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ID PMID Title PublicationDate abstract
30024540 Association of serum/plasma high mobility group box 1 with autoimmune diseases: A systemat 2018 Jul BACKGROUND: High mobility group box 1 (HMGB1) is a kind of proinflammatory mediator to stimulate the innate and adaptive immune system and participates in a number of acute and chronic inflammatory processes after sterile injury or microbial invasion. HMGB1 has been suggested to be involved in the pathogenesis of many autoimmune diseases. However, the results are contradictory or inconclusive among these findings. The aim of this study was to investigate whether serum/plasma HMGB1 levels are associated with autoimmune diseases by comparing the serum/plasma HMGB1 levels in patients with autoimmune disease and healthy controls and to further evaluate whether serum/plasma HMGB1 levels are associated with disease state. METHODS: PubMed, Medline, and Web of science databases (up to October 1, 2017) were used to obtain all relative published literature. Study quality was assessed by the Newcastle-Ottawa scale (NOS). Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effects or random-effect model analysis. RESULTS: A total of 23 original articles of autoimmune diseases were finally included in the meta-analysis. Results revealed that the serum/plasma HMGB1 levels were increased in patients with autoimmune disease, compared to healthy controls. Subgroup analysis showed that serum/plasma HMGB1 levels in patients with active disease state were significantly higher than in those with inactive state. In addition, subgroup analysis based on disease type has indicated that the serum/plasma HMGB1 levels in patients with small vessel vasculitis, systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis and sjogren syndrome were significantly higher, compared to healthy controls. Further subgroup analyses by region showed that plasma/serum HMGB1 levels were higher in Asian and European patients with autoimmune diseases. CONCLUSIONS: Serum/plasma HMGB1 levels in patients with autoimmune diseases are significantly higher than in healthy controls, and may reflect the disease activity.
29974310 Triptolide prevents osteoarthritis via inhibiting hsa-miR-20b. 2019 Feb Triptolide has been widely reported to exhibit potential therapeutic value in multiple inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and psoriasis. Although its safety and efficacy as an anti-inflammatory agent have been verified by many studies, the effect of triptolide on osteoarthritis (OA) was not clearly understood. In this study, we found that triptolide prevented OA development in a surgical destabilization of the medial meniscus (DMM) mouse model. In addition, triptolide inhibited both DMM-induced and LPS-induced expression of pro-inflammatory cytokines in the human monocytic cell line THP-1. Further mechanistic studies showed that the reduction of pro-inflammatory cytokines by triptolide was mediated by the upregulation of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) and downregulation of caspase-1. Finally, we identified that hsa-miR-20b, a microRNA targeting the NLRP3 gene, was downregulated by triptolide. This study provides a novel insight into the effect on triptolide in preventing OA pathogenesis.
29883923 Cerebral amyloid angiopathy-related inflammation with epilepsy mimicking a presentation of 2018 INTRODUCTION: Cerebral amyloid angiopathy-related inflammation (CAA-ri), a rare and treatable variant of cerebral amyloid angiopathy, lacks specific imaging and clinical features, and requires invasive brain biopsy to confirm the diagnosis. We report the case of a patient with nonconvulsive status epilepticus (NCSE) caused by CAA-ri in the right occipital lobe. PRESENTATION OF CASE: A 78-year-old man with a history of hypertension and rheumatoid arthritis was admitted to our hospital following an episode of seizures. CT scan showed a low-attenuating subcortical lesion in the right occipital lobe. MRI revealed the lesion as hypointense on T1-weighted imaging (WI) and hyperintense on T2-WI, showing no enhancement on T1-WI contrast-enhanced with gadolinium. In addition, T2*-weighted gradient-recalled echo (T2*-GRE) and susceptibility-weighted imaging (SWI) revealed extensive cortical microbleeds. Biopsy to determine the exact diagnosis revealed histological findings of reactive changes and perivascular inflammatory infiltration associated with amyloid deposition in vessel walls. These findings were consistent with CAA-ri. Corticosteroid therapy with dexamethasone was initiated for a short period as a diagnostic and therapeutic maneuver, resulting in marked reductions in the lesion. DISCUSSION: CAA is generally associated with intracerebral hemorrhage, dementia, and small cerebral infarctions in the elderly population, but in a small proportion of cases is related to inflammatory responses to vascular deposits of Aβ, as so-called CAA-ri. CONCLUSION: CAA-ri should be considered among the differential diagnoses for causes of unprovoked seizure onset in elderly individuals, when associated with petechial hemorrhages on T2*-GRE and SWI sequences on MRI.
