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ID PMID Title PublicationDate abstract
27909725 Lipoprotein redox status evaluation as a marker of cardiovascular disease risk in patients 2017 Jan Patients with chronic inflammatory disorders (ID) have an increased risk of developing cardiovascular disease, and routinely determined parameters do not reveal the real metabolic status of specific subgroups, such as patients with rheumatoid arthritis (RA). In this study, in order to evaluate state of the art markers for the assessment of cardiometabolic risk, abnormalities in lipoprotein levels in patients with a low‑grade inflammatory status [diabetes mellitus (DM) subgroup] and in patients with a high systemic inflammatory burden (RA subgroup) was determined. The study group comprised patients with ID [DM (n=20) and RA (n=20)], with an aged‑matched control group (n=17). Patient serum was used to determine routine biochemical parameters and to isolate low‑density lipoprotein (LDL) and high‑density lipoprotein (HDL). The heparin‑citrate method was used for LDL precipitation and the phosphotungstic acid‑MgCl2 technique for the isolation of HDL. Further, Amplex Red and advanced oxidation protein product (AOPP) assays were applied to determine lipid peroxides and protein oxidation, respectively, while the levels of serum advanced glycation end products (AGEs) were also determined. Although the differences in the routinely determined lipidemic profile were notable between the DM and RA subgroups, markers of lipid peroxidation and of advanced protein oxidation/glycation did not differ significantly, indicating possible similar oxidative damage of serum lipoproteins. On the whole, as alterations in lipoprotein functionality can occur long before any changes in routinely measured biochemical parameters are observed, more sensitive markers for the assessment of cardiovascular risk are required. As AOPPs, AGEs, oxidized LDL (oxLDL) and especially oxidized HDL (oxHDL) are affected during the early stages of inflammatory disease, and due to their known link to coronary artery disease, it would be wise to include these markers in the routine cardiovascular evaluation of patients with chronic inflammatory disease, such as those with RA.
27632993 Surrogate-assisted feature extraction for high-throughput phenotyping. 2017 Apr 1 OBJECTIVE: Phenotyping algorithms are capable of accurately identifying patients with specific phenotypes from within electronic medical records systems. However, developing phenotyping algorithms in a scalable way remains a challenge due to the extensive human resources required. This paper introduces a high-throughput unsupervised feature selection method, which improves the robustness and scalability of electronic medical record phenotyping without compromising its accuracy. METHODS: The proposed Surrogate-Assisted Feature Extraction (SAFE) method selects candidate features from a pool of comprehensive medical concepts found in publicly available knowledge sources. The target phenotype's International Classification of Diseases, Ninth Revision and natural language processing counts, acting as noisy surrogates to the gold-standard labels, are used to create silver-standard labels. Candidate features highly predictive of the silver-standard labels are selected as the final features. RESULTS: Algorithms were trained to identify patients with coronary artery disease, rheumatoid arthritis, Crohn's disease, and ulcerative colitis using various numbers of labels to compare the performance of features selected by SAFE, a previously published automated feature extraction for phenotyping procedure, and domain experts. The out-of-sample area under the receiver operating characteristic curve and F -score from SAFE algorithms were remarkably higher than those from the other two, especially at small label sizes. CONCLUSION: SAFE advances high-throughput phenotyping methods by automatically selecting a succinct set of informative features for algorithm training, which in turn reduces overfitting and the needed number of gold-standard labels. SAFE also potentially identifies important features missed by automated feature extraction for phenotyping or experts.
