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ID PMID Title PublicationDate abstract
30071926 Hemophagocytic lymphohistiocytosis after certolizumab treatment in a patient with rheumato 2018 Sep Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening syndrome that may be triggered by hereditary factors, autoimmune and immunologic disorders, infectious diseases, malignancies and medications. Suspicion of the disease and early treatment is of paramount importance. Since the presentation of HLH with only skin involvement is rare, early diagnosis may be difficult. A pathologically confirmed HLH case that presented with maculopapular skin lesions after certolizumab treatment is being reported in this presentation.
30013749 Prevalence of celiac disease serological markers in a cohort of Italian rheumatological pa 2018 Summer AIM: To assess the prevalence of celiac disease (CD) serological markers in a cohort of patients referred to an Italian rheumatological outpatient clinic. BACKGROUND: Current guidelines do not suggest CD screening in patients with rheumatological diseases and these subjects are not considered to be at high risk for CD. METHODS: A total of 230 sera of rheumatological patients referred to the Division of Internal Medicine at the Department of Medical and Surgical Sciences between January 2005 and December 2013 were screened for CD by testing IgA antitransglutaminase (TTG IgA), IgG deamidated gliadin peptides (DGP IgG) and IgA antiendomysium (EMA) antibodies. Of the 230 patients tested, 67 had a diagnosis of rheumatoid arthritis (RA), 52 Sjögren's syndrome (SjS), 42 systemic sclerosis (SCL), 35 systemic lupus erythematosus (SLE), 15 mixed connective tissue disease, 11 polymyositis and 10 dermatomyositis. RESULTS: TTG IgA antibodies were identified in 7/230 cases (3%), 3 in SjS (3/42 - 5.8%), 2 in SCL (2/42 - 4.8%), 1 in RA (1/67 - 1.5%) and 1 in SLE sera (1/35 - 2.8%). All the seven sera were also positive for DGP IgG and EMA IgA. DGP IgG were the most frequent antibody detected, being found in 16 (7%) sera. CONCLUSION: This study identified a high prevalence of CD antibodies in adult patients referred to a rheumatology outpatient clinic. These results highlight the importance of CD screening in subjects presenting with rheumatological features.
30002661 Janus Kinase Inhibitor Baricitinib Modulates Human Innate and Adaptive Immune System. 2018 The purpose of this study was to elucidate the mechanism of action of baricitinib on Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling, which involves in human innate and adaptive immune system. The effects of baricitinib were evaluated using human monocyte-derived dendritic cells (MoDCs), plasmacytoid dendritic cells (pDCs), B cells, and T cells. Baricitinib concentration-dependently suppressed the expression of CD80/CD86 on MoDCs and the production of type-I interferon (IFN) by pDCs. Baricitinib also suppressed the differentiation of human B cells into plasmablasts by B cell receptor and type-I IFN stimuli and inhibited the production of interleukin (IL)-6 from B cells. Human CD4(+) T cells proliferated after T cell receptor stimulation with anti-CD3 and anti-CD28 antibody; however, such proliferation was suppressed by baricitinib in a concentration-dependent manner. In addition, baricitinib inhibited Th1 differentiation after IL-12 stimulation and Th17 differentiation by TGF-β1, IL-6, IL-1β, and IL-23 stimulation. Tofacitinib showed similar effects in these experiments. In naive CD4(+) T cells, IFN-α and IFN-γ induced phosphorylation of STAT1, which was inhibited by baricitinib and tofacitinib. Furthermore, IL-6-induced phosphorylation of STAT1 and STAT3 was also inhibited by JAK inhibitors. In conclusion, the results indicated that baricitinib suppresses the differentiation of plasmablasts, Th1 and Th17 cells, as well as innate immunity, such as the T cell stimulatory capacity of dendritic cells. Thus, JAK inhibitors can be potentially clinically effective not only in rheumatoid arthritis but other immune-related diseases.
