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ID PMID Title PublicationDate abstract
34789453 Severe delayed hypersensitivity reactions to IL-1 and IL-6 inhibitors link to common HLA-D 2022 Mar OBJECTIVES: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, delayed hypersensitivity reaction (DHR). We observed DRESS to inhibitors of interleukin 1 (IL-1) or IL-6 in a small group of patients with Still's disease with atypical lung disease. We sought to characterise features of patients with Still's disease with DRESS compared with drug-tolerant Still's controls. We analysed human leucocyte antigen (HLA) alleles for association to inhibitor-related DHR, including in a small Kawasaki disease (KD) cohort. METHODS: In a case/control study, we collected a multicentre series of patients with Still's disease with features of inhibitor-related DRESS (n=66) and drug-tolerant Still's controls (n=65). We retrospectively analysed clinical data from all Still's subjects and typed 94/131 for HLA. European Still's-DRESS cases were ancestry matched to International Childhood Arthritis Genetics Consortium paediatric Still's cases (n=550) and compared for HLA allele frequencies. HLA association also was analysed using Still's-DRESS cases (n=64) compared with drug-tolerant Still's controls (n=30). KD subjects (n=19) were similarly studied. RESULTS: Still's-DRESS features included eosinophilia (89%), AST-ALT elevation (75%) and non-evanescent rash (95%; 88% involving face). Macrophage activation syndrome during treatment was frequent in Still's-DRESS (64%) versus drug-tolerant Still's (3%; p=1.2×10(-14)). We found striking enrichment for HLA-DRB1*15 haplotypes in Still's-DRESS cases versus INCHARGE Still's controls (p=7.5×10(-13)) and versus self-identified, ancestry-matched Still's controls (p=6.3×10(-10)). In the KD cohort, DRB1*15:01 was present only in those with suspected anakinra reactions. CONCLUSIONS: DRESS-type reactions occur among patients treated with IL-1/IL-6 inhibitors and strongly associate with common HLA-DRB1*15 haplotypes. Consideration of preprescription HLA typing and vigilance for serious reactions to these drugs are warranted.
33671965 Early Covert Appearance of Marginal Zone B Cells in Salivary Glands of Sjögren's Syndrome 2021 Feb 15 The C57BL/6.NOD-Aec1Aec2 mouse model has been extensively studied to define the underlying cellular and molecular bioprocesses critical in the onset of primary Sjögren's Syndrome (pSS), a human systemic autoimmune disease characterized clinically as the loss of lacrimal and salivary gland functions leading to dry eye and dry mouth pathologies. This mouse model, together with several gene knockout mouse models of SS, has indicated that B lymphocytes, especially marginal zone B (MZB) cells, are necessary for development and onset of clinical manifestations despite the fact that destruction of the lacrimal and salivary gland cells involves a classical T cell-mediated autoimmune response. Because migrations and functions of MZB cells are difficult to study in vivo, we have carried out ex vivo investigations that use temporal global RNA transcriptomic analyses to profile autoimmunity as it develops within the salivary glands of C57BL/6.NOD-Aec1Aec2 mice. Temporal profiles indicate the appearance of Notch2-positive cells within the salivary glands of these SS-susceptible mice concomitant with the early-phase appearance of lymphocytic foci (LF). Data presented here identify cellular bioprocesses occurring during early immune cell migrations into the salivary glands and suggest MZB cells are recruited to the exocrine glands by the upregulated Cxcl13 chemokine where they recognize complement (C')-decorated antigens via their sphingosine-1-phosphate (S1P) and B cell (BC) receptors. Based on known MZB cell behavior and mobility, we propose that MZB cells activated in the salivary glands migrate to splenic follicular zones to present antigens to follicular macrophages and dendritic cells that, in turn, promote a subsequent systemic cell-mediated and autoantibody-mediated autoimmune T cell response that targets exocrine gland cells and functions. Overall, this study uses the power of transcriptomic analyses to provide greater insight into several molecular events defining cellular bioprocesses underlying SS that can be modelled and more thoroughly studied at the cellular level.