29261752 A comparison of health-related quality of life (HRQoL) across four systemic autoimmune rhe 2017 OBJECTIVES: To compare physical and mental health-related quality of life (HRQoL) across four systemic autoimmune rheumatic diseases (SARD). METHODS: Incident subjects enrolled in four SARD cohorts, namely systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA) and idiopathic inflammatory myopathies (IIM) were studied. The outcomes of interest were baseline Short Form Health Survey physical (PCS) and mental (MCS) component summary scores. Multivariate analysis was conducted to determine whether PCS and MCS scores differed across SARD type. RESULTS: The study included 118 SLE (93% women, mean age 36 years), 108 SSc (79% women, mean age 55), 64 RA (63% women, mean age 58) and 25 IIM (68% women, mean age 49) subjects. Mean PCS scores were 38.9 ± 12.2 in SLE, 37.1 ± 13.3 in RA, 35.0 ± 13.6 in SSc and 28.0 ± 15.4 in IIM. Mean MCS scores were 45.0 ± 13.3 in RA, 44.4 ± 14.7 in SSc, 40.1 ± 14.3 in SLE and 33.6 ± 18.7 in IIM. SARD type was an independent predictor of HRQoL with, in some cases, the magnitude of the differences reaching one standard deviation (IIM worse PCS scores compared to SLE (β -12.23 [95% CI -18.11, -6.36; p<0.001]); IIM worse MCS scores compared to SSc (β -11.05 [95% CI -17.53, -4.58; p = 0.001]) and RA (β -11.72 [95% CI -18.62, -4.81; p = 0.001]). CONCLUSIONS: Cross-SARD research provides a novel approach to gain greater understanding of commonalities and differences across rheumatic diseases. The differences observed warrant further research into correlates and trajectories over time.
29016284 Is Visceral Leishmaniasis Different in Immunocompromised Patients Without Human Immunodefi 2017 Oct Although visceral leishmaniasis (VL) can affect immunocompromised patients, data from the human immunodeficiency virus (HIV) infection context are limited, and the characteristics of VL in other immunosuppression scenarios are not well defined. A retrospective review of all cases of VL in immunocompromised patients from January 1997 to December 2014 in two Spanish hospitals on the Mediterranean coast was performed. We included 18 transplant recipients (kidney: 7, liver: 4, lung: 3, heart: 2, and blood marrow: 2), 12 patients with other causes of immunosuppression (myasthenia gravis: 3 and rheumatoid arthritis: 2), and 73 VL HIV-positive patients. Fever was more common in transplant patients (94.4%) and patients with other types of immunosuppression (100%) than in HIV-positive individuals (73.3%). Hepatomegaly was less common in transplant recipients (27.8%) and patients with other types of immunosuppression (41.7%) compared with HIV-positive patients (69.9%) (P = 0.01; P = 0.001, respectively). Patients with other types of immunosuppression had a median leukocyte count of 1.5 × 10(9)/L, significantly lower than HIV-positive patients (2.5 × 10(9)/L) (P = 0.04). Serology was more commonly positive in nontransplant immunosuppressed individuals (75%) and transplant recipients (78.6%) than in HIV-patients (13.8%) (P < 0.001). Antimonial therapy was rarely used in transplant recipients (1.9%) and never in patients with other immunosuppressive conditions, whereas 34.2% of HIV-positive patients received it (P = 0.05 and P = 0.01, respectively). Mortality was 16.7% in both transplant recipients and patients with other immunosuppressive conditions and 15.1% in HIV-positive patients. The features of VL may be different in immunosuppressed patients, with more fever and less hepatomegaly and leukopenia than in HIV-infected patients.
28890383 Interaction between rhein acyl glucuronide and methotrexate based on human organic anion t 2017 Nov 1 Rhein, a major bioactive compound of many medicinal herbs and the prodrug of diacerein, is often used with low dose of methotrexate as drug combination to treat rheumatoid arthritis. In this study, potential drug-drug interaction between methotrexate and rhein was investigated based on organic anion transporters (OAT). Our study demonstrated that rhein acyl glucuronide (RAG), the major metabolite of rhein in the human blood circulation, significantly inhibited the uptake of p-aminohippurate in hOAT1 transfected cells with IC(50) value of 691 nM and estrone sulfate uptake in hOAT3 transfected cells with IC(50) value of 78.5 nM. As the substrate of both hOAT1 and hOAT3, the methotrexate transport was significantly inhibited by RAG in hOAT1 transfected cells at 50 μM and hOAT3 transfected cells at 1 μM by 69% and 87%, respectively. Further in vivo study showed that after co-administrated with RAG in rats the AUC(0-24) values of methotrexate increased from 3109 to 5370 ng/mL*hr and the t(1/2) was prolonged by 40.5% (from 7.4 to 10.4 h), demonstrating the inhibitory effect of RAG on methotrexate excretion. In conclusion, rhein acyl glucuronide could significantly decrease the transport of methotrexate by both hOAT1 and hOAT3. The combination use of rhein, diacerein or other rhein-containing herbs with methotrexate may cause obvious drug-drug interaction and require close monitoring for potential drug interaction in clinical practice.
