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ID PMID Title PublicationDate abstract
34943240 IFP35 Is a Relevant Factor in Innate Immunity, Multiple Sclerosis, and Other Chronic Infla 2021 Dec 14 Discovered in 1993 by Bange et al., the 35-kDa interferon-induced protein (IFP35) is a highly conserved cytosolic interferon-induced leucine zipper protein with a 17q12-21 coding gene and unknown function. Belonging to interferon stimulated genes (ISG), the IFP35 reflects the type I interferon (IFN) activity induced through the JAK-STAT phosphorylation, and it can homodimerize with N-myc-interactor (NMI) and basic leucine zipper transcription factor (BATF), resulting in nuclear translocation and a functional expression. Casein kinase 2-interacting protein-1 (CKIP-1), retinoic acid-inducible gene I (RIG-I), and laboratory of genetics and physiology 2 Epinephelus coioides (EcLGP2) are thought to regulate IFP35, via the innate immunity pathway. Several in vitro and in vivo studies on fish and mammals have confirmed the IFP35 as an ISG factor with antiviral and antiproliferative functions. However, in a mice model of sepsis, IFP35 was found working as a damage associated molecular pattern (DAMP) molecule, which enhances inflammation by acting in the innate immune-mediated way. In human pathology, the IFP35 expression level predicts disease outcome and response to therapy in Multiple Sclerosis (MS), reflecting IFN activity. Specifically, IFP35 was upregulated in Lupus Nephritis (LN), Rheumatoid Arthritis (RA), and untreated MS. However, it normalized in the MS patients undergoing therapy. The considered data indicate IFP35 as a pleiotropic factor, suggesting it as biologically relevant in the innate immunity, general pathology, and human demyelinating diseases of the central nervous system.
34527567 Risk of rheumatic disease in breast implant users: a qualitative systematic review. 2021 Aug BACKGROUND: Recent studies on the risk of rheumatic disease among breast implant users have reported conflicting results. The primary objective of this study was to provide a systematic and critical review of the literature on the association between breast implants and the risk of rheumatic disease. METHODS: A qualitative systematic review was conducted in PubMed, MEDLINE, EMBASE, EBM-Reviews and CINAHL Complete from database inception to June 23rd, 2021. Eligible papers were full-length articles in English or French reporting original data on the incident risk of rheumatic disease among individuals with and without breast implants. Data were extracted from published reports and appraised using the Newcastle-Ottawa scale. The main outcome was incident risk of systemic sclerosis (SSc), Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), fibromyalgia and other rheumatic disorders and symptoms. RESULTS: Out of 3,425 identified citations, 86 met inclusion criteria. Two cohort studies suggested a two-fold increase in risk of SSc, whereas three case-control studies showed no increase in risk. Three cohort studies did not find an increased risk of incident and confirmed SS among breast implant users, however symptoms of sicca, myalgia and fatigue were reported more frequently. A meta-analysis of heterogenous studies reported a less than two-fold increase in risk of RA. Studies did not support an association with SLE. Insufficient evidence was available for autoimmune myositis and other rheumatic diseases. Implant rupture detected on imaging was not clearly associated with incident rheumatic disease, although no studies specifically examined the risk associated with acute/traumatic rupture. Little data was available on the safety of saline breast implants. Explantation often led to temporary improvement. CONCLUSIONS: Based on a small number of high-quality and methodologically robust studies, an association between breast implants and a small increase in risk of SSc and RA could not be excluded. Symptoms of sicca, myalgia and fatigue were reported more frequently among breast implant users. Overall, there remains much uncertainty in regard to the association between breast implants and the risk of incident rheumatic diseases. Individuals considering the placement of breast implants should be informed of this uncertainty. TRIAL REGISTRATION: This study was registered in the PROSPERO database (#CRD42019133616).
