cholecalciferol and Arthritis--Rheumatoid

Myeloid regulatory cell-based therapy has been shown to be a promising cell-based medicinal approach in organ transplantation and for the treatment of autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, Crohn's disease and multiple sclerosis. Dendritic cells (DCs) are the most efficient antigen-presenting cells and can naturally acquire tolerogenic properties through a variety of differentiation signals and stimuli. Several subtypes of DCs have been generated using additional agents, including vitamin D3, rapamycin and dexamethasone, or immunosuppressive cytokines, such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β). These cells have been extensively studied in animals and humans to develop clinical-grade tolerogenic (tol)DCs. Regulatory macrophages (Mregs) are another type of protective myeloid cell that provide a tolerogenic environment, and have mainly been studied within the context of research on organ transplantation. This review aims to thoroughly describe the ex vivo generation of tolDCs and Mregs, their mechanism of action, as well as their therapeutic application and assessment in human clinical trials.

Topics: Animals; Arthritis, Rheumatoid; Cell- and Tissue-Based Therapy; Cholecalciferol; Dendritic Cells; Diabetes Mellitus, Type 1; Humans; Immune Tolerance; Interleukin-10; Macrophages; Transforming Growth Factor beta

Vitamin D is an important component of the endocrine system that controls calcium homeostasis and bone mineralization. Because of the very short half-life of free serum vitamin D it is stabilized and transported to target tissues by being bound to the vitamin D binding protein (VDBP). The most common polymorphisms: rs4588 and rs7041 in the vitamin D binding protein gene may correlate with differences in vitamin D status in the serum. This review presents data that relate to the presence of genetic variants in the VDBP gene in correlation with certain diseases, mostly concerning cancers (breast, prostate, pancreatic, lung, colorectal, basal cell carcinoma cancer and cutaneous melanoma) or other related diseases (thyroid autoimmunity disorders, obesity, diabetes mellitus, bone metabolism, rheumatoid arthritis, ankylosing spondylitis, asthma, chronic obstructive pulmonary disease, tuberculosis and coronary artery diseases).

Topics: Arthritis, Rheumatoid; Cholecalciferol; Coronary Artery Disease; Diabetes Mellitus; Ergocalciferols; Female; Genetic Predisposition to Disease; Humans; Male; Neoplasms; Obesity; Polymorphism, Single Nucleotide; Pulmonary Disease, Chronic Obstructive; Tuberculosis; Vitamin D-Binding Protein

