Summary Oestrogen treatment down‐regulates B lymphopoiesis in the bone marrow of mice. Meanwhile it up‐regulates immunoglobulin production. To understand better oestrogen action on male mice lacking receptor α (ERα; ERKO mice), ERβ (BERKO both receptors (DERKO mice) or wild‐type (wt) littermates were castrated and treated for 2·5 weeks with 30 μg/kg 17β‐oestradiol (E 2 ) vehicle oil as controls. The was examined by flow cytometry mature B‐cell function studied using an ELISPOT assay...

Oestrogens affect the development and regulation of immune system. To determine role oestrogen receptors alpha (ER-alpha) beta (ER-beta) on system, male ER-alpha (ERKO) ER-beta (BERKO) mice, as well alphabeta-double knockout (DERKO) were studied. Deletion led to hypoplasia both thymus spleen. Interestingly, a higher frequency immature double CD4+ CD8+ thymocytes was found in ER-alpha(-) mice compared with ER-alpha(+) mice. Female oophorectomized BERKO given oestradiol (E2) displayed similar...

Estrogen exerts a variety of important physiological effects, which have been suggested to be mediated via the two known estrogen receptors (ERs), alpha and beta. Three-month-old ovariectomized mice, lacking one or both receptors, were given subcutaneously (2.3 micro g/mouse per day) effects on different estrogen-responsive parameters, including skeletal studied. We found that increased cortical bone dimensions in wild-type (WT) double ER knockout (DERKO) mice. DNA microarray analysis was...

Raloxifene is a selective estrogen receptor modulator approved for the prevention of osteoporosis in postmenopausal women. It by having estrogen-agonistic effects on bone, vessels and blood lipids while it antagonistic mammary uterine tissue. Our aim was to study agonistic properties raloxifene analogue LY117018 (LY) uterus, B lymphopoiesis cell function. Oophorectomized sham-operated animals were treated with s.c. injections equipotent anti-osteoporotic doses 17beta-estradiol (E2) (0.1...

Rho family proteins are prenylated by geranylgeranyltransferase type I (GGTase-I), which normally target to membranes for GTP-loading. However, conditional deletion of GGTase-I in mouse macrophages increases GTP-loading proteins, leading enhanced inflammatory responses and severe rheumatoid arthritis. Here we show that heterozygous the gene Rac1, but not Rhoa Cdc42, reverses inflammation arthritis GGTase-I-deficient mice. Non-prenylated Rac1 has a high affinity adaptor protein Ras...

Vertically oriented graphene (VG) has attracted attention for years, but the growth mechanism is still not fully revealed. The electric field may play a role, direct evidence and exactly what role it plays remains unclear. Here, we conduct systematic study find that in plasma-enhanced chemical vapor deposition, VG preferably occurs at spots where local stronger, example, GaN nanowire tips. On almost round-shaped nanoparticles, instead of being perpendicular to substrate, grows along...

Breast cancer (BC) histological and molecular classifications significantly improved the treatment strategy prognosis. Inhibitor of apoptosis BIRC5/survivin is often overexpressed in cancers, however, indications its importance BC are inconsistent. We integrate BIRC5 protein mRNA measures with clinical associates long-term outcome three independent cohorts Protein levels were measured primary lysates 845 patients West Swedish cohort (VGR-BC) linked to 5- 27-years survival. The results...

Cellular senescence, an irreversible proliferative cell arrest, is caused by excessive intracellular or extracellular stress/damage. Increased senescent cells have been identified in multiple tissues different metabolic and other aging-related diseases. Recently, several human mouse studies emphasized the involvement of senescence development progression NAFLD. Hyperinsulinemia, seen obesity, syndrome, conditions insulin resistance, has linked to adipocytes neurons. Here, we investigate...

Estrogens are important for the male skeleton. Osteoprotegerin (OPG), receptor activator of NF-kappa B ligand (RANKL), interleukin-6 (IL-6), IL-1 and tumor necrosis factor alpha (TNFalpha) have been suggested to be involved in skeletal effects estrogen. We treated orchidectomized mice with estradiol 2 weeks observed a 143% increase trabecular bone mineral density distal metaphysis femur that was associated decreased OPG/RANKL mRNA ratio vertebral bone. A similar also seen after estrogen...

Fibromyalgia (FM) is characterized by chronic pain. Impaired growth hormone responses and reduced serum insulin-like factor 1 (IGF-1) are common in FM. The aim was to examine changes IGF-1, cerebrospinal fluid (CSF), neuropeptides, cytokines during aerobic exercise FM patients.In total, 49 patients (median age, 52 years) with were included the study. They randomized either moderate- high-intensity Nordic Walking (NW) program (n = 26) or supervised low-intensity walking (LIW) 23). Patients...

