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ID PMID Title PublicationDate abstract
25636595 Citrullination and autoimmunity. 2015 Jun Autoimmune diseases are characterized by the body's own immune system attack to the self-tissues, a condition enabled, in predisposed subjects, by the reduction of self-tolerance. A central role has been recently recognized to post-translational modifications, since they can promote generation of neo-(auto)antigens and in turn an autoimmune response. During the last years great attention has been paid to citrullination, because of its role in inducing anti-citrullinated proteins/peptide antibodies (ACPA), a class of autoantibodies with diagnostic, predictive and prognostic value for Rheumatoid Arthritis (RA). Nonetheless, citrullination has been reported to be a process present in a wide range of inflammatory tissues. Indeed, citrullinated proteins have been detected also in other inflammatory arthritides and in inflammatory conditions other than arthritides (polymyositis, inflammatory bowel disease and chronic tonsillitis). Moreover, environmental exposure to cigarette smoke and nanomaterials of air pollution may be able to induce citrullination in lung cells prior to any detectable onset of inflammatory responses, suggesting that protein citrullination could be considered as a sign of early cellular damage. Accordingly, citrullination seems to be implicated in all those para-physiological processes, such as cells death pathways, in which intracellular calcium concentration raises to higher levels than in physiologic conditions: hence, peptidylarginine deiminases enzymes are activated during apoptosis, autophagy and NETosis, processes which are well-known to be implicated in autoimmunity. Taken together, these data support the hypothesis that rather than being a disease-dependent process, citrullination is an inflammatory-dependent condition that plays a central role in autoimmune diseases.
25472926 Occiput/C1-C2 fixations using intra-laminar screw of axis - A long-term follow-up. 2015 Apr BACKGROUND: The surgical management of the craniocervical junction is challenging. Rigid posterior fixation of occiput/C1-C2 can be performed using a variety of surgical techniques including C2 pedicle/pars interarticularis, transarticular and intralaminar screw fixations. METHODS: Forty-one patients were treated with occipital plate/C1 lateral mass and C2 intra-laminar screw fixations for basilar invagination and congenital atlantoaxial subluxation, post-traumatic instability, tuberculous and rheumatoid arthritis-associated atlantoaxial dislocation. Out of forty-one, thirty-six patients had bilateral crossing intra-laminar screws and five had ipsilateral laminar screw fixation bilaterally. RESULTS: Follow-up was done in thirty-nine patients from 6 months to 8 years (mean: 21 months) and solid osseous fusion could be achieved in all (100%). One patient was lost to follow-up and another patient died of a cause unrelated to surgical technique. Pre-operative and post-operative Neurosurgical Cervical Spine Scale showed improvement in all patients having features of myelopathy. There were no neurological or vascular complications. However, nine patients had posterior laminar breach, eight had anterior laminar penetrations and three had wound infections. One patient had transient bulbar palsy and one patient had hardware failure in the form of avulsion of the midline occipital plate. CONCLUSIONS: Intra-laminar screw fixation is a safe alternative to transarticular and transpedicular/pars interarticularis fixation of C2 with advantage of having no risk of injury to vertebral artery and comparable biomechanical and pull-out strength.
25446727 Epidemiology, risk factors and management of cardiovascular diseases in IBD. 2015 Jan IBD is an established risk factor for venous thromboembolism. In the past few years, studies have suggested that patients with IBD might also be at an increased risk of coronary heart disease and stroke. The increased risk is thought to be similar to the level of risk seen in patients with other chronic systemic inflammatory diseases such as rheumatoid arthritis. The risk of developing these conditions is particularly increased in young adults with IBD, and more so in women than in men. Conventional cardiovascular risk factors are not over-represented in patients with IBD, so the increased risk could be attributable to inflammation-mediated atherosclerosis. Patients with IBD often have premature atherosclerosis and have biochemical and genetic markers similar to those seen in patients with atherosclerotic cardiovascular disease. The role of chronic inflammation in IBD-associated cardiovascular disease merits further evaluation. Particular attention should be given to the increased risk observed during periods of increased disease activity and potential modification of the risk by immunosuppressive and biologic therapies for IBD that can modify the disease activity. In addition, preclinical studies suggest that cardiovascular medications such as statins and angiotensin-converting enzyme inhibitors might also favourably modify IBD disease activity, which warrants further evaluation.