34077805 B cells as target for immunotherapy in rheumatic diseases - current status. 2021 Aug This mini-review is a short overview of different therapeutical strategies targeting B cells in systemic autoimmune rheumatic diseases, mainly: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjogren Syndrome (pSS). Many strategies and their rationale are discussed in this review: B cells' depletion (anti-CD20, anti-CD22), long-lived plasma cells depletion (anti-CD19, anti-CD27, anti-CD38 and anti-CD138), changing activation of B cells (anti-BAFF) and inhibiting proteasomes in plasma cells (bortezomib). The past successful therapies and less successful are shown, and the possible reasons for failures are discussed.
34010274 Programmed cell death 1 ligand (PD-L1) on T cells generates Treg suppression from memory. 2021 May A recent study shows that programmed cell death 1 ligand (PD-L1) on activated T cells promotes their conversion to suppressive inducible regulatory T cells (iTregs), preferentially from among memory T cells. This new mechanism may normally protect against autoimmunity but is dysregulated in rheumatoid arthritis.
33589102 Perioperative Management of Rheumatic Disease and Therapies. 2021 Mar Patients with rheumatic disease, including those with systemic lupus erythematous, rheumatoid arthritis, and spondyloarthritis, use total hip and knee arthroplasties at high rates. They represent a particularly vulnerable population in the perioperative setting because of their diseases and the immunosuppressant therapies used to treat them. Careful planning among internists, medical specialists, and the surgical team must therefore occur preoperatively to minimize risks in the postoperative period, particularly infection. Management of immunosuppressant medications, such as conventional synthetic disease-modifying antirheumatic drugs and targeted therapies including biologics, is one avenue by which this infectious risk can be mitigated.
32475188 Which is the best SLE activity index for clinical trials? 2021 Jan Following the advent of molecular targeted drugs, a paradigm shift in treatment similar to that in rheumatoid arthritis has been expected in the treatment of systemic lupus erythematosus (SLE), but clinical trials for drugs that many specialists believed to be effective have failed repeatedly. The causes are not simple, but include the heterogeneity of SLE, inclusion criteria, lack of appropriate disease activity measures, and relapse criteria. This review outlines the disease activity indices used in SLE, discusses their advantages and disadvantages, and describes the ideal activity index.
34842362 Outpatient Use of Antimicrobials in Patients With Rheumatoid Arthritis Before and After Tr 2022 Feb OBJECTIVE: The objective of this study was to investigate the effect of tumor necrosis factor α inhibitor (TNFi) initiation on the use of antimicrobials among biologic-naïve patients with rheumatoid arthritis (RA). METHODS: Information on all biologic-naïve patients with RA was extracted from ICEBIO, a nationwide registry. Each patient was matched on age, sex, and calendar time to five randomly selected individuals from the general population. All filled antimicrobial and glucocorticoid prescriptions in the 2 years before and after initiation of the first TNFi were extracted from the Prescription Medicines Register. Prescriptions were quantified by using the number of filled prescriptions (NP) and defined daily doses. RESULTS: We extracted information on 359 patients with RA and 1795 comparators. During the 24 months before initiating treatment with TNFi, patients with RA received more prescriptions for antimicrobials than their matched general population comparators (mean ± SD: 2.8 ± 3.4 vs 1.6 ± 2.7; P < 0.001). The 24-month mean NP for patients with RA increased to 3.5 ± 3.9 (P < 0.001) after initiating TNFi: antibiotics, 2.6 ± 3.2 to 3.2 ± 3.5 (P < 0.001); antivirals, 0.06 ± 0.5 to 0.16 ± 0.7 (P = 0.004); and antimycotics, 0.14 ± 0.5 to 0.22 ± 0.9 (P = 0.06). The 12-month mean NP was highest in the second year after TNFi initiation (1.9 ± 2.4). No association was found between NP and glucocorticoids, age, body mass index, or pre-TNFi Disease Activity Score 28-joint count and C-reactive protein. CONCLUSION: Patients with RA on TNFi are more commonly treated for infections in the outpatient settings than previously reported. Patients are prescribed more antimicrobials in the 2 years preceding TNFi initiation than the general population, and this use further increases after initiation of TNFi. In contrast to what is reported for infections requiring hospitalization, outpatient antimicrobial use remained elevated for at least 2 years.