34483390 Predictive Factors for Blood Transfusion after Total Knee Arthroplasty. 2021 Aug Objectives  The present paper aims to (1) verify the incidence and volume of blood transfusion among patients undergoing unilateral cemented total knee arthroplasty (TKA) in a single Brazilian reference center; (2) identify pre and perioperative variables to determine subjects with higher risk (i.e., predictive factors) for blood transfusion within 48 hours following surgery; (3) estimate the risk of blood transfusion during the first 48 hours after the procedure. Methods  The initial sample consisted of all patients undergoing TKA from August 2010 to August 2013. After applying the exclusion criteria, 234 patients aged 30 to 83 years old and diagnosed with primary or secondary osteoarthritis due to rheumatoid arthritis remained in the study. Results  Preoperative hemoglobin levels ≤ 12.3 g/dL and ischemia time ≥ 87 minutes were independent predictors for post-TKA blood transfusion, with a relative risk of 2.48 and 1.78, respectively. Approximately half of the TKA patients (51.3%) presenting these two variables required a blood transfusion. Conclusion  The incidence of post-TKA blood transfusion was 33.7%. On average, each transfused patient received 480 mL of packed red blood cells. Preoperative hemoglobin levels ≤ 12.3 g/dL ( p  < 0.001) and ischemia time ≥ 87 minutes ( p  < 0.047) were independent predictors for blood transfusion in TKA using a pneumatic cuff, with a relative risk of 2.48 and 1.78, respectively. Age, gender, diagnosis, or body mass index were not considered independent predictors for the need for blood transfusion up to 48 hours after the procedure.
34228389 Identification of sustainable trypsin active-site inhibitors from Nigrospora sphaerica str 2021 Aug Trypsin is a protein-digesting enzyme that is essential for the growth and regeneration of bone, muscle, cartilage, skin, and blood. The trypsin inhibitors have various role in diseases such as inflammation, Alzheimer's disease, pancreatitis, rheumatoid arthritis, cancer prognosis, metastasis and so forth. From 10 endophytic fungi isolated, we were able to screen only one strain with the required activity. The fungus with activity was obtained as an endophyte from Dendrophthoe falcata and was later identified as Nigrospora sphaerica. The activity was checked by enzyme assays using trypsin. The fungus was fermented and the metabolites were extracted and further purified by bioassay-guided chromatographic methods and the compound isolated was identified using gas chromatography-mass spectrometry. The compound was identified as quercetin. Docking studies were employed to study the interaction. The absorption, distribution, metabolism, and excretion analysis showed satisfactory results and the compound has no AMES and hepatotoxicity. This study reveals the ability of N. sphaerica to produce bioactive compound quercetin has been identified as a potential candidate for trypsin inhibition. The present communication describes the first report claiming that N. sphaerica strain AVA-1 can produce quercetin and it can be considered as a sustainable source of trypsin active-site inhibitors.
34225700 Amino terminal recognition by a CCR6 chemokine receptor antibody blocks CCL20 signaling an 2021 Jul 5 BACKGROUND: CCR6 chemokine receptor is an important target in inflammatory diseases. Th17 cells express CCR6 and a number of inflammatory cytokines, including IL-17 and IL-22, which are involved in the propagation of inflammatory immune responses. CCR6 antagonist would be a potential treatment for inflammatory diseases such as psoriasis or rheumatoid arthritis. The aim of this study is to develop an antagonistic monoclonal antibody (mAb) against human CCR6 receptor (hCCR6). RESULTS: We generate monoclonal antibodies against hCCR6 immunizing Balb/c mice with hCCR6 overexpressing cells. The antibodies were tested by flow cytometry for specific binding to hCCR6, cloned by limiting dilution and resulted in the isolation and purification monoclonal antibody 1C6. By ELISA and flow cytometry, was determined that the antibody obtained binds to hCCR6 N-terminal domain. The ability of 1C6 to neutralize hCCR6 signaling was tested and we determined that 1C6 antibody were able to block response in β-arrestin recruitment assay with IC(50) 10.23 nM, but did not inhibit calcium mobilization. In addition, we found in a chemotaxis assay that 1C6 reduces the migration of hCCR6 cells to their ligand CCL20. Finally, we determined by RT-qPCR that the expression of IL-17A in Th17 cells treated with 1C6 was inhibited. CONCLUSIONS: In the present study, we applied whole cell immunization for successfully obtain an antibody that is capable to neutralize hCCR6 signaling and to reduce hCCR6 cells migration and IL-17 expression. These results provide an efficient approach to obtain therapeutic potential antibodies in the treatment of CCR6-mediated inflammatory diseases.