25355199 Citrullinated Autoantigens: From Diagnostic Markers to Pathogenetic Mechanisms. 2015 Oct The conversion of an arginine residue in a protein to a citrulline residue, a reaction carried out by enzymes called peptidylarginine deiminases (PADs), is rather subtle. One of the terminal imide groups in arginine is replaced by oxygen in citrulline, thus resulting in the loss of positive charge and the gain of 1 dalton. This post-translational modification by PAD enzymes is conserved in vertebrates and affects specific substrates during development and in various mature cell lineages. Citrullination offers a unique perspective on autoimmunity because PAD activity is stringently regulated, yet autoantibodies to citrullinated proteins predictably arise. Autoantigens recognized by anti-citrullinated protein antibodies (ACPA) include extracellular proteins such as filaggrin, collagen II, fibrinogen, and calreticulin; membrane-associated proteins such as myelin basic protein; cytoplasmic proteins such as vimentin and enolase; and even nuclear proteins such as histones. Some ACPA are remarkably effective as diagnostics in autoimmune disorders, most notably rheumatoid arthritis (RA). Several ACPA can be observed before other clinical RA manifestations are apparent. In patients with RA, ACPA may attain a sensitivity that exceeds 70 % and specificity that approaches 96-98 %. The biological context that may account for the induction of ACPA emerges from studies of the cellular response of the innate immune system to acute or chronic stimuli. In response to infections or inflammation, neutrophil granulocytes activate PAD, citrullinate multiple autoantigens, and expel chromatin from the cell. The externalized chromatin is called a neutrophil extracellular "trap" (NET). Citrullination of core and linker histones occurs prior to the release of chromatin from neutrophils, thus implicating the regulation of citrullinated chromatin release in the development of autoreactivity. The citrullination of extracellular autoantigens likely follows the release of NETs and associated PADs. Autoantibodies to citrullinated histones arise in RA, systemic lupus erythematosus, and Felty's syndrome patients. The citrullination of linker histone H1 may play a key role in NET release because the H1 histone regulates the entry and exit of DNA from the nucleosome. Juxtaposition of citrullinated histones with infectious pathogens and complement and immune complexes may compromise tolerance of nuclear autoantigens and promote autoimmunity.
25171660 Ultrasonographic assessment of diurnal variation in the femoral condylar cartilage thickne 2015 Apr OBJECTIVE: In vivo measurement of articular cartilage thickness is a significant marker of structural joint damage in many inflammatory or noninflammatory diseases including rheumatoid arthritis or osteoarthritis. The aim of this study was to assess the diurnal variation of femoral condylar cartilage thickness (FCT) in young adults by using ultrasonography. DESIGN: The thickness of femoral articular cartilage was measured in healthy volunteers at 8:00-9:00 a.m. and 4:00-5:00 p.m. on the same day using standard sonographic methods. Three midpoint measurements were taken from each knee at the lateral femoral condyle, femoral intercondylar area, and medial femoral condyle. RESULTS: The FCT significantly decreased in all the areas assessed. The maximal decrease (in millimeters) in the mean (standard deviation) FCT was in the right lateral femoral condyle (0.21 [0.24]) and left medial femoral condyle (0.21 [0.21]) followed by the right medial femoral condyle (0.19 [0.23]), left lateral femoral condyle (0.19 [0.19]), left femoral intercondylar area (0.13 [0.30]), and right femoral intercondylar area (0.11 [0.33]). The mean diurnal change in FCT from a.m. to p.m. reached up to 10.6%. CONCLUSIONS: This study suggests that the FCT significantly decreased in all of the measured areas from a.m. to p.m. Future studies, particularly those assessing the effect of any pharmacologic or nonpharmacologic applications on cartilage thickness in the weight-bearing joints, should be designed bearing in mind that cartilage thickness has diurnal variations. Assessment of diurnal variation in cartilage thickness in elderly osteoarthritic or nonosteoarthritic populations warrants further research.
