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ID PMID Title PublicationDate abstract
31984898 Diversity-Oriented Synthetic Approaches for Furoindoline: A Review. 2019 The furo [2,3-b] indoline ring system is one of the most important structural units in various natural products. It has been known to have inherent biological activities and is utilized as a synthetic target for a number of natural compounds; therefore, this has contributed to a great demand for the growth of synthetic methods for this ring system. Most important compounds with furoindoline ring system are physovenine, madindoline A and B and makomotindoline etc. These compounds are well known to exhibit biological activity against different diseases such as glaucoma, cancer, cachexia, Castleman's disease, rheumatoid arthritis, etc. The current article focuses on various synthetic approaches for furoindoline containing compounds and essential furoindoline moiety, such as oxindole-5-O-tetrahydropyranyl ether route etc., and various other diastereoand enantio- controlled approach in a very concise way.
31850225 The Emerging Roles of Extracellular Vesicles in Osteosarcoma. 2019 Extracellular vesicles (EVs) are heterogeneous nanosized vesicles that are constitutively released by virtually all types of cells. They have been isolated in almost all body fluids. EVs cargo consists of various molecules (nucleic acids, proteins, lipids, and metabolites), that can be found on EVs surface and/or in their lumen. EVs structure confer stability and allow the transfer of their cargo to specific cell types over a distance. EVs play a critical role in intercellular communication in physiological and pathological settings. The broadening of knowledge on EVs improved our comprehension of cancer biology as far as tumor development, growth, metastasis, chemoresistance, and treatment are concerned. Increasing evidences suggest that EVs have a significant role in osteosarcoma (OS) development, progression, and metastatic process. The modulation of inflammatory communication pathways by EVs plays a critical role in OS and in other bone-related pathological conditions such as osteoarthritis and rheumatoid arthritis. In this review we describe the emerging data on the role of extracellular vesicles in osteosarcoma and discuss the effects and function of OS-derived EVs focusing on their future applicability in clinical practice.
31645201 Current standardized therapeutic approach for uveitis in Japan. 2019 Sep Uveitis is an ocular disease associated with systemic immune-mediated diseases such as rheumatoid arthritis, inflammatory bowel disease and ankylosing spondylitis; and infectious diseases. Infectious uveitis occasionally shows symptoms similar to those of non-infectious uveitis. Therefore, distinguishing between non-infectious and infectious uveitis is critical for definitive diagnosis and appropriate choice of treatment. Once the cause of infection is known, treatment can be promptly initiated. However, in contrast to infectious uveitis, non-infectious uveitis is more difficult to diagnose clinically. Eliminating the possibility of infectious uveitis is important because unlike the infectious type, non-infectious uveitis is treated with immunosuppressive drugs such as corticosteroids and biological agents. Compared to other countries, the drugs available in Japan are limited. Cyclosporin A is the only immunosuppressive drug available for treating uveitis in Japan, and infliximab and adalimumab are the only biological drugs that have been approved for use in the treatment of uveitis in Japan. In this review, I describe the characteristics of typical non-infectious uveitis in Japan and its treatment methods.
31328474 [Advances in research of bispecific antibodies for antivirus therapy]. 2019 Jul 25 With the rapid development of antibody genetic engineering, bispecific antibody technology has been advanced. They are capable of binding two or more different epitopes simultaneously, thus offering specific advantages over natural monoclonal antibodies in immunotherapy. Bispecific antibodies have been successfully used in cancer therapy (e.g. melanoma, Hodgkin's lymphoma, liver cancer, and stomach cancer) and inflammation therapy (e.g. rheumatoid arthritis, psoriasis and Crohn's disease), but are still in their early stage for viral immunotherapy. In this study, we reviewed the research progress of bispecific antibodies for immunotherapy of virus infections, especially those with good effects in vivo and in vitro, to provide references for the research and development of bispecific antibodies for antivirus treatment.
31213202 Interleukin-17: Functional and Structural Features, Application as a Therapeutic Target. 2019 Jan Cytokines of the IL-17 family play a key role in the host organism defense against bacterial and fungal infections. At the same time, upregulated synthesis of IL-17 cytokines is associated with immunoinflammatory and autoimmune diseases such as psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and others. The members of this family are important therapeutic targets in the treatment of various human chronic inflammatory disorders. Elucidation of signaling pathways involving IL-17 family proteins and analysis of the structure of cytokine complexes with specific antibodies, inhibitors, and receptors are essential for the development of new drugs for the therapy of immunoinflammatory rheumatic diseases.
