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ID PMID Title PublicationDate abstract
28188938 Multipotent Stem Cell and Current Application. 2017 Jan Stem cells are self-renewing and undifferentiated cell types that can be differentiate into functional cells. Stem cells can be classified into two main types based on their source of origin: Embryonic and Adult stem cells. Stem cells also classified based on the range of differentiation potentials into Totipotent, Pluripotent, Multipotent, and Unipotent. Multipotent stem cells have the ability to differentiate into all cell types within one particular lineage. There are plentiful advantages and usages for multipotent stem cells. Multipotent Stem cells act as a significant key in procedure of development, tissue repair, and protection. Multipotent Stem cells have been applying in treatment of different disorders such as spinal cord injury, bone fracture, autoimmune diseases, rheumatoid arthritis, hematopoietic defects, and fertility preservation.
28679990 [Myelodysplastic syndrome with neutrophilic dermatosis successfully treated with azacitidi 2017 A 66-year-old male underwent prednisolone (PSL) therapy of 13 mg/day for rheumatoid arthritis (RA). Antiphospholipid antibody syndrome, neutrophilic dermatosis (ND), and myelodysplastic syndrome (MDS) developed. Treatment of MDS required red cell concentrate transfusion, and second courses of azacitidine therapy (75 mg/m(2) daily, intravenous injection for 7 consecutive days) led to hematologic remission. Furthermore, ND improved early after the start of azacitidine therapy, making it possible to decrease the dose of PSL. After 12th courses of azacitidine therapy, treatment was discontinued and the long-term remission of MDS and ND has been maintained. During the course, the level of matrix metalloproteinase-3, as a marker of RA, also decreased. There are few case reports of MDS in which azacitidine was effective for autoimmune diseases, including ND. We report the present case.
29021708 Effects of ginseng on stress-related depression, anxiety, and the hypothalamic-pituitary-a 2017 Oct Ginseng effectively regulates the immune response and the hormonal changes due to stress, thus maintaining homeostasis. In addition to suppressing the occurrence of psychological diseases such as anxiety and depression, ginseng also prevents stress-associated physiological diseases. Recent findings have revealed that ginseng is involved in adjusting the hypothalamic-pituitary-adrenal axis and controlling hormones, thus producing beneficial effects on the heart and brain, and in cases of bone diseases, as well as alleviating erectile dysfunction. Recent studies have highlighted the potential use of ginseng in the prevention and treatment of chronic inflammatory diseases such as diabetes, rheumatoid arthritis, and allergic asthma. However, the mechanism underlying the effects of ginseng on these stress-related diseases has not been completely established. In this review, we focus on the disease pathways caused by stress in order to determine how ginseng acts to improve health. Central to our discussion is how this effective and stable therapeutic agent alleviates the anxiety and depression caused by stress and ameliorates inflammatory diseases.
28986809 Review on antioxidants and evaluation procedures. 2017 Oct 6 Antioxidants are the substances that are capable of counteracting the damaging effects of the physiological process of oxidation occur in animal tissues. These may be nutrients (vitamins and minerals) as well as enzymes (proteins) in our body that assist in chemical reactions. They are believed to play a role in preventing the development of chronic diseases like cancer, diabetes, heart disease, stroke, Alzheimer's disease, rheumatoid arthritis, and cataracts etc. The present review article emphasizes on the various aspects of oxidants and antioxidants viz. definition, types, causes, mechanism, functions, adverse effects along with various in vivo and in vitro models of evaluation of antioxidant activity of new molecule, compounds or any plant or plant part. This review is one of its kinds which will be of great importance for researchers working in this area in search of antioxidant moieties and their biological evaluation.