25129839 Diurnal and twenty-four hour patterning of human diseases: acute and chronic common and un 2015 Jun The symptom intensity and mortality of human diseases, conditions, and syndromes exhibit diurnal or 24 h patterning, e.g., skin: atopic dermatitis, urticaria, psoriasis, and palmar hyperhidrosis; gastrointestinal: esophageal reflux, peptic ulcer (including perforation and hemorrhage), cyclic vomiting syndrome, biliary colic, hepatic variceal hemorrhage, and proctalgia fugax; infection: susceptibility, fever, and mortality; neural: frontal, parietal, temporal, and occipital lobe seizures, Parkinson's and Alzheimer's disease, hereditary progressive dystonia, and pain (cancer, post-surgical, diabetic neuropathic and foot ulcer, tooth caries, burning mouth and temporomandibular syndromes, fibromyalgia, sciatica, intervertebral vacuum phenomenon, multiple sclerosis muscle spasm, and migraine, tension, cluster, hypnic, and paroxysmal hemicranial headache); renal: colic and nocturnal enuresis and polyuria; ocular: bulbar conjunctival redness, keratoconjunctivitis sicca, intraocular pressure and anterior ischemic optic neuropathy, and recurrent corneal erosion syndrome; psychiatric/behavioral: major and seasonal affective depressive disorders, bipolar disorder, parasuicide and suicide, dementia-associated agitation, and addictive alcohol, tobacco, and heroin cravings and withdrawal phenomena; plus autoimmune and musculoskeletal: rheumatoid arthritis, osteoarthritis, axial spondylarthritis, gout, Sjögren's syndrome, and systemic lupus erythematosus. Knowledge of these and other 24 h patterns of human pathophysiology informs research of their underlying circadian and other endogenous mechanisms, external temporal triggers, and more effective patient care entailing clinical chronopreventive and chronotherapeutic strategies.
28491277 Meta-analysis of crowdsourced data compendia suggests pan-disease transcriptional signatur 2016 Background: The proliferation of publicly accessible large-scale biological data together with increasing availability of bioinformatics tools have the potential to transform biomedical research. Here we report a crowdsourcing Jamboree that explored whether a team of volunteer biologists without formal bioinformatics training could use OMiCC, a crowdsourcing web platform that facilitates the reuse and (meta-) analysis of public gene expression data, to compile and annotate gene expression data, and design comparisons between disease and control sample groups. Methods: The Jamboree focused on several common human autoimmune diseases, including systemic lupus erythematosus (SLE), multiple sclerosis (MS), type I diabetes (DM1), and rheumatoid arthritis (RA), and the corresponding mouse models. Meta-analyses were performed in OMiCC using comparisons constructed by the participants to identify 1) gene expression signatures for each disease (disease versus healthy controls at the gene expression and biological pathway levels), 2) conserved signatures across all diseases within each species (pan-disease signatures), and 3) conserved signatures between species for each disease and across all diseases (cross-species signatures). Results: A large number of differentially expressed genes were identified for each disease based on meta-analysis, with observed overlap among diseases both within and across species. Gene set/pathway enrichment of upregulated genes suggested conserved signatures (e.g., interferon) across all human and mouse conditions. Conclusions: Our Jamboree exercise provides evidence that when enabled by appropriate tools, a "crowd" of biologists can work together to accelerate the pace by which the increasingly large amounts of public data can be reused and meta-analyzed for generating and testing hypotheses. Our encouraging experience suggests that a similar crowdsourcing approach can be used to explore other biological questions.