30908306 Modulatory Effects of Pregnancy on Inflammatory Bowel Disease. 2019 Mar The disease course of autoimmune diseases such as rheumatoid arthritis is altered during pregnancy, and a similar modulatory role of pregnancy on inflammatory bowel disease (IBD) has been proposed. Hormonal, immunological, and microbial changes occurring during normal pregnancy may interact with the pathophysiology of IBD. IBD consists of Crohn's disease and ulcerative colitis, and because of genetic, immunological, and microbial differences between these disease entities, they may react differently during pregnancy and should be described separately. This review will address the pregnancy-induced physiological changes and their potential effect on the disease course of ulcerative colitis and Crohn's disease, with emphasis on the modulation of epithelial barrier function and immune profiles by pregnancy hormones, microbial changes, and microchimerism.
31649620 Melanocortin Regulation of Inflammation. 2019 Adrenocorticotropic hormone (ACTH), and α-, β-, and γ-melanocyte-stimulating hormones (α-, β-, γ-MSH), collectively known as melanocortins, together with their receptors (melanocortin receptors), are components of an ancient modulatory system. The clinical use of ACTH in the treatment of rheumatoid arthritis started in 1949, originally thought that the anti-inflammatory action was through hypothalamus-pituitary-adrenal axis and glucocorticoid-dependent. Subsequent decades have witnessed extensive attempts in unraveling the physiology and pharmacology of the melanocortin system. It is now known that ACTH, together with α-, β-, and γ-MSHs, also possess glucocorticoid-independent anti-inflammatory and immunomodulatory effects by activating the melanocortin receptors expressed in the brain or peripheral immune cells. This review will briefly introduce the melanocortin system and highlight the action of melanocortins in the regulation of immune functions from in vitro, in vivo, preclinical, and clinical studies. The potential therapeutic use of melanocortins are also summarized.
31462834 Mixed-etiology leg ulcers in a patient on long-term glucocorticoid therapy. 2019 Chronic leg ulceration is a frequent condition in elderly patients. Chronic wounds that are nonresponsive to 3-month therapy affect approximately 6.5 million people in the United States with a prevalence of 1% and costs estimated at 25 billion dollars per year. Although the main causes are venous insufficiency, lower extremity arterial disease and diabetes, in many cases the etiology is multi-factorial. Approximately 20-23% of non-healing wounds that are refractory to vascular intervention have other etiologies including vasculitis, rheumatoid arthritis and Sjögren syndrome. Adverse drug interactions are the least commonly considered, especially those which involve disease-modifying anti-rheumatic drugs. The authors present a report on a female patient with reported Sjögren syndrome, multiple morbidities and non-healing lower limb ulceration that developed during treatment with methotrexate, and no significant improvement after discontinuation of the drug and after vascular surgery. Microvascular deterioration caused by beta-blockers was considered decisive. Calcium-blocker replacement brought complete healing in the follow-up.
31193896 Cortisone in Popular Culture: Roueché, Ray, and Hench. 2019 Jun In this article, the authors offer a new perspective on how the administration of Compound E (ie, cortisone) to a volunteer Mayo Clinic patient with rheumatoid arthritis and the patient's subsequent miraculous improvement led not only to a major, successful clinical trial but also a Nobel Prize. The early and late side effects as an undesirable outcome of treatment of corticosteroids would soon follow. Corticosteroid side effects became known in popular culture, first through an indepth article in The New Yorker by medical journalist Berton Roueché, and later through a major fiction film, Bigger than Life, directed by Nicholas Ray. The film used cortisone as a plot device to "unmask" what the filmmaker perceived to be the lie of middle class prosperity in America of the 1950s. Bigger than Life is also a cinematic argument against the use of cortisone. Dr. Philip Hench was also connected to Bigger than Life, and the Ray-Hench connection is further explored based on newly found material. The discovery of "wonder drug" cortisone and its potential side effects-all carefully described in the Roueché article but exaggerated in Nicholas Ray's film in the 1950s-show how medicine can be portrayed in popular culture.