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; Circadian Rhythm; Circular Dichroism; Cisplatin; Citric Acid; Clinical Competence; Clinical Laboratory Techniques; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clostridioides difficile; Clostridium Infections; Coculture Techniques; Cohort Studies; Cold Temperature; Colitis; Collagen Type I; Collagen Type I, alpha 1 Chain; Collagen Type XI; Color; Connective Tissue Diseases; Copper; Coronary Angiography; Coronavirus 3C Proteases; Coronavirus Infections; Cost of Illness; Counselors; COVID-19; COVID-19 Testing; Creatine Kinase; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Cryoelectron Microscopy; Cryosurgery; Crystallography, X-Ray; Cues; Cultural Competency; Cultural Diversity; Curriculum; Cyclic AMP Response Element-Binding Protein; Cyclin-Dependent Kinase Inhibitor p21; Cycloparaffins; Cysteine Endopeptidases; Cytokines; Cytoplasm; Cytoprotection; Databases, Factual; Denitrification; Deoxycytidine; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Diatoms; Diet; Diet, High-Fat; Dietary Exposure; Diffusion Magnetic Resonance Imaging; Diketopiperazines; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Disease Progression; Disease-Free Survival; DNA; DNA Damage; DNA Glycosylases; DNA Repair; DNA-Binding Proteins; DNA, Bacterial; DNA, Viral; Docetaxel; Dose Fractionation, Radiation; Dose-Response Relationship, Drug; Down-Regulation; Doxorubicin; Drosophila; Drosophila melanogaster; Drug Carriers; Drug Delivery Systems; Drug Liberation; Drug Repositioning; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Drug Therapy, Combination; Edema; Edible Grain; Education, Graduate; Education, Medical, Graduate; Education, Pharmacy; Ehlers-Danlos Syndrome; Electron Transport Complex III; Electron Transport Complex IV; Electronic Nicotine Delivery Systems; Emergency Service, Hospital; Empathy; Emulsions; Endothelial Cells; Endurance Training; Energy Intake; Enterovirus A, Human; Environment; Environmental Monitoring; Enzyme Assays; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Epoxide Hydrolases; Epoxy Compounds; Erythrocyte Count; Erythrocytes; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Estrogens; Etanercept; Ethiopia; Ethnicity; Ethylenes; Exanthema; Exercise; Exercise Test; Exercise Tolerance; Extracellular Matrix; Extracorporeal Membrane Oxygenation; Eye Infections, Fungal; False Negative Reactions; Fatty Acids; Fecal Microbiota Transplantation; Feces; Female; Femur Neck; Fermentation; Ferritins; Fetal Development; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Fibroblasts; Fibroins; Fish Proteins; Flavanones; Flavonoids; Focus Groups; Follow-Up Studies; Food Handling; Food Supply; Food, Formulated; Forced Expiratory Volume; Forests; Fractures, Bone; Fruit and Vegetable Juices; Fusobacteria; G1 Phase Cell Cycle Checkpoints; G2 Phase Cell Cycle Checkpoints; Gamma Rays; Gastrectomy; Gastrointestinal Microbiome; Gastrointestinal Stromal Tumors; Gefitinib; Gels; Gemcitabine; Gene Amplification; Gene Expression; Gene Expression Regulation; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Gene-Environment Interaction; Genotype; Germany; Glioma; Glomerular Filtration Rate; Glucagon; Glucocorticoids; Glycemic Control; Glycerol; Glycogen Synthase Kinase 3 beta; Glycolipids; Glycolysis; Goblet Cells; Gram-Negative Bacterial Infections; Granulocyte Colony-Stimulating Factor; Graphite; Greenhouse Effect; Guanidines; Haemophilus influenzae; HCT116 Cells; Health Knowledge, Attitudes, Practice; Health Personnel; Health Services Accessibility; Health Services Needs and Demand; Health Status Disparities; Healthy Volunteers; Heart Failure; Heart Rate; Heart Transplantation; Heart-Assist Devices; HEK293 Cells; Heme; Heme Oxygenase-1; Hemolysis; Hemorrhage; Hepatitis B; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Hepatocytes; Hexoses; High-Throughput Nucleotide Sequencing; Hippo Signaling Pathway; Histamine; Histamine Agonists; Histidine; Histone Deacetylase 2; HIV Infections; HIV Reverse Transcriptase; HIV-1; Homebound Persons; Homeodomain Proteins; Homosexuality, Male; Hospice and Palliative Care Nursing; HSP70 Heat-Shock Proteins; Humans; Hyaluronan Receptors; Hydrogen; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydrolysis; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemia; Hypoglycemic Agents; Hypoxia; Idiopathic Interstitial Pneumonias; Imaging, Three-Dimensional; Imatinib Mesylate; Immunotherapy; Implementation Science; Incidence; INDEL Mutation; Induced Pluripotent Stem Cells; Industrial Waste; Infant; Infant, Newborn; Inflammation; Inflammation Mediators; Infliximab; Infusions, Intravenous; Inhibitory Concentration 50; Injections; Insecticides; Insulin-Like Growth Factor Binding Protein 5; Insulin-Secreting Cells; Interleukin-1; Interleukin-17; Interleukin-8; Internship and Residency; Intestines; Intracellular Signaling Peptides and Proteins; Ion Transport; Iridaceae; Iridoid Glucosides; Islets of Langerhans Transplantation; Isodon; Isoflurane; Isotopes; Italy; Joint Instability; Ketamine; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Kidney Neoplasms; Kinetics; Klebsiella pneumoniae; Knee Joint; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Lactate Dehydrogenase 5; Laparoscopy; Laser Therapy; Lasers, Semiconductor; Lasers, Solid-State; Laurates; Lead; Leukocyte L1 Antigen Complex; Leukocytes, Mononuclear; Light; Lipid Peroxidation; Lipopolysaccharides; Liposomes; Liver; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Locomotion; Longitudinal Studies; Lopinavir; Lower Urinary Tract Symptoms; Lubricants; Lung; Lung Diseases, Interstitial; Lung Neoplasms; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating; Lymphoma, Mantle-Cell; Lysosomes; Macrophages; Male; Manganese Compounds; MAP Kinase Kinase 4; Mass Screening; Maternal Health; Medicine, Chinese Traditional; Melanoma, Experimental; Memantine; Membrane Glycoproteins; Membrane Proteins; Mesenchymal Stem Cell Transplantation; Metal Nanoparticles; Metalloendopeptidases; Metalloporphyrins; Methadone; Methane; Methicillin-Resistant Staphylococcus aureus; Mexico; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Mice, Nude; Mice, SCID; Mice, Transgenic; Microarray Analysis; Microbial Sensitivity Tests; Microbiota; Micronutrients; MicroRNAs; Microscopy, Confocal; Microsomes, Liver; Middle Aged; Milk; Milk, Human; Minority Groups; Mitochondria; Mitochondrial Membranes; Mitochondrial Proteins; Models, Animal; Models, Molecular; Molecular Conformation; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Epidemiology; Molecular Structure; Molecular Weight; Multilocus Sequence Typing; Multimodal Imaging; Muscle Strength; Muscle, Skeletal; Muscular Diseases; Mutation; Mycobacterium tuberculosis; Myocardial Stunning; Myristates; NAD(P)H Dehydrogenase (Quinone); Nanocomposites; Nanogels; Nanoparticles; Nanotechnology; Naphthalenes; Nasal Cavity; National Health Programs; Necrosis; Needs Assessment; Neoadjuvant Therapy; Neonicotinoids; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm Transplantation; Neoplasms; Neoplastic Stem Cells; Netherlands; Neuroblastoma; Neuroprotective Agents; Neutrophils; NF-kappa B; NFATC Transcription Factors; Nicotiana; Nicotine; Nitrates; Nitrification; Nitrites; Nitro Compounds; Nitrogen; Nitrogen Dioxide; North Carolina; Nuclear Magnetic Resonance, Biomolecular; Nuclear Proteins; Nucleic Acid Hybridization; Nucleosomes; Nutrients; Obesity; Obesity, Morbid; Oceans and Seas; Oncogene Protein v-akt; Oncogenes; Oocytes; Open Reading Frames; Osteoclasts; Osteogenesis; Osteoporosis; Osteoporosis, Postmenopausal; Outpatients; Ovarian Neoplasms; Ovariectomy; Overweight; Oxazines; Oxidants; Oxidation-Reduction; Oxidative Stress; Oxides; Oxidoreductases; Oxygen; Oxygen Inhalation Therapy; Oxygenators, Membrane; Ozone; Paclitaxel; Paenibacillus; Pain Measurement; Palliative Care; Pancreatic Neoplasms; Pandemics; Parasympathetic Nervous System; Particulate Matter; Pasteurization; Patient Preference; Patient Satisfaction; Pediatric Obesity; Permeability; Peroxiredoxins; Peroxynitrous Acid; Pharmaceutical Services; Pharmacists; Pharmacy; Phaseolus; Phenotype; Phoeniceae; Phosphates; Phosphatidylinositol 3-Kinases; Phospholipid Transfer Proteins; Phospholipids; Phosphorus; Phosphorylation; Photoperiod; Photosynthesis; Phylogeny; Physical Endurance; Physicians; Pilot Projects; Piperidines; Pituitary Adenylate Cyclase-Activating Polypeptide; Plant Extracts; Plant Leaves; Plant Proteins; Plant Roots; Plaque, Atherosclerotic; Pneumonia; Pneumonia, Viral; Point-of-Care Testing; Polyethylene Glycols; Polymers; Polysorbates; Pore Forming Cytotoxic Proteins; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Postprandial Period; Poverty; Pre-Exposure Prophylaxis; Prediabetic State; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy, High-Risk; Prenatal Exposure Delayed Effects; Pressure; Prevalence; Primary Graft Dysfunction; Primary Health Care; Professional Role; Professionalism; Prognosis; Progression-Free Survival; Prolactin; Promoter Regions, Genetic; Proof of Concept Study; Proportional Hazards Models; Propylene Glycol; Prospective Studies; Prostate; Protein Binding; Protein Biosynthesis; Protein Isoforms; Protein Kinase Inhibitors; Protein Phosphatase 2; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases; Protein Structure, Tertiary; Protein Transport; Proteoglycans; Proteome; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-myc; Proto-Oncogene Proteins c-ret; Proto-Oncogene Proteins p21(ras); Proton Pumps; Protons; Protoporphyrins; Pseudomonas aeruginosa; Pseudomonas fluorescens; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Pulmonary Veins; Pyrazoles; Pyridines; Pyrimidines; Qualitative Research; Quinoxalines; Rabbits; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Histamine H3; Receptors, Immunologic; Receptors, Transferrin; Recombinant Proteins; Recurrence; Reference Values; Referral and Consultation; Regional Blood Flow; Registries; Regulon; Renal Insufficiency, Chronic; Reperfusion Injury; Repressor Proteins; Reproducibility of Results; Republic of Korea; Research Design; Resistance Training; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory Insufficiency; Resuscitation; Retinal Dehydrogenase; Retreatment; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Ribosomal Proteins; Ribosomes; Risk Assessment; Risk Factors; Ritonavir; Rivers; RNA Interference; RNA-Seq; RNA, Messenger; RNA, Ribosomal, 16S; RNA, Small Interfering; Rosuvastatin Calcium; Rural Population; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Salivary Ducts; Salivary Gland Neoplasms; San Francisco; SARS-CoV-2; Satiation; Satiety Response; Schools; Schools, Pharmacy; Seasons; Seawater; Selection, Genetic; Sequence Analysis, DNA; Serine-Threonine Kinase 3; Sewage; Sheep; Sheep, Domestic; Shock, Hemorrhagic; Signal Transduction; Silver; Silymarin; Single Photon Emission Computed Tomography Computed Tomography; Sirolimus; Sirtuin 1; Skin; Skin Neoplasms; Skin Physiological Phenomena; Sleep Initiation and Maintenance Disorders; Social Class; Social Participation; Social Support; Soil; Soil Microbiology; Solutions; Somatomedins; Soot; Specimen Handling; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis; Spinal Fractures; Spirometry; Staphylococcus aureus; STAT1 Transcription Factor; STAT3 Transcription Factor; Streptomyces coelicolor; Stress, Psychological; Stroke; Stroke Volume; Structure-Activity Relationship; Students, Medical; Students, Pharmacy; Substance Abuse Treatment Centers; Sulfur Dioxide; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Analysis; Survival Rate; Survivin; Sweden; Swine; Swine, Miniature; Sympathetic Nervous System; T-Lymphocytes, Regulatory; Talaromyces; Tandem Mass Spectrometry; tau Proteins; Telemedicine; Telomerase; Telomere; Telomere Homeostasis; Temperature; Terminally Ill; Th1 Cells; Thiamethoxam; Thiazoles; Thiophenes; Thioredoxin Reductase 1; Thrombosis; Thulium; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Time Factors; Titanium; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Transcription Factor AP-1; Transcription Factors; Transcription, Genetic; Transcriptional Activation; Transcriptome; Transforming Growth Factor beta1; Transistors, Electronic; Translational Research, Biomedical; Transplantation Tolerance; Transplantation, Homologous; Transportation; Treatment Outcome; Tretinoin; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Tubulin Modulators; Tumor Microenvironment; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Twins; Ultrasonic Therapy; Ultrasonography; Ultraviolet Rays; United States; Up-Regulation; Uranium; Urethra; Urinary Bladder; Urodynamics; Uromodulin; Uveitis; Vasoconstrictor Agents; Ventricular Function, Left; Vero Cells; Vesicular Transport Proteins; Viral Nonstructural Proteins; Visual Acuity; Vital Capacity; Vitamin D; Vitamin D Deficiency; Vitamin K 2; Vitamins; Volatilization; Voriconazole; Waiting Lists; Waste Disposal, Fluid; Wastewater; Water Pollutants, Chemical; Whole Genome Sequencing; Wine; Wnt Signaling Pathway; Wound Healing; Wounds and Injuries; WW Domains; X-linked Nuclear Protein; X-Ray Diffraction; Xanthines; Xenograft Model Antitumor Assays; YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