29868136 Prevalence of Family History of Autoimmune Disorders in Juvenile Systemic Lupus Erythemato 2018 Mar One of the causes of infants' hospitalizations is bronchiolitis, while different viral agents could be causative agents. As there is little information regarding the common agents of bronchiolitis in Iranian infants, we designed this study to determine which agents were responsible for hospitalization due to bronchiolitis among infants in an Iranian tertiary center. Two hundred and three infants with bronchiolitis who were hospitalized in Bahrami hospital were enrolled. Data regarding age, sex, duration of hospitalization, exposure to smoking, previous antibiotic usage and fever were collected for all enrolled cases. Throat sample by means of soap was collected and rapid test with immunochromatography (IC) test was performed. Rapid test was positive in 59 (29%) cases and three cases had concomitant infection with two viruses. The most common viral agent was RSV (Respiratory Syncytial Virus). Mean age was significantly lower in cases with RSV or RSV+ adenovirus infectious in comparison with other two groups (adenovirus or influenza only), while mean duration of hospitalization was significantly longer in RSV/RSV+ adenovirus group. RSV is the most common viral etiology of bronchiolitis in Iranian infants less than one year old, which is related with younger age and longer duration of hospitalization. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Near 10% of affected children have a relative with SLE. Autoimmune diseases are more common in relatives of children with SLE. As there is no study regarding the prevalence of autoimmune disease in cases with pediatric SLE, we designed this study to evaluate the prevalence of autoimmune disease in children with SLE. In this cross sectional study, 50 children with SLE and 50 healthy children were enrolled. A structured questionnaire was used to collect data regarding the presence of autoimmune diseases in relatives. One thousand eight hundred and thirty two relatives were evaluated in the case group and 1699 in the control group. The number of relatives with autoimmune diseases was significantly higher in the case group (26 vs 10). The most common autoimmune diseases were lupus, followed by thyroid diseases among cases, and thyroid diseases and rheumatoid arthritis in controls. According to the results of this study, the prevalence of autoimmune disorders is more common in relatives of children with SLE than in those of controls.
29794403 BST106 Protects against Cartilage Damage by Inhibition of Apoptosis and Enhancement of Aut 2018 Aug 1 Chrysanthemum zawadskii var. latilobum (CZ) has been used as a traditional medicine in Asian countries for the treatment of inflammatory diseases. Recently, CZ extract was shown to inhibit differentiation of osteoclasts and provide protection against rheumatoid arthritis. The aim of this study was to investigate the molecular mechanisms of BST106, the ethanol extract of CZ, for cartilage protection in monosodium iodoacetate (MIA)-induced osteoarthritis (OA), particularly focusing on apoptosis and autophagy. BST106 (50, 100, and 200 mg/kg) was orally administered once daily to MIA-induced OA rats. Swelling, limping, roentgenography, and histomorphological changes were assessed 28 d after MIA injection. Biochemical parameters for matrix metalloproteinase (MMP), apoptosis, and autophagy were also assessed. BST106 ameliorated the severity of swelling and limping after MIA injection. Roentgenographic and histomorphological examinations revealed that BST106 reduced MIA-induced cartilage damage. BST106 decreased MIA-induced increases in MMP-2 and MMP-13 mRNA levels. Increased levels of serum cartilage oligomeric matrix protein and glycosaminoglycan release were attenuated by BST106. Furthermore, BST106 suppressed the protein expression of proapoptotic molecules and increased the protein expression of autophagosome- and autolysosome-related molecules. These findings indicate that BST106 protects against OA-induced cartilage damage by inhibition of the apoptotic pathway and restoration of impaired autophagic flux.
29677409 Is There an Association Between Heparin-Induced Thrombocytopenia (HIT) and Autoimmune Dise 2018 Mar BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a drug-induced, immunoglobulin G medicated autoimmune disorder associated with several negative clinical outcomes including increased morbidity, mortality, and increased medical costs. Previous studies have shown associations between comorbid autoimmune diseases, but there is little known about associations between HIT and autoimmunity. PURPOSE: To provide clinical data to suggest an association between HIT and autoimmunity. METHODS: Retrospective chart review of 59 cases with a diagnosis of HIT and 251 matched controls without a HIT diagnosis, comparing the prevalence of autoimmunity in each group. SETTING: A single, large upper Midwest health care system. RESULTS: Patients with a diagnosis of HIT were significantly more likely to have a comorbid autoimmune disease than those without a HIT diagnosis (55.9% vs 10.8%, P < 0.001). In disease-specific analyses, patients with a diagnosis of HIT were significantly more likely to have a diagnosis of antiphospholipid syndrome (15.3% vs 0.0%, P < 0.001), systemic lupus erythematous (8.5% vs 0.4%, P = 0.001), rheumatoid arthritis (5.1% vs 0.0%, P = 0.007), Hashimoto's thyroiditis (13.6% vs 3.6%, P = 0.006), or nonischemic cardiomyopathy (5.1% vs 0.0%, P = 0.007). Patients diagnosed with HIT were significantly older than controls (P < 0.001). CONCLUSION: This novel study gives evidence to suggest an association between HIT and autoimmune disease and suggests a need for more research into the relationship between HIT and autoimmunity. These results could alter the anticoagulation management of venous thromboembolism and acute coronary syndrome in patients with a previously identified autoimmune disease.