30598239 Health related quality of life aspects not captured by EQ-5D-5L: Results from an internati 2019 Feb BACKGROUND: In this paper we discuss and present evidence on whether a generic Health Related Quality of Life (HRQoL) measurement tool, the EQ-5D-5L, captures the dimensions of quality of life (QoL) which patients consider significant. METHODS: An online survey, of individuals with a chronic condition, mainly breast cancer (BC), blood cancers (BLC), rheumatoid arthritis (RA), asthma, and rare diseases (RD) was conducted to collect data on HRQoL and important QoL aspects that respondents thought were not captured by the EQ-5D-5L. Patient organisations across 47 countries were invited to voluntarily share the survey tool with their membership network. RESULTS: 767 responses from 38 countries showed that important QoL aspects were not captured by EQ-5D-5L for 51% of respondents, including fatigue (19%) and medication side effects (12%), among others. Fatigue (17%) was also the most commonly reported QoL aspect that changed over the course of patients' illness, suggesting that the current version of the EQ-5D-5L might miss capturing significant clinical changes in important QoL domains. CONCLUSIONS: Utilisation of the EQ-5D-5L in HRQoL measurement raises inconsistencies in capturing QoL attributes and changes in disease-specific patient populations. Further research is needed to clarify the extent to which other generic HRQoL measurement tools capture the aspects of health that really matter for patients.
30572252 Regulatory B cells in inflammatory diseases and tumor. 2019 Feb As antigen-presenting cells (APC), B cells exert a variety of immune regulatory functions mainly by presenting antigens, triggering immune response, and producing antibodies for immune regulation. Regulatory B cells (Bregs) are special subpopulations of B cells with immune-regulating or immune-suppressing properties and play a role in peripheral tolerance. Bregs suppress immune response through inhibiting the differentiation of dendritic cells (DCs), suppressing the proliferation of helper T1(TH1) cells and helper T17 (TH17) cells, inducing the differentiation of fork head transcription factor p3 positive regulatory T cells (FoxP3(+) Tregs). Different subsets of Bregs have distinct phenotypes and markers. Different subsets of Bregs participate in immune modulation by different ways. The absence or loss of Bregs exacerbates the severity of many disease such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and graft-versus-host-disease (GVHD). Bregs are also involved in tumor immunosuppressive effect and inhibit the antitumor immune process. In this article, we review the research advances of Bregs in autoimmune diseases, GVHD and tumor.
30557630 KIT as a therapeutic target for non-oncological diseases. 2019 May KIT is a receptor tyrosine kinase that after binding to its ligand stem cell factor activates signaling cascades linked to biological processes such as proliferation, differentiation, migration and cell survival. Based on studies performed on SCF and/or KIT mutant animals that presented anemia, sterility, and/or pigmentation disorders, KIT signaling was mainly considered to be involved in the regulation of hematopoiesis, gametogenesis, and melanogenesis. More recently, novel animal models and ameliorated cellular and molecular techniques have led to the discovery of a widen repertoire of tissue compartments and functions that are being modulated by KIT. This is the case for the lung, heart, nervous system, gastrointestinal tract, pancreas, kidney, liver, and bone. For this reason, the tyrosine kinase inhibitors that were originally developed for the treatment of hemato-oncological diseases are being currently investigated for the treatment of non-oncological disorders such as asthma, rheumatoid arthritis, and alzheimer's disease, among others. The beneficial effects of some of these tyrosine kinase inhibitors have been proven to depend on KIT inhibition. This review will focus on KIT expression and regulation in healthy and pathologic conditions other than cancer. Moreover, advances in the development of anti-KIT therapies, including tyrosine kinase inhibitors, and their application will be discussed.