Topics: Arthritis, Rheumatoid; Bone Density; Bone Resorption; Calcium, Dietary; Cholecalciferol; Cytokines; Glycoproteins; Humans; Methotrexate; Osteoclasts; Osteoporosis; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Synovial Membrane

The aim of this study was to evaluate differences in T helper cell sub-types and osteoclast (OCs) precursors in peripheral blood between patients affected by early rheumatoid arthritis (eRA) and healthy controls. The effect of administration of cholecalcipherol on clinical and laboratory parameters was subsequently evaluated, by a parallel, randomized double blind, placebo controlled trial. Thirty nine eRA patients and 31 age-matched controls were enrolled and compared for levels of 25OH vitamin D, T helper cell sub-types, OCs precursors including both classical and non-classical and pro-inflammatory cytokines at baseline. Eligible patients were female ≥18 years of age with a diagnosis of RA, as defined by the American College of Rheumatology 2010 criteria for <6 months prior to inclusion in the study. Patients with auto-immune or inflammatory diseases other than RA were excluded. Patients treated with glucocorticoids (GCs), disease modifying activity drugs and biologic agents within the past 6 months were also excluded. In the second phase of the study, eRA patients were randomly assigned to standard treatment with methotrexate (MTX) and GCs with (21) or without (18) cholecalcipherol (300,000 IU) and followed for 3 months; the randomization was done by computer generated tables to allocate treatments. Three patients didn't come back to the follow up visit for personal reasons. None of the patients experienced adverse events. The main outcome measures were T cells phenotypes, OCs precursors and inflammatory cytokines. Secondary outcome measure were clinical parameters. In eRA, 25OH vitamin D levels were significantly lower. CD4+/IFNγ+,CD4+/IL4+, CD4+/IL17A+ and CD4+IL17A+IFNγ+, cells were increased in eRA as well as non-classical OCs precursors, whereas T regulatory cells were not altered. TNFα, TGFβ1, RANKL, IL-23 and IL-6 were increased in eRA. Non-classical OCs, IL-23 and IL-6 correlated with disease severity and activity. Standard treatment with MTX and GC ameliorated clinical symptoms and reduced IL-23, whereas it did not affect CD4+ cells sub-sets nor OCs precursors. After 3 months, the combined use of cholecalcipherol significantly ameliorated the effect of treatment on global health. In eRA, a significant imbalance in T CD4+ sub-types accompanied by increased levels of non-classical OCs precursors and pro-inflammatory cytokines was observed. A single dose of cholecalcipherol (300,000 IU) combined with standard treatment significantly ameliorates p

Topics: Adolescent; Adult; Age of Onset; Aged; Antirheumatic Agents; Arthritis, Rheumatoid; Case-Control Studies; Cell Differentiation; Cholecalciferol; Cytokines; Double-Blind Method; Female; Glucocorticoids; Humans; Immunologic Factors; Methotrexate; Middle Aged; Osteoclasts; Severity of Illness Index; T-Lymphocytes, Helper-Inducer; Treatment Outcome

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; Circadian Rhythm; Circular Dichroism; Cisplatin; Citric Acid; Clinical Competence; Clinical Laboratory Techniques; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clostridioides difficile; Clostridium Infections; Coculture Techniques; Cohort Studies; Cold Temperature; Colitis; Collagen Type I; Collagen Type I, alpha 1 Chain; Collagen Type XI; Color; Connective Tissue Diseases; Copper; Coronary Angiography; Coronavirus 3C Proteases; Coronavirus Infections; Cost of Illness; Counselors; COVID-19; COVID-19 Testing; Creatine Kinase; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Cryoelectron Microscopy; Cryosurgery; Crystallography, X-Ray; Cues; Cultural Competency; Cultural Diversity; Curriculum; Cyclic AMP Response Element-Binding Protein; Cyclin-Dependent Kinase Inhibitor p21; Cycloparaffins; Cysteine Endopeptidases; Cytokines; Cytoplasm; Cytoprotection; Databases, Factual; Denitrification; Deoxycytidine; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; 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Forced Expiratory Volume; Forests; Fractures, Bone; Fruit and Vegetable Juices; Fusobacteria; G1 Phase Cell Cycle Checkpoints; G2 Phase Cell Cycle Checkpoints; Gamma Rays; Gastrectomy; Gastrointestinal Microbiome; Gastrointestinal Stromal Tumors; Gefitinib; Gels; Gemcitabine; Gene Amplification; Gene Expression; Gene Expression Regulation; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Gene-Environment Interaction; Genotype; Germany; Glioma; Glomerular Filtration Rate; Glucagon; Glucocorticoids; Glycemic Control; Glycerol; Glycogen Synthase Kinase 3 beta; Glycolipids; Glycolysis; Goblet Cells; Gram-Negative Bacterial Infections; Granulocyte Colony-Stimulating Factor; Graphite; Greenhouse Effect; Guanidines; Haemophilus influenzae; HCT116 Cells; Health Knowledge, Attitudes, Practice; Health Personnel; Health Services Accessibility; Health Services Needs and Demand; Health Status Disparities; Healthy Volunteers; 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YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

Functional disability is a major concern in patients with rheumatoid arthritis (RA). This retrospective study investigated the risk factors for vertebral fractures (VFs) in postmenopausal RA patients and determined the impact of VFs on functional status. Data from a cohort of 200 postmenopausal RA patients in a single hospital registry were analyzed. Demographic and clinical data, imaging data from spine radiographs, and bone mineral density (BMD) data were collected from the patients at baseline and at the final visit (a mean of 2.9 years after the first visit). Risk factors for incident VFs and their impact on the modified health assessment questionnaire (mHAQ) were analyzed. Twenty-eight patients (14%) developed new VFs (NVFs). Logistic regression analysis adjusted for age, BMI, and disease duration revealed that daily dose of prednisolone, femoral neck BMD, use of active vitamin D3, and use of a bisphosphonate at baseline were factors associated with NVF, with odds ratios (95% confidence interval) of 1.27 (1.05-1.54), 0.94 (0.91-0.97), 0.34 (0.13-0.89), and 0.31 (0.12-0.82), respectively. Patients with NVF exhibited worse mHAQ scores and a greater increase in mHAQ scores from baseline compared with those without NVF. In conclusion, incident VFs were associated with reduced functional status in postmenopausal patients with RA. It is important to prevent VFs to maintain the functional status of RA patients.