31190864 Novel cancer therapy targeting microbiome. 2019 In the human intestinal tract, there are more than 100 trillion symbiotic bacteria, which form the gut microbiota. Approximately 70% of the human immune system is in the intestinal tract, which prevents infection by pathogenic bacteria. When the intestinal microbiota is disturbed, causing dysbiosis, it can lead to obesity, diabetes mellitus, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, autism spectrum disorder and cancer. Recent metabolomics analyses have also made the association between the microbiota and carcinogenesis clear. Here, we review the current evidence on the association between the microbiota and gastric, bladder, hepatobiliary, pancreatic, lung and colorectal cancer. Moreover, several animal studies have revealed that probiotics seem to be effective for the prevention of carcinogenesis to some extent. In this review, we focused on this relationship between the microbiota and cancer, and considered how to prevent cancer using strategies involving the gut microbiota.
30916904 [Paradoxical psoriasis induced by anti-TNF - a clinical challenge]. 2019 Mar 27 Anti-TNFs have revolutionized the management of numerous chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Although anti-TNF drugs are highly effective, 2-5 % of treated patients develop psoriasis-like skin lesions called paradoxical psoriasis. Paradoxical psoriasis is specific to anti-TNFs and it is, despite clinically resembling classical psoriasis, immunologically distinct. As it frequently requires cessation of the anti-TNF therapy, paradoxical psoriasis is a critical drug side effect and a challenge in the management of patients with chronic inflammatory diseases. In this review, we discuss the clinical, histological and pathogenic distinctions between the two entities and the management of patients developing paradoxical psoriasis.
31205138 Gastrointestinal Manifestations of Rheumatological Diseases. 2019 Sep Rheumatological diseases (RDs) represent a diverse group of diseases that are inherited or related to environmental factors. RDs frequently affect the gastrointestinal (GI) tract, and gastroenterologists are often asked to evaluate patients with symptoms thought to represent an underlying or coexisting RD. GI manifestations of RDs vary based on the organ involved as well as the extent and duration of involvement. Although most manifestations of RD are nonspecific and not life-threatening, the chronicity and severity of symptoms can be debilitating and may lead to serious injury. This narrative review discusses the most common RD encountered by gastroenterologists: systemic lupus erythematosus, systemic sclerosis (scleroderma), dermatomyositis/polymyositis, rheumatoid arthritis, Sjögren syndrome, overlap syndromes, mixed connective tissue disease, Ehlers-Danlos syndromes, and other vasculitides. Each section begins with a brief overview of the condition, followed by a discussion of the etiopathophysiology, physical examination findings, GI manifestations, diagnostic tools (i.e., serologic, imaging, endoscopic, and functional), and treatment options.
30930377 [Clinical Pharmaceutical Research Based on New Proteome Analysis Based on Chromatographic 2019 Comprehensive identification of antigens in immune complexes (IC-antigens) is beneficial to provide insights into pathophysiology and could form the basis for novel diagnostic and treatment strategies for many immune-related diseases. Immune complexome analysis is a method for comprehensively identifying and profiling IC-antigens in biological fluids (such as serum and cerebrospinal fluid). We applied this strategy to the analysis of circulating ICs in autoimmune diseases (rheumatoid arthritis, Sjögren's syndrome, systemic scleroderma, and systemic lupus erythematosus), infectious diseases, and cancers. Fluorogenic derivatization-liquid chromatography-tandem mass spectrometry (FD-LC-MS/MS) consists of fluorogenic derivatization of proteins, followed by HPLC of the derivatized proteins, isolation of the proteins differentially expressed in a certain group, enzymatic digestion of the isolated proteins followed by LC-tandem MS using a database-searching algorithm for protein identification. We have applied this method to understand the cardioprotective effect of pre-administration of docetaxel in adriamycin/docetaxel combination anti-cancer therapy, and the cellular processes that are affected by non-steroidal anti-inflammatory drugs (NSAIDs) in mouse stomach tissue during ulcer formation.