30463058 Development of Inflammatory Immune Response-Related Drugs Based on G Protein-Coupled Recep 2018 G protein-coupled receptor kinase 2 (GRK2), as a vital Ser/Thr kinase, is an important regulatory protein in the inflammatory immune response (IIR) by maintaining the balance between the function of inflammatory immune cells and non-conventional inflammatory immune cells and regulating inflammatory immune cell infiltration, inflammatory cytokine secretion, and the signaling associated with endothelial function. However, the imbalance of GRK2 expression and activity plays an important role in the development of IIR-related diseases, such as hypertension, heart failure, Alzheimer's disease, type 2 diabetes mellitus, insulin resistance, rheumatoid arthritis, thyroid cancer, multiple sclerosis, and liver cancer. Small molecule GRK2 inhibitors, including balanol, Takeda inhibitors, paroxetine and derivatives, M119 and gallein, peptides, RNA aptamers, Raf kinase inhibitory protein, and microRNAs, that can directly inhibit GRK2 kinase activity have been identified by different strategies. This review discusses recent progress in one of the hallmark molecular abnormalities of GRK2 in IIR-related diseases and explores the soft regulation of IIR by innovative drugs reducing the excessive activity of GRK2 to basal levels, without damaging normal physiological function, to ameliorate inflammatory disorders.
30428504 Initial presentation determines clinical entity in patients with anti-centromere antibody 2019 Jan AIM: Anti-centromere antibody (ACA) is often detected in patients with autoimmune diseases, including limited cutaneous systemic sclerosis (SSc), Sjögren's syndrome (SS), and primary biliary cholangitis (PBC). The association between autoimmune disease and ACA positivity remains unclear. We sought to clarify the clinical features of ACA-positive patients and their association with autoantibodies. METHOD: A total of 309 cases of a discrete-speckled pattern anti-nuclear antibody (ANA) test and/or positive ACA who visited our department were retrospectively enrolled. Clinical and immunological data were collected and statistically analyzed. RESULT: A proportion of second and/or third ANA patterns were speckled (16%), homogenous (7%), cytoplasmic (3%) and/or nucleolar (3%). Of the 309 patients, 186 had Raynaud's phenomenon, 149 had sclerodactyly, and 162 had oral and/or ocular dryness. A total of 214 patients were classified into 17 autoimmune diseases based on their symptoms at the initial visit, while the other 95 patients did not meet any criteria. Most of the 214 patients were diagnosed with SSc and/or SS; 25 and 22 additional patients were diagnosed with rheumatoid arthritis and PBC, respectively. Higher titers of immunoglobulins were observed in patients diagnosed with autoimmune disease compared to patients without a diagnosis. The mean observation period was 80 months. Three additional patients received interim diagnoses based on new symptoms or organ involvement. In the other patients, the diagnosis made at the first visit was not changed over the observation period. CONCLUSION: Our study confirmed that many ACA-positive cases can be classified into an autoimmune disease type on presentation.
29881431 Isolation and Characterization of Novel Phage Displayed scFv Fragment for Human Tumor Necr 2018 Spring Tumor necrosis factor alpha (TNF-α) expression amplifies to excess amounts in several disorders such as rheumatoid arthritis and psoriasis. Although, Anti-TNF biologics have revolutionized the treatment of these autoimmune diseases, formation of anti-drug antibodies (ADA) has dramatically affected their use. The next generation antibodies (e.g. Fab, scFv) have not only reduced resulted immunogenicity, but also proved several benefits including better tumor penetration and more rapid blood clearance. Using affinity selection procedures in this study, a scFv antibody clone was isolated from naïve Tomlinson I phage display library that specifically recognizes and binds to TNF-α. The TNF-α recombinant protein was expressed in genetically engineered Escherichia coli SHuffle(®) T7 Express, for the first time, which is able to express disulfide-bonded recombinant proteins into their correctly folded states. ELISA-based affinity characterization results indicated that the isolated novel 29.2 kDa scFv binds TNF-α with suitable affinity. In-silico homology modeling study using 'ModWeb' as well as molecular docking study using Hex program confirmed the scFv and TNF-α interactions with a scFv-TNF- α binding energy of around -593 kj/mol which is well in agreement with our ELSIA results. The cloned scFv antibody may be potentially useful for research and therapeutic applications in the future.