28076752 Methotrexate-associated primary hepatic malignant lymphoma following hepatectomy: A case r 2017 INTRODUCTION: Recently, immunosuppressant-associated malignant lymphoma (ML) cases have been increasing along with the development of several effective immunosuppressant drugs for rheumatoid arthritis (RA). Among methotrexate (MTX)-associated lymphoproliferative disorders, primary hepatic lymphoma (PHL) in patients with RA following surgical resection has not been reported previously. PRESENTATION OF CASE: A 65-year-old woman who is a hepatitis B virus carrier with a history of RA was admitted. MTX was introduced seven years prior as an RA treatment. Her laboratory data showed no elevation of several tumor markers, and liver function test results were normal. On contrasted computed tomography (CT) scanning, a slightly enhanced tumor was detected at the early phase, and tumor staining was sustained at the delayed phase. Further, subsegmentectomy of the S6 was performed. The pathological diagnosis was diffuse large B-cell lymphoma. However, positron emission tomography-CT and bone marrow aspiration sample showed no resident sign of ML. DISCUSSION: Diagnosis of PHL before surgery is difficult. If the mass lesion was solitary and had a certain degree of size, then resection could be performed for its treatment and diagnosis. The treatment for ML requires a diagnosis of the subtypes to select a therapeutic agent and determine the prognosis. Once a precise preoperative diagnosis was made, withdrawing MTX could be the first treatment in case of MTX-related ML. CONCLUSION: Long-term usage of immunosuppressant drugs could cause proliferative ML. Considering the increasing occurrence of MTX-related ML, withdrawing MTX should be considered, especially in patients with long-term immunosuppressant usage for RA.
28040536 Th9 cells and IL-9 in autoimmune disorders: Pathogenesis and therapeutic potentials. 2017 Feb Naïve CD4(+) T cells are pleiotropically divided into various T helper (Th) cell subsets, according to their pivotal roles in the regulation of immune responses. The differentiation of Th9 cells, an interleukin (IL)-9 producing subset, can be impacted by specific environmental cues, co-stimulation with transforming growth factor β (TGF-β) and IL-4, and other regulatory factors. Although IL-9 has been recognized as a classical Th2-related cytokine, recent studies have indicated that IL-9-producing cells contribute to a group of autoimmune disorders including systemic lupus erythematosus (SLE), multiple sclerosis (MS), inflammatory bowel diseases (IBD), rheumatoid arthritis (RA) and psoriasis. Studies of Th9 cells in autoimmune diseases, although in their infancy, are expected to be of growing interest in the study of potential mechanisms of cytokine regulatory pathways and autoimmune pathogenesis. Several in vitro and in vivo pre-clinical trials have been conducted to explore potential therapeutic strategies by targeting the IL-9 pathway. Specifically, anti-IL-9 monoclonal antibodies (mAbs) and IL-9 inhibitors may potentially be used for the clinical treatment of allergic diseases, autoimmune diseases or cancers. Here, we review recent research on Th9 cells and IL-9 pertaining to cell differentiation, biological characteristics and pivotal cellular inter-relationships implicated in the development of various diseases.
27639376 Prevalence of osteoporosis in the Italian population and main risk factors: results of Bon 2016 Sep 17 BACKGROUND: BoneTour is a campaign conducted throughout the Italian territory for the assessment of Italian people bone status and for the prevention of osteoporosis. METHODS: A total of 7305 sequential subjects of both sexes were screened, collecting clinical data through the FRAX™ questionnaire, and measuring heel bone stiffness by Quantitative Ultrasonography (QUS). The 10-year risk for hip and major osteoporotic fractures was calculated taking into account personal or family history of fragility fracture, smoking, alcohol abuse, rheumatoid arthritis, prolonged steroids assumption. Additional risk factors were evaluated, including early menopause, poor sunlight exposure, low dietary calcium intake, physical inactivity, number of pregnancies, months of lactation, tobacco cigarettes smoked per year, specific causes of secondary osteoporosis. Through a correlation study, the influence of each factor on the development of osteoporosis was analyzed. RESULTS: As many as 18 % of women suffer from osteoporosis, as defined by QUS T-score. The calculation of FRAX™ confirmed the weight of the already known risk factors. The correlation study revealed the significance of some additional factors, such as hyperthyroidism, nephrolithiasis, Crohn disease, ulcerative colitis, celiac disease, poor sun exposure, and oophorectomy before age 50. CONCLUSIONS: The high prevalence of secondary osteoporosis in the Italian population clearly indicates the importance of additional risk factors not yet included in the FRAX™ algorithm, for which preventive measures should be considered. Screening campaigns may allow both early diagnosis and access to treatment.
