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Ebsen Blanchard posted an update 3 days, 11 hours ago
1 cell inhibition. Interestingly, also CD20 antibodies target highly inflammatory TH cells and hamper TH17 differentiation by IL-6 reductions. Moreover, recovery rates of TH cells best correlate with long-term efficacy after therapeutical immunodepletion. We conclude that central memory TH17.1 cells play a pivotal role in MS pathogenesis and they represent a major target of MS therapeutics.Rheumatoid arthritis (RA) is a chronic aggressive arthritis that is characterized with systemic inflammation response, the production of abnormal antibodies, and persistent synovitis. PF-573228 datasheet One of the key mechanisms underlying the pathogenesis of RA is the imbalance of CD4 + T lymphocyte subsets, from T helper (Th) 17 cells and regulatory T (Treg) cells to T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells, which can mediate autoimmune inflammatory response to promote the overproduction of cytokines and abnormal antibodies. Although the treatment of RA has greatly changed due to the discovery of biological agents such as anti-TNF, the remission of it is still not satisfactory, thus, it is urgently required new treatment to realize the sustained remission of RA via restoring the immune tolerance. Interleukin-2 (IL-2) has been discovered to be a pleiotropic cytokine to promote inflammatory response and maintain immune tolerance. Low-dose IL-2 therapy is a driver of the imbalance between autoimmunity and immune tolerance towards immune tolerance, which has been tried to treat various autoimmune diseases. Recent researches show that low-dose IL-2 is a promising treatment for RA. In this review, we summarize the advances understandings in the biology of IL-2 and highlight the impact of the IL-2 pathway on the balance of Th17/Treg and Tfh/Tfr aiming to investigate the role of IL-2-mediated immune tolerance in RA and discuss the application and the therapeutic prospect of low-dose IL-2 in the treatment of RA.Spondyloarthritis (SpA) are a heterogeneous group of inflammatory chronic diseases characterized by sharing common pathogenic, clinical and radiologic features. The aim of this review is to support clinicians in understanding and managing this complex disease, from pathogenesis to therapeutic targets, through a systematic review of the current literature in accordance with PRISMA guidelines and checklist. HLA-B27 has been found to be associated with axial involvement either in SA and in PsA patients it might be involved through presentation of an “arthritogenic peptide” to autoreactive CD8+ T cells or might accumulate in misfolded form and induce production pro-inflammatory cytokines by binding to several innate immune receptors. This genetic background in combination with mechanical stress leads to the activation of both innate and acquired immune responses as well as a possible role of autoimmunity in SpA pathogenesis. The release of IL-23 and IL-17 is relevant for their systemic and local effect on bone, inducing the activation of osteoclasts. Thus, the regulatory role of IL-17 on fibroblasts, osteoblasts and chondrocytes has an impact in both synovial inflammation and joint destruction. Innovative therapies targeting IL-12/23 and IL-17 and the use of small targeted synthetic molecules, as JAK-inhibitors, proved to be effective in SpA patients representing an alternative strategy to TNF-inhibitors.
The aim of this study was to verify β2-AR expression in oral squamous cell carcinoma cell lines (SCC-9 and SCC-25), and to investigate the role of this receptor in migration and invasion of these neoplastic cells.
SCC-9 and SCC-25 cells were investigated for gene and protein expression of β2-AR. Cell migration and invasion were analyzed by wound healing assay and transwell invasion camera system. Different concentrations (0.1, 1 and 10 μM) of norepinephrine were used to stimulate, and 1 μM propranolol was used to block the beta-adrenergic receptors on cancer cells. Differences in median values of SCC-9 and SCC-25 and β2-AR protein expression were analyzed by Friedman test and in case of significant differences; pairwise comparisons were performed using Bonferroni correction.
The results showed that the β2-AR gene and protein expression were observed in both oral cancer cell lines. The concentration of 10 μM of norepinephrine significantly inhibited (p ≤ 0.05) migration of SCC-9 and SCC-25 cell lines. Furthermore, there was a significant reduction (p ≤ 0.05) in the effect of norepinephrine on cell migration when the β2-AR was inhibited by propranolol. The blockade by propranolol showed a tendency to reverse the effect of norepinephrine on the invasiveness of SCC-9 and SCC-25.
The use of beta-adrenergic receptor agonists could become an adjuvant therapeutic target in the treatment of this malignancy.
The use of beta-adrenergic receptor agonists could become an adjuvant therapeutic target in the treatment of this malignancy.
The presentin situ study aims to examine the influence of the polyphenolic tea drugs fragaria vesca, hamamelis and tormentil on the initial oral bioadhesion.
Initial biofilm formation was performed on bovine enamel slabs which were carried intraorally by 12 subjects. After 1 min of intraoral pellicle formation, the subjects rinsed with fragaria vesca, tormentil (0.8 mg/8 mL) and hamamelis (0.2 mg/8 mL) for 10 min. Tap water served as negative control, 0.2 % CHX as positive control. The investigations took place on different days (wash-out 2 days). Afterwards, fluorescence microscopy has been performed per test solution (n = 5) and per subject (n = 12) to visualize bacterial adhesion and glucan formation (8 h oral exposition) with DAPI, ConA and BacLight. Additionally, TEM was used to visualize the pellicle ultrastructure and expectorate samples. Statistical evaluation was carried out using the Kruskal-Wallis- (p < 0.5), Mann-Whitney U test (p < 0.5) and Bonferroni-Holm-correction (p < 0.1).
Rinsing with the polyphenolic tea extracts reduced significantly initial bacterial colonization (DAPI) compared to the negative control. There was no significant difference betweenfragaria vesca, hamamelis and tormentil. All solutions showed a reducing effect on the glucan formation. No significant difference was observed between fragaria vesca and CHX. Considerable alterations of the pellicle’s ultrastructure manifested by an increase in thickness and electron density resulted from rinsing with the three polyphenolic aqueous extracts.
Fragaria vesca, hamamelis and tormentil significantly reduce initial bioadhesion and glucan formation in situ and are therefore recommended as adjuvant antibacterial oral therapeutics.
Fragaria vesca, hamamelis and tormentil significantly reduce initial bioadhesion and glucan formation in situ and are therefore recommended as adjuvant antibacterial oral therapeutics.