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ID PMID Title PublicationDate abstract
32453039 Spondyloarthritis evolution: what is in your history? 2020 Jul PURPOSE OF REVIEW: This review encompasses a detailed history of spondyloarthritis (SpA) evolution as early as the 17th century, continues on to the current concept of SpA, and ends with current gaps in our understandings of SpA. RECENT FINDINGS: Until the early 1960s, ankylosing spondylitis and other SpA family members were considered to be variants of rheumatoid arthritis (RA). The formal medical community separated them from RA at that time, and shortly thereafter they were recognized to be inter-connected based on shared clinical, laboratory, and imaging features. The last two decades have witnessed the formal distinction between axial and peripheral SpA and the connections that exist between nonradiographic and radiographic axial SpA. Recent studies have revealed different microbial compositions among patients with SpA and healthy controls and also between HLA-B27 positive and negative healthy individuals. SUMMARY: Further investigation of the roles of intestinal microbiome and physical force transduction toward SpA pathogenesis, strategies to improve delay in SpA diagnosis, biomarkers to better predict radiographic progression, and modification of current classification criteria to better address the axial and peripheral groups are gaps in our understandings that pose top priorities for SpA research.
32223931 Helper-like Innate Lymphoid Cells in Humans and Mice. 2020 May The innate lymphoid cell (ILC) family consists of natural killer (NK) cells, helper-like lymphoid cells (ILC1s, ILC2s, and ILC3s), and lymphoid tissue inducer (LTi) cells. Helper-like ILCs are considered the innate counterpart of T-helper cells because of similarities in their cytokine output and expression of key transcription factors. ILCs provide and regulate innate immune functions before the development of adaptive immunity. They are involved in host defense against pathogens, inflammation, tissue repair, and metabolic homeostasis. However, they can also be involved in inflammatory disorders and carcinogenesis. In this review, we summarize the latest research on ILC development and plasticity in humans and mice, focusing on the pathogenic role of helper-like ILCs in inflammatory disorders, such as asthma, Crohn's disease (CD), and rheumatoid arthritis (RA).
33552242 Human endogenous retroviruses in cancer: Expression, regulation and function. 2021 Feb Human endogenous retroviruses (HERVs) are the remnants of ancient retroviruses that infected human germline cells and became integrated into the human genome millions of years ago. Although most of these sequences are incomplete and silent, several potential pathological roles of HERVs have been observed in numerous diseases, such as multiple sclerosis and rheumatoid arthritis, and especially cancer, including breast cancer and pancreatic carcinoma. The present review investigates the expression signatures and complex regulatory mechanisms of HERVs in cancer. The long terminal repeats-driven transcriptional initiation of HERVs are regulated by transcription factors (such as Sp3) and epigenetic modifications (such as DNA methylation), and are influenced by environmental factors (such as ultraviolet radiation). In addition, this review focuses on the dual opposing effects of HERVs in cancer. HERVs can suppress cancer via immune activation; however, they can also promote cancer. HERV env gene serves a prime role in promoting carcinogenesis in certain malignant tumors, including breast cancer, pancreatic cancer, germ cell tumors, leukemia and Kaposi's sarcoma. Also, HERV ENV proteins can promote cancer via immune suppression. Targeting ENV proteins is a potential future antitumor treatment modality.
33131480 [The place of riociguat in the treatment of patients with pulmonary arterial hypertension 2020 Oct 14 Pulmonary hypertension (PH) can develop in different systemic autoimmune rheumatic diseases (SARD), such as systemic scleroderma (SSD), systemic lupus erythematosus, rheumatoid arthritis, and mixed connective tissue disease In most cases, patients with SARD develop WHO group I PH (pulmonary arterial hypertension associated with systemic connective tissue diseases, PAH-SCTD). General prevalence of this pathology reaches 15 cases per million adults. Most cases of PAH-SCTD are induced by SSD. Survival of PAH-SCTD patients is generally lower than survival of patients with other forms of LAH. Treatment of any SARD, including in LAH, implies a complex approach using glucocorticoids, disease-modifying anti-rheumatic drugs (cyclophosphamide, methotrexate, azathioprine, and others), and genetically engineered biologics. Specific targeted therapy is indicated for most patients with PAH-SCTD. The representative of a new class (soluble guanylate cyclase (sGC) stimulators), riociguat, has been approved for the treatment of PAH. This drug has a unique double mechanism of action: (i) sGC sensibilization to endogenous nitric oxide (NO) by stabilizing the NO-sGC bond; and (ii) direct, NO-independent sGC stimulation. For patients with PAH-SCTD, riociguat is the major alternative to phosphodiesterase-5 inhibitors both as monotherapy and combination therapy.