33504309 Mental Health Problems Experienced by Patients with Rheumatic Diseases During COVID-19 Pan 2021 BACKGROUND: Patients with rheumatic diseases are more likely to suffer from anxiety, depression and insomnia. Yet, little is known about mental health status during COVID-19 pandemic. OBJECTIVE: This study aims to measure the prevalence of mental health disorders among patients with rheumatic diseases in the era of COVID-19 pandemic and to determine potential risk factors for major symptoms of depression, anxiety, and insomnia in participants. METHODS: Participants with rheumatic diseases were asked to complete a questionnaire using a telephonic interview. Sociodemographic and rheumatic disease characteristics were recorded. Mental health status was assessed by the patient health questionnaire-9 (PHQ-9), generalized anxiety disorder (GAD)-7, and insomnia severity index (ISI) questionnaires to detect depression, anxiety and insomnia symptoms, respectively. RESULTS: We included 307 patients in the survey. Rheumatoid arthritis was the most frequent diagnosis (55%). Of all participants, 7.5% had known depression and 5.5% known anxiety. Mental health disorders were insomnia (34.9%), anxiety (33.2%), and depression (24.4%). Major symptoms of insomnia, anxiety, and depression were noted in respectively, 19.9%, 12.4%, and 7.8% of participants. Risk factors for major insomnia were male gender (OR= 4.36, 95% CI 2.06 to 9.25; p<0.0001), low socioeconomic status (OR= 2.64, 95% CI 1.44 - 4.83; p<0.002) and having rheumatoid arthritis (OR= 2.00, 95% CI 1.04 to 3.84; p<0.036). Major anxiety was associated with low monthly income (OR=1.79, 95% CI 1.07 to 3.01; p<0.026), and higher Numerical Rating Scale (NRS) of pain (OR=1.795, 95% CI 1.074 to 2.994 ; p<0.026). Major depression was associated with the worsening of rheumatic disease (OR=1.86, 95% CI 1.06 to 3.26; p<0.03). CONCLUSION: A high frequency of undiagnosed depression, anxiety and insomnia symptoms was found in rheumatic patients. Rheumatologists should be aware of these comorbidities, especially in the era of COVID-19 pandemic.
34105576 β-Adrenoceptor regulation of metabolism in U937 derived macrophages. 2021 Aug 1 Macrophages have important roles in the immune system including clearing pathogens and wound healing. Metabolic phenotypes in macrophages have been associated with functional phenotypes, where pro-inflammatory macrophages have an increased rate of glycolysis and anti-inflammatory macrophages primarily use oxidative phosphorylation. β-adrenoceptor (βAR) signalling in macrophages has been implicated in disease states such as cancer, atherosclerosis and rheumatoid arthritis. The impact of βAR signalling on macrophage metabolism has not been defined. Using metabolomics and proteomics, we describe the impact of βAR signalling on macrophages treated with isoprenaline. We found that βAR signalling alters proteins involved in cytoskeletal rearrangement and redox homeostasis of the cell. We showed that βAR signalling in macrophages shifts glucose metabolism from glycolysis towards the tricarboxylic acid cycle and pentose phosphate pathways. We also show that βAR signalling perturbs purine metabolism by accumulating adenylate and guanylate pools. Taken together, these results indicate that βAR signalling shifts metabolism to support redox processes and upregulates proteins involved in cytoskeletal changes, which may contribute to βAR effects on macrophage function.
34054459 Two Cases of Cutaneous Adverse Effects Induced by Tumor Necrosis Factor-Alpha Inhibitors. 2021 Jan Here, we report two cases of cutaneous adverse effects possibly induced by the use of tumor necrosis factor-alpha (TNF-α) inhibitors. The first case presented alopecia areata (AA) and atopic dermatitis (AD) that developed during the treatment of ulcerative colitis using infliximab; the other case presented urticaria and AD that developed during the treatment of rheumatoid arthritis using etanercept. AA, AD, and urticaria are relatively common skin diseases; however, they are not well known as adverse effects of TNF-α inhibitors. Although immunological studies were not performed, the clinical courses suggested that these skin disorders might have developed as a result of an immune four-way imbalance in T helper 1 (Th1), Th2, Th17, and regulatory T cells by the administration of TNF-α inhibitors.