28748510 Clinical characteristics of autoimmune rheumatic disease-related organizing pneumonia. 2018 Apr To study the clinical characteristics of autoimmune rheumatic disease-related organizing pneumonia (AIRD-OP), the clinical presentation, radiological findings, treatment, and outcome of AIRD-OP patients were analyzed, in comparison with patients with cryptogenic organizing pneumonia (COP). A total of 131 OP patients were identified, including 57 cases of AIRD-OP, 35 cases of COP, and 39 cases of other disease-related OPs. Among AIRD-OP patients, 36 (63%) presented the symptoms of OP at onset. The primary disease of AIRDs included Sjogren's syndrome (38%), polymyositis/dermatomyositis (23%), rheumatoid arthritis (23%), and undifferentiated AIRD. Compared with COP patients, the prevalence of patients having cough and malaise at baseline was significantly lower (54.4 vs 82.9%, P < 0.05; 49.1 vs 70.6%, P < 0.05), and the signs of moist rales and crackles were more common in AIRD-OP patients (54.4 vs 32.4%, P < 0.05; 49.1 vs 26.5%, P < 0.05). Lung function (TLC%, FVC%) was more significantly reduced in AIRD-OP patients (72 vs 97%, P < 0.05;75 vs 96%, P < 0.05). The dosage of corticosteroids prescribed was significantly higher in AIRD-OP patients (44 vs 37 mg/day, P < 0.05). The complete recovery rate was slightly lower in AIRD-OP patients (22.2 vs 29%, P > 0.05) with a tendency towards higher recurrence rate in AIRD-OP patients (32.7 vs 14.3%, P < 0.05). AIRD-OP may be the most common cause of OP. OP can be the initial presentation of AIRD. Compared with COP patients, AIRD-OP patients are characterized with occult onset but more severe lung involvement and higher recurrence rate.
28696952 Total Elbow Arthroplasty: A Systematic Review. 2017 Jul BACKGROUND: Most total elbow arthroplasty (TEA) designs aim to replicate anatomy and provide stability in the treatment of the degenerative elbow joint. Given the promising results that have been reported following the use of TEA for the treatment of complex fractures, the indications for this procedure are growing. The objective of the present study was to review the most recent literature on the results of the most commonly performed TEAs. METHODS: A comprehensive literature search was conducted. All relevant studies were reviewed according to a set of predefined inclusion and exclusion criteria. After the initial assessment, 2 authors extracted data from the included articles. Groups were created on the basis of the design of TEA implant, the type of implant (linked or unlinked), and the indication for treatment. Outcome parameters were survival rate, pain, range of motion, complications, and specific elbow outcome scores. RESULTS: Seventy-three articles involving a total of 9,379 TEAs were included. The level of evidence was primarily Level IV. Nineteen specific designs of TEA implants were described, including the Souter-Strathclyde (n = 2,387), Coonrad-Morrey (n = 1,586), Kudo (n = 560), and GSB III (n = 498). The most common indication for TEA was rheumatoid arthritis (70%). The weighted mean survival rate for the linked and unlinked prostheses was 85.5% at 7.8 years and 74% at 12.3 years, respectively. For the Coonrad-Morrey, Souter-Strathclyde, and GSB III, the weighted mean survival rate was 87.2% at 7.2 years, 70.6% at 14.2 years, and 81.7% at 9.5 years, respectively. The range of motion after TEA was good overall, with a mean flexion angle of 129° and a mean extension lag angle of 30°. The complication rates ranged from 11% to 38%, with clinical loosening being the most frequently reported complication (7%). CONCLUSIONS: The results of TEA are respectable overall. It appears that there are small differences between designs. However, despite the fairly good functional results and elbow scores, the survival and complication rates are still not as favorable as those following arthroplasties in other joints. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
