of the HK2 mutant and MJ incubation reversed the invasive and migrative phenotype induced by FL-HK2 after PDGF stimulation, and MJ also decreased the expression of C-X-C Motif Chemokine Ligand 1 (CXCL1) and Collagen Type I Alpha 1 Chain (COL1A1). Of interest, tofacitinib but not methotrexate had an effect on HK2 dissociation from the mitochondria. In murine models, MJ treatment significantly decreased arthritis severity, whereas HK2FL was able to induce synovial hypertrophy as opposed to HK2ΔN.ConclusionOur results suggest that mitochondrial HK2 regulates the aggressive phenotype of RA FLS. New therapeutic approaches to dissociate HK2 from mitochondria offer a safer approach than global glycolysis inhibition

Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70

Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-gamma-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-gamma expression. NKT1 cells are also present in the synovial fluid of arthritis patients. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFN-gamma production, but also the protective function of iNKT cells in arthritis

Development and Function of CD94-Deficient Natural Killer Cells

The CD94 transmembrane-anchored glycoprotein forms disulfide-bonded heterodimers with the NKG2A subunit to form an inhibitory receptor or with the NKG2C or NKG2E subunits to assemble a receptor complex with activating DAP12 signaling proteins. CD94 receptors expressed on human and mouse NK cells and T cells have been proposed to be important in NK cell tolerance to self, play an important role in NK cell development, and contribute to NK cell-mediated immunity to certain infections including human cytomegalovirus. We generated a gene-targeted CD94-deficient mouse to understand the role of CD94 receptors in NK cell biology. CD94-deficient NK cells develop normally and efficiently kill NK cell-susceptible targets. Lack of these CD94 receptors does not alter control of mouse cytomegalovirus, lymphocytic choriomeningitis virus, vaccinia virus, or Listeria monocytogenes. Thus, the expression of CD94 and its associated NKG2A, NKG2C, and NKG2E subunits is dispensable for NK cell development, education, and many NK cell functions

Post‐pandemic cities: an urban lexicon of accelerations/decelerations

COVID-19 has stimulated renewed societal and academic debate about the future of cities and urban life. Future visons have veered from the ‘death of the city’ to visual renderings and limited experiments with novel 15 minute neighbourhoods. Within this context, we as a diverse group of urban scholars sought to examine the emergent ‘post’-COVID city through the production of an urban lexicon that investigates its socio-material contours. The urban lexicon makes three contributions. First, to explore how the pandemic has accelerated certain processes and agendas, while at the same time, other processes, priorities and sites have been decelerated and put on hold. Second, to utilise this framing to examine the impacts of the pandemic on how cities are governed, how urban geographies are managed and lived, and how care emerged as a vital urban resource. Third, to tease out what might be temporary intensifications and what may become configurational in urban governance, platforming, density, technosolutionism, dwelling, crowds, respatialisation, reconcentration, care, improvisation and atmosphere. The urban lexicon proposes a vocabulary for describing and understanding some of the key contours of the emergent post-pandemic city