28522454 Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjögren's syndr 2017 Aug OBJECTIVES: Multiomics study was conducted to elucidate the crucial molecular mechanisms of primary Sjögren's syndrome (SS) pathology. METHODS: We generated multiple data set from well-defined patients with SS, which includes whole-blood transcriptomes, serum proteomes and peripheral immunophenotyping. Based on our newly generated data, we performed an extensive bioinformatic investigation. RESULTS: Our integrative analysis identified SS gene signatures (SGS) dysregulated in widespread omics layers, including epigenomes, mRNAs and proteins. SGS predominantly involved the interferon signature and ADAMs substrates. Besides, SGS was significantly overlapped with SS-causing genes indicated by a genome-wide association study and expression trait loci analyses. Combining the molecular signatures with immunophenotypic profiles revealed that cytotoxic CD8 -T cells- were associated with SGS. Further, we observed the activation of SGS in cytotoxic CD8 T cells isolated from patients with SS. CONCLUSIONS: Our multiomics investigation identified gene signatures deeply associated with SS pathology and showed the involvement of cytotoxic CD8 T cells. These integrative relations across multiple layers will facilitate our understanding of SS at the system level.
29112130 Role of Immunological Memory Cells as a Therapeutic Target in Multiple Sclerosis. 2017 Nov 7 Pharmacological targeting of memory cells is an attractive treatment strategy in various autoimmune diseases, such as psoriasis and rheumatoid arthritis. Multiple sclerosis is the most common inflammatory disorder of the central nervous system, characterized by focal immune cell infiltration, activation of microglia and astrocytes, along with progressive damage to myelin sheaths, axons, and neurons. The current review begins with the identification of memory cell types in the previous literature and a recent description of the modulation of these cell types in T, B, and resident memory cells in the presence of different clinically approved multiple sclerosis drugs. Overall, this review paper tries to determine the potential of memory cells to act as a target for the current or newly-developed drugs.
28930898 It's All in the Wrist: Diagnosis and Management of Carpal Tunnel Syndrome. 2017 Sep/Oct Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy accounting for 90% of similar disorders, occurring in 3.8% of the population, common in adults aged 40-60 years, and is associated with an average 32 lost days of work and lost productivity. In addition to occupational exposure, there are several common chronic disorders that can preclude CTS, obesity, diabetes mellitus, rheumatoid arthritis, pregnancy, metabolic syndrome, and thyroid disorder, to name a few. Therefore, it is important for the primary care provider to have knowledge in this syndrome. The purpose of the article is to inform the provider about the etiology, presentation, diagnosis, and treatment of CTS, as well as the implications for job-associated CTS.
28168136 Palisaded Granulomatous Dermatitis Associated with Ulcerative Colitis: A Comprehensive Lit 2017 Jan 6 Palisaded granulomatous dermatitis is an uncommon pathologic condition potentially associated with several disorders. These include drugs, inflammatory bowel disease, multiple myelomas, rheumatoid arthritis, and systemic lupus erythematosus. An illustrative case of a man with palisaded granulomatous dermatitis who subsequently developed ulcerative colitis is described, and the characteristics of other individuals with ulcerative colitis-associated palisaded granulomatous dermatitis are reviewed. PubMed was used to search the following terms: palisaded, interstitial, granulomatous, dermatitis, ulcerative colitis, and neutrophilic. Papers were obtained and references were reviewed. Ulcerative colitis-associated palisaded granulomatous dermatitis is uncommon. Palisaded granulomatous dermatitis-associated ulcerative colitis has been reported in four individuals. The palisaded granulomatous dermatitis appeared from six years prior to diagnosis to 19 years following diagnosis of the patient's gastrointestinal disease. In addition to individual and grouped papular lesions on the elbows, the morphology of palisaded granulomatous dermatitis can also present as indurated linear plaques overlying the metacarpophalangeal (MCP) joints and proximal fingers.