28687046 Formulation and in vitro/in vivo evaluation of chitosan-based film forming gel containing 2017 Nov The film forming gel, adhered to skin surfaces upon application and formed a film, has an advantage onto skin to provide protection and continuous drug release to the application site. This study aimed to prepare a chitosan-based film forming gel containing ketoprofen (CbFG) and to evaluate the CbFG and film from CbFG (CbFG-film). CbFG were prepared with chitosan, lactic acid and various skin permeation enhancers. The physicochemical characteristics were evaluated by texture analysis, viscometry, SEM, DSC, XRD and FT-IR. To identify the mechanism of skin permeation, in vitro skin permeation study was conducted with a Franz diffusion cell and excised SD-rat and hairless mouse dorsal skin. In vivo efficacy assessment in mono-iodoacetate (MIA)-induced rheumatoid arthritis animal model was also conducted. CbFG was successfully prepared and, after applying CbFG to the excised rat dorsal skin, the CbFG-film was also formed well. The physicochemical characteristics of CbFG and CbFG-film could be explained by the grafting of oleic acid onto chitosan in the absence of catalysts. In addition, CbFG containing oleic acid had a higher skin permeation rate in comparison with any other candidate enhancers. The in vivo efficacy study also confirmed significant anti-inflammatory and analgesic effects. Consequently, we report the successful preparation of chitosan-based film forming gel containing ketoprofen with excellent mechanical properties, skin permeation and anti-inflammatory and analgesic effects.
28487154 Long-term mortality in patients with ST-segment elevation myocardial infarction is associa 2017 Aug 1 BACKGROUND: Cardiovascular (CV) mortality is higher in patients with rheumatoid arthritis (RA), in particular when anti-citrullinated protein antibodies (ACPA) are present. Recently, ACPA have also been described in a cohort of patients without RA, but with coronary artery disease (CAD). It is however unknown if ACPA can consistently be found in patients with CAD, and if ACPA are associated with mortality in these patients. The purpose of this study was to assess the relationship between ACPA and long-term outcomes including mortality in patients with ST-elevation myocardial infarction (STEMI) without RA. METHODS: All patients with STEMI from the MISSION! Intervention Study were analyzed. Patients with RA were excluded. The association between ACPA (anti-CCP3) at baseline and 10year mortality and re-infarction was investigated. RESULTS: In total, 29 (11%) of 275 included patients were ACPA-positive, substantiating the previous description of ACPA in CAD patients. Increased cumulative cardiac mortality was observed in ACPA-positive patients in comparison with ACPA-negative patients. Moreover, after correction for other associated factors, ACPA-positivity was associated with long-term mortality (HR 3.1 [CI 1.4-7.1] p-value=0.01) and long-term combined endpoint of re-infarction and death (HR 2.4 [1.2-4.6] p-value=0.01). CONCLUSION: In STEMI patients without RA, the presence of ACPA is independently associated with long-term mortality and the combined endpoint of re-infarction and death. ACPA in patients with and without RA might act as an independent pro-atherogenic factor.
28460421 Calreticulin inhibits inflammation-induced osteoclastogenesis and bone resorption. 2017 Dec Osteoclasts play key roles in bone remodeling and pathologic osteolytic disorders such as inflammation, infection, bone implant loosening, rheumatoid arthritis, metastatic bone cancers, and pathological fractures. Osteoclasts are formed by the fusion of monocytes in response to receptor activators of NF-κB-ligand (RANKL) and macrophage colony stimulating factor 1 (M-CSF). Calreticulin (CRT), a commonly known intracellular protein as a calcium-binding chaperone, has an unexpectedly robust anti-osteoclastogenic effect when its recombinant form is applied to osteoclast precursors in vitro or at the site of bone inflammation externally in vivo. Externally applied Calreticulin was internalized inside the cells. It inhibited key pro-osteoclastogenic transcription factors such as c-Fos and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1)-in osteoclast precursor cells that were treated with RANKL in vitro. Recombinant human Calreticulin (rhCRT) inhibited lipopolysaccharide (LPS)-induced inflammatory osteoclastogenesis in the mouse calvarial bone in vivo. Cathepsin K molecular imaging verified decreased Cathepsin K activity when rhCalreticulin was applied at the site of LPS application in vivo. Recombinant forms of intracellular proteins or their derivatives may act as novel extracellular therapeutic agents. We anticipate our findings to be a starting point in unraveling hidden extracellular functions of other intracellular proteins in different cell types of many organs for new therapeutic opportunities. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2658-2666, 2017.