29752913 Development and validation of a targeted affinity-enrichment and LC-MS/MS proteomics appro 2018 Aug BACKGROUND: The anti-tumor necrosis factor alpha (TNFα) therapeutic monoclonal antibodies (mAbs), such as adalimumab, are widely used in the treatment of rheumatoid arthritis, inflammatory bowel diseases, and other auto-immune diseases. The administration of adalimumab can elicit the immune responses from some patients, resulting in the formation of anti-drug antibodies (ADAbs). The ADAbs can diminish the therapeutic effects of adalimumab by neutralizing the TNFα binding site or increasing its clearance from circulation. METHODS: To effectively monitor the therapeutic concentrations of adalimumab, we developed and validated a targeted quantitative proteomic assay to determine the circulating concentrations of adalimumab. Since drug effects can be attenuated by ADAbs, the method adopted an affinity-enrichment step to selectively quantify the bioavailable forms of adalimumab in patient serum samples. RESULTS: The performance of the LC-MS/MS based assay provides the analytical measuring range and precisions applicable for the therapeutic monitoring of adalimumab. It also provides comparable results to a cell-based activity assay when evaluating patient samples with different concentrations of adalimumab. CONCLUSION: Our assay can quantify both sub-therapeutic and therapeutic concentrations of bioavailable adalimumab in patient serum samples. This assay design provides an alternative to isotope-labeled peptides approach currently adopted in targeted proteomics methods.
29670620 Semaphorin3A: A Potential Therapeutic Tool for Lupus Nephritis. 2018 BACKGROUND: The immune regulatory properties of semaphorin3A (sema3A) (both innate and adaptive) are well established in many in vitro studies. The injection of sema3A into a mice model of rheumatoid arthritis was proven to be highly beneficial, both in attenuating clinical symptoms and in decreasing inflammatory mechanisms. OBJECTIVES: This study was designed in order to assess the possible therapeutic benefits of sema3A following its injection into female NZB/W mice. METHODS: Forty-eight NZB/W mice were recruited for this study. Thirty mice were treated as a "prevention group" and 18 were used as a "treatment group." Eight-week-old mice were acclimated and then divided into the two abovementioned groups. RESULTS: The injection of sema3A into young mice (at week 12) before the onset of disease (the prevention group) delayed the appearance of proteinuria. Here, the median time to severe proteinuria was 110 days, 95% CI: 88-131. However, in mice in which the empty vector was injected, the median time to severe proteinuria was 63 days, 95% CI: 0-139. sema3A treatment, significantly reduced renal damage, namely, it prevented the deposition of immune complexes in the glomeruli. When sema3A was injected at the onset of proteinuria (the treatment group), aiming to treat rather than to prevent disease in these mice, survival was increased and the deterioration of proteinuria was delayed. CONCLUSION: Semaphorin3A is highly beneficial in reducing lupus nephritis in NZB/W mice. It delays the appearance and deterioration of proteinuria, and increases the survival rates in these mice. The regulatory mechanisms of sema3A involve both innate and adaptive immune responses. Further studies will establish the idea of applying sema3A in the treatment of lupus nephritis.