29652048 [Should a doctor take into consideration the influence of climatic factors? Deliberations 2018 Apr 9 The authors analyze the monograph of the Uzbek scientists professor Z.R. Zununov, I.H. Nurov, and S.Z. Zununova «Essays of arid medicine» (Tashkent: «KAMALAK-PRESS» publishing house, 2016;540). The book presents the results of the comprehensive bioclimatic assessment of the arid zones of Uzbekistan, their extreme climatic conditions (such as high intensity and solar radiation and the considerable duration of its period, dry air and summer heat, sandstorms (the so-called «Afghans»), and the great variety of the natural health-improving factors including mineral waters, microclimate of the speleotherapeutic cave, the desert dune sand, etc. The work is based on the authors' conceptual theory of «arid/meteorological stress syndrome», underlain by the hypothesis of the predominant role of hyperthermal weather hypoxia. A wide range of issues id discussed related to weather and climate adaptation of the healthy subjects (both indigenous and non-indigenous residents) and the patients suffering from ischemic heart disease, chronic obstructive pulmonary disease, and rheumatoid arthritis. Of special interest are the methods proposed for the correction of dysadaptive changes including the application of the natural balneotherapeutic factors existing in the arid zone (hydrogen sulphide and iodine-bromine balneotherapy, climatic therapy, speleotherapy, and psammotherapy (arenation). An important definitive conclusion at which the authors arrive is the necessity of the experimental observations in agreement with the requirements of the medico-biological ethics.
29598831 Smoking under hypoxic conditions: a potent environmental risk factor for inflammatory and 2018 Mar 30 Autoimmune disease management presents a significant challenge to medical science. Environmental factors potentially increase the risk of developing inflammatory and autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and lupus. Among various environmental stresses, cigarette smoke and hypoxia have both been reported to lead to an enhanced risk of inflammatory and autoimmune diseases.In this review, we shed light on all reported mechanisms whereby cigarette smoke and a hypoxic environment can induce inflammatory and autoimmune diseases and discuss how hypoxic conditions influence the cigarette smoke-induced threat of inflammatory and autoimmune disease development.Cigarette smoke and hypoxia both lead to increased oxidative stress and production of reactive oxygen species and other free radicals, which have various effects including the generation of autoreactive pro-inflammatory T cells and autoantibodies, reductions in T regulatory (T(reg)) cell activity, and enhanced expression of pro-inflammatory mediators [e.g., interleukin-6 (IL-6), interleukin-4 (IL-4) and interleukin-8 (IL-8)]. Accordingly, smoking and hypoxic environments may synergistically act as potent environmental risk factors for inflammatory and autoimmune diseases. To our knowledge, no studies have reported the direct association of cigarette smoke and hypoxic environments with the risk of developing inflammatory and autoimmune diseases.Future studies exploring the risk of autoimmune disease development in smokers at high altitudes, particularly military personnel and mountaineers who are not acclimatized to high-altitude regions, are required to obtain a better understanding of disease risk as well as its management.
29468959 In-silico Studies of Isolated Phytoalkaloid Against Lipoxygenase: Study Based on Possible 2018 AIM AND OBJECTIVE: Lipoxygenase (LOX) enzymes play an important role in the pathophysiology of several inflammatory and allergic diseases including bronchial asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, rheumatoid arthritis and chronic obstructive pulmonary disease. Inhibitors of the LOX are believed to be an ideal approach in the treatment of diseases caused by its over-expression. In this regard, several synthetic and natural agents are under investigation worldwide. Alkaloids are the most thoroughly investigated class of natural compounds with outstanding past in clinically useful drugs. In this article, we have discussed various alkaloids of plant origin that have already shown lipoxygenase inhibition in-vitro with possible correlation in in silico studies. MATERIALS AND METHODS: Molecular docking studies were performed using MOE (Molecular Operating Environment) software. Among the ten reported LOX alkaloids inhibitors, derived from plant, compounds 4, 2, 3 and 1 showed excellent docking scores and receptor sensitivity. RESULT AND CONCLUSION: These compounds already exhibited in vitro lipoxygenase inhibition and the MOE results strongly correlated with the experimental results. On the basis of these in vitro assays and computer aided results, we suggest that these compounds need further detail in vivo studies and clinical trial for the discovery of new more effective and safe lipoxygenase inhibitors. In conclusion, these results might be useful in the design of new and potential lipoxygenase (LOX) inhibitors.