33127706 Foreign body episcleral suture granulomas mimicking nodular anterior scleritis. 2020 Oct 30 Scleritis is an idiopathic condition that may sometimes be associated with systemic immunological like disorders rheumatoid arthritis, Wegener's granulomatosis and systemic lupus erythematosus. A variety of foreign material has been reported to result in granuloma formation in various parts of the body. We report a case of inflamed episcleral granulomas mimicking severe nodular anterior scleritis in a healthy Caucasian woman who underwent strabismus surgery in her childhood. Foreign body reaction on the episcleral/scleral surface is rare. It is extremely unusual for a non-absorbable suture that was used for childhood strabismus surgery to incite an acute inflammatory episode mimicking nodular anterior scleritis as in our case. As the strabismus surgery was performed 37 years prior to her presentation with anterior scleritis, we were unable to obtain any details of this surgical procedure. We presume that a non-absorbable suture like braided polyester or prolene may have been used.
32942118 Inflammatory colitis associated with Teriflunomide. 2020 Nov Teriflunomide is an oral disease modifying therapy for relapsing-remitting multiple sclerosis (RRMS). Gastrointestinal (GI) side effects occurred in 15-17.9% of patients in the clinical trials and usually were mild and self-limiting. Few cases of inflammatory colitis related to teriflunomide and leflunomide, a prodrug which converts to teriflunomide and is used in the treatment of rheumatoid arthritis, have been reported but no clinical data is available except for a single case of lymphocytic colitis. We here report a 49-year-old man with RRMS who developed severe diarrhea and weight loss six months after starting teriflunomide and eventually was found to have multiple ulcers and inflammatory changes consistent with Crohn's disease. After stopping teriflunomide and chelation therapy, he was started on immunotherapy for Crohn's given the highly inflammatory degree of GI symptoms and histology findings.
34872256 IMMUNE-MEDIATED INTRAOCULAR INFLAMMATION. A REVIEW. 2020 Winter Immune mediated inflammatory diseases are categorized into autoimmune and autoinflammatory. Autoimmune etiology is represented by autoreactive lymphocytes or autoantibodies, e.g. primary Sjögrens syndrome or rheumatoid arthritis. Ocular specific diseases with presumed autoimmune origin are sympathetic ophthalmia or birdshot chorioretinopathy. Autoinflammatory diseases are caused by mutations in regulatory genes for specific immunity. Hereditary periodic fevers represent monogenic autoinflammatory diseases; eye specific is Blau syndrome also named sarcoidosis with early onset. This article reviews the actual knowledge about immune mediated uveitides, their immunological mechanisms and the possible trigger role of infection in autoimmune inflammation. Immune privilege provides a protection of the eye against any strong immune reaction to foreign antigen, based on physical, immune, humoral and molecular mechanisms. Antigens hidden within the eye are revealed in case of damage of hematoretinal barrier caused by infection or mechanical insult. These ocular antigens have not been set as tolerable during the development and immune reaction is initiated subsequently. Current studies demonstrate that uveogenic trigger might be generated by own microbiome, particularly when dysregulated, so called dysbiosis. There is a known association between idiopathic inflammatory bowel disease with ankylosing spondylitis and anterior uveitis in humans. Intensive research is focused on microbiome and immune mediated inflammatory disease to influence therapeutically the intestinal microbiome. The animal models are used to study the immunopathological mechanisms of uveitis and the new therapeutic strategies, because of relatively low incidence of immune mediated uveitis in humans.