28444759 Dysregulated CD46 shedding interferes with Th1-contraction in systemic lupus erythematosus 2017 Jul IFN-γ-producing T helper 1 (Th1) cell responses mediate protection against infections but uncontrolled Th1 activity also contributes to a broad range of autoimmune diseases. Autocrine complement activation has recently emerged as key in the induction and contraction of human Th1 immunity: activation of the complement regulator CD46 and the C3aR expressed by CD4(+) T cells via autocrine generated ligands C3b and C3a, respectively, are critical to IFN-γ production. Further, CD46-mediated signals also induce co-expression of immunosuppressive IL-10 in Th1 cells and transition into a (self)-regulating and contracting phase. In consequence, C3 or CD46-deficient patients suffer from recurrent infections while dysregulation of CD46 signaling contributes to Th1 hyperactivity in rheumatoid arthritis and multiple sclerosis. Here, we report a defect in CD46-regulated Th1 contraction in patients with systemic lupus erythematosus (SLE). We observed that MMP-9-mediated increased shedding of soluble CD46 by Th1 cells was associated with this defect and that inhibition of MMP-9 activity normalized release of soluble CD46 and restored Th1 contraction in patients' T cells. These data may deliver the first mechanistic explanation for the increased serum CD46 levels observed in SLE patients and indicate that targeting CD46-cleaving proteases could be a novel avenue to modulate Th1 responses.
28369180 Possible Interaction Between Cigarette Smoking and HLA-DRB1 Variation in the Risk of Folli 2017 Apr 15 Follicular lymphoma (FL) risk is strongly associated with germline genetic variation in human leukocyte antigen (HLA) class II. Cigarette smoking has been suggested to increase FL risk, primarily among women. We hypothesized that amino acids in HLA-antigen D-related β1 subunit (DRB1) interact with smoking in FL risk, as shown for rheumatoid arthritis. We analyzed 373 patients with FL and 818 controls from 2 population-based case-control studies in Sweden and Denmark (1999-2003). Haplotypes in HLA-DRB1 were imputed at amino acid positions 11, 13, 28, 30, and 70-74 (shared epitope). We estimated the relative risk of FL as odds ratios with 95% confidence intervals for different smoking status/haplotype combinations. Interaction was defined as departure from additivity of effects and quantified by the attributable proportion (AP). Relative to never-smokers carrying no shared epitope alleles, smoking was associated with the risk of FL among all subjects (for former smokers, odds ratio (OR) = 2.20, 95% confidence interval (CI): 1.10, 4.41; ORcurrent = 3.56, 95% CI: 1.60, 7.92) and women (ORformer = 2.95, 95% CI: 1.18, 7.37; ORcurrent = 5.63, 95% CI: 2.07, 15.3) carrying 2 shared epitope alleles but not among those carrying zero or 1 shared epitope allele. Smoking and shared epitope status interacted significantly as measured by AP (overall, AP = 0.6, 95% CI: 0.15, 1.0; for women, AP = 0.5, 95% CI: 0.005, 1.0). These results suggest a possible interaction between smoking and HLA-DRB1-associated antigen presentation in FL risk and provide a model to further unravel FL etiology.