29461680 Reducing-Autophagy Derived Mitochondrial Dysfunction during Resveratrol Promotes Fibroblas 2018 Jul In rheumatoid arthritis patients, the fibroblast-like synovial cells (FLS) growth is not controlled normally, but is similar to the tumor cells proliferation in histology. Our previous studies have shown that resveratrol inhibits the proliferation of FLS and promotes FLS apoptosis. However, the molecular mechanisms involved in resveratrol-induced FLS apoptosis have not been determined yet. Here, we showed that the FLS cell viability (following pretreatment with 5 µM H(2) O(2) for 24 hr) exhibited better proliferation performance than at other concentrations via the CCK-8 assay. The cell apoptotic rate increased with the increasing concentration of resveratrol (0, 40, 80, 160, 320 μM), as detected by TdT-mediated dUTP nick-end labeling (TUNEL) staining and western blotting. Furthermore, the expression level of autophagy-related proteins (LC3A/B, ATG-5) decreased with the increased concentration of resveratrol, as determined by immunofluorescence and western blot analysis. We also showed that resveratrol induced FLS mitochondrial morphology change. Moreover, mitochondrial function detection showed that the mitochondrial membrane potential was lost with the increased concentration of resveratrol as examined by the JC-1 assay. The production of ATP in cells was positively and negatively correlated with the resveratrol concentration. Simultaneously, the intracellular calcium release and calcium influx decreased gradually with the increase in resveratrol concentration. Therefore, we proposed that resveratrol can reduce the level of autophagy in FLS. The decrease in the autophagy level can lead to the accumulation of reactive oxygen species, which may result in mitochondrial dysfunction and promotion of FLS apoptosis. Anat Rec, 301:1179-1188, 2018. © 2018 Wiley Periodicals, Inc.
31364980 Effects of childhood psychological trauma on rheumatic diseases. 2019 Jul OBJECTIVE: The etiology of rheumatic diseases is unclear, but it is thought that environmental factors added to immunogenetic mechanisms in chronic inflammatory diseases play a role. Many inflammatory disorders, autoimmune diseases, and painful conditions have been shown to be associated with the psychological trauma of childhood. The aim of the present study was to investigate childhood psychological trauma that is considered to be one of the environmental factors that initiate inflammation on patients with rheumatic diseases. METHODS: In our study, a total of 440 patients (220 patients who have rheumatic diseases as the case group and 220 patients who have no rheumatic disease as the control group) were examined. The Childhood Trauma Questionnaire-28 (CTQ-28) was administered and was completed by the patients. This was a cross-sectional study design. RESULTS: No statistically significant differences were found between the case and control groups with respect to age, gender, marital status, and educational level. The CTQ-28 scale was found to be significantly higher in patients with rheumatic diseases (ankylosing spondylitis, rheumatoid arthritis, and connective tissue disease) in our study. CONCLUSION: We think that childhood psychiatric traumas are effective in the etiopathogenesis of rheumatic diseases. To make this relationship more understandable, multidisciplinary research and long-term follow-up studies are needed to examine neuroendocrine, genetic, and epidemiological factors.