33938438 Leprosy as a Diagnostic Challenge in the United States. 2021 A 63-year-old woman from Central Florida presented to an outside clinic with a 2-year history of a progressive, asymptomatic cutaneous eruption and arthralgias. Her past medical history was significant for reported seronegative rheumatoid arthritis, for which adalimumab, methotrexate, and low-dose prednisone therapy were initiated 5 years prior. The skin eruption occurred shortly after a 4-week hospitalization during which these medications were withheld. At her initial outside evaluation, a biopsy was performed and interpreted as subacute cutaneous lupus erythematosus (SCLE). She was treated with hydroxychloroquine without improvement. A repeat biopsy was reported as consistent with interstitial granulomatous dermatitis (IGD). There was no improvement with potent topical corticosteroids.
32063021 Mimickers of Hill-Sachs Lesions [Formula: see text]. 2021 May The purpose of this article is to describe the imaging appearance, etiology, clinical features, and treatment of rare presentations of common bone and joint diseases known to mimic Hill-Sachs lesions. Knowledge of uncommonly encountered manifestations of ankylosing spondylitis, rheumatoid arthritis, septic joint, hyperparathyroidism, hydroxyapatite deposition disease, malignant bone tumors, and benign bone cysts which mimic traumatic Hill-Sachs lesions is important for radiologists to guide the clinical care of patients who present with shoulder symptoms.
34664888 Premature atrial contractions with multiple patterns of aberrant conduction followed by to 2021 Sep 17 RATIONALE: Recent studies have shown that QT interval prolongation is associated with disease severity and predicts mortality in systemic inflammatory diseases, particularly rheumatoid arthritis. Systemic pro-inflammatory cytokines released from synovial tissues in rheumatoid arthritis, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, could have direct effects on cardiac electrophysiology, particularly changes in the expression and function of potassium and calcium channels, resulting in QT interval prolongation on surface electrocardiogram (ECG) and an increased predisposition to develop lethal ventricular arrhythmias. However, reports on torsade de pointes (TdP) due to acquired long QT syndrome in patients with polymyalgia rheumatica (PMR) are limited. PATIENT CONCERNS: An 85-year-old Japanese woman with active PMR developed first syncope. DIAGNOSIS: Frequent premature atrial contractions (PACs) with multiple patterns of aberrant conduction, QT interval prolongation, and morphological T-U wave variability followed by TdP were documented. PACs were the first beat of TdP. INTERVENTIONS: Amiodarone, together with magnesium and potassium, was intravenously administered. However, TdP resulted in a ventricular arrhythmic storm, for which sedation with mechanical ventilatory support, temporary overdrive cardiac pacing, and intravenous landiolol administration in addition to multiple direct current shocks were effective. OUTCOMES: Approximately 2 years later, the patient was treated with amiodarone, propranolol, and prednisolone. She did not undergo implantable cardioverter-defibrillator implantation and was quite well, with no recurrence of ventricular tachyarrhythmia. LESSONS: IL-6 hyperproduction in inflamed tissues has been widely confirmed in PMR. Frequent PACs with various patterns of aberrant conduction, QT interval prolongation, and morphological T-U wave variability followed by TdP, for which IL-6-mediated enhancement of L-type Ca2+ current and inhibition of the rapid component of the delayed rectifier K+ current are the most likely mechanisms, were documented in an elderly Japanese woman with PMR. ECG may be recorded once in patients with active PMR even when these patients do not complain of palpitation or syncope. If QT interval prolongation or arrhythmia, including even PACs, is observed, follow-up ECG may be warranted, particularly for patients with some risk factors for QT prolongation that could lead to TdP, such as advanced age, female sex, hypopotassemia, and polypharmacy.
