Kristiansenmitchell7684

Background Rheumatoid arthritis (RA) is a systematic autoimmune disease which may lead to joint dysfunction and disability. Aberrant migration and invasion of fibroblast-like synoviocytes (FLSs) is one of the most predominant etiopathogenesis of RA. Quercetin is a bioflavonoid which is implicated in the development of RA, yet its role in regulating the migration and invasion of FLSs is still elusive. The aim of this study is to investigate the impact of quercetin treatment on migration and invasion of FLSs and the underlying mechanism.Methods Capacity of migration and invasion of FLSs were assessed using transwell assay. Immunofluorescence assay was used to determine the expression of F-actin. The RNA levels of miR-146a and GATA transcription factor 6 (GATA6) were measured using quantitative real-time PCR. Western blot was used to examine the protein level of GATA6. The correlation between miR-146a and GATA6 was validated using luciferase reporter assay.Results Transwell assay revealed that the migration and invasion of FLSs were significantly inhibited after quercetin treatment, which was also proved by decreased expression of F-actin. The RNA level of miR-146a was decreased in RA tissues and was negatively related to the expression of GATA transcription factor 6 (GATA6). Quercetin treatment elevated the RNA level of miR-146a, but suppressed the expression of GATA6 in FLSs. Further luciferase reporter assay validated that GATA6 is a downstream target of miR-146a. TGF-beta activation Besides, miR-146a inhibited the migration and invasion of FLSs, and further GATA6 over-expression abrogated the miR-146a-induced inhibition. In addition, specific anti-miR-146a inhibitor abolished quercetin-mediated suppression of migration and invasion of FLSs.Conclusion Our study suggested that quercetin suppresses the migration and invasion of FLSs via regulating the miR-146a/GATA6 axis.Opsoclonus, an uncommon clinical sign, and is often described in the context of opsoclonus myoclonus ataxia syndrome (OMAS). OMAS may be paraneoplastic or postinfectious. However, opsoclonus with or without OMAS may occur in association with a wide gamut of infections. Infection-associated opsoclonus/OMAS (IAO) needs recognition as a separate entity, since it demands relatively brief immunosuppression, symptomatic treatment, and has a better outcome. Case records of children, who presented with opsoclonus to a tertiary-care teaching hospital of North India over a period of 1 year (2017-2018), were reviewed. Those with opsoclonus in the setting of an acute infection/febrile illness (symptomatic opsoclonus; IAO) were included. Of 15 children with opsoclonus, 6 children [median age 42 months (range 8 months to 7 years); 2 boys] had opsoclonus associated with an infective or febrile illness. Additional clinical findings in these children included myoclonus (n = 2), ataxia (n = 4) and behavioral abnormalities (n = 4). All these patients had an associated neurologic or nonneurologic illness- scrub typhus (n = 1), tuberculous meningitis (n = 1), mumps encephalitis (n = 1), brainstem encephalitis (n = 1), acute cerebellitis (n = 1), and subacute sclerosing panencephalitis (SSPE, n = 1). Children with acute cerebellitis, brainstem encephalitis, and mumps encephalitis were treated with steroids while those with scrub typhus, tuberculosis, and SSPE were treated with antibiotics, antitubercular therapy, and Isoprinosine, respectively. None of them needed long-term maintenance immunotherapy. The evaluation for tumor was negative in all. Three of the 6 children are functionally normal at the last follow-up. Acute neuro infections may trigger opsoclonus. A careful analysis of clinical data and suitable investigations can help differentiate these children from those with OMAS. This distinction may avoid unwarranted long-term immunosuppression.Background While the role of lysosomal membrane permeabilization (LMP) in NP-induced inflammatory responses has been recognized, the underlying mechanism of LMP is still unclear. The assumption has been that zinc oxide (ZnO)-induced LMP is due to Zn2+; however, little is known about the role of ZnO nanoparticles (NP) in toxicity.Methods We examined the contribution of intact ZnO NP on membrane permeability using red blood cells (RBC) and undifferentiated THP-1 cells as models of particle-membrane interactions to simulate ZnO NP-lysosomal membrane interaction. The integrity of plasma membranes was evaluated by transmission electron microscopy (TEM) and confocal microscopy. ZnO NP dissolution was determined using ZnAF-2F, Zn2+ specific probe. The stability of ZnO NP inside the phagolysosomes of phagocytic cells, differentiated THP-1, alveolar macrophages, and bone marrow-derived macrophages, was determined.Results ZnO NP caused significant hemolysis and cytotoxicity under conditions of negligible dissolution. Fully ionized Zn2SO4 caused slight hemolysis, while partially ionized ZnO induced significant hemolysis. Confocal microscopy and TEM images did not reveal membrane disruption in RBC and THP-1 cells, respectively. ZnO NP remained intact inside the phagolysosomes after a 4 h incubation with phagocytic cells.Conclusions These studies demonstrate the ability of intact ZnO NP to induce membrane permeability and cytotoxicity without the contribution of dissolved Zn2+, suggesting that ZnO NP toxicity does not necessarily depend upon Zn2+. The stability of ZnO NP inside the phagolysosomes suggests that LMP is the result of the toxic effect of intact ZnO NP on phagolysosomal membranes.Background The efficacy of maintenance tocolytic therapy after successful arrest of preterm labor remains controversial. The purpose of this study was to evaluate the efficacy of 400 mg of daily vaginal progesterone (cyclogest) after successful parenteral tocolysis to increase latency period and improvement of neonatal outcomes in women with threatened preterm labor.Materials and methods In this randomized, double-blind, placebo-controlled trial, 85 participants were randomly allocated to either 400 mg daily of vaginal progesterone (n = 45) or placebo (n = 40) until 34 weeks of gestation. The primary outcomes were the time until delivery (latency period) and cervical length after 1 week of treatment. Secondary outcome were GA on delivery, type of delivery, incidence of low birth weight, perinatal morbidity and mortality.Results Longer mean latency until delivery (53.6 ± 16.8 versus 34.5 ± 12.9) days p = .0001; longer mean of gestational age on delivery (37.5 ± 2.2 versus 34.2 ± 2.1) weeks p = .0001; cervical length after 1 week of treatment (27.