29651912 Effects of diclofenac on the pharmacokinetics of celastrol in rats and its transport. 2018 Dec CONTEXT: Diclofenac and celastrol are always used together for the treatment of rheumatoid arthritis; the herb-drug interaction potential between diclofenac and celastrol is still unknown. OBJECTIVE: This study investigates the effects of diclofenac on the pharmacokinetics of celastrol in rats. MATERIALS AND METHODS: Twelve male Sprague-Dawley rats were divided into two groups and received celastrol (1 mg/kg) or both celastrol (1 mg/kg) and diclofenac (10 mg/kg) by oral gavage, and blood samples were collected via the oculi chorioideae vein and determined using the LC-MS method developed in this study. Additionally, the effects of diclofenac on the transport of celastrol were investigated using a Caco-2 cell transwell model. RESULTS: Diclofenac could significantly (p < 0.05) decrease the C(max) (from 66.93 ± 10.28 to 41.25 ± 8.06 ng/mL) and AUC(0-t) (from 765.84 ± 163.61 to 451.33 ± 110.88 μg × h/L) of celastrol in rats. The efflux ratio of celastrol increased significantly (p < 0.05) from 3.12 to 4.55 with the treatment of diclofenac. DISCUSSION AND CONCLUSION: These results indicated that diclofenac could decrease the system exposure of celastrol in rats when they are co-administered, and these effects might be exerted via decreasing its absorption in intestine.
29610730 Comparison of the efficacy of dispensing granules with traditional decoction: a systematic 2018 Feb BACKGROUND: Dispensing granules have been developed for about 20 years. However, whether they are as effective as the traditional decoction kept unclear. This systematic review and meta-analysis was made to assess the efficacy of dispensing granules compared with traditional decoction. METHODS: We searched four databases since their inception to 9th September in 2016. Two authors independently identified trials, extracted data and assessed risk of bias with Cochrane Reviewer's Handbook 5.0. We conducted meta-analysis with RevMan 5.1.0 software for eligible and appropriate trials. RESULTS: In the end, 7,035 participants from 51 randomized controlled trials (RCTs) which compared dispensing granules with traditional decoction were included in this systematic review. There were 33 different kinds of diseases for investigation, of which 8 RCTs observed common cold, 4 RCTs observed migraine. For rheumatoid arthritis, insomnia and hypertension, there were 3 RCTs reported respectively. The last RCTs reported different kinds of diseases in one or two trials. The majority of trials were in low methodological quality. Thirty-eight (74.5%) RCTs showed that the efficacy of dispensing granules were similar with traditional decoction, 6 (11.8%) RCTs reported that the therapeutic efficacy of dispensing granules were significantly better than traditional decoction. We conducted meta-analysis for 4 trials investigating patients with migraine. The results showed that dispensing granules reduced headache frequency by about 1.03 attacks per month as compared to traditional decoction. No evidence was found in terms of migraine intensity and duration. CONCLUSIONS: The low quality of RCTs and conflicting results made it difficult to draw a definite conclusion. In the future, it needs much more evidence to explore the efficacy and safety of dispensing granules. N-of-1 trials and fuzzy comprehensive evaluation methods may be better choices for assessing the efficacy of them than RCTs.
29575885 Periodontal condition in patients of the specialist Outpatient Clinics at the Institute of 2018 Mar 14 INTRODUCTION: Periodontal disease is a chronic inflammation which, if remains untreated, can lead to the loss of teeth and supporting structures. Evidence data support the relationship of periodontal disease with the development and course of diseases such as heart attack, stroke, hypertension, chronic renal diseases, rheumatoid arthritis or diabetes. OBJECTIVE: The aim of the study was to conduct an assessment of periodontal status and periodontal needs in people from the rural environment who were patients of selected specialist outpatient clinics at the Institute of Rural Health in Lublin, Poland. MATERIAL AND METHODS: The examined population included 450 patients. The Community Periodontal Index of Treatment Needs, which is a measure of the assessment of the selected periodontal symptoms incidence, was used. The obtained data was discussed and analyzed with Chi-square test. RESULTS: The data obtained revealed that a healthy periodontium occurred only in 5.1% of respondents, tartar in 41.6%, pathological pockets of 3.5-5.5 mm in 23.6%, and pockets deeper than 5.5 mm in 5.8% of patients. Most people with healthy periodontium were in the youngest age group. In the analyzed group, 7.1% of patients required specialized comprehensive periodontal treatment, and only 6.5% of the examined persons did not show any need for periodontal treatment. CONCLUSIONS: Patients of specialist clinics of the Institute of Rural Health who formed the analyzed group, had affected periodontium which required comprehensive periodontal treatment. The alarmingly high percentage of people over 55 years of age with advanced periodontopathy may translate into an increased risk of cause-and-effect incidence of systemic diseases.