30882048 Isometric Contraction of the Quadriceps Improves the Accuracy of Intra-Articular Injection 2018 Dec 20 BACKGROUND: Intra-articular injection is an important technique for treating rheumatoid arthritis and osteoarthritis of the knee. However, medication is often inaccurately injected outside of the joint. We devised an intra-articular injection method in which the needle is inserted into the suprapatellar bursa while the patient maintains isometric contraction of the quadriceps. This isometric contraction method is based on the concept that isometric contraction of the quadriceps induces contraction of the articularis genus muscle, thus expanding the lumen of the suprapatellar bursa. METHODS: Intra-articular injections were performed on 150 osteoarthritic knees without effusion. The knees were alternately assigned to the isometric quadriceps method group (75 knees) and non-activated quadriceps method group (75 knees). Prior to joint injection, the anterior-posterior dimension of each suprapatellar bursa was measured to ascertain its expansion. The isometric quadriceps method was performed with the quadriceps and the articularis genus muscle maintained in a contracted state. The non-activated quadriceps method was performed in a relaxed state. Ultrasound guidance was not used for either method. Subsequently, an ultrasonic probe was used only to confirm whether the intra-articular injections were successful. We compared the accuracy of injections performed between the 2 groups. RESULTS: Suprapatellar expansion was significantly larger (p < 0.001) using the isometric quadriceps method (2.1 ± 1.4 mm [range, 0 to 5 mm]) than using the non-activated quadriceps method (0.8 ± 0.7 mm [range, 0 to 2 mm]). The percentage of accurate intra-articular injections was significantly higher (p = 0.0287) using the isometric quadriceps method (93%) compared with the non-activated quadriceps method (80%). CONCLUSIONS: In comparison with the non-activated quadriceps method, the isometric quadriceps method led to a larger expansion of the suprapatellar bursa, which should lead to more accurate intra-articular injections. The isometric quadriceps method is effective in reducing inaccurate injections into the synovium or surrounding fatty tissues. CLINICAL RELEVANCE: Putting force on the quadriceps muscle increases the success rate of intra-articular injection of the knee. The results of this study could provide a clinically relevant injection technique for future treatment.
30562791 [Systemic lupus erythematosus with acquired hemophilia A: a case report]. 2018 Dec 18 Acquired hemophilia A (AHA) is anunusual disease resulting from autoantibodies (inhibitors) against coagulation factor VIII (FVIII) and clinically manifests as bleeding, which sometimes can cause potentially limb-threatening or life-threatening situations. AHA is associated with cancers, auto-immune disorders, infections, dermatologic conditions and certain medications, among which it is commonly secondary to multiple rheumatologic conditions, such as rheumatoid arthritis, systemic lupus erythematosus (SLE), pollymyositis, autoimmune hemolytic anemia and undifferentiated connective tissue disease. In autoimmune diseases, it may be the result of autoantibody producing against FVIII, and some cases of AHA may act as the first manifestation of SLE. AHA should be suspected in patients who have spontaneously hemorrhagic events with an isolated prolonged activated partial thromboplastin time (APTT), reduced FVIII activity and a negative lupus anticoagulant (LA). When FVIII inhibitor is found, it can be diagnosed. The management of AHA focuses on the following goals: (1) controlling and preventing bleeding, (2) eradication of the inhibitor, (3) treatment of the underlying disease. Here, a case of AHA in a patient with lupus is reported. A 53-year-old man with a 4-year history of SLE developed arthralgia and ecchymotic skin lesions after arthrocentesis of knee joint. Ultrasound confirmed the presence of an intramuscular hematoma. Coagulation tests revealed that FVIII activity reduced to 1% and a prolonged APTT (92.2 s), FVIII inhibitors were found to be as high as 60.0 Bethesda Units. Initial treatments with methylprednisolone 200 mg/d were started but new hemorrhagic manifestation occurred and hisbiological indexes were not good. Then the patient was treated with intravenous pulse corticosteroids (methylprednisolone 500 mg/d), intravenous cyclophosphamide, and also plasma and prothrombin complex infusion. Subsequently, FVIII activity returned within normal ranges, FVIII inhibitors decreased and clinical improvement was significantly obtained. The patient's condition kept stable till now.Hemorrhagic events due to production of antibodies directed against coagulation factors were rarely observed in SLE and attentions should be paid to the association between SLE and AHA.Bypass treatment was considered as the immediate antihemorrhagic treatment. Corticosteroid combined with immunosuppressor was recommended as the main therapy to eradicate the inhibitors. However we still lack the therapeutic guidelines and standardized treatment in patients of AHA with SLE at present.