28254841 STAT5 phosphorylation in CD4 T cells from patients with SLE is related to changes in their 2017 Jun Activation of the STAT5 signaling pathway up-regulates antiapoptotic protein Bcl2 and drives proliferation of autoreactive conventional CD4 T cells (T(cons)). In systemic lupus erythematosus (SLE), an increased T cell Bcl2 content and perturbed homeostasis of CD45RA(-)FOXP3(hi) activated regulatory T cells (aT(regs)) were described. We assessed T(con)/T(reg) subsets and phosphorylation of STAT5 (pSTAT5) in blood T cells from patients with SLE by using conventional and imaging flow cytometry. Forty-one patients with SLE, 33 healthy controls, and 29 patients with rheumatoid arthritis were included. Long-term monitoring was performed in 39 patients with SLE, which were followed longitudinally for up to 1000 d. Significantly increased Bcl2 protein content in T cells from patients with SLE was associated with IL-7-dependent STAT5 activation, expressed as increased basal levels and nuclear localization of pSTAT5. pSTAT5 levels were significantly increased in the FOXP3 low-expressing CD4(+) T cell subsets but not in the aT(reg) subset, which was significantly decreased in patients with SLE. In contrast to aT(reg), SLE T(con) displayed significantly increased pSTAT5 and Bcl2 levels. Moreover, the percentage of T(con)-expressing proliferation marker Ki-67 was significantly increased in patients with SLE and was positively correlated with CD4 T cell pSTAT5 levels. Finally, a subgroup of patients characterized by an increased T(con)-pSTAT5/aT(reg)-pSTAT5 ratio experienced a more aggressive-relapsing disease course and displayed higher time-adjusted cumulative CD4 T cell pSTAT5 levels during follow-up, which were positively correlated with time-adjusted cumulative disease activity. Our results indicate that imbalanced STAT5 phosphorylation, which is related to Bcl2 and Ki-67 expression, may confer survival and proliferative advantage to T(con) over aT(reg) and could represent a possible marker of SLE disease severity.
28209290 Efficacy, safety and pharmacokinetics of biosimilars of anti-tumor necrosis factor-α agen 2017 May OBJECTIVE: To evaluate the efficacy and safety of biosimilars of anti-tumor necrosis factor (TNF)-α agents compared to their reference agents in immune mediated diseases. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) assessing the efficacy and safety of biosimilars of anti-TNF-α agents compared to their reference agents in patients with various immune mediated diseases. The outcomes were the rates of clinical response and adverse events among patients treated with biosimilars compared to their reference agents. Additionally, occurrence of anti-drug antibodies with the use of biosimilars was compared to the reference agents. RESULTS: Nine studies reporting outcomes in 3291 patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) were identified (5 infliximab, 2 adalimumab, and 2 etanercept). No RCTs in other diseases were found. Biosimilars of infliximab showed similar rates of clinical response compared to the reference agent in RA and AS. Frequency of anti-drug antibody and adverse events were similar except for a slightly, but significantly, higher risk of upper respiratory tract infections with biosimilar (RR 1.54, P = 0.047, 95% confidence interval (CI) = 1.01-2.37). Biosimilar of adalimumab showed no differences among any outcomes compared to the reference agent. Biosimilars of etanercept showed no differences for clinical response and frequency of adverse events, but showed a significantly lower rate of anti-drug antibodies at 24-30 weeks (RR 0.05, P <0.0001%, 95% CI = 0.01-0.21). CONCLUSION: In the present study, biosimilars of anti-TNF-α agents had an overall comparable efficacy and safety profile compared to their reference agents in RA and AS supporting their use for these conditions.
27757507 The obesity-related pathology and Th17 cells. 2017 Apr Chronic inflammation associated with obesity plays a major role in the development of metabolic diseases, cancer, and autoimmune diseases. Among Th subsets, Th17 cells are involved in the pathogenesis of autoimmune disorders such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, steroid-resistant asthma, and multiple sclerosis. Accumulating data suggest that reciprocal interactions between the metabolic systems and immune system play pivotal roles in the pathogenesis of obesity-associated diseases. We herein outline the developing principles in the control of T cell differentiation and function via their cellular metabolism. Also discussed are recent findings that changes in the intracellular metabolism, including fatty acid metabolism, affect the Th17 cell function in obese individuals. Finally, we will also highlight the unique molecular mechanism involved in the activation of retinoid-related orphan receptor-gamma-t (RORγt) by intracellular metabolism and discuss a new therapeutic approach for treating autoimmune disorders through the inhibition of RORγt.