34139817 [The association between shift work and lower extremity osteoarthritis among retired worke 2021 Jun 6 Objective: To investigate the association between shift work and the risk of lower extremity osteoarthritis. Methods: The study population came from the Dongfeng-Tongji cohort established in 2008. In September 2008, the Dongfeng Motor Company in Hubei Province was to recruit all retired workers who voluntarily participated in the survey as the research objects. During the follow-up conducted from April to October 2013, a total of 14 438 retired workers, i.e. all of the participants who underwent physical examination were investigated about demographic characteristics, lifestyles, occupation history, and lower extremity joint-related medical history, and additionally completed lower extremity joint examinations. After excluding individuals with missing data regarding lower extremity osteoarthritis, with the history of lower extremity joint trauma, or with history of rheumatoid arthritis (N=532), data from 13 906 participants was analyzed in the study. Multivariate logistic regression models were used to estimate the association between shift work and lower extremity osteoarthritis. After stratified by the duration of shift work, multivariate logistic regression models were used to analyze the relationship between the duration after leaving from shift work and lower extremity osteoarthritis. Results: Finally, a total of 13 906 retired employees included 7 560 (54.4%) females with a mean age of 64.74 (standard deviation 8.23) years old. 5 537 (39.8%) workers had ever engaged in shift work, including 2 004 (14.4%) workers with 1-9 years of shift work and 3 533 (25.4%) workers with ≥ 10 years of shift work. The prevalence of lower extremity osteoarthritis was 7.0%, while the prevalence of knee osteoarthritis and hip osteoarthritis were 6.7% and 0.7%, respectively. Compared with daytime workers, shift workers showed a 22% increase in the risk of lower extremity osteoarthritis (OR=1.22, 95%CI:1.06-1.40). Each 5-year increase in the duration of shift work was associated with a 4% increase in the risk of lower extremity osteoarthritis (OR=1.04, 95%CI:1.01-1.08). With the extension of the duration after leaving from shift work, the risk of lower extremity osteoarthritis decreased. Similar relationships were found between shift work and the risk of knee osteoarthritis, as well as hip osteoarthritis. Conclusion: Shift work was associated with the increased risk of lower extremity osteoarthritis.
34021490 Comparison of the AAPT Fibromyalgia Diagnostic Criteria and Modified FAS Criteria with Exi 2021 Jun INTRODUCTION: Recently, new sets of diagnostic criteria were proposed, including criteria by the ACTTION-American Pain Society Pain Taxonomy (AAPT) group and Fibromyalgia Assessment Status (FAS) 2019 modified criteria for fibromyalgia (FM). Here, we explored the performances of the AAPT criteria and modified FAS criteria for diagnosing FM compared to existing American College of Rheumatology (ACR) criteria. METHODS: We enrolled 95 patients with FM and 108 patients who had other rheumatologic disorders, including rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, and myofascial pain syndrome. All patients were classified using proposed criteria including the 1990, 2010, 2011, and 2016 versions of the ACR criteria. RESULTS: In patients with existing FM diagnoses, FM was diagnosed in 56.8% using the AAPT criteria and in 60.0% using the modified FAS criteria. However, FM was diagnosed in 37.9%, 97.9%, 90.5%, and 94.7% of those patients using the 1990, 2010, 2011, and 2016 ACR criteria, respectively. For the AAPT criteria, the sensitivity was 56.8% and the specificity was 94.4%. For the modified FAS criteria, the sensitivity was 60.0% and the specificity was 92.6%. The areas under the receiver-operating characteristic curve were 0.852 (95% confidence interval [CI] 0.801-0.903) for the AAPT criteria and 0.903 (95% CI 0.861-0.944) for the modified FAS criteria, which were lower than the existing ACR criteria. CONCLUSIONS: Although the AAPT criteria and modified FAS criteria have simplified the diagnostic criteria to facilitate patient identification, their poor diagnostic accuracy will limit the adoption and spread of these criteria in routine clinical practice.