30742401 Piroxicam Therapy and CYP2C9 Genotype. 2012 Piroxicam (brand name Feldene) is a nonsteroidal anti-inflammatory drug (NSAID) used to treat osteoarthritis and rheumatoid arthritis. Piroxicam provides pain relief and reduces inflammation. Piroxicam is primarily metabolized by CYP2C9. Individuals who lack CYP2C9 activity (“CYP2C9 poor metabolizers”) have an increased exposure to piroxicam, and an increased risk of side effects. Like all NSAIDs, piroxicam increases the risk of serious cardiovascular events, including myocardial infarction and stroke, and serious gastrointestinal (GI) adverse events such as bleeding, ulceration, and perforation. The standard dose of piroxicam for osteoarthritis and rheumatoid arthritis in adults is 20 mg once daily. But for all patients, the lowest effective dose of piroxicam should be used for the shortest length of time, consistent with the treatment goals of each individual (1). The FDA-approved drug label for piroxicam states that a dose reduction should be considered in “patients who are known or suspected to be poor CYP2C9 metabolizers based on genotype or previous history/experience with other CYP2C9 substrates (such as warfarin and phenytoin)”. Dose reductions should be considered because these patients may have abnormally high plasma levels of piroxicam caused by reduced metabolic clearance. However, specific dose reductions based on CYP2C9 phenotype are not provided (Table 1) (1). As for all NSAIDs, piroxicam is contraindicated in patients with a known hypersensitivity, a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or another NSAID, and following coronary artery bypass graft (CABG) surgery. Piroxicam should also be avoided by pregnant women starting at 30 weeks gestation.
30317071 Thymosins in multiple sclerosis and its experimental models: moving from basic to clinical 2019 Jan BACKGROUND: Multiple sclerosis (MS) afflicts more than 2.5 million individuals worldwide and this number is increasing over time. Within the past years, a great number of disease-modifying treatments have emerged; however, efficacious treatments and a cure for MS await discovery. Thymosins, soluble hormone-like peptides produced by the thymus gland, can mediate immune and non-immune physiological processes and have gained interest in recent years as therapeutics in inflammatory and autoimmune diseases. METHODS: Pubmed was searched with no time constraints for articles using a combination of the keywords "thymosin/s" or "thymus factor/s" AND "multiple sclerosis", mesh terms with no language restriction. RESULTS: Here, we review the state-of-the-art on the effects of thymosins on MS and its experimental models. In particular, we describe what is known in this field on the roles of thymosin-α1 (Tα1) and -β4 (Tβ4) as potential anti-inflammatory as well as neuroprotective and remyelinating molecules and their mechanisms of action. CONCLUSION: Based on the data that Tα1 and Tβ4 act as anti-inflammatory molecules and as inducers of myelin repair and neuronal protection, respectively, a possible therapeutic application in MS for Tα1 and Tβ4 alone or combined with other approved drugs may be envisaged. This approach is reasonable in light of the current clinical usage of Tα1 and data demonstrating the safety, tolerability and efficacy of Tβ4 in clinical practice.
31830393 [Acute renal failure secondary to DRESS syndrome]. 2019 Dec 9 We report here the case of a 63-year-old man, diagnosed with rheumatoid arthritis, who presented fever, weakness, diarrhea, chest, limbs and face erythema 20 days after starting of therapy with salazopyrin; these symptoms only partially and temporarily subsided after early drug withdrawal. The subsequent intake of mesalazine during acute colitis, after 48 hours, determined a sever relapse characterized by high fever, general malaise, diffuse morbilliform rash on the trunk, face and limbs with visceral involvement (acute renal and hepatic injury). At this time the diagnosis of "Drug reaction with eosinophilia and systemic symptoms", or DRESS, was done according to "Regiscar" criteria. Mesalazine was therefore suspended and steroid therapy begun, inducing a slow but complete remission within two months.
30983882 Erratum to "Increased Expression of TLR10 in B Cell Subsets Correlates with Disease Activi 2019 [This corrects the article DOI: 10.1155/2018/9372436.].