Topics: Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Bone Density; Bone Density Conservation Agents; Cholecalciferol; Diphosphonates; Female; Femur Neck; Humans; Middle Aged; Postmenopause; Prednisolone; Radiography; Spinal Fractures

The aim of the study was to prospectively investigate the effects of HRT on serum soluble receptor for advanced glycation end product (sRAGE) levels in RA patients and to determine whether sRAGE production is related to bone/cartilage metabolism.. Eighty-eight post-menopausal RA patients were randomized to receive vitamin D3 and calcium supplementation with or without HRT (oestradiol plus noretisterone acetate). The levels of total sRAGE in sera were measured before, 1 and 2 years after treatment initiation. Potential associations between sRAGE levels, bone/cartilage metabolic markers and BMD were investigated.. Patients receiving HRT displayed significantly decreased levels of serum sRAGE at 1 and 2 years as compared with levels at study entry. The increase in serum oestradiol was associated with the decline in sRAGE levels. Importantly, sRAGE levels at baseline significantly correlated with bone/cartilage turnover markers including C-terminal propeptide of type I procollagen, carboxyterminal telopeptide of type I collagen and cartilage oligomeric matrix protein, and the decrease of sRAGE levels paralleled with diminished concentration of these molecules. BMD in hip and femoral neck and progression of Larsen score at 1 year were associated with baseline sRAGE levels. The decline in sRAGE levels significantly correlated with an increase in total BMD following 2 years of treatment in patients receiving HRT but not in the control group.. Our findings suggest that HRT decreases the levels of endogenous sRAGE in post-menopausal RA patients implicating its role in sRAGE regulation. In addition, serum sRAGE was associated with BMD and markers of bone/cartilage metabolism. These data suggest that sRAGE is involved directly or indirectly in bone metabolism. Trial registration. Current Controlled Trials, ISRCTN46523456, http://www.controlled-trials.com/isrctn/search.html?srch=ISRCTN46523456.

Topics: Alkaline Phosphatase; Arthritis, Rheumatoid; Biomarkers; Bone and Bones; Bone Density; Bone Resorption; Calcium; Cartilage; Cartilage Oligomeric Matrix Protein; Cholecalciferol; Estradiol; Estrogen Replacement Therapy; Extracellular Matrix Proteins; Female; Glycoproteins; Humans; Matrilin Proteins; Middle Aged; Norethindrone; Norethindrone Acetate; Peptide Fragments; Postmenopause; Procollagen; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Statistics, Nonparametric

The aim of this study was to investigate associations between serum levels of resistin, an adipokine and markers of inflammation, bone metabolism, plasma lipids and kidney function in post-menopausal RA patients and to evaluate if HRT during 2 yrs affected resistin levels.. Eighty-eight women were randomly allocated to receive HRT, vitamin D(3) and calcium or vitamin D(3) and calcium alone. Serum levels of resistin, IL-1beta, IL-1 receptor antagonist (IL-1Ra), IL-6, IL-6 soluble receptor, TNF-alpha were measured by ELISA, markers of bone metabolism, carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and carboxyterminal propeptide of type I procollagen by RIA, ESR, CRP, Hb, creatinine and lipids by standard laboratory techniques, BMD and total lean mass (TLM) by DXA and joint destruction by Larsen score. Resistin was also measured in 42 healthy control women.. There was no difference in resistin concentration between patients and healthy controls. Resistin was significantly correlated with IL-1Ra, CRP, TNF-alpha, ICTP, glucocorticosteroids and Larsen score and inversely with BMD, hip and with TLM. In multiple regression analysis, IL-1Ra, TLM and use of corticosteroids remained determinants of resistin. Patients treated with HRT displayed significant increase in resistin compared with controls in the first but not the second year.. Resistin was associated with increased inflammation, particularly by the acute-phase reactant IL-1Ra antagonizing IL-1beta, joint destruction, glucocorticosteroids and with reduced BMD and TLM. These findings suggest resistin being a significant mediator in the inflammatory process in RA. Further studies examining the mechanisms behind the relation between resistin and IL-1Ra are encouraged. HRT does not seem to have important long-term effect on resistin.

Topics: Aged; Aging; Arthritis, Rheumatoid; Biomarkers; Calcium; Cholecalciferol; Estrogen Replacement Therapy; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Middle Aged; Postmenopause; Resistin; Severity of Illness Index

It is well known that oestrogen has immunomodulatory properties. We have previously shown disease ameliorating effects of hormone replacement therapy (HRT) in post-menopausal women with rheumatoid arthritis (RA). The aim of this study was to investigate the effects of HRT and the patients inflammatory state on humoral and cell-mediated immune responses. Eighty-eight post-menopausal RA women were allocated to receive HRT (oestradiol and noretisterone acetate), vitamin D3 and calcium or vitamin D3 and calcium alone in a 2-year randomized controlled trial. Immunoglobulins (IgM, IgG and IgA) in serum were measured by nephelometry and rheumatoid factor (RF) concentration by enzyme-linked immunosorbent assay. Immunization with influenza vaccine was performed to quantitate humoral response to recall antigen and tuberculin skin test with purified protein derivative (PPD) to test T-cell-mediated immune response. These immune related measures were correlated with demographic and disease-related variables. HRT during 2 years did not alter concentrations of Ig, RF, IgM response to influenza vaccine or the PPD reaction. The increase in IgM against influenza vaccine was significantly positively correlated with signs of disease activity; C-reactive protein, disease activity score 28 and inversely with haemoglobin. In contrast, PPD reactivity was inversely associated with disease activity. In conclusion, long-term HRT in RA does not influence Ig or autoantibody concentrations in serum and has no significant impact on humoral and cell-mediated immune responses to recall antigens. Interestingly, high disease activity was associated to increased humoral but decreased cell-mediated immune responses irrespectively of hormone treatment.

Topics: Aged; Antibodies, Viral; Antibody Formation; Arthritis, Rheumatoid; Calcium; Cholecalciferol; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Estrogen Replacement Therapy; Estrogens; Female; Humans; Hypersensitivity, Delayed; Immunity, Cellular; Immunoglobulin M; Influenza Vaccines; Middle Aged; Outcome Assessment, Health Care; Postmenopause; Progesterone; Rheumatoid Factor; Single-Blind Method; Tuberculin Test

This study aimed to evaluate the effects of hormone replacement therapy (HRT), known to prevent osteoporosis and fractures, on markers of bone and cartilage metabolism. Furthermore, we assessed whether changes in these markers corresponded to alterations in bone mineral density and radiographic joint destructions in postmenopausal women with rheumatoid arthritis. Eighty-eight women were randomized to receive HRT, calcium, and vitamin D3, or calcium and vitamin D3 alone, for 2 years. Bone turnover was studied by analyzing serum levels of C-terminal telopeptide fragments of type I collagen (CTX-I), C-terminal telopeptide of type I collagen (ICTP), bone sialoprotein, and C-terminal propeptide of type I procollagen (PICP) and cartilage turnover by urinary levels of collagen type II C-telopeptide degradation fragments (CTX-II) and cartilage oligomeric matrix protein (COMP) in serum. Treatment with HRT resulted in decrease in CTX-I (P < 0.001), ICTP (P < 0.001), PICP (P < 0.05), COMP (P < 0.01), and CTX-II (P < 0.05) at 2 years. Reductions in CTX-I, ICTP, and PICP were associated with improved bone mineral density. Of the markers tested, CTX-I reflected bone turnover most sensitively; it was reduced by 53 +/- 6% in the patients receiving HRT. Baseline ICTP (P < 0.001), CTX-II (P < 0.01), and COMP (P < 0.05) correlated with the Larsen score. We suggest that biochemical markers of bone and cartilage turnover may provide a useful tool for assessing novel treatment modalities in arthritis, concerning both joint protection and prevention of osteoporosis.

Topics: Aged; Arthritis, Rheumatoid; Biomarkers; Bone Density; Bone Resorption; Calcium; Cartilage; Cholecalciferol; Drug Therapy, Combination; Female; Hormone Replacement Therapy; Humans; Middle Aged; Time

To determine the effects of low dose methotrexate (MTX) on bone mineral density (BMD) of patients with rheumatoid arthritis (RA).. We examined the relationship between BMD and disease modifying antirheumatic drug (DMARD) use with data from a prospective, randomized, placebo controlled trial assessing the effects of calcium and vitamin D3 supplementation on BMD of patients with RA. Measurements of BMD of the lumbar spine and femoral neck were performed at baseline and at yearly followup visits over 3 years.. Information about DMARD use and BMD was available for 133 patients at baseline, and for 95 patients at Year 3. Lumbar spine and femoral neck BMD of MTX and non-MTX treated patients were similar at the start of the study. At the end of 3 years of followup, there was no significant differences in the change in BMD of the femoral neck and lumbar spine in MTX and non-MTX treated patients, in general. However, patients treated with prednisone > or = 5 mg/day plus MTX had greater loss of BMD in the lumbar spine than patients treated with a similar dose of prednisone without MTX (difference -8.08% over 3 years; p = 0.004).. At the end of 3 years, low dose MTX use was not associated with change in femoral neck or lumbar spine BMD in patients who were not treated with corticosteroids. However, among patients treated with prednisone > or = 5 mg/day, combined treatment with MTX and prednisone was associated with greater bone loss in the lumbar spine than treatment with prednisone without MTX.