28592200 Anti-carbamylated protein antibodies in systemic lupus erythematosus patients with articul 2018 Jan Objective Several studies have evaluated the prevalence of rheumatoid factor (RF) and anti-citrullinated proteins antibodies (ACPA) in systemic lupus erythematosus (SLE) patients but no data are available on the anti-carbamylated proteins (anti-CarP), a new biomarker for rheumatoid arthritis (RA). We evaluated the anti-CarP prevalence in SLE patients with joint involvement and the associations with different phenotypes. Methods Seventy-eight SLE patients with joint involvement were enrolled (F/M 73/5; mean ± SD age 47.6 ± 11.2 years; mean ± SD disease duration 214.3 ± 115.6 months). As control groups, we evaluated SLE patients without joint manifestations ( N = 15), RA ( N = 78) and healthy individuals (HS, N = 98). Anti-CarP were assessed by home-made ELISA in all patients and controls, RF and ACPA in SLE patients with joint involvement (commercial ELISA kit). Results The prevalence of anti-CarP in SLE patients with joint involvement was similar to RA ( p = NS) and significantly higher compared with SLE without joint involvement and HS ( p < 0.0001, p < 0.0001, respectively). Four patients were positive for all three antibodies: seventy-five percent of these showed Jaccoud arthropathy. Fourty-five percent of ACPA-ve/RF-ve patients were anti-CarP + ve. Conclusions The evaluation of anti-CarP in SLE joint involvement demonstrated a prevalence of almost 50%, similar to RA and significantly higher than SLE without joint involvement and HS.
29357802 Conjugates of Cell Adhesion Peptides for Therapeutics and Diagnostics Against Cancer and A 2017 Overexpressed cell-surface receptors are hallmarks of many disease states and are often used as markers for targeting diseased cells over healthy counterparts. Cell adhesion peptides, which are often derived from interacting regions of these receptor-ligand proteins, mimic surfaces of intact proteins and, thus, have been studied as targeting agents for various payloads to certain cell targets for cancers and autoimmune diseases. Because many cytotoxic agents in the free form are often harmful to healthy cells, the use of cell adhesion peptides in targeting their delivery to diseased cells has been studied to potentially reduce required effective doses and associated harmful side-effects. In this review, multiple cell adhesion peptides from extracellular matrix and ICAM proteins were used to selectively direct drug payloads, signal-inhibitor peptides, and diagnostic molecules, to diseased cells over normal counterparts. RGD constructs have been used to improve the selectivity and efficacy of diagnostic and drug-peptide conjugates against cancer cells. From this precedent, novel conjugates of antigenic and cell adhesion peptides, called Bifunctional Peptide Inhibitors (BPIs), have been designed to selectively regulate immune cells and suppress harmful inflammatory responses in autoimmune diseases. Similar peptide conjugations with imaging agents have delivered promising diagnostic methods in animal models of rheumatoid arthritis. BPIs have also been shown to generate immune tolerance and suppress autoimmune diseases in animal models of type-1 diabetes, rheumatoid arthritis, and multiple sclerosis. Collectively, these studies show the potential of cell adhesion peptides in improving the delivery of drugs and diagnostic agents to diseased cells in clinical settings.
28012936 Results of daily oral dosing with up to 60,000 international units (iu) of vitamin D3 for 2017 Oct In the 1930's and 1940's, vitamin D was reported to be an effective treatment for a number of diseases, including asthma, psoriasis, rheumatoid arthritis, rickets and tuberculosis. High doses were used, 60,000 to 300,000 IU a day for asthma, and 200,000 to 600,000 IU a day for rheumatoid arthritis. Toxicity from hypercalcemia occurred after prolonged oral dosing with these supraphysiologic doses. Assays for measuring vitamin D in the blood were not available, and blood levels of vitamin D associated with hypercalcemia were unknown. A 2011 report on vitamin D toxicity showed that hypercalcemia resolved when 25-hydroxyvitamin D (25OHD) blood levels dropped below 400ng/ml in 2 patients with blood levels ranging from 645ng/ml to 1220ng/ml after accidental ingestion of massive doses of vitamin D. We now know that vitamin D is made in the skin in amounts ranging up to 25,000 IU a day with exposure to UVB radiation. There is little data on the safety and blood levels of 25OHD and calcium after prolonged daily intake of amounts of vitamin D in this range. In this report, one subject took increasing daily doses of vitamin D3 for 6 years starting in April 2009: 6500 IU for 6 months; increasing to 10,000 IU for 13 months; 20,000 IU for 24 months; 40,000 IU for 12 months; 50,000 IU for 10 months, and 60,000 IU since October 2014. 25OHD blood levels were 28, 81, 204, 216, 225, 166, and 218ng/ml. Subject 2 began 10,000 IU in Nov 2011, increased to 20,000 IU in Feb 2014, 25,000 IU in June 2014, and 30,000 IU in Oct 2014, and then decreased to 20,000 IU in June 2015. 25OHD blood levels were 96.6, 161.1 and 106.9ng/ml. He reported marked clinical improvement in his asthma. Subject 3 started on daily 10,000 IU in Sept 2013, increasing to 20,000 IU on Nov 2013. 25OHD blood levels were 31.4, 102, 164, 148, and 143ng/ml. No one developed hypercalcemia or any adverse events. The major finding of this case series is prolonged daily dosing of vitamin D3 with doses of 10,000 to 60,000 IU was safely tolerated.