31479110 The Effect of Chloroquine on the Development of Dry Eye in Sjögren Syndrome Animal Model. 2019 Sep 3 PURPOSE: Sjögren syndrome (SS) is an autoimmune disease characterized by the inflammatory destruction of salivary and lacrimal glands (LG). Chloroquine (CQ) was known as an immunomodulatory drug and in the inhibition of autophagy. The purpose of the study is to investigate the effect of CQ on the development of dry eye in NOD-LtJ mice. METHODS: NOD-LtJ mice were observed, during which the occurrence of dry eye was confirmed by tear secretion, corneal staining, and the infiltration of foci into the LG from 13-week-old mice. Intraperitoneal (IP) administration of CQ was performed in 13-week-old mice for 4 weeks and maintained untreated for another 4 weeks. Additionally, CQ was injected IP in 19-week-old mice for 2 weeks from when the disease was fully developed. RESULTS: Interestingly, the expression of autophagy marker ATG5 and LC3B-II was observed in the LG from week 5. When CQ had been administered for 4 weeks from week 13 and then maintained untreated for 4 weeks, tear secretion, corneal staining score, foci formation in the LG, conjunctival goblet cells and proinflammatory cytokine expressions were significantly better than untreated mice. The infiltration of immune cells and the expression of autophagy markers in LG were decreased in the CQ group. These indices improved significantly as well when the 19-week-old mice with severe clinical phenotypes had been treated with CQ for 2 weeks. CONCLUSIONS: This study demonstrated that autophagy was induced in the early stages of the SS model and that CQ treatment in the early stages could inhibit disease progression.
31335688 Cluster of differentiation 30 expression in lacrimal gland and conjunctival tissues in pat 2019 Jul INTRODUCTION: Sjögren's syndrome (SS) often causes lymphoproliferative disorders such as malignant lymphoma and macroglobrinemia. Approximately 5% of long-term follow-up SS patients develop malignant lymphoma. Recently, the tumor necrosis factor receptor superfamily cluster of differentiation 30 (CD30) has been thought to be implicated in malignant cells in organs affected by Hodgikin lymphoma or in a prognostic marker of diffuse large B cell lymphoma. In this study, we investigated CD30 expression in lacrimal gland and conjunctiva in patients with SS. METHODS: We examined lacrimal gland and conjunctival tissues for the diagnosis from 3 female SS patients with a median age of 51 and 3 female chronic graft-versus-host disease (cGVHD) patients with a median age of 41. Histological analysis of these tissues of the remaining samples was conducted by methods including immunohistochemistry and electron microscopy (#20090277). We analyzed the expression and localization of cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), cluster of differentiation 20 (CD20), CD30, and Interferon-γ in tissue sections prepared from lacrimal glands and conjunctiva in 3 each of SS and cGVHD patients. RESULTS: There were more B cells and plasma cells in lobules of SS-affected lacrimal glands than in those of their cGVHD-affected counterparts. Interferon-γ was expressed on endothelia of capillaries in SS-affected lacrimal gland and conjunctival tissues whereas it was expressed on fibroblasts in their GVHD-affected equivalents. Furthermore, lacrimal glands and conjunctiva disordered by SS had a greater number of CD30 cells than those disordered by cGVHD. CONCLUSION: Our results suggest that CD30 cells are increased in lacrimal glands and conjunctiva affected by SS and that a subset of SS patients are thereby at risk of development malignant lymphoma.
30742448 Cytokine Profiles in Autoantibody Defined Subgroups of Systemic Lupus Erythematosus. 2019 Mar 1 The aim of this study was to evaluate how the cytokine profiles differed between autoantibody based subgroups of systemic lupus erythematosus (SLE). SLE is a systemic autoimmune disease, characterized by periods of flares (active disease) and remission (inactive disease). The disease can affect many organ systems, e.g., skin, joints, kidneys, heart, and the central nervous system (CNS). SLE patients often have an overproduction of cytokines, e.g., interferons, chemokines, and interleukins. The high cytokine levels are part of the systemic inflammation, which can lead to tissue injury. In the present study, SLE patients were divided into five groups based on their autoantibody profiles. We thus defined these five groups: ANA negative, antiphospholipid (aPL) positive, anti-Sm/anti-RNP positive, Sjögren's syndrome (SS) antigen A and B positive, and patients positive for more than one type of autoantibodies (other SLE). Cytokines were measured using Mesoscale Discovery (MSD) multiplex analysis. On the basis of the cytokine data, ANA negative patients were the most deviating subgroup, with lower levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-12/IL-23p40, and interferon gamma-induced protein (IP)-10. Despite low cytokine levels in the ANA negative group, autoantibody profiles did not discriminate between different cytokine patterns.