30513071 Utilization of High-Cost Interventions for Targeted Clinical Conditions During the Early S 2019 Oct This study compared utilization patterns of high-cost services and medications for patients receiving care from Accountable Care Organization (ACO)-participating physicians and those receiving care from non-ACO physicians during the initial phases of ACO development in a commercially insured environment. Patients ≥18 years (≥40 years for chronic obstructive pulmonary disease [COPD]) with prevalent rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 2 diabetes, COPD, or chronic low back pain between January 1, 2012, and August 31, 2014 were identified in the HealthCore Integrated Research Database(SM). Patients were assigned to the ACO cohort if their primary treating physician was contracted to the health plan through an ACO agreement. Each clinical condition was stratified for severity of illness. Cohort utilization patterns were compared for the 12-month period following the index encounter. The primary outcome measures show that there was no statistically significant utilization difference between the ACO and non-ACO cohorts for 90% of the 82 comparisons made. It is expected that some measures will achieve significant difference simply because of having this many comparisons, but no clear pattern was identified. This study did not observe statistically significant differences in utilization of high-cost services and medications between ACO and non-ACO cohorts with limited experience in the ACO model. Future analyses with longer study durations, at later stages of ACO development, tracking a more granular level of physician organizational structure, and with designs that integrate clinical and administrative data are essential to better understand the impact of payment innovation strategies using an ACO structure.
30372858 Exploration of the therapeutic aspects of Lck: A kinase target in inflammatory mediated pa 2018 Dec Lck, a non-receptor src family kinase, plays a vital role in various cellular processes such as cell cycle control, cell adhesion, motility, proliferation and differentiation. As a 56 KDa protein, Lck phosphorylates tyrosine residues of various proteins such as ZAP-70, ITK and protein kinase C. The structure of Lck is comprised of three domains, one SH3 in tandem with a SH2 domain at the amino terminal and the kinase domain at the carboxy terminal. Physiologically, Lck is involved in the development, function and differentiation of T-cells. Additionally, Lck regulates neurite outgrowth and maintains long-term synaptic plasticity in neurons. Given a major role of Lck in cytokine production and T cell signaling, alteration in expression and activity of Lck may result in various diseased conditions like cancer, asthma, diabetes, rheumatoid arthritis, psoriasis, inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, atherosclerosis etc. This article provides evidence and information establishing Lck as one of the therapeutic targets in various inflammation mediated pathophysiological conditions.
30195777 Integrative Analysis of lncRNAs in Th17 Cell Lineage to Discover New Potential Biomarkers 2018 Sep 7 Th17 cells play a critical role in the pathogenesis of autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, and inflammatory bowel disease. Despite the extensive investigation into this T cell lineage, little is understood regarding the role of Th17 lineage-specific lncRNAs (long non-coding RNAs) > 200 nt. lncRNAs may influence disease through a variety of mechanisms; their expression could be regulated by SNPs. lncRNAs can also affect the expression of neighboring genes or complementary miRNAs, and their expression may have lineage-specific patterns. In the system biology study presented here, the effective lncRNAs from different criteria were predicted for each autoimmune disease, and we then evaluated their expression levels in 50 MS patients compared to 25 controls using qRT-PCR. We identified changes in the expression levels of AL450992.2, AC009948.5, and RP11-98D18.3 as potential peripheral blood mononuclear cell (PBMC) biomarkers for MS among our studied lncRNAs in which co-expression analysis of AL450992.2 had the most AUCs, and the relationship to RORC was also assessed. We propose that the recurrently deregulated lncRNAs identified in this report could provide a valuable resource for studies aimed at delineating the relationship between functional lncRNAs and autoimmune disorders.
29849899 Antihypertensive Effect of Ethanolic Extract from Acanthopanax sessiliflorus Fruits and Qu 2018 Acanthopanax sessiliflorus (Rupr. & Maxim.) Seem., which belongs to the Araliaceae family, mainly inhabits Korea, China, and Japan. Traditionally, Acanthopanax species have been used as treatment for several diseases such as diabetes, tumors, and rheumatoid arthritis. Especially, its fruits have many biological functions including antitumor, immunostimulating, antithrombosis, and antiplatelet activities. Recently, the extract of A. sessiliflorus fruit has been reported to have antithrombotic and antiplatelet activities related to the alleviation of hypertension. Therefore, we investigated the antihypertensive effect of ethanolic extract from A. sessiliflorus fruits (DHP1501) through in vivo, ex vivo, and in vitro studies. In this study, DHP1501 demonstrated free radical scavenging capacity, enhanced endothelial nitric oxide (NO) production, and inhibited angiotensin-converting enzyme (ACE) activity in spontaneously hypertensive rats (SHRs), resulting in the improvement of vascular relaxation and decrease in blood pressure in the hypertensive animal model. These results suggest that A. sessiliflorus fruit extract may be a promising functional material for the prevention and treatment of hypertension. Furthermore, this study demonstrated the utility of MS-based active compounds for the quality control of DHP1501.