32509724 Gold(III) Complexes: An Overview on Their Kinetics, Interactions With DNA/BSA, Cytotoxic A 2020 In the last few years, metallodrugs play a key role in the development of medicinal chemistry. The choice of metal ion, its oxidation state and stability, and the choice of inert and labile ligands are just some of the very important facts which must be considered before starting the synthesis of complexes with utilization in medicinal purpose. As a result, a lot of compounds of different transition metal ions found application for diagnostic and therapeutic purpose. Beside all, gold compounds have attracted particular attention. It is well-known that gold compounds could be used for the treatment of cancer, HIV, rheumatoid arthritis (chrysotherapy), and other diseases. This metal ion has unoccupied d-sublevels and possibility to form compounds with different oxidation states, from -1 to +5. However, gold(I) and gold(III) complexes are dominant in chemistry and medicine. Especially, gold(III) complexes are of great interest due to their structural similarity with cisplatin. Accordingly, this review summarizes the chemistry of some mononuclear and polynuclear gold(III) complexes. Special attention is given to gold(III) complexes with nitrogen-donor inert ligands (aliphatic or aromatic that have a possibility to stabilize complex) and their kinetic behavior toward different biologically relevant nucleophiles, mechanism of interaction with DNA/bovine serum albumin (BSA), cytotoxic activity, as well as computational calculations.
32305984 Comorbidities in the Elderly and Their Possible Influence on Vaccine Response. 2020 The following chapter is focused on the impact of comorbidities on the effectiveness of vaccination in older persons. Relevant comorbidities are cardiovascular diseases like hypertension, coronary artery disease or congestive heart failure, which lead to reduction of vaccine immunogenicity; or chronic obstructive pulmonary disease with a decline in lung function and a higher risk for pneumonia or infections due to influenza. End-stage renal disease has a high impact on developing infections and causes immune dysfunction over all parts of the immune system. Depression and dementia as well as psychological stress are associated with poor antibody response and a higher range of inflammation markers. Chronic inflammatory processes like rheumatoid arthritis also alter the immune system. In addition, geriatric syndromes and lowered functional status have implications for the vaccination response. Malnutrition is characterized by depletion of structural and functional proteins. This leads to a low antibody response. Negative immunomodulatory effects are also observed in vitamin D insufficiency. Frailty as well is associated with immunological changes and lowered performance in the activities of daily living, but moderate physical activity improves immune function.
32256634 Research Progress on Anti-Inflammatory Effects and Mechanisms of Alkaloids from Chinese Me 2020 As the spectrum of diseases keeps changing and life pace keeps going faster, the probability and frequency of diseases caused by human inflammatory reactions also keep increasing. How to develop effective anti-inflammatory drugs has become the hotspot of researches. It has been found that alkaloids from Chinese medical herbs have anti-inflammatory, analgesic, antitumor, anticonvulsant, diuretic, and antiarrhythmic effects, among which the anti-inflammatory effect is very prominent and commonly used in the treatment of rheumatoid arthritis, ankylosing spondylitis, and other rheumatic immune diseases, but its mechanism of action has not been well explained. Based on this, this paper will classify alkaloids according to structural types and review the plant sources, applicable diseases, and anti-inflammatory mechanisms of 16 kinds of alkaloids commonly used in clinical treatment, such as berberine, tetrandrine, and stephanine, with the aim of providing a reference for drug researches and clinical applications.
31956585 Molecular pathobiology of scleritis and its therapeutic implications. 2020 Scleritis and other autoimmune diseases are characterized by an imbalance in the levels of pro-inflammatory and anti-inflammatory molecules with the balance tilted more towards the former due to the failure of recognition of self. The triggering of inflammatory process could be ascribed to the presence of cytoplasmic DNA/chromatin that leads to activation of cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway and enhanced expression of NF-κB that results in an increase in the production of pro-inflammatory bioactive lipids. Bioactive lipids gamma-linolenic acid (GLA), dihomo-GLA (DGLA), prostaglandin E1 (PGE1), prostacyclin (PGI2) and lipoxin A4, resolvins, protectins and maresins have anti-inflammatory actions, bind to DNA to render it non-antigenic and are decreased in autoimmune diseases. These results suggest that efforts designed to enhance the production of anti-inflammatory bioactive lipids may form a new approach to autoimmune diseases. Local injection or infusion of lipoxins, resolvins, protectins and maresins or their precursors such as arachidonic acid may be exploited in the prevention and management of autoimmune diseases including scleritis, uveitis and lupus/rheumatoid arthritis.