Topics: Absorptiometry, Photon; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Bone Density; Calcium; Cholecalciferol; Drug Therapy, Combination; Female; Femur Neck; Humans; Lumbar Vertebrae; Male; Methotrexate; Middle Aged; Osteoporosis; Prednisone; Prospective Studies

Therapy with low-dose corticosteroids is commonly used to treat allergic and autoimmune diseases. Long-term use of corticosteroids can lead to loss of bone mineral density and higher risk for vertebral fractures. Calcium and vitamin D3 supplementation is rational therapy for minimizing bone loss, but little evidence for its effectiveness exists.. To assess 1) the effects of supplemental calcium and vitamin D3 on bone mineral density of patients with rheumatoid arthritis and 2) the relation between the effects of this supplementation and corticosteroid use.. 2-year randomized, double-blind, placebo-controlled trial.. University outpatient-care facility.. 96 patients with rheumatoid arthritis, 65 of whom were receiving treatment with corticosteroids (mean dosage, 5.6 mg/d).. Calcium carbonate (1000 mg/d) and vitamin D3 (500 IU/d) or placebo.. Bone mineral densities of the lumbar spine and femur were determined annually.. Patients receiving prednisone therapy who were given placebo lost bone mineral density in the lumbar spine and trochanter at a rate of 2.0% and 0.9% per year, respectively. Patients receiving prednisone therapy who were given calcium and vitamin D3 gained bone mineral density in the lumbar spine and trochanter at a rate of 0.72% (P = 0.005) and 0.85% (P = 0.024) per year, respectively. In patients receiving prednisone therapy, bone mineral densities of the femoral neck and the Ward triangle did not increase significantly with calcium and vitamin D3. Calcium and vitamin D3 did not improve bone mineral density at any site in patients who were not receiving corticosteroids.. Calcium and vitamin D3 prevented loss of bone mineral density in the lumbar spine and trochanter in patients with rheumatoid arthritis who were treated with low-dose corticosteroids.

Topics: Adult; Aged; Arthritis, Rheumatoid; Bone Density; Calcium Carbonate; Cholecalciferol; Double-Blind Method; Female; Femur; Food, Fortified; Glucocorticoids; Humans; Lumbar Vertebrae; Male; Middle Aged; Prednisone

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic of severe coronavirus disease 2019 (COVID-19).. The RA dataset (GSE93272) and the. A total of 199 DEGs were extracted from the GSE93272 and GSE33341 datasets. KEGG analysis of enrichment pathways were NLR signaling pathway, cell membrane DNA sensing pathway, oxidative phosphorylation, and viral infection. Positive/negative regulation of the immune system, regulation of the interferon-I (IFN-I; IFN-α/β) pathway, and associated pathways of the immunological response to viruses were enriched in GO and ClueGO analyses. PPI network and Cytoscape platform identified the top 10 hub genes: RSAD2, IFIT3, GBP1, RTP4, IFI44, OAS1, IFI44L, ISG15, HERC5, and IFIT5. The pathways are mainly enriched in response to viral and bacterial infection, IFN signaling, and 1,25-dihydroxy vitamin D3. IFI44, OAS1, IFI44L, ISG15, and HERC5 are the five hub genes shared by RA, COVID-19, and SAB. The pathways are primarily enriched for response to viral and bacterial infections. The TF-hub gene network and miRNA-hub gene network identified YY1 as a key TF and hsa-mir-1-3p and hsa-mir-146a-5p as two important miRNAs related to IFI44. IFI44 was identified as a hub gene by validating GSE17755, GSE55235, and GSE13670. Immune cell infiltration analysis showed a strong positive correlation between activated dendritic cells and IFI44 expression.. IFI144 was discovered as a shared biomarker and disease target for RA, COVID-19, and SAB by this study. IFI44 negatively regulates the IFN signaling pathway to promote viral replication and bacterial proliferation and is an important molecular target for SARS-CoV-2 and

Topics: Antigens; Arthritis, Rheumatoid; Biomarkers; Cholecalciferol; COVID-19; Cytoskeletal Proteins; Humans; Immune Evasion; Interferons; MicroRNAs; SARS-CoV-2; Staphylococcal Infections; Staphylococcus aureus

To evaluate the status of vitamin D in women with rheumatoid arthritis (RA) and establish its associations with comorbidity, disease activity, and body composition components.. 86 women with RA (average age 58.18.5 years) were enrolled in the study. We analyzed the relationship of vitamin D levels with clinical and laboratory parameters and with the results of two-energy x-ray absorptiometry. MannWhitney or KruskalWallis, 2 and Spearman tests were performed using Statistica for Windows 10.0 (StatSoft Inc., USA).. Vitamin D level was 22.4 [17.8; 27.3] ng/ml: deficiency was detected in 33%, and insufficiency in 46% of women with RA. Only 41% of patients with low vitamin D levels received supplements of cholecalciferol, while only 9% in a sufficient dose. 25(OH)D level was significantly lower in RA patients with sarcopenia, obesity, high activity according to DAS28 and in those who did not receive vitamin D supplements. There werent differences in 25(OH)D levels among subgroups of patient according to age, fertility, BMD status, comorbidity index, RA duration, ESR and CRP levels, medical therapy performed.. 79% of patients with RA had low levels of vitamin D, while less than half of them received additional cholecalciferol supplements. Low vitamin D levels in RA patients were associated with high disease activity, sarcopenia, and obesity.. Цель. Оценить статус витамина D у женщин с ревматоидным артритом (РА) и установить его ассоциации с коморбидностью, активностью заболевания и компонентами состава тела. Материалы и методы. В исследование включены 86 женщин с РА, средний возраст 58,18,5 года. Проведены анкетирование, денситометрическое и лабораторное обследование. Проанализирована связь уровня витамина D c клинико-анамнестическими, лабораторными данными и результатами денситометрии. Анализ выполнен с использованием U-теста МаннаУитни или критерия КраскелаУоллиса, метода 2 и корреляционного анализа по Спирмену с помощью пакета Statistica for Windows 10.0 (StatSoft Inc., USA). Результаты. Уровень витамина D составил 22,4 [17,8; 27,3] нг/мл, дефицит выявлен у 33%, а недостаточность у 46% женщин с РА. Только 41% пациентов из числа лиц с низким уровнем 25(ОН)D дополнительно принимали колекальциферол, при этом лишь 9% в достаточной дозе. Уровень 25(ОН)D значимо ниже у больных РА с саркопенией, ожирением, высокой активностью по DAS28, а также у лиц, не получавших дополнительно препараты витамина D, в то же время не выявлено различий в зависимости от возраста, фертильности, состояния минеральной плотности кости, индекса коморбидности, длительности РА, показателей скорости оседания эритроцитов и С-реактивного белка, характера проводимой терапии. Заключение. Низкий уровень витамина D имели 79% пациентов с РА, в то же время менее 1/2 из них получали дополнительно колекальциферол. Низкий уровень витамина D ассоциировался с наличием у них высокой активности заболевания, саркопенией и ожирением.