Significance Aberrant insulin-like growth factor 1 receptor (IGF1R)/insulin signaling in brain has recently been linked to neurodegeneration diabetes mellitus and Alzheimer’s disease. In this study, we demonstrate that functional disability pain patients with rheumatoid arthritis (RA) experimental RA are associated hippocampal inflammation inhibition of IGF1R/insulin substrate (IRS1) signal, reproducing an IGF1/insulin-resistant state. This restricts formation new neurons the hippocampus,...

CD8+ T cells have an emerging role in RA. Resent research indicates a causal relationship between the non-exhausted state of cells, defined by lost function PD-1, and development arthritis. We investigated how smoking contributes to phenotype cause survivin release serum. compared serum levels smokers non-smokers 252 RA 168 healthy subjects. Nicotine effects on were studied peripheral blood women, bone marrow nicotine treated mice sorted CD8 spleen vitro using flow cytometry quantitative...

Summary Oestrogen has a dichotomous effect on the immune system. T and B lymphopoiesis in thymus bone marrow is suppressed, whereas antibody production stimulated by oestrogen. In this study importance of oestrogen receptors (ER) ER‐α ER‐β aged system was investigated 18 months old‐wild type (WT), (ERKO), (BERKO) double (DERKO) knock‐out mice, compared with 4 old WT mice. Cell phenotypes marrow, spleen thymus, frequency immunoglobulin (Ig) spot forming cells (SFC) were determined. We show...

Abstract Generalized osteoporosis in postmenopausal rheumatoid arthritis (RA) is caused both by estrogen deficiency and the inflammatory disease. The relative importance of each these factors unknown. aim this study was to establish a murine model RA, evaluate mechanisms menopause arthritis-related osteoporosis. To mimic DBA/1 mice were ovariectomized, followed induction type II collagen-induced arthritis. After had been killed, paws collected for histology, one femur bone mineral density...

Survivin is known as an inhibitor of apoptosis and a positive regulator cell division. We have recently identified survivin predictor joint destruction in patients with rheumatoid arthritis (RA). Flt3 ligand (Flt3L) expressed the inflamed joints has adjuvant properties arthritis. Studies on 90 RA (median age 60.5 years [range, 24–87], disease duration 10.5 0–35]) show strong association between levels Flt3L blood. Here, we present experimental evidence connecting signaling. Treatment BALB/c...

Abstract Survivin is a proto-oncogene that regulates cell division and apoptosis. It molecular marker of cancer. Recently, survivin has emerged as feature RA, associated with severe joint damage poor treatment response. The present study examined if inhibition affects experimental arthritis, which was induced in mBSA-immunized mice by an injection mBSA the knee or developed spontaneously collagen type II-immunized mice. transcription lentivirus shRNA construct alleviated inflammation reduced...

The identification of biomarkers that predict optimal and individual choices treatment for patients with rheumatoid arthritis gains increasing attention. purpose this study was to investigate if the proto-oncogene survivin might aid in decisions early arthritis. Serum levels were measured 302 who completed Swedish pharmacotherapy (SWEFOT) trial at baseline, 3, 12, 24 months. Survivin > 0.45 ng/mL considered positive. Based on status, core set outcomes measuring disease activity, functional...

// Karin M. E. Andersson 1, * , Mikael Brisslert Nicola Filluelo Cavallini 1 Mattias N. D. Svensson 4 Amanda Welin Malin C. Erlandsson Michael J. Ciesielski 2 Gergely Katona 3 Maria I. Bokarewa Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University Gothenburg, Sweden Neurosurgery, Roswell Park Cancer Institute State New York School Medicine Biomedical Sciences, Buffalo, NY, USA Chemistry Molecular Biology, Division Cellular La Jolla for Allergy &...

ABSTRACT TKs are intracellular signaling molecules essential for cell homeostasis. Inhibition of is used in treatment malignancies and diabetes mellitus. The present study evaluated the role Flt3 antigen-induced arthritis. Mice were immunized with mBSA, arthritis was induced by an i.a. injection mBSA. Treatment inhibitor sunitinib started together mBSA immunization or induction mBSA-injected joints morphologically signs synovitis bone/cartilage destruction. Markers bone metabolism antibody...

Abstract Introduction High levels of the oncoprotein survivin may be detected in majority patients with early rheumatoid arthritis (RA). Survivin is a sensitive predictor joint damage and persistent disease activity. Survivin-positive are often poor responders to antirheumatic biological treatment. The aim this study was investigate reproducibility status its significance for clinical immunological assessment RA patients. Methods were measured 339 from Better Anti-Rheumatic FarmacOTherapy...

T-helper cells producing interleukin (IL)-17A and IL-17F cytokines (Th17 cells) are considered the source of autoimmunity in rheumatoid arthritis (RA). In this study, we characterized specific pathogenic features Th17 RA. By using nano-string technology, analyzed transcription 419 genes peripheral blood CCR6+CXCR3− CD4+ 14 RA patients 6 healthy controls identified 109 discriminating from controls. had an aggressive profile addition to signature IL-17, IL-23 IL-21, transcriptional regulators...