27613732 Factors Associated with Repeated Health Resource Utilization in Patients with Diverticulit 2017 Jan Conservative management trends in diverticulitis may lead to increased hospitalizations secondary to repeated attacks. The study aimed to characterize trends in management and risk-assess patients with diverticulitis that required multiple admissions to identify high utilizers. A total of 265,724 patients with diverticulitis were identified from 1995 to 2014 from the New York SPARCS database. Patients with ≥2 hospital admissions were stratified across demographics, comorbidities, insurance status, and surgical intervention. In total, 42,850 patients had ≥2 hospital admissions. Risk factors for ≥2 admissions included younger age, White race, obesity, hypertension, pulmonary disease, hypothyroidism, rheumatoid arthritis, and depression. Fifty-two percent of these patients went on to have surgery. The percentage of elective cases increased from 59 to 70 %, while emergent cases conversely decreased from 41 to 30 %. One in five patients admitted with diverticulitis required two or more admissions. Numerous patient factors were correlated with increased risk of readmission. These factors may be used to guide treatment decisions and help reduce economic burden in frequent utilizers. Trends in surgery rates for these patients could reflect improved treatment options and/or changing clinical practice patterns.
27577940 Polymyalgia rheumatica and risk of coronary artery disease: a systematic review and meta-a 2017 Jan Several chronic inflammatory disorders, such as rheumatoid arthritis and systemic lupus erythematosus, are associated with an increased risk of coronary artery disease (CAD) as a result of accelerated atherosclerosis. However, the data on CAD risk of polymyalgia rheumatica (PMR), one of the most common chronic inflammatory disorders in older adults, remain unclear due to limited number of epidemiological studies. To further investigate this possible association, this systematic review and meta-analysis of observational studies was performed to compare the risk of CAD in patients with PMR versus subjects without it. Published studies indexed in MEDLINE and EMBASE were searched from inception to April 2016 using the terms "polymyalgia rheumatica" combined with the terms for CAD. The inclusion criteria were: (1) observational studies published as original studies to evaluate the risk of CAD among patients with PMR; (2) published odds ratios, relative risk or hazard ratio or standardized incidence ratio with 95 % confidence intervals (CI) in the studies; and (3) subjects without PMR were used as comparators in cohort studies and cross-sectional studies, while subjects without CAD were used as comparators in case-control studies. Point estimates and standard errors were extracted from individual studies and were combined by the generic inverse variance method of DerSimonian and Laird. Four studies with 34,569 patients with PMR were identified and included in this meta-analysis. The pooled risk ratio of CAD in patients with PMR was 1.72 (95 % CI 1.21-2.45). The statistical heterogeneity of this meta-analysis was high with an I (2) of 97 %.