33816332 Auranofin Resistance in Toxoplasma gondii Decreases the Accumulation of Reactive Oxygen Sp 2021 Auranofin, a reprofiled FDA-approved drug originally designed to treat rheumatoid arthritis, has emerged as a promising anti-parasitic drug. It induces the accumulation of reactive oxygen species (ROS) in parasites, including Toxoplasma gondii. We generated auranofin resistant T. gondii lines through chemical mutagenesis to identify the molecular target of this drug. Resistant clones were confirmed with a competition assay using wild-type T. gondii expressing yellow fluorescence protein (YFP) as a reference strain. The predicted auranofin target, thioredoxin reductase, was not mutated in any of our resistant lines. Subsequent whole genomic sequencing analysis (WGS) did not reveal a consensus resistance locus, although many have point mutations in genes encoding redox-relevant proteins such as superoxide dismutase (TgSOD2) and ribonucleotide reductase. We investigated the SOD2 L201P mutation and found that it was not sufficient to confer resistance when introduced into wild-type parasites. Resistant clones accumulated less ROS than their wild type counterparts. Our results demonstrate that resistance to auranofin in T. gondii enhances its ability to abate oxidative stress through diverse mechanisms. This evidence supports a hypothesized mechanism of auranofin anti-parasitic activity as disruption of redox homeostasis.
33297790 Preparation, characterization and in-Vitro/in-Vivo evaluation of meloxicam extruded pellet 2021 Jan OBJECTIVE: The present study involved enhancement of Meloxicam (MX) oral absorption for rapid onset of therapeutic action. A challenging approach using hot-melt-extrusion technique (HME) for production of stable novel preparation of MX pellets was successfully proposed. METHODS: Manipulating HME processing parameters (barrel-temperatures and screw-speed) and proper polymer(s) selection (Soluplus, a combination of Soluplus/Poloxamar and Polyethylene Glycol 6000) were the main strategies involved for productive extrusion of MX. Evaluation of MX solid-state (TGA, DSC and PLM), absolute percent crystallinity, in-vitro dissolution (in acidic/aqueous pHs), and stability testing in accelerated conditions up to 6-months as well as a long-term shelf for 36-months were performed. A comparative bioavailability study of selected MX-Pellets was carried-out against the innovator product (Mobic(®)) in 6 healthy volunteers under fed-conditions. RESULTS: TGA, DSC and PLM analyses proved the dispersion of MX in amorphous-state within polymeric matrix by HME. MX/Soluplus pellets exhibited the lowest crystallinity % and best dissolution performance among other polymers in both pHs. In addition, presence of Soluplus safeguards final pellets stability under different storage conditions. MX rate of absorption (T(max)) from Soluplus-based pellets attained a value of 45 min, which was 6-times faster than Mobic(®) (4.5 hr). CONCLUSION: A promising oral MX formula prepared by HME was successfully developed with a rapid onset of analgesic action (T(max) of 45 mins; almost 2-times faster than reported intramuscular injection), hence appropriate in the early relief of pain associated with rheumatoid arthritis and osteoarthritis. Moreover, the proposed formula was physico-chemically stable up to 36 months of shelf-life storage.
32956854 Incidence of and risk for osteonecrosis of the jaw in Korean osteoporosis patients treated 2021 Feb PURPOSE: To estimate the incidence of osteonecrosis of the jaw (ONJ) in patients treated with bisphosphonates (BPs) and to identify clinical risk factors that increase the risk for ONJ in Korean osteoporosis patients. METHODS: We used data acquired from the Korean National Health Insurance Service. Among 2,140,149 participants with osteoporosis in 2012, we selected 164,926 new BP users and 164,926 age- and sex-matched control subjects. The control group included only patients with no prescriptions for BPs between January 1, 2011, and December 31, 2016. Participants were followed for 4 years. RESULTS: Over the 4-year follow-up period, the cumulative incidence rates of ONJ were 20.9 and 6.9 per 100,000 person-years in the BP and control groups, respectively. The BP group had an increased risk for ONJ compared to the control group after adjusting for multiple variables (hazard ratio [HR] 3.72, 95% CI 2.70-5.11). Advanced age (≥70 years), comorbid diseases such as diabetes, hypertension, and rheumatoid arthritis (RA) were independent risk factors for the development of ONJ. In addition, tooth extraction (HR 9.85), gingivitis, and periodontal disease (HR 4.78) were strongly associated with ONJ. CONCLUSIONS: ONJ incidence was 21 per 100,000 person-years in osteoporosis patients receiving bisphosphonates. Clinical factors including advanced age, diabetes, RA, dental disease, as well as BP use were significantly associated with ONJ.
