The phenotype of circulating follicular-helper T cells in patients with rheumatoid arthritis defines CD200 as a potential therapeutic target

Rheumatoid arthritis (RA) is a systemic autoimmune disease primarily affecting synovial joints in which the development of autoantibodies represents a failure of normal tolerance mechanisms, suggesting a role for follicular helper T cells (TFH) in the genesis of autoimmunity. To determine whether quantitative or qualitative abnormalities in the circulating TFH cell population exist, we analysed by flow cytometry the number and profile of these cells in 35 patients with RA and 15 matched controls. Results were correlated with patient characteristics, including the presence of autoantibodies, disease activity, and treatment with biologic agents. Circulating TFH cells from patients with RA show significantly increased expression of the immunoglobulin superfamily receptor CD200, with highest levels seen in seropositive patients (P=0.0045) and patients treated with anti-TNFα agents (P=0.0008). This occurs in the absence of any change in TFH numbers or overt bias towards Th1, Th2, or Th17 phenotypes. CD200 levels did not correlate with DAS28 scores (P=0.887). Although the number of circulating TFH cells is not altered in the blood of patients with RA, the TFH cells have a distinct phenotype. These differences associate TFH cells with the pathogenesis of RA and support the relevance of the CD200/CD200R signalling pathway as a potential therapeutic target

Role of Aquaporins in Breast Cancer Progression and Metastasis

There are various limitations regarding the current pharmacological options for the treatment of breast cancer in terms of efficacy, target selectivity, side effect profile and survival. Endocrine-based therapy for hormone-sensitive cancers such as that of the breast is one of the most effective and well-tolerated therapeutic options but is hampered by either intrinsic or acquired resistance, resulting in a more aggressive form of the disease. It is generally agreed that this process occurs in parallel with cellular transition from epithelial to mesenchymal phenotype (EMT), with consequent enhancement of proliferative capacity, migrative ability and invasive potential. Aquaporins (AQPs) represent a large family of water channel proteins which are widely distributed in various tissues and which play a role in the physiological maintenance of the extracellular environment particularly to regulate electrolyte-water balance. Accumulating evidence shows that expression of several AQPs is modulated in cancer tissues, and this correlates with tumor grade. AQPs 1 and 3–5 are also involved in breast cancer invasion, through modulating the activity of various growth factors, signaling molecules and proteolytic enzymes. We review current data on the involvement of these proteins in processes associated with malignant progression and discuss possible applications of AQP-based therapy as an effective means of inhibiting cancer cells from metastasizing

Diagnosis of giant cell arteritis

© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.GCA is the most common form of primary systemic vasculitis affecting older people. It is considered a clinical emergency because it can lead to irreversible blindness in around 20% of untreated cases. High doses of glucocorticoids should be initiated promptly to prevent disease-related complications; however, glucocorticoids therapy usually results in significant toxicity. Therefore, correct diagnosis is crucial. For many years, temporal artery biopsy has been considered the diagnostic ‘gold standard’ for GCA, but it has many limitations (including low sensitivity). US has proven to be effective for diagnosing GCA and can reliably replace temporal artery biopsy in particular clinical settings. In cases of suspected GCA with large-vessel involvement, other imaging modalities can be used for diagnosis (e.g. CT and PET). Here we review the current evidence for each diagnostic modality and propose an algorithm to diagnose cranial-GCA in a setting with rapid access to high quality US.info:eu-repo/semantics/publishedVersio

Expression of basic fibroblast growth factor, FGFR1 and FGFR2 in normal and malignant human breast, and comparison with other normal tissues.