31493927 The sex ratio at birth (2). 2020 Feb This second of two Best Practise Guidelines will continue to explore facets pertaining to factors that influence the sex ratio at birth (M/F). The papers include a quantitative study in the United States, investigating the effects of Thanksgiving Day, Christmas Day and Valentine's Day on M/F (which rises). A second paper is devoted to the factor that most influences M/F worldwide: male offspring preference. The third paper focusses on radiation which appears to be the only toxin/stressor that increases M/F by culling female in excess of male foetuses. The paper investigates the effects of the Mainz research nuclear reactor in Germany. Yet another paper reviews seasonality of M/F. Two more theoretical papers discuss the significance of low M/F of offspring and of siblings of probands with systemic lupus erythematosus or rheumatoid arthritis, implicating a common role for testosterone. In yet another paper, high levels of maternal first-trimester intrauterine testosterone are also implicated in male sex, autism, gender dysphoria and non-right-handedness. Finally, a paper reviews the effects of toxoplasmosis on M/F since may be one of the most important environmental factors on this ratio. It is hoped that this second set of papers will further provide stimulation and provocation for research on this intriguing topic.
31109966 Vagus Nerve Stimulation and the Cardiovascular System. 2020 Feb 3 The vagus nerve plays an important role in maintaining physiological homeostasis, which includes reflex pathways that regulate cardiac function. The link between vagus nerve activity and the high-frequency component of heart rate variability (HRV) has been well established, correlating with vagal tone. Recently, vagus nerve stimulation (VNS) has been investigated as a therapeutic for a multitude of diseases, such as treatment-resistant epilepsy, rheumatoid arthritis, Crohn's disease, and asthma. Because of the vagus nerve's innervation of the heart, VNS has been identified as a potential therapy for cardiovascular disorders, such as cardiac arrest, acute myocardial infarction, and stroke. Here, we review the current state of preclinical and clinical studies, as well as the potential application of VNS in relation to the cardiovascular system.
32610637 Obesity and Morbidity Risk in the U.S. Veteran. 2020 Jun 29 The obesity epidemic in the United States has been well documented and serves as the basis for a number of health interventions across the nation. However, those who have served in the U.S. military (Veteran population) suffer from obesity in higher numbers and have an overall disproportionate poorer health status when compared to the health of the older non-Veteran population in the U.S. which may further compound their overall health risk. This study examined both the commonalities and the differences in obesity rates and the associated co-morbidities among the U.S. Veteran population, utilizing data from the 2018 Behavioral Risk Factor Surveillance System (BRFSS). These data are considered by the Centers for Disease Control and Prevention (CDC) to be the nation's best source for health-related survey data, and the 2018 version includes 437,467 observations. Study findings show not only a significantly higher risk of obesity in the U.S. Veteran population, but also a significantly higher level (higher odds ratio) of the associated co-morbidities when compared to non-Veterans, including coronary heart disease (CHD) or angina (odds ratio (OR) = 2.63); stroke (OR = 1.86); skin cancer (OR = 2.18); other cancers (OR = 1.73); chronic obstructive pulmonary disease (COPD) (OR = 1.52), emphysema, or chronic bronchitis; arthritis (OR = 1.52), rheumatoid arthritis, gout, lupus, or fibromyalgia; depressive disorders (OR = 0.84), and diabetes (OR = 1.61) at the 0.95 confidence interval level.