34863654 The role of IL-17 and anti-IL-17 agents in the immunopathogenesis and management of autoim 2022 Jan Interleukin-17 (IL-17) is a proinflammatory cytokine involved in chronic inflammation occurring during the pathogenesis of allergy, malignancy, and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and psoriasis. IL-17 is produced by multiple cell types of adaptive and innate immunity, including T helper 17 cells, CD8 + T cells, γδ T cells, natural killer T cells, and innate lymphoid cells. Monoclonal antibodies (mAbs) targeting IL-17 and/or IL-17R would be a potential approach to study this therapeutic tool for these diseases. In the current review, we aimed to highlight the characteristics of IL-17 and its important role in the pathogenesis of related diseases. Critical evaluation of the mAbs targeting IL-17A and IL-17 receptors (e.g., Ixekizumab, Secukinumab, and Brodalumab) in various immune-mediated diseases will be provided, and finally, their clinical efficacy and safety will be reported.
34506768 Loxoprofen enhances intestinal barrier function via generation of its active metabolite by 2021 Oct 1 Nonsteroidal anti-inflammatory drugs (NSAIDs) are used worldwide as antipyretic analgesics and agents for rheumatoid arthritis and osteoarthritis, but known to cause damage to the gastrointestinal mucosae as their serious adverse effects. Few studies showed the impairment of intestinal epithelial barrier function (EBF) by high concentrations (0.5-1 mM) of NSAIDs, but the underlying mechanism is not fully understood. This study is aimed at clarifying effects at a low concentration (50 μM) of three NSAIDs, loxoprofen (Lox), ibuprofen and indomethacin, on intestinal EBF using human intestinal epithelial-like Caco-2 cells. Among those NSAIDs, Lox increased the transepithelial electric resistance (TER) value, decreased the paracellular Lucifer yellow CH (LYCH) permeability, and upregulated claudin (CLDN)-1, -3 and -5, indicating that low doses of Lox enhanced EBF through increasing expression of CLDNs. Lox is known to be metabolized to a pharmacologically active metabolite, (2S,1'R,2'S)-loxoprofen alcohol (Lox-RS), by carbonyl reductase 1 (CBR1), which is highly expressed in human intestine. CBR1 was expressed in the Caco-2 cells, and the pretreatment with a CBR1 inhibitor suppressed both the Lox-evoked CLDN upregulation and EBF enhancement. In addition, the treatment of the cells with Lox-RS resulted in higher TER value and lower LYCH permeability than those with Lox. Thus, Lox-RS synthesized by CBR1 may greatly contribute to the improving efficacy of Lox on the barrier function. Since EBF is decreased in inflammatory bowel disease, we finally examined the effect of Lox on EBF using the Caco-2/THP-1 co-culture system, which is used as an in vitro inflammatory bowel disease model. Lox significantly recovered EBF which was impaired by inflammatory cytokines secreted from THP-1 macrophages. These in vitro observations suggest that Lox enhances intestinal EBF, for which the metabolism of Lox to Lox-RS by CBR1 has an important role.