The expression of basic fibroblast growth factor (bFGF) and two of its receptors, FGFR1 and FGFR2, was detected using the polymerase chain reaction, and quantified by comparison to the relative amount of product obtained following co-amplification of the ubiquitous glyceraldehyde phosphate dehydrogenase transcript. Varying levels were found in the vast majority of both cancer and non-malignant breast biopsies as well as in samples of several other normal human tissues. Significantly less bFGF was present in cancers (P less than 0.0001). Similarly, FGFR2 product was also much less in cancer tissues (P = 0.0078), as was FGFR1 (P = 0.002). FGFR1 levels in cancers tended to be higher in those which were oestrogen receptor positive (P less than 0.06). Amplification of different coding regions showed evidence of variant forms of FGFR1 RNA. Cancers appeared to have a significantly greater proportion of PCR product corresponding to the region between the third immunoglobulin like domain and the tyrosine kinase domain (P = 0.046). Differential expression was observed in breast cell lines, with bFGF in the normal derived HBL100, HBR SV1.6.1 and 184A1 but little or none in ZR-75-1, MCF-7, T47D and MDA-MB-231. FGFR1 was present in most of these but FGFR2 was absent from T47D, MDA-MB-231 and HBL100. ZR-75-1 cells had a marked preponderance of FGFR1 variants lacking part of the coding sequence. Aberrant receptor processing may provide clues concerning the role of FGF's and their potential involvement in malignancy

Extracellular Vesicles: A Mechanism to Reverse Metastatic Behaviour as a New Approach to Cancer Therapy

Extracellular vesicles (EVs) are membrane-bound particles shed from nearly all cell types into the extracellular environment. This collective term includes vesicles ranging in size from 30 nm to 5 μm in diameter. Various isolation techniques are used in different studies to separate EVs with no consensus protocol. EVs are released from cells under normal physiological conditions as well as in stressful and pathological conditions. In malignancies, they have been shown to be useful circulating markers for risk assessment, early diagnosis, monitoring of therapeutic effectiveness and prognosis. In addition, they appear to influence cell death and growth, angiogenesis, immune surveillance, extracellular matrix degradation and metastasis. In this respect, EVs have generated considerable interest for their potential use in cancer therapeutics. Since they appear to be responsible for transference of cellular components between cells and thereby transfer of functional characteristics of the donor to the recipient, two strategies for their role in cancer therapeutics may be envisaged. The first would be to prevent formation and/or shedding of EVs to prevent communication to or from cancer cells. The second would be to utilize them as carriers to deliver inhibitory/toxic components into cancer cells to destroy or neutralize them. In this review, we discuss the current state of research on characterization of EVs and highlight possible strategies for their use in cancer therapy

Implementasi Model Pembelajaran Teams Games Tournament di SD Margorejo 01 Kecamatan Pati

This study aims to develop students' understanding of events, facts, concepts and generalizations related to real life. The Teams Game Tournament model is a learning model that includes activities for all students regardless of position, includes the role of students as peers, and includes elements of play and reinforcement. The Teams Game Tournament learning model is expected to provide improvement and enhancement of learning. Based on the results of research conducted in Class V SD Negeri Margorejo 01 Pati, it can be concluded that the Teams Game Tournament learning model can improve teacher skills, student learning outcomes in the cognitive, affective, and psychomotor fields in learning Citizenship Education on freedom of association

Relationship of Cholinesterase Activity with Blood Glucose Levels Due to Pesticide Exposure to Farmers in Mlokorejo Village

Increase in blood glucose levels can be caused by the long-term use of pesticides by farmers. This study aims to determine whether there is a correlation between the activity of cholinesterase as an indicator of exposure to pesticides and blood glucose of farmers in Mlokorejo Village, Jember Regency. The research method is observational-analytic with a cross-sectional study design. Data in the form of general characteristics of the sample were obtained through interviews, while the data of the activity of cholinesterase and blood glucose levels of farmers were obtained at the Biochemical Laboratory of the Faculty of Medicine, Jember University. The sample size of this study is 30 samples. All of the samples are having an increased activity of cholinesterase. Most of the samples are having normal blood glucose levels. Based on the results of statistical analysis using the Spearman correlation test (a= 0.05), it was concluded that there was no significant correlation between the two variables (p = 0,191). Keywords: blood glucose, cholinesterase, pesticide