29126988 Morinda officinalis How. - A comprehensive review of traditional uses, phytochemistry and 2018 Mar 1 ETHNOPHARMACOLOGICAL RELEVANCE: The medicinal plant Morinda officinalisHow. (MO) and its root have long been used in traditional medicines in China and northeast Asia as tonics for nourishing the kidney, strengthening the bone and enhancing immunofunction in the treatment of impotence, osteoporosis, depression and inflammatory diseases such as rheumatoid arthritis and dermatitis. AIM OF THE REVIEW: This review aims to sum up updated and comprehensive information about traditional usage, phytochemistry, pharmacology and toxicology of MO and provide insights into potential opportunities for future research and development of this plant. METHODS: A bibliographic investigation was performed by analyzing the information available on MO in the internationally accepted scientific databases including Pubmed, Scopus and Web of Science, SciFinder, Google Scholar, Yahoo, Ph.D. and M.Sc. dissertations in Chinese. Information was also obtained from some local and foreign books on ethnobotany and ethnomedicines. RESULTS: The literature supported the ethnomedicinal uses of MO as recorded in China for various purposes. The ethnomedical uses of MO have been recorded in many regions of China. More than 100 chemical compounds have been isolated from this plant, and the major constituents have been found to be polysaccharides, oligosaccharides, anthraquinones and iridoid glycosides. Crude extracts and pure compounds of this plant are used as effective agents in the treatment of depression, osteoporosis, fatigue, rheumatoid arthritis, and infertility due to their anti-depressant, anti-osteoporosis, pro-fertility, anti-radiation, anti-Alzheimer disease, anti-rheumatoid, anti-fatigue, anti-aging, cardiovascularprotective, anti-oxidation, immune-regulatory, and anti-inflammatory activities. Pharmacokinetic studies have demonstrated that the main components of MO including monotropein and deacetyl asperulosidic acid are distributed in various organs and tissues. The investigation on acute toxicity and genotoxicity indicated that MO is nontoxic. There have no reports on significant adverse effect at a normal dose in clinical application, but MO at dose of more than 1000mg/kg may cause irritability, insomnia and unpleasant sensations in individual cases. CONCLUSION: MO has emerged as a good source of traditional medicines. Some uses of this plant in traditional medicines have been validated by pharmacological investigations. However, the molecular mechanism, structure-activity relationship, and potential synergistic and antagonistic effects of its multi-components such as polysaccharides, oligosaccharides, anthraquinones and iridoid glycosides need to be further elucidated, and the structural feature of polysaccharides also need to be further clarified. Sophisticated analytical technologies should be developed to comprehensively evaluate the quality of MO based on HPLC-fingerprint and content determination of the active constituents, knowing that these investigations will help further utilize this plant.
27890169 Hepatitis C Virus Infection and Rheumatic Diseases: The Impact of Direct-Acting Antiviral 2017 Feb Chronic hepatitis C virus (HCV) infection is associated with liver and extrahepatic complications, including B-cell lymphoma, cardiovascular and kidney diseases, glucose metabolism impairment and rheumatic conditions ie, arthralgia, myalgia, cryoglobulinemia vasculitis, sicca syndrome and the production of autoantibodies. The treatment has long been based on interferon alpha (IFN) that was found poorly effective, and contraindicated in many autoimmune/inflammatory disorders because of possible exacerbation of rheumatic disorders. The recent emergence of new oral IFN-free combinations offers an opportunity for HCV infected patients with autoimmune/inflammatory disorders to be cured with a short treatment duration and low risk of side effects.
28465508 CD8 T cells contribute to lacrimal gland pathology in the nonobese diabetic mouse model of 2017 Sep Sjögren syndrome is an autoimmune disease characterized by targeted destruction of the lacrimal and salivary glands resulting in symptoms of severe ocular and oral dryness. Despite its prevalence, the mechanisms driving autoimmune manifestations are unclear. In patients and in the nonobese diabetic (NOD) mouse model of Sjögren syndrome, lymphocytic infiltrates consist of CD4 and CD8 T cells, although the role of CD8 T cells in disease pathogenesis has been largely unexplored. Here, we evaluated the contribution of CD8 T cells to lacrimal and salivary gland autoimmunity. Within the lacrimal and salivary glands of NOD mice, CD8 T cells were proliferating, expressed an activated phenotype, and produced inflammatory cytokines. Transfer of purified CD8 T cells isolated from the cervical lymph nodes (LNs) of NOD mice into NOD-severe combined immunodeficiency recipients resulted in inflammation of the lacrimal glands, but was not sufficient to cause inflammation of the salivary glands. Lacrimal gland-infiltrating CD8 T cells displayed a cytotoxic phenotype, and epithelial cell damage in the lacrimal glands was observed in recipients of CD8 T cells regardless of the presence of CD4 T cells. Collectively, our results demonstrate that CD8 T cells have a pathogenic role in lacrimal gland autoimmunity. The gland-specific pathogenicity of CD8 T cells makes them a valuable resource to further understand the mechanisms that discriminate lacrimal versus salivary gland autoimmunity and for the development of new therapeutics that target the early stages of disease.