30185362 Epithelioid myxofibrosarcoma developing at the injection site of Adalimumab therapy for ps 2018 Jul The interplay between inflammation and cancer is the subject of intense interest. The recent approval of a number of checkpoint inhibitors has opened novel therapeutic pathways for several cancers. Conversely, biologic suppressors of inflammation, such as Tumor Necrosis Factor (TNF) inhibitors, have been utilized over the past two decades for the management of chronic inflammatory autoimmune diseases. While the overall rates of malignancy in patients using anti TNF therapies are not elevated, increased risk has been established for cutaneous malignancy, particularly carcinoma. In subsets of patients, such as those with rheumatoid arthritis, a modestly increased incidence of melanoma is also documented. Herewith, we present the first reported instance of a sarcoma of the dermis and superficial subcutaneous tissue at the injection site of Adalimumab in a woman being treated for psoriatic synovitis. We review the literature and suggest that a more nuanced documentation of adverse events is needed to clarify the iatrogenic risk of rare cancers, such as soft tissue sarcomas, in patients taking these biological therapies.
29379249 Is there a clinical usefulness for radiolabeled somatostatin analogues beyond the consolid 2017 Oct The somatostatin (SS) receptor scintigraphy (SRS), using octreotide radiolabelled with (111)In (Ocreoscan©, OCT), is a consolidated diagnostic procedure in patients with neuroendocrine tumors (NET) because of an increased expression of somatostatin receptors (SS-R) on neoplastic cells. Uptake of SS analogues (SSA) can also be due to SS-R expression on nonmalignant cells when activated as lymphocytes, macrophages, fibroblasts, vascular cells. Because of this uptake, clinical indications can be found either in neoplasms not overexpressing SS-R, as nonsmall cell lung cancer, and in active benign diseases. Nevertheless, clinical application of SRS has not found clinical relevance yet. In this paper, we discuss the nononcologic fields of clinical interest in which SRS could play a clinical role such as diagnosis, prognosis, and therapy of benign and chronic diseases such as sarcoidosis, histiocytosis, rheumatoid arthritis, idiopathic pulmonary fibrosis, and Graves' ophthalmopathy.
28184292 Rituximab therapy in pemphigus and other autoantibody-mediated diseases. 2017 Rituximab, a monoclonal antibody targeting the B cell marker CD20, was initially approved in 1997 by the United States Food and Drug Administration (FDA) for the treatment of non-Hodgkin lymphoma. Since that time, rituximab has been FDA-approved for rheumatoid arthritis and vasculitides, such as granulomatosis with polyangiitis and microscopic polyangiitis. Additionally, rituximab has been used off-label in the treatment of numerous other autoimmune diseases, with notable success in pemphigus, an autoantibody-mediated skin blistering disease. The efficacy of rituximab therapy in pemphigus has spurred interest in its potential to treat other autoantibody-mediated diseases. This review summarizes the efficacy of rituximab in pemphigus and examines its off-label use in other select autoantibody-mediated diseases.