Topics: Arthritis, Rheumatoid; Avitaminosis; Body Composition; Cholecalciferol; Comorbidity; Female; Humans; Middle Aged; Obesity; Sarcopenia; Severity of Illness Index; Vitamin D; Vitamins

To investigate the correlation between sarcopenia and nailfold microcirculation and serum 25-hydroxycholecalciferol [25 (OH) D3] (instead of 25-hydroxyvitamin D) and IL-17 levels in female rheumatoid arthritis (RA) patients.. 130 female rheumatoid arthritis (RA) patients and 80 healthy controls were tested. Nailfold capillaroscopic scores (NFCS) were measured. Bioimpedance analysis (BIA) was used to measure skeletal muscle mass. Enzyme-linked immunosorbant assay (ELISA) was used to detect the levels of IL-17, IL-6 and TNF-α. Serum 25 (OH) D3 concentration was determined by photochemical immunoassay. The correlation was analyzed by Pearson's correlation, and the influencing factors were analyzed by binary logistic regression.. (1) Compared with the control group, NFCS and serum IL-17 levels were higher in the RA group, while the serum 25 (OH) D3 and skeletal mass index (SMI) were lower. (2) Pearson correlation analysis found: SMI was positively correlated with 25 (OH) D3 (r=0.515, P<0.001), SMI was negatively correlated with IL-17 (r=-0.468, P<0.001), SMI was negatively correlated with NFS (r = -0.229, P=0.009); (3) Logistic regression analysis: serum 25 (OH) D3 was a protective factor for sarcopenia (OR=0.392, P=0.016); IL-17, C-reactive protein, and NFS were risk factors for sarcopenia (OR=1.516, P=0.049; OR=1.469, P=0.045; OR=3.497, P=0.002).. Secondary sarcopenia in RA is common and is closely related to microcirculation abnormalities. Increased NFCS is a risk factor for sarcopenia. Decreased serum 25 (OH) D3 levels and increased IL-17 are also risk factors for sarcopenia, but the mechanisms involved in sarcopenia and microcirculation abnormalities need further investigation.

Topics: Arthritis, Rheumatoid; Calcifediol; Cholecalciferol; Female; Humans; Interleukin-17; Microcirculation; Sarcopenia

This study aims to investigate the regulatory mechanism of 1,25-(OH)2D3 on the proliferation of fibroblast-like synoviocytes (FLS) and expressions of pro-inflammatory cytokines in rheumatoid arthritis (RA) rats via microRNA-22 (miR-22).. A rat model of RA was established with a subcutaneous injection of type II collagen. After treated with different concentrations of 1,25-(OH)2D3 the proliferation of FLS was estimated by the MTT method, and the optimal concentration of 1,25-(OH)2D3 was selected for further experiments. Cell proliferation was detected by MTT. Cell cycle and apoptosis were analyzed by FCM. The IL-1β, IL-6, IL-8, and PGE2 protein expressions were determined by ELISA, and MMP-3, INOS, and Cox-2 mRNA expressions were measured by qRT-PCR.. The rat model of RA was successfully established. Compared with the blank group, the 1,25-(OH)2D3 and miR-22 inhibitors groups exhibited higher proliferation inhibition and apoptosis rates, lower levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and PGE2), and decreased mRNA expressions of MMP-3, INOS, and Cox-2. The miR-22 mimics group had lower proliferation inhibition and apoptosis rates, elevated expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 than the blank group. In contrast to the 1,25-(OH)2D3 group, the proliferation inhibition and apoptosis rates were down-regulated, and the expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 were up-regulated in the 1,25-(OH)2D3 + miR-22 mimics group.. Our study demonstrated that 1,25-(OH)2D3 inhibits the proliferation of FLS and alleviates inflammatory response in RA rats by down-regulating miR-22.

Topics: Animals; Antagomirs; Apoptosis; Arthritis, Rheumatoid; Cell Proliferation; Cells, Cultured; Cholecalciferol; Cyclooxygenase 2; Cytokines; Dinoprostone; Disease Models, Animal; Down-Regulation; Fibroblasts; Male; Matrix Metalloproteinase 3; MicroRNAs; Nitric Oxide Synthase Type II; Rats; Rats, Sprague-Dawley; Synoviocytes

The induction of tolerance has been proposed as a therapeutic strategy for arthritis aiming to decrease progression of the pathology, probably by promoting suppressor mechanisms of the autoimmune response. This work aimed to confirm whether the treatment with vitamin D3 could synergize oral tolerance induced by hydrolyzed collagen peptides, in our experimental model of antigen induced arthritis in New Zealand rabbits. Clinical observation of the phenomenon indicates that simultaneous treatment with hydrolyzed collagen peptides and vitamin D3 was beneficial when compared with no treatment, for arthritic animals, and for arthritic animals that received treatment with only hydrolyzed collagen peptides or vitamin D3. Treatment with hydrolyzed collagen peptides caused diminished proinflammatory cytokine levels, an effect synergized significantly by the simultaneous treatment with vitamin D3. The anatomical-pathological studies of the animals that received both treatments simultaneously showed synovial tissues without lymphocytic and plasma cell infiltrates, and without vascular proliferation. Some of the synovial tissue of the animals of these groups showed a slight decrease in Galectin-3 expression. We propose that simultaneous oral treatment with vitamin D3 and hydrolyzed collagen peptides could increase the immunoregulatory effect on the process of previously triggered arthritis. We used articular cartilage hydrolysate and not collagen II because peptides best expose antigenic determinants that could induce oral tolerance. Oral tolerance may be considered in the design of novel alternative therapies for autoimmune disease and we have herein presented novel evidence that the simultaneous treatment with vitamin D3 may synergize this beneficial effect.

Topics: Administration, Oral; Animals; Arthritis, Rheumatoid; Cholecalciferol; Collagen; Cytokines; Female; Humans; Peptides; Rabbits; Synovial Membrane

The effect of vitamin D3 in oral solution (VD3 ) and vitamin D3 -loaded nanocapsules (NC-VD3 ) was analysed in animals with complete Freund's adjuvant (CFA) induced arthritis (AR). For this purpose, we evaluated scores for arthritis, thermal hyperalgesia and paw oedema, as well as histological analyses and measurements of the activity of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) and ecto-adenosine deaminase (E-ADA) enzymes in rat lymphocytes. Haematological and biochemical parameters were also determined. The doses administered were 120 UI/day of VD3 and 15.84 UI/day of NC-VD3 . Fifteen days after the induction of AR, the groups were treated for 15 days with vitamin D3 . The results demonstrated that VD3 was able to reduce arthritis scores, thermal hyperalgesia and paw oedema in rats with CFA-induced arthritis. However, treatment with NC-VD3 did not reduce arthritis scores. The histological analyses showed that both formulations were able to reduce the inflammatory changes induced by CFA. The activity of E-NTPDase in rat lymphocytes was higher in the AR compared with the control group, while the activity of E-ADA was lower. This effect was reversed after the 15-day treatment. Data from this study indicates that both forms of vitamin D3 seem to contribute to decreasing the inflammatory process induced by CFA, possibly altering the activities of ectoenzymes. Copyright © 2016 John Wiley & Sons, Ltd.. The effects promoted by both formulations of vitamin D3 , either in oral solution or nanoencapsulated form, strongly suggests the softening of the inflammatory process induced by complete Freund's adjuvant (CFA), possibly altering the E-NTPDase and E-ADA activities. However, it is known that vitamin D has a beneficial effect on the modulation of the immune system components responsible for the inflammatory process. Moreover, the establishment of responses to treatment with vitamin D3 may provide an alternative for inhibiting the proinflammatory response, assisting in our understanding of the immunopathology of this disease and possibly improving the signs and symptoms that hinder the quality of life of patients with rheumatoid arthritis.. Evaluation of the effects on the E-NTPDase and E-ADA activities in an animal model of induced arthritis. Two formulations of vitamin D3 were used: form oral solution and nanoencapsulated. Vitamin D3 seems to contribute to the inflammatory process induced by CFA. Vitamin D3 possibly alters the E-NTPDase and E-ADA activities. Vitamin D3 may be an alternative supplementary treatment for chronic arthritis.