31267472 The Epidemiology and Clinical Manifestations of Autoimmunity in Selective IgA Deficiency. 2020 Feb Selective immunoglobulin A deficiency (SIgAD) is the most common primary immunodeficiency, defined as an isolated deficiency of IgA (less than 0.07 g/L). Although the majority of people born with IgA deficiency lead normal lives without significant pathology, there is nonetheless a significant association of IgA deficiency with mucosal infection, increased risks of atopic disease, and a higher prevalence of autoimmune disease. To explain these phenomena, we have performed an extensive literature review to define the geoepidemiology of IgA deficiency and particularly the relative risks for developing systemic lupus erythematosus, hyperthyroidism, hypothyroidism, type 1 diabetes mellitus, Crohn's disease, ulcerative colitis, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, and vitiligo; these diseases have strong data to support an association. We also note weaker associations with scleroderma, celiac disease, autoimmune hepatitis, immune thrombocytopenic purpura, and autoimmune hemolytic anemia. Minimal if any associations are noted with myasthenia gravis, lichen planus, and multiple sclerosis. Finally, more recent data provide clues on the possible immunologic mechanisms that lead to the association of IgA deficiency and autoimmunity; these lessons are important for understanding the etiology of autoimmune disease.
32209733 Effects of Diabetes Mellitus on the Disposition of Tofacitinib, a Janus Kinase Inhibitor, 2020 Jul 1 Tofacitinib, a Janus kinase inhibitor, was developed for the treatment of rheumatoid arthritis. Recently, it has been associated with an increased change in arthritis development in patients with diabetes. Herein, we evaluated the pharmacokinetics of tofacitinib after intravenous (10 mg/kg) and oral (20 mg/kg) administration to rats with streptozotocin-induced diabetes mellitus and control rats. Following intravenous administration of tofacitinib to rats with streptozotocin-induced diabetes mellitus, area under the plasma concentration-time curve from time zero to infinity of tofacitinib was significantly smaller (33.6%) than that of control rats. This might be due to the faster hepatic intrinsic clearance (112%) caused by an increase in the hepatic cytochrome P450 (CYP) 3A1(23) and the faster hepatic blood flow rate in rats with streptozotocin-induced diabetes mellitus than in control rats. Following oral administration, area under the plasma concentration-time curve from time zero to infinity of tofacitinib was also significantly smaller (55.5%) in rats with streptozotocin-induced diabetes mellitus than that in control rats. This might be due to decreased absorption caused by the higher expression of P-glycoprotein and the faster intestinal metabolism caused by the higher expression of intestinal CYP3A1(23), which resulted in the decreased bioavailability of tofacitinib (33.0%) in rats with streptozotocin-induced diabetes mellitus. In summary, our findings indicate that diabetes mellitus affects the absorption and metabolism of tofacitinib, causing faster metabolism and decreased intestinal absorption in rats with streptozotocin-induced diabetes mellitus.
32614457 Novel methodology to perform incurred sample reanalysis on dried blood spot cards: Experim 2020 Nov Different options on performing incurred sample reanalysis (ISR) on dried blood spot (DBS) cards were investigated using drugs belonging to various therapeutic areas: (a) darolutamide (to treat prostate cancer) and (b) filgotinib (to treat rheumatoid arthritis). The proposed novel methodology included the generation of half-DBS and quarter-DBS discs after initial blood collection using the full-DBS discs. Accordingly, blood collection via DBS was performed in male BALB/c mice following intravenous and oral dosing of darolutamide; in male Sprague Dawley rats following intravenous and oral dosing of filgotinib. The ISR data generated from the full-DBS disc, half-DBS disc and quarter-DBS disc were compared for the assessment of the proposed methodology. Quantification of darolutamide and filgotinib was accomplished using liquid chromatography-electrospray ionization/tandem mass spectrometry methods. Darolutamide and filgotinib ISR samples, which were collected and prepared using full-, half- and quarter-DBS discs, met the acceptance criteria for ISR analysis. In conclusion, this is the first report showing a viable tool for the performance of ISR on DBS cards. The use of quarter- or half-DBS discs would aid in not only ISR but also in long-term storage experiments of analytes because it would avoid the need for additional blood sampling in patients.