34498436 Perceived Risk and Associated Shielding Behaviors in Patients With Rheumatoid Arthritis Du 2021 Dec OBJECTIVE: To investigate the perceived risk of coronavirus disease 2019 (COVID-19) infection and outcomes as well as shielding practices among patients with rheumatoid arthritis (RA) during the COVID-19 pandemic. METHODS: We surveyed participants with RA in a large health care system between July 16 and November 8, 2020. Participants reported RA treatment, COVID-19 risk perception, and shielding practices (eg, masks, social distancing, and quarantining). We examined the association of demographic and disease-specific factors with risk perception and the association of risk perception with shielding practices. RESULTS: Of 494 participants, 195 (40%), 169 (34%), and 130 (26%) strongly agreed, agreed, or were uncertain/disagreed that their RA put them at higher risk for COVID-19 or poor outcomes, respectively. Younger age (odds ratio [OR]: 0.98), having a comorbidity (OR: 1.60), and biologic disease-modifying antirheumatic drug (bDMARD) use (OR: 1.75) were independently associated with a higher perceived risk. Among those who strongly agreed, agreed, or were uncertain/disagreed that they had greater risk, 165 (85%), 118 (70%), and 69 (53%), respectively, practiced all three shielding measures (P < 0.0001). Those who strongly agreed or agreed that they were at higher risk were more likely to use all three shielding practices (OR: 4.16 and 1.97, respectively). bDMARD use and glucocorticoid use were associated with using all three shielding measures (OR: 1.99 and 1.81, respectively). CONCLUSION: Perception of COVID-19 risk among patients with RA varies substantially. Factors associated with perceived risk are different from those found to be associated with worse outcomes in observational studies. Greater perceived risk is associated with more strict shielding, which has implications for patient education and mental health.
34140951 Citrullination and PAD Enzyme Biology in Type 1 Diabetes - Regulators of Inflammation, Aut 2021 The generation of post-translational modifications (PTMs) in human proteins is a physiological process leading to structural and immunologic variety in proteins, with potentially altered biological functions. PTMs often arise through normal responses to cellular stress, including general oxidative changes in the tissue microenvironment and intracellular stress to the endoplasmic reticulum or immune-mediated inflammatory stresses. Many studies have now illustrated the presence of 'neoepitopes' consisting of PTM self-proteins that induce robust autoimmune responses. These pathways of inflammatory neoepitope generation are commonly observed in many autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and type 1 diabetes (T1D), among others. This review will focus on one specific PTM to self-proteins known as citrullination. Citrullination is mediated by calcium-dependent peptidylarginine deiminase (PAD) enzymes, which catalyze deimination, the conversion of arginine into the non-classical amino acid citrulline. PADs and citrullinated peptides have been associated with different autoimmune diseases, notably with a prominent role in the diagnosis and pathology of rheumatoid arthritis. More recently, an important role for PADs and citrullinated self-proteins has emerged in T1D. In this review we will provide a comprehensive overview on the pathogenic role for PADs and citrullination in inflammation and autoimmunity, with specific focus on evidence for their role in T1D. The general role of PADs in epigenetic and transcriptional processes, as well as their crucial role in histone citrullination, neutrophil biology and neutrophil extracellular trap (NET) formation will be discussed. The latter is important in view of increasing evidence for a role of neutrophils and NETosis in the pathogenesis of T1D. Further, we will discuss the underlying processes leading to citrullination, the genetic susceptibility factors for increased recognition of citrullinated epitopes by T1D HLA-susceptibility types and provide an overview of reported autoreactive responses against citrullinated epitopes, both of T cells and autoantibodies in T1D patients. Finally, we will discuss recent observations obtained in NOD mice, pointing to prevention of diabetes development through PAD inhibition, and the potential role of PAD inhibitors as novel therapeutic strategy in autoimmunity and in T1D in particular.