29375128 Epigenetic regulation in B-cell maturation and its dysregulation in autoimmunity. 2018 Jul B cells have a critical role in the initiation and acceleration of autoimmune diseases, especially those mediated by autoantibodies. In the peripheral lymphoid system, mature B cells are activated by self or/and foreign antigens and signals from helper T cells for differentiating into either memory B cells or antibody-producing plasma cells. Accumulating evidence has shown that epigenetic regulations modulate somatic hypermutation and class switch DNA recombination during B-cell activation and differentiation. Any abnormalities in these complex regulatory processes may contribute to aberrant antibody production, resulting in autoimmune pathogenesis such as systemic lupus erythematosus. Newly generated knowledge from advanced modern technologies such as next-generation sequencing, single-cell sequencing and DNA methylation sequencing has enabled us to better understand B-cell biology and its role in autoimmune development. Thus this review aims to summarize current research progress in epigenetic modifications contributing to B-cell activation and differentiation, especially under autoimmune conditions such as lupus, rheumatoid arthritis and type 1 diabetes.
29369534 Autoimmunity in uveitis. 2018 Aug PURPOSE: Recent insights into the pathogenesis of immune-mediated diseases proposed a new classification, which includes autoimmune and auto-inflammatory diseases. The prevalence of specific autoimmune and auto-inflammatory diseases in uveitis and/or scleritis is not yet known. In this study, we examine the presence of systemic immune-mediated diseases in patients with uveitis and/or scleritis and put a special emphasis on autoimmune disorders by reporting on their clinical manifestations and visual prognosis. METHODS: In this retrospective study, we reviewed data of 1327 patients presenting with uveitis and/or scleritis between January 2010 and July 2016 at the Erasmus Medical Center, Rotterdam, the Netherlands. All patients with noninfectious uveitis and/or scleritis were classified according to novel criteria for immune-mediated diseases. Various clinical data, including visual acuity (VA), of patients with uveitis of autoimmune origin were registered during 5-year follow-up. RESULTS: The origin of uveitis was in 5% (62/1327) autoimmune, in 15% (197/1327) auto-inflammatory and in 14% (180/1327) mixed autoimmune/auto-inflammatory. Patients with classical autoimmune connective tissue disease (N = 17) suffered mostly from rheumatoid arthritis and granulomatosis with polyangiitis and exhibited predominantly scleritis (53%). After 5 years of follow-up, none of the eyes of these patients developed legal blindness (VA of <0.1). The VA in patients with uveitis associated with autoimmune neuro-ophthalmological diseases (multiple sclerosis and neuromyelitis optica; N = 27) remained stable over time. CONCLUSION: Uveitis and scleritis of autoimmune origin were observed in 5% of the total series. The term autoimmune uveitis should not be used as a synonym for intraocular inflammation of noninfectious origin.
29275858 Engineered Sialylation of Pathogenic Antibodies In Vivo Attenuates Autoimmune Disease. 2018 Jan 25 Self-reactive IgGs contribute to the pathology of autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. Paradoxically, IgGs are used to treat inflammatory diseases in the form of high-dose intravenous immunoglobulin (IVIG). Distinct glycoforms on the IgG crystallizable fragment (Fc) dictate these divergent functions. IgG anti-inflammatory activity is attributed to sialylation of the Fc glycan. We therefore sought to convert endogenous IgG to anti-inflammatory mediators in vivo by engineering solubilized glycosyltransferases that attach galactose or sialic acid. When both enzymes were administered in a prophylactic or therapeutic fashion, autoimmune inflammation was markedly attenuated in vivo. The enzymes worked through a similar pathway to IVIG, requiring DC-SIGN, STAT6 signaling, and FcγRIIB. Importantly, sialylation was highly specific to pathogenic IgG at the site of inflammation, driven by local platelet release of nucleotide-sugar donors. These results underscore the therapeutic potential of glycoengineering in vivo.