32020828 Modeling of cumulative effects of time-varying drug exposures on within-subject changes in 2020 Sep An accurate assessment of the safety or effectiveness of drugs in pharmaco-epidemiological studies requires defining an etiologically correct time-varying exposure model, which specifies how previous drug use affects the outcome of interest. To address this issue, we develop, and validate in simulations, a new approach for flexible modeling of the cumulative effects of time-varying exposures on repeated measures of a continuous response variable, such as a quantitative surrogate outcome, or a biomarker. Specifically, we extend the linear mixed effects modeling to estimate how past and recent drug exposure affects the way individual values of the outcome change throughout the follow-up. To account for the dosage, duration and timing of past exposures, we rely on a flexible weighted cumulative exposure methodology to model the cumulative effects of past drug use, as the weighted sum of past doses. Weights, modeled with unpenalized cubic regression B-splines, reflect the relative importance of doses taken at different times in the past. In simulations, we evaluate the performance of the model under different assumptions concerning (i) the shape of the weight function, (ii) the sample size, (iii) the number of the longitudinal observations and (iv) the intra-individual variance. Results demonstrate the accuracy of our estimates of the weight function and of the between- and within-patients variances, and good correlation between the observed and predicted longitudinal changes in the outcome. We then apply the proposed method to re-assess the association between time-varying glucocorticoid exposure and weight gain in people living with rheumatoid arthritis.
32803042 Antiarthritic Potential of Comprehensively Standardized Extract of Alternanthera bettzicki 2020 Aug 11 Alternanthera bettzickiana is being used as a folk remedy for treating arthritis by conventional healers in Thailand. The current research was undertaken to explore the antiarthritic potential of A. bettzickiana ethanolic extract (ABEE). Plant characterization, molecular docking, and in vitro and in vivo (ABEE at 250, 500, and 1000 mg/kg was administered orally to rats once daily for 28 days) studies to explore the antiarthritic effect and enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) analyses were performed. Oxidative stress biomarkers (superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA)) in the serum and histopathological and radiographic assessment of joints were also carried out. Gallic acid, catechin, chlorogenic acid, sinapic acid, quercetin, and γ- and α-tocopherol were identified in high-performance liquid chromatography (HPLC). Molecular docking revealed a strong interaction between these compounds and cyclooxygenase (COX) enzymes. The extract significantly subdued paw swelling and arthritic scoring, inhibited cachexia, and considerably improved biochemical and hematological modifications. SOD and CAT levels increased and the MDA level decreased in ABEE-treated rats dose-dependently. Radiographic and histopathological analyses also supported the antiarthritic effect of ABEE, which was linked with the downregulation of nuclear factor (NF)-kB, COX-2, interleukin (IL)-6, tumour necrosis factor (TNF)-α, and IL-1β and upregulation of IL-10, I-kB, and IL-4 as compared to disease control rats. Results suggested that A. bettzickiana possessed antiarthritic potential, supporting its folkloric use for treating rheumatoid arthritis.
32468899 Pneumococcal antibody protection in patients with autoimmune inflammatory rheumatic diseas 2020 Sep Objectives: The aims of this cross-sectional study were to assess the pneumococcal antibody coverage in patients with autoimmune inflammatory rheumatic disease (AIRD) and to identify predictors associated with inadequate protective antibody levels. Method: Antibodies to 12 serotypes occurring in the commonly applied pneumococcal vaccines in Denmark were measured in AIRD patients with a diagnosis of rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis attending the Department of Rheumatology at the North Denmark Regional Hospital. Immunization against pneumococcal infection was defined as a geometric mean level ≥ 1 μg antibodies/mL. Clinical information about vaccination status and disease/treatment history was retrieved from the medical file system. Results: Results of antibody measurement and vaccination status were available from 346 AIRD patients, of whom 200 (58%) were registered as receiving pneumococcal vaccination, whereas the remaining 146 patients (42%) were not. Of all 346 patients, only 61 (18%) were measured with an adequate level of protective antibodies (30% vs 1%, respectively). Methotrexate treatment at the time of vaccination and increasing age were identified as predictors of poor vaccination outcome in multiple logistic regression analysis. Conclusions: This post-vaccination study showed that less than one-fifth of the AIRD patients are adequately protected against pneumococcal infection, although the immunization programme had been implemented in more than half of the study population. Development of improved vaccination strategies is required to achieve a higher immunization coverage rate and more efficient lasting antibody response.