33521818 Effects of physical activity on vascular function in autoimmune rheumatic diseases: a syst 2021 Jul 1 OBJECTIVES: To summarize existing evidence and quantify the effects of physical activity on vascular function and structure in autoimmune rheumatic diseases (ARDs). METHODS: Databases were searched (through March 2020) for clinical trials evaluating the effects of physical activity interventions on markers of micro- and macrovascular function and macrovascular structure in ARDs. Studies were combined using random effects meta-analysis, which was conducted using Hedges' g. Meta-analyses were performed on each of the following outcomes: microvascular function [i.e. skin blood flow or vascular conductance responses to acetylcholine (ACh) or sodium nitropusside (SNP) administration]; macrovascular function [i.e. brachial flow-mediated dilation (FMD%) or brachial responses to glyceryl trinitrate (GTN%); and macrovascular structure [i.e. aortic pulse wave velocity (PWV)]. RESULTS: Ten studies (11 trials) with a total of 355 participants were included in this review. Physical activity promoted significant improvements in microvascular [skin blood flow responses to ACh, g = 0.92 (95% CI 0.42, 1.42)] and macrovascular function [FMD%, g = 0.94 (95% CI 0.56, 1.02); GTN%, g = 0.53 (95% CI 0.09, 0.98)]. Conversely, there was no evidence for beneficial effects of physical activity on macrovascular structure [PWV, g = -0.41 (95% CI -1.13, 0.32)]. CONCLUSIONS: Overall, the available clinical trials demonstrated a beneficial effect of physical activity on markers of micro- and macrovascular function but not on macrovascular structure in patients with ARDs. The broad beneficial impact of physical activity across the vasculature identified in this review support its role as an effective non-pharmacological management strategy for patients with ARDs.
33446184 Network pharmacology modeling identifies synergistic interaction of therapeutic and toxico 2021 Jan 15 BACKGROUND: Tripterygium hypoglaucum Hutch (THH) both has prominent efficacy and unwarranted toxicity in the treatment of autoimmune diseases. Nevertheless, its pharmacological and toxicological profiles still remain to be elucidated. In the current study, the network pharmacology approach was applied to identify synergistic interaction and mechanism of efficacy and toxicity for THH from a holistic perspective. METHODS: The compounds from THH were collected using literature retrieval and relevant databases. After the production of putative therapeutic targets for dominant diseases and harmful targets of adverse reactions (ADRs) induced by THH, the protein-protein interactions (PPIs), topological analysis and pathway enrichment were established to distinguish the hub targets and pathways. Additionally, the binding activity of candidate ingredients with core targets were revealed by molecular docking simulation. RESULTS: A total of eight bioactive components in THH were enrolled, and 633 targets were responsible for rheumatoid arthritis (RA), 1067 targets were corresponding to systemic lupus erythematosus (SLE), 1318 targets of ADRs were obtained. The results of enrichment analysis among THH-RA, THH-SLE and THH-ADR networks indicated that pathway in cancer, hepatitis B, rheumatoid arthritis, and PI3K-Akt signaling pathway might participate in THH for treating RA and SLE. Besides, the mechanism of ADRs that induced by THH were associated with viral carcinogenesis, p53 signaling pathway, PI3K-Akt signaling pathway, and so on. Whereas, these active ingredients of THH exerted the superior binding activities with crucial targets including STAT3, VEGFA, TP53 and MMP9 that functioned synergistically efficacy and toxicity as observed via molecular docking simulation. CONCLUSION: The present research preliminarily interpreted the synergistic interaction of therapeutic and toxicological mechanisms for THH through the comprehensive analysis of relationship and binding activity between primary components and core targets, providing a feasible and promising approach to facilitate the development of toxic and irreplaceable herbs.
34769338 Contribution of Dysregulated DNA Methylation to Autoimmunity. 2021 Nov 2 Epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs are known regulators of gene expression and genomic stability in cell growth, development, and differentiation. Because epigenetic mechanisms can regulate several immune system elements, epigenetic alterations have been found in several autoimmune diseases. The purpose of this review is to discuss the epigenetic modifications, mainly DNA methylation, involved in autoimmune diseases in which T cells play a significant role. For example, Rheumatoid Arthritis and Systemic Lupus Erythematosus display differential gene methylation, mostly hypomethylated 5'-C-phosphate-G-3' (CpG) sites that may associate with disease activity. However, a clear association between DNA methylation, gene expression, and disease pathogenesis must be demonstrated. A better understanding of the impact of epigenetic modifications on the onset of autoimmunity will contribute to the design of novel therapeutic approaches for these diseases.