27273740 Familial frontal fibrosing alopecia treated with dutasteride, minoxidil and artificial hai 2017 Aug A 46-year-old premenopausal woman presented with familial frontal fibrosis alopecia affecting the temples bilaterally. The diagnosis was confirmed histologically. Her past history included rheumatoid arthritis treated with hydroxychloroquine 400 mg daily and methotrexate 20 mg weekly. Serial intralesional injections of triamcinolone did not limit the progression of hair loss. Treatment with dutasteride 0.1 mg daily and minoxidil 1 mg daily stabilised hair loss and artificial fibre hair transplantation initially led to a satisfactory cosmetic outcome. Unfortunately, the patient developed implant folliculitis uncontrolled by antibiotics, necessitating the removal of the fibres 12 months post-transplantation.
25619281 Successful delivery in a patient with clinically amyopathic dermatomyositis during pregnan 2017 Mar A 37-year-old woman with rheumatoid arthritis and interstitial lung disease (ILD) developed clinically amyopathic dermatomyositis (CADM) after achieving pregnancy through in vitro fertilization. She was given oral prednisolone, which improved her respiratory status, and delivered a healthy baby at 35 weeks' gestation. There are few reports of successful outcomes for CADM during pregnancy; to the best of our knowledge, this is the first report of successful delivery in a patient with both CADM and ILD.
28503820 The P2X7 receptor-NLRP3 inflammasome complex predicts the development of non-Hodgkin's lym 2017 Aug BACKGROUND: P2X7 receptor (P2X7R), trigger of acute inflammatory responses via the NLRP3 inflammasome, is hyperfunctioning in patients with Sjögren's syndrome (SS), where it stimulates IL-18 production. Some patients with SS develop a mucosa-associated lymphoid tissue non-Hodgkin's lymphoma (MALT-NHL). OBJECTIVES: To prospectively evaluate the involvement and the putative prognostic role of this inflammatory pathway in the development of MALT-NHL. METHODS: A total of 147 women with SS have been prospectively followed for a mean of 52 months, relating the expression and function of the P2X7R-inflammasome axis in salivary glands and circulating lymphomonocytes to the prognosis and the degree of the disease. RESULTS: At baseline, gene expression of P2X7R and of the inflammasome components NLRP3, caspase-1 and IL-18 increased according to the presence of germinative centres and was higher in autoantibody-positive individuals and strongly higher in those developing a MALT-NHL over the follow-up. Glandular expression of IL-18 was threefold higher in MALT-NHL than in controls or in the other patients with SS. P2X7R did not colocalize with generic markers of inflammatory infiltrate, like CD20, being selectively expressed by epithelial cells. P2X4R, sharing functional characteristics with P2X7R, did not differ in SS and controls. The increased P2X7R gene and protein expression was tissue specific, no difference being observed in peripheral lymphomonocytes between SS with MALT-NHL and SS not developing MALT-NHL. CONCLUSION: We propose the P2X7R-inflammasome axis as a novel potential pathway involved in both SS exocrinopathy and lymphomagenesis, reinforcing the hypothesis of a key role of IL-18, via its increased P2X7R-mediated production, in the pathogenesis of lymphoproliferative malignancies, and opening novel opportunities for the early diagnosis of lymphoproliferative complications and the development of potential targeted therapies.
28918831 A Comparative Analysis of Serum IgG4 Levels in Patients With IgG4-Related Disease and Othe 2017 Sep OBJECTIVE: Elevated serum IgG4 levels are an important hallmark for diagnosing IgG4-related disease (IgG4-RD) but can also be found and reported in other diseases. The present study intended to compare the serum IgG4 levels in both IgG4-RD and non-IgG4-RD and determine the serum IgG4 levels in patients with IgG4-RD before and after glucocorticoid therapy. METHODS: The study included 323 patients from Anhui Medical University Affiliated Provincial Hospital (China) and was conducted from July 2014-January 2016. A total of 25 patients were eventually diagnosed as having IgG4-RD, according to the IgG4-RD diagnostic criteria. Our study also included 108 patients with connective tissue disease, 94 patients with pancreatic lesions, 66 patients with bile duct lesions, 13 patients with carcinoma of the duodenal papilla and 20 control participants. The assay for serum IgG4 detection was peformed using the nephelometric method. RESULTS: Elevated levels of serum IgG4 (>1.35g/L) were detected in all patients with IgG4-RD, and reduced levels of serum IgG4 (<1.35g/L) were found in all patients with non-IgG4-RD. The serum IgG4 level in patients with IgG4-RD after glucocorticoid therapy was significantly lower than that before glucocorticoid therapy (t = 2.426, P = 0.04). CONCLUSIONS: High levels of IgG4 were observed in IgG4-RD. However, a diagnosis of IgG4 disease can not only be dependent on the detection of elevated serum IgG4 levels but also may need clinical manifestations, serology, histopathology and other comprehensive information for verification.