27365996 Rheumatology in India: a Bird's Eye View on Organization, Epidemiology, Training Programs 2016 Jul India is home to the world's second largest population. Rheumatology is an emerging specialty in India. We reviewed organization, epidemiology and training facilities for Rheumatology in India. Also, we also looked at publications in the field of rheumatology from India from over the past six years using Scopus and Medline databases. Despite rheumatologic disorders affecting 6%-24% of the population, rheumatology in India is still in its infancy. Till recently, there were as few as two centers in the country training less than five fellows per year. However, acute shortage of specialists and increasing patient numbers led to heightened awareness regarding the need to train rheumatologists. Subsequently, six new centers have now started 3-year training programs in rheumatology. The epidemiology of rheumatic diseases in India is being actively studies under the Community Oriented Programme for Control of Rheumatic Diseases (COPCORD) initiative. The most number of publications on rheumatic diseases from India are on rheumatoid arthritis, lupus and osteoporosis, many of which have been widely cited. Major collaborators worldwide are USA, UK and France, whereas those from Asia are Japan, Saudi Arabia and Singapore. The Indian Rheumatology Association (IRA) is the national organization of rheumatologists. The flagship publication of the IRA, the Indian Journal of Rheumatology, is indexed in Scopus and Embase. To conclude, rheumatology in India is an actively expanding and productive field with significant contributions to world literature. There is a need to train more personnel in the subject in India.
27256975 Stem cell transplantation and mesenchymal cells to treat autoimmune diseases. 2016 Jun Since the start of the international stem cell transplantation project in 1997, over 2000 patients have received a haematopoietic stem cell transplant (HSCT), mostly autologous, as treatment for a severe autoimmune disease, the majority being multiple sclerosis (MS), systemic sclerosis (SSc) and Crohn's disease. There was an overall 85% 5-year survival and 43% progression-free survival. Around 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many cases, e.g. systemic sclerosis, morphological improvement such as reduction of skin collagen and normalization of microvasculature was documented, beyond any predicted known effects of intense immunosuppression alone. It is hoped that the results of the three running large prospective randomized controlled trials will allow modification of the protocols to reduce the high transplant-related mortality which relates to regimen intensity, age of patient, and comorbidity. Mesenchymal stromal cells (MSC), often incorrectly called stem cells, have been the intense focus of in vitro studies and animal models of rheumatic and other diseases over more than a decade. Despite multiple plausible mechanisms of action and a plethora of positive in vivo animal studies, few randomised controlled clinical trials have demonstrated meaningful clinical benefit in any condition so far. This could be due to confusion in cell product terminology, complexity of clinical study design and execution or agreement on meaningful outcome measures. Within the rheumatic diseases, SLE and rheumatoid arthritis (RA) have received most attention. Uncontrolled multiple trial data from over 300 SLE patients have been published from one centre suggesting a positive outcome; one single centre comparative study in 172 RA was positive. In addition, small numbers of patients with Crohn's disease, multiple sclerosis, primary Sjögren's disease, polymyositis/dermatomyositis and type II diabetes mellitus have received MSC therapeutically. The possible reasons for this apparent mismatch between expectation and clinical reality will be discussed.
27215923 Risk of Autoimmunity in EoE and Families: A Population-Based Cohort Study. 2016 Jul OBJECTIVES: Recent genome-wide association studies have suggested possible genetic associations between eosinophilic esophagitis (EoE) and genes associated with autoimmunity. No studies to date have looked at potential genetic association of EoE with specific autoimmune diseases by evaluating such diagnoses within family members. Investigate the risk of specific autoimmune disease within EoE probands and their extended family members. METHODS: The Utah Population Database offers a unique opportunity to link medical records from over 85% of Utah's population to genealogy records representing Utah. We searched for associations of specific autoimmune diseases in probands diagnosed with EoE and their extended family members (e.g., first cousins). Comparisons were made to age- and sex-matched controls and their respective families at a 5:1 ratio. RESULTS: Excess risk for multiple autoimmune conditions was detected in subjects with a diagnosis of EoE. Celiac, Crohn's, ulcerative colitis (UC), rheumatoid arthritis, IgA deficiency, CVID, multiple sclerosis (MS), and Hashimoto's thyroiditis were found at increased risk in first-degree relatives of EoE subjects. UC, systemic sclerosis, and MS had nominally significant associations within second-degree family members of EoE subjects; and, in reverse analysis, probands and their families with the above three conditions were at an increased risk for EoE suggesting shared genetic factors with EoE. CONCLUSIONS: Patients with EoE have an increased risk of multiple autoimmune diseases. Possible shared genetic etiologies were observed between EoE and UC, systemic sclerosis, and MS. Practitioners should be aware of these comorbid associations and query all EoE patients and family members for symptoms of these diseases.