Topics: Adenosine Deaminase; Administration, Oral; Animals; Anti-Inflammatory Agents; Antigens, CD; Apyrase; Arthritis, Rheumatoid; Cholecalciferol; Disease Models, Animal; Female; Freund's Adjuvant; Lymphocytes; Nanocapsules; Nanoparticles; Rats, Wistar; Solutions

Tolerogenic dendritic cells (tDCs) are a promising therapeutic tool for specific induction of immunological tolerance. Human tDCs can be generated ex vivo using various compounds. However, the compound(s) most suitable for clinical application remain undefined. We compared the tolerogenic properties of tDCs treated with protein kinase C inhibitor (PKCI), dexamethasone, vitamin D3 (Vit D3), rapamycin (Rapa), interleukin (IL)-10, transforming growth factor (TGF)-β, and a combination of peroxisome proliferator-activated receptor γ agonist and retinoic acid. All tDCs had a semi-mature DC phenotype. PKCI-, TGF-β-, and Rapa-tDCs showed CCR7 expression and migration to CCL19, but other tDCs showed little or none. PKCI- and IL-10-tDCs induced functional regulatory T cells more strongly than other tDCs. The tolerogenic properties of all tDCs were stable against proinflammatory stimuli. Furthermore, PKCI-tDCs were generated from patients with rheumatoid arthritis and primary Sjögren's syndrome. Therefore, PKCI-tDCs showed the characteristics best suited for tolerance-inducing therapy.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Chemotaxis; Cholecalciferol; Cytokines; Dendritic Cells; Dexamethasone; Female; Humans; Immune Tolerance; Male; Middle Aged; Phagocytosis; PPAR gamma; Protein Kinase C; Protein Kinase Inhibitors; Sirolimus; Sjogren's Syndrome; T-Lymphocytes, Regulatory; Transforming Growth Factor beta; Tretinoin

To investigate the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)₂D₃] on T helper cell type 17 (Th17) cytokines and therapeutic mechanism in patients with rheumatoid arthritis (RA).. Peripheral blood mononuclear cells (PBMCs) from healthy donors and RA patients were collected. The PBMCs were stimulated with anti-CD3/anti-CD28 monoclonal antibodies in the absence or presence of 1,25(OH)₂D₃and methotrexate (MTX). After co-culture, the serum levels of Th17 cytokines interleukin (IL)-17, IL-6, tumour necrosis factor alpha (TNFα) were analyzed by cytometric bead array (CBA). The level of IL-22 was analyzed by enzyme-linked immunosorbent assay (ELISA). The independent samples t test and one-way analysis of variance (ANOVA) were used for statistical analysis.. The levels of cytokines IL-17, TNFα, IL-6 and IL-22 in RA group were significantly higher than those in the control group [(43 ± 6)ng/L, (5.91 ± 2.53)ng/L, (16.6 ± 12.0)ng/L, (51 ± 17)ng/L vs (21 ± 3)ng/L, (2.63 ± 0.27)ng/L, (4.2±2.3)ng/L, (22 ± 14)ng/L]. Each of the three different 1,25(OH)₂D₃doses inhibited secretion of IL-17[(533 ± 47) pg/ml, (426 ± 55)pg/ml, (319 ± 86)pg/ml], TNFα[(424 ± 82)pg/ml, (382 ± 79)pg/ml, (326 ± 87)pg/ml], and IL-6[(5 513 ± 3 429)pg/ml, (4 555 ± 3 157)pg/ml, (3 748 ± 1 919)pg/ml] in RA group (P < 0.05), yet no statistical difference was found in IL-22 secretion with a trend of decrease after treatment of 1,25(OH)₂D₃. Three different doses of MTX inhibited secretion of IL-17 [(452 ± 50) pg/ml, (372 ± 67) pg/ml, (315 ± 104)pg/ml] and TNFα [(319 ± 74)pg/ml, (292 ± 59)pg/ml, (266 ± 64)pg/ml] in RA group (P < 0.05).However, levels of IL-6 and IL-22 were not affected after treated with MTX.. Our data indicated that 1,25(OH)₂D₃may play as an immune modulating agent to suppress Th17 cell cytokines. Supplement of vitamin D has the effective potential to treat patients with RA or other Th17 cell mediated autoimmune disorders.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Case-Control Studies; Cholecalciferol; Cytokines; Dose-Response Relationship, Drug; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-17; Interleukin-22; Interleukin-6; Interleukins; Leukocytes, Mononuclear; Male; Methotrexate; Middle Aged; RNA, Messenger; Th17 Cells; Tumor Necrosis Factor-alpha; Vitamin D; Vitamins

Tumoral necrosis factor alpha blockers are very efficient in the treatment of many inflammatory systemic diseases, including rheumatoid arthritis and psoriasis. However, a paradoxical arouse of psoriasiform lesions may occur in a few patients taking anti-TNFα. The etiology of this rare side effect is still a mystery, and its treatment may be difficult. The authors report the resolution of adalimumab-induced psoriasis in a woman with rheumatoid arthritis after the use of high vitamin D(3) doses for the treatment of vitamin D deficiency. This is the first report of resolution of anti-TNFα-induced psoriasiform lesions by high doses of vitamin D(3) in a patient with rheumatoid arthritis and vitamin D deficiency. This case raises interesting questions on the role of vitamin D deficiency in the pathogenesis of this side effect and on the possible usefulness of high-dose vitamin D(3) in its treatment.

Topics: Adalimumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antirheumatic Agents; Arthritis, Rheumatoid; Biomarkers; Cholecalciferol; Drug Substitution; Female; Humans; Middle Aged; Psoriasis; Risk Factors; Rituximab; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha; Vitamin D; Vitamin D Deficiency; Vitamins

Inflammatory bone destruction is a prominent feature and a cause of substantial morbidity in several inflammatory diseases, including rheumatoid arthritis (RA), periodontitis, and peri-prosthetic loosening. Osteoclasts are unique, multinucleated giant cells that effectively resorb bone and thus are directly responsible for bone destruction in several inflammatory diseases. PI3K/Akt/mTOR pathway has been well known to play important roles in regulating adaptive and innate immune cell function. In addition to play roles in immune responses, several lines of evidence demonstrate that PI3K/Akt/mTOR pathway is critical for osteoclast differentiation and survival. These results suggest that inhibition of PI3K/Akt/mTOR pathway could protect against bone destruction in inflammatory diseases, including RA. However, the clinical use of mTOR inhibitors may be hampered due to limited clinical efficacy and frequent toxic side effects. In the treatment of RA, combination therapy with various disease-modifying antirheumatic drugs (DMARDs) has been suggested to improve the therapeutic efficacy and limit the side effects. In this report, we show several experimental evidences that vitamin D(3) modulates mTOR pathway, and present a hypothesis that the combination of mTOR inhibitor and vitamin D(3) can effectively inhibit osteoclast differentiation and function in chronic inflammatory condition such as RA, therefore this combination will be a powerful therapeutic regimen in preventing the inflammation-induced bone destruction in RA.