33301910 Comprehensive evaluation on anti-inflammatory and anti-angiogenic activities in vitro of f 2021 Mar 25 ETHNOPHARMACOLOGICAL RELEVANCE: Genkwa flos, as a traditional herb, is the dried flower buds of Daphne genkwa Sieb.et Zucc. It is used in traditional medicine for the treatment of cough, sore throats, edema. AIM OF THE STUDY: The study aimed to explore a new mathematical method for multivariate evaluation, investigate the anti-inflammatory and anti-angiogenic activities of flavonoids in Daphne Genkwa under ex vivo conditions. MATERIALS AND METHODS: The flavonoids monomers in Daphne Genkwa were separated by preparative liquid chromatography and identified by HPLC-ESI-ITMS. An in vitro inflammatory model of macrophage RAW264.7 induced by LPS and an angiogenesis model of human umbilical vein endothelial cells induced by TNF-α were established. Flavonoids were extracted and prepared for intervention to detect the amount of secretion after drug intervention to reflect the anti-inflammatory and anti-angiogenic activities of each component. In addition, a new mathematical method, which combined principal component analysis and efficacy coefficient method, was adopted in pharmacodynamic evaluation. RESULTS: Fourteen flavonoids monomers were separated by preparative liquid chromatography and identified by HPLC-ESI-ITMS including H1 (hydroxygenkwanin-5-O-β-D-glucoside), H2 (apigenin-7-O-β-D-glucoside), H3 (kaempferol-3-O-β-D-glucoside), H4 (hydroxygenkwanin-5-O-β-D-primeveroside), H5 (apigenin-5-O-β-D-primeveroside), H6 (apigenin-7-O-β-D-glucuronide), H7 (luteolin-5-O-β-D-glucopyranoside), H8 (genkwain-5-O-β-D- glucoside), H9 (luteolin), H10 (Daphnodorin G), H11 (tiliroside), H12 (apigenin), H13 (3'- hydroxygenkwain) and H14 (genkwanin). We found that most of flavonoids down-regulated VCAM and MMP-3, while H1, H8, H9, H14 reduced VEGF and ICAM was only decreased by H14. CONCLUSION: Genkwanin may be the most active anti-rheumatoid arthritis flavonoids in Daphne genkwa. Meanwhile, the new mathematical method used in the study provided a new direction for solving the problem of multi-index pharmacodynamic evaluation.
33259751 Clinical features and outcomes from the Singapore Sjögren's syndrome study. 2021 Feb OBJECTIVE: To study the clinical features, treatment and outcomes of primary Sjögren's Syndrome (pSS) in a Singapore cohort from an outpatient rheumatology clinic. METHODS: Computerised Physician Order entry records of patients who fulfilled the 2016 ACR-EULAR classification criteria for pSS between 1993 and 2013 were retrospectively analysed. RESULTS: There were 102 patients, of which 96 (94.1%) were females, and 91 (89.2%) Chinese. Mean age at diagnosis was 49.3 ± 11.8 years, mean disease duration was 9.0 ± 4.6 years. The most common manifestations were keratoconjunctivitis sicca (99.0%), xerostomia (96.1%), arthralgia/arthritis (56.9%). Exocrine glandular enlargement comprised parotidomegaly (28, 27.5%), with concurrent submandibular and lacrimal gland enlargement in one. The nervous system (15.7%) was the most commonly affected internal organ, with peripheral nervous system (peripheral neuropathy, mononeuritis multiplex) involvement more common than central. Hydroxychloroquine was most frequently used (88.2%), followed by methotrexate (7.8%) and azathioprine (6.9%). Pulsed intravenous (IV) methylprednisolone 500 mg/day for 3 days was used in 5 patients followed by oral (4) or IV cyclophosphamide (1) for cardiomyopathy and interstitial lung disease (1), and neurological involvement (4). These comprised neuromyelitis optica, transverse myelopathy, cranial neuropathy, mononeuritis multiplex and/or peripheral neuropathy alone or in combination. Intravenous immunoglobulins (2.0%) was used for sensory neuropathy and mononeuritis multiplex; rituximab (1.0%) in 1 patient for treatment of non-Hodgkin's B-cell lymphoma. There were no deaths. CONCLUSION: Musculoskeletal manifestations were common, with the nervous system (peripheral more than central) the most common internal organ involved. Lymphoma was uncommon despite up to one-third of the cohort developing glandular enlargement.