34452074 Bioengineered Nanoparticles Loaded-Hydrogels to Target TNF Alpha in Inflammatory Diseases. 2021 Jul 21 Rheumatoid Arthritis (RA) is an incurable autoimmune disease that promotes the chronic impairment of patients' mobility. For this reason, it is vital to develop therapies that target early inflammatory symptoms and act before permanent articular damage. The present study offers two novel therapies based in advanced drug delivery systems for RA treatment: encapsulated chondroitin sulfate modified poly(amidoamine) dendrimer nanoparticles (NPs) covalently bonded to monoclonal anti-TNF α antibody in both Tyramine-Gellan Gum and Tyramine-Gellan Gum/Silk Fibroin hydrogels. Using pro-inflammatory THP-1 (i.e., human monocytic cell line), the therapy was tested in an inflammation in vitro model under both static and dynamic conditions. Firstly, we demonstrated effective NP-antibody functionalization and TNF-α capture. Upon encapsulation, the NPs were released steadily over 21 days. Moreover, in static conditions, the approaches presented good anti-inflammatory activity over time, enabling the retainment of a high percentage of TNF α. To mimic the physiological conditions of the human body, the hydrogels were evaluated in a dual-chamber bioreactor. Dynamic in vitro studies showed absent cytotoxicity in THP-1 cells and a significant reduction of TNF-α in suspension over 14 days for both hydrogels. Thus, the developed approach showed potential for use as personalized medicine to obtain better therapeutic outcomes and decreased adverse effects.
34440897 Occurrence and Antigenic Specificity of Perinuclear Anti-Neutrophil Cytoplasmic Antibodies 2021 Aug 19 Perinuclear anti-neutrophilic cytoplasmic antibodies (P-ANCA) recognize heterogeneous antigens, including myeloperoxidase (MPO), lactoferrin, elastase, cathepsin-G and bactericidal/permeability-increasing protein. Although P-ANCA have diagnostic utility in vasculitides, they may also be found in patients with various other systemic autoimmune rheumatic diseases (SARDs). Nevertheless, the clinical significance and the targets recognized by P-ANCA in such patients remain unclear. For this purpose, herein we investigated the occurrence of ANCA-related antigenic specificities in 82 P-ANCA-positive sera by multiplex ELISA, as well as their association with other autoantibodies. The P-ANCA-positive sera corresponded to patients with vasculitides (n = 24), systemic lupus erythematosus (n = 28), antiphospholipid syndrome (n = 5), Sjögren's syndrome (n = 7), rheumatoid arthritis (n = 3), systemic scleroderma (n = 1), sarcoidosis (n = 1) and Hashimoto's thyroiditis (n = 13). In most P-ANCA-positive patients studied (51/82, 62.3%), these autoantibodies occurred in high titers (>1:160). The analysis of P-ANCA-positive sera revealed reactivity to MPO in only 50% of patients with vasculitides, whereas it was infrequent in the other disease groups studied. Reactivity to other P-ANCA-related autoantigens was also rarely detected. Our findings support that high P-ANCA titers occur in SARD. The P-ANCA-positive staining pattern is associated with MPO specificity in vasculitides, while in other autoimmune diseases, it mostly involves unknown autoantigens.
34361816 Eco-Friendly UPLC-MS/MS Method for Determination of a Fostamatinib Metabolite, Tamatinib, 2021 Jul 31 Fostamatinib is a prodrug of the active metabolite tamatinib, which is a spleen tyrosine kinase (Syk) inhibitor used in the treatment of primary chronic adult immune thrombocytopenia and rheumatoid arthritis. A highly sensitive, rapid, reliable, and green method was developed and validated using ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS) for quantification of tamatinib in rat plasma. Ibrutinib was used as internal standard and liquid-liquid extraction was applied using tert-butyl methyl ether. The analyte was separated on an Acquity(TM) CSH C(18) (2.1 mm × 100 mm, 1.7 µm) column using mobile phase consisting of 10 mM ammonium acetate and acetonitrile (10:90) and the flow rate was 0.25 mL/min. Electrospray ionization (ESI) was carried out in positive mode. Quantitation of tamatinib and the IS was performed using multiple reaction monitoring mode with precursor-to-product transitions of m/z 471.1 > 122.0 and m/z 441.1 > 84.0, respectively. The calibration range was 0.1-1000.0 ng/mL and the linearity of the method was ≥0.997. The developed method greenness was investigated. All principal parameters for the method, including linearity, accuracy, precision, recovery, and stability, were within acceptable ranges. Tamatinib pharmacokinetic study in rats was successfully carried out using the developed method.