Topics: Arthritis, Rheumatoid; Cholecalciferol; Humans; Models, Theoretical; TOR Serine-Threonine Kinases

Topics: Arthritis, Rheumatoid; Cholecalciferol; Diabetes Mellitus, Type 2; Humans; Osteoporosis; Respiratory Tract Infections; Vitamin D Deficiency

Rheumatoid arthritis (RA) is often complicated by generalized osteopenia due to increased bone resorption by osteoclasts. We analysed a number of cellular and humoral factors that influence osteoclast formation from circulating precursors in RA patients.. Monocytes isolated from RA patients and normal controls were cultured with macrophage colony-stimulating factor (M-CSF) and nuclear factor-kappaB ligand (RANKL), or with RANKL-expressing UMR106 cells and 1,25 dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. Osteoclast differentiation was assessed by expression of tartrate-resistant acid phosphatase (TRAP) and vitronectin receptors (VNR) and lacunar resorption.. Osteoclasts formed from RA patients exhibited increased resorptive activity but there was no difference in the relative proportion of circulating osteoclast precursors between RA patients and normal controls. Osteoclast precursors in RA patients were not more sensitive to the osteoclastogenic effects of 1,25(OH)(2)D(3), M-CSF or RANKL. Dexamethasone, but not interleukin (IL) 1beta, tumour necrosis factor alpha and IL-6, increased osteoclast formation and lacunar resorption.. There is an increase in the extent of lacunar resorption carried out by osteoclasts formed from circulating precursors in RA patients. This is not due to an increase in the number of circulating precursors or increased sensitivity to the osteoclastogenic effects of 1,25(OH)(2)D(3), M-CSF, RANKL or inflammatory cytokines. Our findings suggest that increased osteoclast functional activity rather than osteoclast formation is more likely to play a role in the generalized bone loss that occurs in RA, and that corticosteroids stimulate osteoclast formation and resorption.

Topics: Adult; Aged; Arthritis, Rheumatoid; Bone Resorption; Carrier Proteins; Case-Control Studies; Cell Division; Cells, Cultured; Cholecalciferol; Culture Media, Conditioned; Dexamethasone; Female; Humans; Interleukin-1; Interleukin-6; Macrophage Colony-Stimulating Factor; Male; Membrane Glycoproteins; Middle Aged; Monocytes; Osteoclasts; Osteoporosis; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Reference Values; Sensitivity and Specificity; Tumor Necrosis Factor-alpha

Renal stones are reported to be one of the causes of hematuria in patients with juvenile rheumatoid arthritis (RA). We performed abdominal ultrasonography on patients with RA to investigate the frequency of renal stones and whether renal stones are related to hematuria.. We conducted abdominal ultrasonography in 224 patients with RA (42 men, 182 women). Mean age was 61.4 years, and the mean duration of disease was 13.5 years.. Renal stones were defined as hyperechoic spots with acoustic shadows, and they were observed in 37 patients. We also noticed hyperechoic spots without acoustic shadows in 50 patients. Five of these 50 patients also had renal stones. Twenty-one patients showing hyperechoic spots without acoustic shadows underwent computed tomographic scans, and apparent calcifications were observed in 10 patients. Age and sex matched controls had a significantly lower incidence of renal stones and hyperechoic spots without acoustic shadows than did patients with RA. Hematuria was more frequently observed in patients with RA with renal stones than in those without renal stones or hyperechoic spots without acoustic shadows. Urinary calcium/creatinine (Ca/Cr) ratios were elevated in patients compared to controls. Urinary Ca/Cr ratios in patients taking vitamin D3 were higher than those of patients not receiving the vitamin. Administration of vitamin D3 also was associated with increased incidence of renal stones.. We observed a high incidence of renal stones in patients with RA. Hematuria was more prevalent in patients with RA with renal stones than in those without. These results suggest the importance of performing abdominal ultrasonography on patients with RA.

Topics: Aged; Arthritis, Rheumatoid; Biopsy; Calcium; Cholecalciferol; Creatinine; Female; Hematuria; Humans; Kidney; Kidney Calculi; Male; Middle Aged; Tomography, X-Ray Computed; Ultrasonography

Human cartilage glycoprotein 39 (HC gp-39) has been described as a major secreted product of cultured articular chondrocytes, synovial fibroblasts, and the osteosarcoma line MG63. However, its expression in these cells types has not been directly linked to corresponding cell types in vivo. In this report, expression of HC gp-39 is demonstrated from peripheral blood-derived macrophages in association with their differentiation from monocytes to macrophages. Consistent with macrophage specificity, HC gp-39 expression is also induced upon selective stimulation of the pluripotent promyelocytic leukemia cell line HL-60 toward the monocyte/macrophage lineage with vitamin D3 or phorbol 12-myristate 13-acetate (PMA), while treatments stimulating granulocyte and eosinophilic pathways do not induce expression. Furthermore, HC gp-39 expression levels correlate with the degree of morphological differentiation induced by PMA and vitamin D3 treatments. PMA-induced mRNA expression occurs by 36 h and is a secondary transcriptional response since its synthesis is inhibited by cycloheximide. Apparently, HC gp-39 expression is tied to later events in the differentiation of monocytes into macrophages. The in vivo significance of these results is validated by the in situ detection of HC gp-39 mRNA in inflammatory macrophages associated with rheumatoid synovium. Thus, macrophages appear to be an important source of HC gp-39, which has been shown to be present at elevated levels in the blood and synovium of rheumatoid arthritis patients. The implications of this extend well beyond the previously restricted observations in cell types associated with the joint and suggest a potential involvement of macrophage-derived HC gp-39 in other aspects of inflammation, tissue remodeling, and host defense.

Topics: Adipokines; Arthritis, Rheumatoid; Cartilage, Articular; Cell Differentiation; Cell Line; Cells, Cultured; Chitinase-3-Like Protein 1; Cholecalciferol; Cycloheximide; Glycoproteins; HL-60 Cells; Humans; Inflammation; Jurkat Cells; Kinetics; Lectins; Macrophages; Monocytes; Polymerase Chain Reaction; Recombinant Proteins; Reference Values; RNA, Messenger; Synovial Membrane; Tetradecanoylphorbol Acetate; Transcription, Genetic

1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) has been shown to modulate lymphocyte activation in vitro. Through binding to specific receptors 1,25-(OH)2 D3 inhibits proliferation, immunoglobulin production and the release of cytokines. Moreover, 1,25-(OH)2 D3 is efficiently produced by activated monocytes. These findings suggest that 1,25-(OH)2 D3 may play a role as a regulator of immunological activation. Consequently, we found it of interest to study the serum levels of the two major metabolites of vitamin D3 in patients with systemic lupus erythematosus (SLE) (n = 21), rheumatoid arthritis (RA) (n = 29) and osteoarthritis (n = 12). In patients with SLE the levels of 25-OH D3 were below those of the healthy controls (p = 0.0008) and OA (p = 0.0168). The levels 1,25-(OH)2 D3 corresponded to normal levels. There were no significant correlations between 25-OH D3 levels and clinical or paraclinical disease manifestations. Further, the phenotypic distribution of Gc-globulin, which binds vitamin D3 metabolites in circulation, was normal. The serum concentrations of 1,25-(OH)2 D3 and 25-OH D3 in patients with RA and OA corresponded to those of the controls. Although the cause of the reduced 25-OH D3 levels in SLE patients is unclear, possible beneficial effects of administration of vitamin D to these patients should be considered.

Topics: Adult; Aged; Antirheumatic Agents; Arthritis, Rheumatoid; Calcifediol; Calcitriol; Cholecalciferol; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Osteoarthritis; Vitamin D-Binding Protein

Cellular mechanisms accounting for the osteolysis of rheumatoid erosions are poorly understood. Cells were isolated and characterised from the synovium of 16 patients with rheumatoid arthritis (RA) and four patients with osteoarthritis and their ability to resorb bone was assessed using a scanning electron microscope bone resorption assay. Macrophages were the major cell type isolated from the synovium of patients with RA. These produced extensive roughening of the bone surface without resorption pit formation. This low grade type of bone resorption was not affected by systemic (calcitonin, parathyroid hormone, 1,25-dihydroxyvitamin D3) or local (interleukin 1, prostaglandin E2) factors influencing bone resorption. Macrophage mediated bone resorption differs qualitatively and quantitatively from that of osteoclasts but is likely to play an important part in the development of marginal erosions in RA.

Topics: Adult; Aged; Arthritis, Rheumatoid; Bone and Bones; Bone Resorption; Calcitonin; Cells, Cultured; Cholecalciferol; Female; Humans; Interleukin-1; Macrophages; Male; Microscopy, Electron, Scanning; Middle Aged; Osteoarthritis; Parathyroid Hormone; Prostaglandins; Rheumatic Diseases; Synovial Membrane