27131574 Natural products for treatment of bone erosive diseases: The effects and mechanisms on inh 2016 Jul Excessive bone resorption plays a central role on the development of bone erosive diseases, including osteoporosis, rheumatoid arthritis, and periodontitis. Osteoclasts, bone-resorbing multinucleated cells, are differentiated from hemopoietic progenitors of the monocyte/macrophage lineage. Regulation of osteoclast differentiation is considered an effective therapeutic target to the treatment of pathological bone loss. Natural plant-derived products, with potential therapeutic and preventive activities against bone-lytic diseases, have received increasing attention in recent years because of their whole regulative effects and specific pharmacological activities, which are more suitable for long-term use than chemically synthesized medicines. In this review, we summarized the detailed research progress on the active compounds derived from medical plants with potential anti-resorptive effects and their molecular mechanisms on inhibiting osteoclast formation and function. The active ingredients derived from natural plants that are efficacious in suppressing osteoclastogenesis and bone resorption include flavonoids, terpenoids (sesquiterpenoids, diterpenoids, triterpenoids), glycosides, lignans, coumarins, alkaloids, polyphenols, limonoids, quinones and others (steroid, oxoxishhone, fatty acid). Studies have shown that above natural products exert the inhibitory effects via regulating many factors involved in the process of osteoclast differentiation and bone resorption, including the essential cytokines (RANKL, M-CSF), transcription factors (NFATc1, c-Fos), signaling pathways (NF-κB, MAPKs, Src/PI3K/Akt, the calcium ion signaling), osteoclast-specific genes (TRAP, CTSK, MMP-9, integrin β3, OSCAR, DC-STAMP, Atp6v0d2) and local factors (ROS, LPS, NO). The development of osteoclast-targeting natural products is of great value for the prevention or treatment of bone diseases and for bone regenerative medicine.
27059884 Anti-inflammatory properties of the vagus nerve: potential therapeutic implications of vag 2016 Oct 15 Brain and viscera interplay within the autonomic nervous system where the vagus nerve (VN), containing approximately 80% afferent and 20% efferent fibres, plays multiple key roles in the homeostatic regulations of visceral functions. Recent data have suggested the anti-inflammatory role of the VN. This vagal function is mediated through several pathways, some of them still debated. The first one is the anti-inflammatory hypothalamic-pituitary-adrenal axis which is stimulated by vagal afferent fibres and leads to the release of cortisol by the adrenal glands. The second one, called the cholinergic anti-inflammatory pathway, is mediated through vagal efferent fibres that synapse onto enteric neurons which release acetylcholine (ACh) at the synaptic junction with macrophages. ACh binds to α-7-nicotinic ACh receptors of those macrophages to inhibit the release of tumour necrosis (TNF)α, a pro-inflammatory cytokine. The last pathway is the splenic sympathetic anti-inflammatory pathway, where the VN stimulates the splenic sympathetic nerve. Norepinephrine (noradrenaline) released at the distal end of the splenic nerve links to the β2 adrenergic receptor of splenic lymphocytes that release ACh. Finally, ACh inhibits the release of TNFα by spleen macrophages through α-7-nicotinic ACh receptors. Understanding of these pathways is interesting from a therapeutic point of view, since they could be targeted in various ways to stimulate anti-inflammatory regulation in TNFα-related diseases such as inflammatory bowel disease and rheumatoid arthritis. Among others, VN stimulation, either as an invasive or non-invasive procedure, is becoming increasingly frequent and several clinical trials are ongoing to evaluate the potential effectiveness of this therapy to alleviate chronic inflammation.