34353059 Molecular mechanism of Wutou Decoction in the treatment of osteoarthritis: a bioinformatic 2021 Jul BACKGROUND: Osteoarthritis (OA) is a chronic joint disease characterized by cartilage destruction and periarticular osteophyte formation. One therapeutic option for this condition, the Wutou Decoction (WTD) Chinese medicine formula, is satisfactory in its efficacy. Here, we used bioinformatic and molecular docking techniques to investigate the mechanism of action of WTD in the treatment of OA. METHODS: The active compounds (and their target proteins) of 5 Chinese herbs in WTD were obtained by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The action targets of WTD for OA were obtained by searching the Therapeutic Target Database and by mining the microarray data in the Gene Expression Omnibus. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to identify key targets for OA treatment with the help of Database for Annotation, Visualization, and Integrated Discovery. Based on the Cytoscape software version 3.6.1, the visual networks of the "TCM drugs-Active Compounds-Targets-Diseases" and protein-protein interaction of the key targets of WTD for the treatment of OA were constructed. The core active compounds and the key targets obtained were molecularly docked and validated. RESULTS: Analyses revealed 140 active compounds in WTD, 123 of which had a total of 163 corresponding targets. In addition, 331 differentially expressed genes and 227 OA-related targets were obtained. The interaction networks among 32 key targets were identified. The biological processes of WTD in treating OA mainly involved regulation of inflammatory factors, transcription of genetic materials, cell cycle, angiogenesis, and endocrine regulation. The signaling pathways involved mainly included TNF signaling pathway, rheumatoid arthritis signaling pathway, cancer-related signals, vascular endothelial growth factor signaling pathway, and osteoclast differentiation signaling pathways. Molecular docking showed that 7 core compounds including quercetin and kaempferol had strong affinities with key target proteins for the WTD treatment of OA. CONCLUSIONS: WTD with multi-component can treats OA through multi-pathway. Its active compounds, including quercetin and kaempferol, can exert their therapeutic effects on OA by acting on TNF, PTGS2, MMP2, IL-6, IL-1β, and other key targets to regulate inflammation, immunity, autophagy, and endocrine-related signaling pathways.
34258812 Effect of ICD-9-CM to ICD-10-CM coding system transition on identification of common condi 2021 Dec PURPOSE: To evaluate the effect of diagnostic coding system transition on the identification of common conditions recorded in Taiwan's national claims database. METHODS: Using the National Health Insurance Research Database, we estimated the 3-month prevalence of recorded diagnosis of 32 conditions based on the ICD-9-CM codes in 2014-2015 and the ICD-10-CM codes in 2016-2017. Two algorithms were assessed for ICD-10-CM: validated ICD-10 codes in the literature and codes translated from ICD-9-CM using an established mapping algorithm. We used segmented regression analysis on time-series data to examine changes in the 3-month prevalence (both level and trend) before and after the ICD-10-CM implementation. RESULTS: Significant changes in the level were found in 19 and 11 conditions when using the ICD-10 codes from the literature and mapping algorithm, respectively. The conditions with inconsistent levels by both of the algorithms were valvular heart disease, peripheral vascular disease, mild liver disease, moderate to severe liver disease, metastatic cancer, rheumatoid arthritis and collagen vascular diseases, coagulopathy, blood loss anemia, deficiency anemia, alcohol abuse, and psychosis. Nine conditions had significant changes in the trend when using the ICD-10 codes from the literature or mapping algorithm. CONCLUSIONS: Less than half of the 32 conditions studied had a smooth transition between the ICD-9-CM and ICD-10-CM coding systems. Researchers should pay attention to the conditions where the coding definitions result in inconsistent time series estimates.