29225172 Role of allograft inflammatory factor-1 in bleomycin-induced lung fibrosis. 2018 Jan 8 Allograft inflammatory factor-1 (AIF-1) is a protein expressed by macrophages infiltrating the area around the coronary arteries in a rat ectopic cardiac allograft model. We previously reported that AIF-1 is associated with the pathogenesis of rheumatoid arthritis and skin fibrosis in sclerodermatous graft-versus-host disease mice. Here, we used an animal model of bleomycin-induced lung fibrosis to analyze the expression of AIF-1 and examine its function in lung fibrosis. The results showed that AIF-1 was expressed on lung tissues, specifically macrophages, from mice with bleomycin-induced lung fibrosis. Recombinant AIF-1 increased the production of TGF-β which plays crucial roles in the mechanism of fibrosis by mouse macrophage cell line RAW264.7. Recombinant AIF-1 also increased both the proliferation and migration of lung fibroblasts compared with control group. These results suggest that AIF-1 plays an important role in the mechanism underlying lung fibrosis, and may provide an attractive new therapeutic target.
29119937 Use of human Dihydroorotate Dehydrogenase (hDHODH) Inhibitors in Autoimmune Diseases and N 2018 BACKGROUND: Human dihydroorotate dehydrogenase (hDHODH, EC 1.3.5.2), a flavindependent mitochondrial enzyme involved in de novo pyrimidine biosynthesis, is a validated therapeutic target for the treatment of autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis. However, human DHODH inhibitors have also been investigated as treatment for cancer, parasite infections (i.e. malaria) and viruses as well as in the agrochemicals industry. OBJECTIVE: An overview of current knowledge of hDHODH inhibitors and their potential uses in diseases where hDHODH is involved. METHOD: This review focuses on recent advances in the development and application of hDHODH inhibitors, specifically covering the patent field, starting from a brief description of enzyme topography and of the strategies usually followed in designing its selective inhibitors. RESULTS: The most important and well-described novelty is the fact that the discovery, in the autumn of 2016, that hDHODH inhibitors are able to induce in vivo myeloid differentiation has led to the possibility of developing novel hDHODH based treatments for Acute Myelogenous Leukemia (AML). CONCLUSION: The review will describe a variety of specific inhibitor classes and conclude on recent and future therapeutic perspectives for this target.
28866631 Association of gender-specific risk factors in metabolic and cardiovascular diseases: an N 2018 Jan In the present cross-sectional study, based on National Health and Nutrition Examination Survey (NHANES, 2007-2010) cohorts, various risk factors for metabolic syndrome (MetS) and cardiovascular diseases (CVDs) were analyzed (n=12,153). The variables analyzed include, demographics, comorbidities associated with MetS or CVD, behavioral and dietary factors, while the primary endpoints were the prevalence of MetS and CVD. The prevalence of MetS and CVD was slightly higher in males as compared with females (42.50% and 7.65% vs 41.29% and 4.13%, respectively). After controlling for confounding factors, advanced age, family history of diabetes mellitus (DM), overweight, and obesity were significantly associated with the likelihood of MetS, irrespective of gender differences. In males, the diagnosis of prostate cancer and regular smoking were additional risk factors of MetS, whereas, advanced age, family history of heart attack or angina, health insurance coverage, diagnosis of rheumatoid arthritis or depression, obesity and low calorie intake were identified as risk factors for CVD. In addition to the above risk factors, higher physical activity and vitamin D insufficiency were also found to increase the risk of CVD in females. Furthermore, obesity was a higher risk factor for MetS than CVD. Emerging risk factors for CVD identified in this study has major clinical implications. Of interest is the correlation of higher physical activity and the risk of CVD in women and the role of depression and lower calorie intake in general population.