26994530 Genetic polymorphisms of interleukin-22 in patients with ulcerative colitis. 2016 Apr BACKGROUND: Ulcerative colitis (UC) is a multifactorial and polygenic disease. Interleukin-22 (IL-22) is an immunomodulatory cytokine that belongs to the IL-10 family. Currently, some IL-22 polymorphisms have been associated with inflammatory processes such as rheumatoid arthritis and psoriasis vulgaris, but there are no studies on UC. AIM: The aim of this work was to study the frequency of polymorphisms of IL-22 in Mexican patients with UC. METHODS: We studied a total of 199 Mexican patients with confirmed UC and 697 healthy controls. All individuals were born in Mexico, at least three family generations earlier. A blood sample was obtained from the UC patients and healthy controls in order to perform DNA extraction and then to determine the frequency of IL-22 polymorphisms (rs2227485, rs2272478, rs2227491). RESULTS: No statistical significance was found in the gene and genotype frequencies of three SNPs of IL-22 (rs2227485, rs2272478, rs2227491) between the UC patients and healthy controls. No association was found between those IL-22 SNPs and clinical features of UC. CONCLUSIONS: There was no association between IL-22 SNPs (rs2227485, rs2272478, rs2227491) and the development of UC in a Mexican population.
26981519 Osteoporotic Fracture Risk Assessment Using Bone Mineral Density in Korean: A Community-ba 2016 Feb BACKGROUND: Fracture-risk assessment tool (FRAX) using just clinical risk factors of osteoporosis has been developed to estimate individual risk of osteoporotic fractures. We developed prediction model of fracture risk using bone mineral density (BMD) as well as clinical risk factors in Korean, and assessed the validity of the final model. METHODS: To develop and validate an osteoporotic FRAX, a total of 768 Korean men and women aged 50 to 90 years were followed for 7 years in a community-based cohort study. BMD as well as clinical risk factors for osteoporotic fracture including age, sex, body mass index, history of fragility fracture, family history of fracture, smoking status, alcohol intake, use of oral glucocorticoid, rheumatoid arthritis, and other causes of secondary osteoporosis were assessed biannually. RESULTS: During the follow-up period, 86 osteoporotic fractures identified (36 in men and 50 in women). The developed prediction models showed high discriminatory power and had goodness of fit. CONCLUSIONS: The developed a Korean specific prediction model for osteoporotic fractures can be easily used as a screening tool to identify individual with high risk of osteoporotic fracture. Further studies for validation are required to confirm the clinical feasibility in general Korean population.
26969025 Critical Link Between Epigenetics and Transcription Factors in the Induction of Autoimmuni 2016 Jun Autoimmune diseases occur when the immune system loses tolerance to self-antigens, inducing inflammation and tissue damage. The pathogenesis of autoimmune diseases has not been elucidated. A growing mountain of evidence suggests the involvement of genetic and epigenetic factors in the development of these disorders. Genetic mapping has identified several candidate variants in autoimmune conditions. However, autoimmune diseases cannot be explained by genetic susceptibility alone. The fact that there is only 20 % of concordance for systemic lupus erythematosus (SLE) in homozygotic twins is an indication that epigenetics and environment may also play significant roles. Epigenetics refer to inheritable and potentially reversible changes in DNA and chromatin that regulate gene expression without altering the DNA sequence. The primary mechanisms of epigenetic regulation include DNA methylation, histone modification, and non-coding RNA-mediated regulation. The regulation on gene expression by epigenetics is similar to that by transcription factors (TFs), and the normal execution of biological event is controlled by a combination of epigenetic modifications and TFs. These two mechanisms share similar regulatory logistics and cooperate in part by influencing activity of the binding sites of target genes. In addition, the promoters of TFs have been found themselves to be modified by epigenetic regulators and TFs can also induce epigenetic changes. There is a two-way street in which interplay between epigenetic regulation and TFs plays a role in the pathogenesis of SLE, rheumatoid arthritis, type 1 diabetes, systemic sclerosis, and multiple sclerosis. Understanding of pathogenesis of these autoimmune diseases will help define potential targets for therapeutic strategies.