28926640 Aire-deficient mice provide a model of corneal and lacrimal gland neuropathy in Sjögren's 2017 Sjögren's syndrome (SS) is a chronic, autoimmune exocrinopathy that leads to severe dryness of the mouth and eyes. Exocrine function is highly regulated by neuronal mechanisms but little is known about the link between chronic inflammation, innervation and altered exocrine function in the diseased eyes and exocrine glands of SS patients. To gain a better understanding of neuronal regulation in the immunopathogenesis of autoimmune exocrinopathy, we profiled a mouse model of spontaneous, autoimmune exocrinopathy that possess key characteristics of peripheral neuropathy experienced by SS patients. Mice deficient in the autoimmune regulator (Aire) gene developed spontaneous, CD4+ T cell-mediated exocrinopathy and aqueous-deficient dry eye that were associated with loss of nerves innervating the cornea and lacrimal gland. Changes in innervation and tear secretion were accompanied by increased proliferation of corneal epithelial basal cells, limbal expansion of KRT19-positive progenitor cells, increased vascularization of the peripheral cornea and reduced nerve function in the lacrimal gland. In addition, we found extensive loss of MIST1+ secretory acinar cells in the Aire -/- lacrimal gland suggesting that acinar cells are a primary target of the disease, Finally, topical application of ophthalmic steroid effectively restored corneal innervation in Aire -/- mice thereby functionally linking nerve loss with local inflammation in the aqueous-deficient dry eye. These data provide important insight regarding the relationship between chronic inflammation and neuropathic changes in autoimmune-mediated dry eye. Peripheral neuropathies characteristic of SS appear to be tightly linked with the underlying immunopathological mechanism and Aire -/- mice provide an excellent tool to explore the interplay between SS-associated immunopathology and peripheral neuropathy.
28621822 cDNA microarray analysis identifies NR4A2 as a novel molecule involved in the pathogenesis 2017 Oct To examine genes expressed specifically in labial salivary glands (LSGs) of patients with Sjögren's syndrome (SS) in comparison with those of patients with immunoglobulin (Ig)G4-related disease (IgG4-RD), and to identify the genes involved in the pathogenesis of SS. Gene expression in LSGs of SS patients, IgG4-RD patients and healthy controls (HC) was analysed by cDNA microarray. Quantitative polymerase chain reaction (qPCR) was used to validate the up-regulation of differentially expressed genes (DEGs) in SS. Protein production of the validated gene in LSGs was examined by immunofluorescence (IF) assay. The association of molecular functions of the gene with the pathological conditions in SS was examined using peripheral blood lymphocytes. Among 1320 DEGs up-regulated in SS, qPCR confirmed the up-regulation of NR4A2 in LSGs of SS compared with IgG4-RD. IF staining showed higher production of NR4A2 in nuclei of CD4(+) T cells and interleukin (IL)-17-producing cells in LSGs of SS, compared with IgG4-RD. Over-expression of NR4A2 mRNA was observed in peripheral CD4(+) T cells of SS patients, compared with HC. Nuclear NR4A2 expression in T helper type 17 (Th17)-polarized CD4(+) T cells determined by cellular IF was significantly higher in SS than in HC. Importazole, an inhibitor of importin-β, inhibited nuclear transport of NR4A2 and Th17 polarization along with IL-21 expression in naive CD4(+) T cells under Th17-polarizing conditions, but did not alter retinoic acid receptor-related orphan receptor C (RORC) expression. NR4A2 seems to promote Th17 polarization via increased expression and intranuclear localization in CD4(+) T cells of SS patients, which could play a critical role in the pathogenesis of SS.