29575574 No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chro 2018 Aug Since the successful conquest of many acute, communicable (infectious) diseases through the use of vaccines and antibiotics, the currently most prevalent diseases are chronic and progressive in nature, and are all accompanied by inflammation. These diseases include neurodegenerative (e.g. Alzheimer's, Parkinson's), vascular (e.g. atherosclerosis, pre-eclampsia, type 2 diabetes) and autoimmune (e.g. rheumatoid arthritis and multiple sclerosis) diseases that may appear to have little in common. In fact they all share significant features, in particular chronic inflammation and its attendant inflammatory cytokines. Such effects do not happen without underlying and initially 'external' causes, and it is of interest to seek these causes. Taking a systems approach, we argue that these causes include (i) stress-induced iron dysregulation, and (ii) its ability to awaken dormant, non-replicating microbes with which the host has become infected. Other external causes may be dietary. Such microbes are capable of shedding small, but functionally significant amounts of highly inflammagenic molecules such as lipopolysaccharide and lipoteichoic acid. Sequelae include significant coagulopathies, not least the recently discovered amyloidogenic clotting of blood, leading to cell death and the release of further inflammagens. The extensive evidence discussed here implies, as was found with ulcers, that almost all chronic, infectious diseases do in fact harbour a microbial component. What differs is simply the microbes and the anatomical location from and at which they exert damage. This analysis offers novel avenues for diagnosis and treatment.
29559975 TANK-Binding Kinase 1-Dependent Responses in Health and Autoimmunity. 2018 The pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is driven by genetic predisposition and environmental triggers that lead to dysregulated immune responses. These include the generation of pathogenic autoantibodies and aberrant production of inflammatory cytokines. Current therapies for RA and other autoimmune diseases reduce inflammation by targeting inflammatory mediators, most of which are innate response cytokines, resulting in generalized immunosuppression. Overall, this strategy has been very successful, but not all patients respond, responses can diminish over time and numerous side effects can occur. Therapies that target the germinal center (GC) reaction and/or antibody-secreting plasma cells (PC) potentially provide a novel approach. TANK-binding kinase 1 (TBK1) is an IKK-related serine/threonine kinase best characterized for its involvement in innate antiviral responses through the induction of type I interferons. TBK1 is also gaining attention for its roles in humoral immune responses. In this review, we discuss the role of TBK1 in immunological pathways involved in the development and maintenance of antibody responses, with particular emphasis on its potential relevance in the pathogenesis of humoral autoimmunity. First, we review the role of TBK1 in the induction of type I IFNs. Second, we highlight how TBK1 mediates inducible T cell co-stimulator signaling to the GC T follicular B helper population. Third, we discuss emerging evidence on the contribution of TBK1 to autophagic pathways and the potential implications for immune cell function. Finally, we discuss the therapeutic potential of TBK1 inhibition in autoimmunity.
29536775 Resolution of co-eluting isomers of anti-inflammatory drugs conjugated to carbonic anhydra 2018 Dec Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by a faulty autoimmune response. Recently, it was reported that some human carbonic anhydrases (CAs) isoforms are overexpressed in inflamed synovium of RA patients. New CA inhibitors (CAIs) incorporating CA-binding moiety and the cyclooxygenase inhibitor tail (nonsteroidal anti-inflammatory drug [NSAID] type) were studied. The aim of this work is the evaluation of the chemical stability of NSAID - CAI hybrids towards spontaneous or enzymatic hydrolysis by LC-MS/MS. The analytes are isomer pairs of 6- or 7-hydroxycoumarin, their different fragment ions abundances allowed the development of a mathematical tool (LEDA) to distinguish them. LEDA reliability at ng mL(-1) level was checked (>90%), being proved the effectiveness in the correct assignment of the isomer present in the sample. The hybrids resulted stable in all tested matrices allowing us to conclude that these compounds reach the target tissues unmodified, opening perspectives for their development in the treatment of inflammation.