28719732 Genome-Wide Association Meta-Analysis Reveals Novel Juvenile Idiopathic Arthritis Suscepti 2017 Nov OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease and has a strong genomic component. To date, JIA genetic association studies have had limited sample sizes, used heterogeneous patient populations, or included only candidate regions. The aim of this study was to identify new associations between JIA patients with oligoarticular disease and those with IgM rheumatoid factor (RF)-negative polyarticular disease, which are clinically similar and the most prevalent JIA disease subtypes. METHODS: Three cohorts comprising 2,751 patients with oligoarticular or RF-negative polyarticular JIA were genotyped using the Affymetrix Genome-Wide SNP Array 6.0 or the Illumina HumanCoreExome-12+ Array. Overall, 15,886 local and out-of-study controls, typed on these platforms or the Illumina HumanOmni2.5, were used for association analyses. High-quality single-nucleotide polymorphisms (SNPs) were used for imputation to 1000 Genomes prior to SNP association analysis. RESULTS: Meta-analysis showed evidence of association (P < 1 × 10(-6) ) at 9 regions: PRR9_LOR (P = 5.12 × 10(-8) ), ILDR1_CD86 (P = 6.73 × 10(-8) ), WDFY4 (P = 1.79 × 10(-7) ), PTH1R (P = 1.87 × 10(-7) ), RNF215 (P = 3.09 × 10(-7) ), AHI1_LINC00271 (P = 3.48 × 10(-7) ), JAK1 (P = 4.18 × 10(-7) ), LINC00951 (P = 5.80 × 10(-7) ), and HBP1 (P = 7.29 × 10(-7) ). Of these, PRR9_LOR, ILDR1_CD86, RNF215, LINC00951, and HBP1 were shown, for the first time, to be autoimmune disease susceptibility loci. Furthermore, associated SNPs included cis expression quantitative trait loci for WDFY4, CCDC12, MTP18, SF3A1, AHI1, COG5, HBP1, and GPR22. CONCLUSION: This study provides evidence of both unique JIA risk loci and risk loci overlapping between JIA and other autoimmune diseases. These newly associated SNPs are shown to influence gene expression, and their bounding regions tie into molecular pathways of immunologic relevance. Thus, they likely represent regions that contribute to the pathology of oligoarticular JIA and RF-negative polyarticular JIA.
28303668 Beliefs about medicines among Hong Kong hospital outpatients. 2017 Dec OBJECTIVES: (1) To identify demographic characteristics associated with different patients' belief attitudes among older Hong Kong hospital outpatients. (2) To identify important implementation criteria for developing a more effective adherence-improving intervention. METHODS: Six hundred and ninety-eight patients completed a questionnaire consisting of demographic information and Belief about Medicines Questionnaire. Findings were statistically analysed. KEY FINDINGS: Among respondents, 56.9% were either in the hesitant (Mixed-feelings and Indifferent) or negative (Distrustful) medication belief constructs. The majority of these patients were younger females, with better education, taking fewer regular medications and for shorter duration. Rheumatoid and gout accounted for 46.1% of cases in the Distrustful construct, while cardiovascular and diabetic conditions accounted for 63.8% of cases in the positive (In-favour) construct. Patients' concerns about medications were reaffirmed to be a predominant factor affecting medication beliefs. The mean Necessity-Concern Differential scores in the two hesitant constructs illustrated that patients within these two constructs were more pliant towards medicines and, therefore, were predicted to be more subject to modification. CONCLUSIONS: Our results identified the demographic characteristics of patients with negative or hesitant belief attitudes about medicines. In order to effectively achieve improvement in long-term beliefs about medications, the design of interventions should target positively modifying belief attitudes in these two patient groups. Furthermore, addressing patients' concern about their medicines was reaffirmed to be an important criterion for researchers to focus on when designing effective interventions in the future.