34087408 Structure elucidation and anti-inflammatory mechanism of difengpienol C, a new neolignan i 2021 Sep Illicium difengpi is well-known as its stem barks that have been widely used in the Traditional Chinese Medicine (TCM) for therapy rheumatoid arthritis and traumatic injury. To comprehensive utilization of resources, the phytochemical investigation on the branches and leaves of this plant was carried out, which led to the isolation of an undescribed neolignan along with three known lignans. Their structures were elucidated on the basis of extensive spectroscopic data and the new compound was elucidated as a neolignan possessing a dihydropyran ring formed by a unique conjugation way and named difengpienol C. Difengpienol C showed the strongest anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, which powerfully inhibited nitric oxide (NO), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) production and suppressed the mRNA transcription of inducible nitric oxide synthase (iNOS), IL-6 and TNF-α. Besides, difengpienol C blocked the activation of TLR4/MyD88/NF-κB signaling pathway. Therefore, difengpienol C might be a potent agent for anti-inflammatory drug development, and the non-traditional medicinal parts of Illicium difengpi can be identified as the source of natural anti-inflammatory molecules.
34084766 Bioactive α-Pyrone Derivatives from the Endophytic Fungus Diaporthe sp. CB10100 as Induci 2021 Inducible nitric oxide synthase (iNOS) produces NO from l-arginine and plays critical roles in inflammation and immune activation. Selective and potent iNOS inhibitors may be potentially used in many indications, such as rheumatoid arthritis, pain, and neurodegeration. In the current study, five new compounds, including a dibenzo-α- pyrone derivative ellagic acid B (5) and four α-pyrones diaporpyrone A-D (9-12), together with three known compounds (6-8), were isolated from the endophytic fungus Diaporthe sp. CB10100. The structures of these new natural products were unambiguously elucidated using NMR, HRESIMS or electronic circular dichroism calculations. Ellagic acid B (5) features a tetracyclic 6/6/6/6 ring system with a fused 2H-chromene, which is different from ellagic acid (4) with a fused 2H-chromen-2-one. Both 2-hydroxy-alternariol (6) and alternariol (7) reduced the expression of iNOS at protein levels in a dose-dependent manner, using a lipopolysaccharide (LPS)-induced RAW264.7 cell models. Also, they decreased the protein expression levels of pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6 and monocyte chemotactic protein 1. Importantly, 6 and 7 significantly reduced the production of NO as low as 10 μM in LPS-induced RAW264.7 cells. Molecular docking of 6 and 7 to iNOS further suggests that both of them may interact with iNOS. Our study suggests that 6 and 7, as well as the alternariol scaffold may be further developed as potential iNOS inhibitors.
34058810 [Serological screening and analysis of clinical characteristics for celiac disease in susc 2021 Jun 1 Objective: To determine the seroprevalence of celiac disease in susceptible population, and to analyze the relationship between demographic characteristics, dietary habits, lifestyle and serological positivity so as to provide guidance for the prevention and treatment of celiac disease in Southern China. Methods: A total of 1 273 individuals who participated in Guangdong Province Health Screening Program in 2015, were selected as serologically positive subjects of celiac disease, including people with irritable bowel syndrome, colitis, diarrhea, anemia, low BMI, short stature, type 1 diabetes mellitus (T1DM), rheumatoid arthritis (RA), ankylosing spondylitis, psoriasis and bristol grade=6 or 7. All subjects were tested for serum IgA anti-tissue transglutaminase antibodies (TTGA), IgA antibodies against deamidated gliadin peptides(DGPA) and IgG against deamidated gliadin peptides (DGPG). Dietary habits, lifestyle and demographic characteristics were compared in subgroups. Results: The seroprevalence of celiac disease in susceptible population was 0.94% (95%CI 0.54%-1.64%) including 0.08% (1/1 273) for TTGA, 0.47% (6/1 273) for DGPA, and 0.39% (5/1 273) for DGPG. The seropositive rate was 3.6% (1/28) in patients with psoriasis, 2.1% (2/95) in the low BMI group, 1.9% (1/53) in T1DM group, 1.8% (3/169) in diarrhea group and 1.1% (5/463) in RA group. No significant difference was found in age, gender, high carbohydrate diet or lifestyle between the negative and the positive subjects. Conclusions: In Southern China, the seropositive rate of celiac disease is 0.94% in susceptible population, which prompts an urgent need of serological screening for early diagnosis.