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ID PMID Title PublicationDate abstract
29225201 3-Bromopyruvate as a potential pharmaceutical in the light of experimental data. 2017 Dec 8 3-Bromopyruvate (3-BrPA) is an halogenated analogue of pyruvic acid known for over four decades as an alkylating agent reacting with thiol groups of many proteins. It enters animal cells like a lactate: via monocarboxylic acid transporters. Increasing interest in this compound, in recent times, is mainly due to hopes associated with its anticancer action. It is based on the impairment of energy metabolism of tumor cells by inhibiting enzymes in the glycolysis pathway (hexokinase II, glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate kinase) and the oxidative phosphorylation (succinate dehydrogenase). Two cases of clinical application of this compound in the treatment of advanced cancers were reported. By using 3-BrPA, rheumatoid arthritis in SKG mice has been reduced. This compound has also antiparasitic activity: lowers cell viability of Trypanosoma brucei, decreases intracellular proliferation of Toxoplasma gondii and reduces the metabolic activity of Schistosoma mansoni. It also has antifungal properties; particularly it acts strongly on Cryptococcus neoformans, as well as Saccharomyces cerevisiae. An inhibitory effect on bacterial enzymes was also described on: isocitrate lyase from Escherichia coli, Mycobacterium tuberculosis, Pseudomonas indigofera and 2-methylisocitrate lyase, succinate dehydrogenase and acetohydroxylic acid synthase from Escherichia coli. Wherever undesirable (cancer, parasitic) cells differ from normal by more intense glycolysis and higher energy needs, there is a good chance of successful 3-BrPA use. However, this compound acts on all cells and it, therefore, seems that its future as a pharmaceutical is dependent upon the development of appropriate methods for its effective and safe application.
29181361 Insufficiency Fractures at Unusual Sites: A Case Series. 2017 Jul INTRODUCTION: Insufficiency fractures (IFs) are a subtype of stress fractures commonly associated with osteoporosis and Vitamin D deficiency. These nontraumatic fractures often occur in the pelvis and spine, but the involvement of other unusual sites is also not very uncommon. Plain radiographs and magnetic resonance imaging scan are the most commonly used imaging modalities for the diagnosis of IF. CASE REPORT: We are presenting a series of five cases of IFs at unusual sites, along with a detailed literature review on this individual. A 50-year-old male patient with chronic kidney disease presented with both femoral neck and right lesser trochanter IF which was managed with cannulated screws. A 53-year-old male patient on steroid presented with sternum IF. A 26-year-old male patient presented with Vitamin D deficiency and accessory navicular IF. A 60-year-old female on bisphosphonate therapy came with bilateral femoral shaft fracture. All these three patients were managed conservatively. Another 62-year-old male patient with rheumatoid arthritis presented with sacrum IF which was managed with cannulated screw fixation. CONCLUSION: IFs are a subtype of stress fractures commonly associated with osteoporosis and Vitamin D deficiency. A good clinical examination along with proper radiological investigation facilitates early diagnosis of IF in the osteoporotic bone. An early diagnosis helps in deciding the definitive course of treatment and to obtain a good result. An undisplaced fracture can be managed nonoperatively by treating the underlying medical cause, but fractures at the risk of displacement or a displaced fracture may need operative treatment.
28959211 Oxidative Stress in Oral Diseases: Understanding Its Relation with Other Systemic Diseases 2017 Oxidative stress occurs in diabetes, various cancers, liver diseases, stroke, rheumatoid arthritis, chronic inflammation, and other degenerative diseases related to the nervous system. The free radicals have deleterious effect on various organs of the body. This is due to lipid peroxidation and irreversible protein modification that leads to cellular apoptosis or programmed cell death. During recent years, there is a rise in the oral diseases related to oxidative stress. Oxidative stress in oral disease is related to other systemic diseases in the body such as periodontitis, cardiovascular, pancreatic, gastric, and liver diseases. In the present review, we discuss the various pathways that mediate oxidative cellular damage. Numerous pathways mediate oxidative cellular damage and these include caspase pathway, PERK/NRF2 pathway, NADPH oxidase 4 pathways and JNK/mitogen-activated protein (MAP) kinase pathway. We also discuss the role of inflammatory markers, lipid peroxidation, and role of oxygen species linked to oxidative stress. Knowledge of different pathways, role of inflammatory markers, and importance of low-density lipoprotein, fibrinogen, creatinine, nitric oxide, nitrates, and highly sensitive C-reactive proteins may be helpful in understanding the pathogenesis and plan better treatment for oral diseases which involve oxidative stress.
28871249 Neutralization of Human Interleukin 23 by Multivalent Nanobodies Explained by the Structur 2017 The heterodimeric cytokine interleukin (IL) 23 comprises the IL12-shared p40 subunit and an IL23-specific subunit, p19. Together with IL12 and IL27, IL23 sits at the apex of the regulatory mechanisms shaping adaptive immune responses. IL23, together with IL17, plays an important role in the development of chronic inflammation and autoimmune inflammatory diseases. In this context, we generated monovalent antihuman IL23 variable heavy chain domain of llama heavy chain antibody (V(HH)) domains (Nanobodies(®)) with low nanomolar affinity for human interleukin (hIL) 23. The crystal structure of a quaternary complex assembling hIL23 and several nanobodies against p19 and p40 subunits allowed identification of distinct epitopes and enabled rational design of a multivalent IL23-specific blocking nanobody. Taking advantage of the ease of nanobody formatting, multivalent IL23 nanobodies were assembled with properly designed linkers flanking an antihuman serum albumin nanobody, with improved hIL23 neutralization capacity in vitro and in vivo, as compared to the monovalent nanobodies. These constructs with long exposure time are excellent candidates for further developments targeting Crohn's disease, rheumatoid arthritis, and psoriasis.
28758179 Clinical Outcomes of Posterior C1 and C2 Screw-Rod Fixation for Atlantoaxial Instability. 2017 Jun 14 AIM: In this study, we aimed at sharing our experiences and contributing to the literature by making a retrospective analysis of the patients we operated with screw-rod system for atlantoaxial instability in our clinic. MATERIAL AND METHODS: Archive files of adult patients, who were operated for posterior C1-C2 stabilization with screw and rod in our clinic between January 2006 and January 2016, were analyzed. 28 patients, who had pre and post-operative images, follow-up forms and who were followed for at least one year, were analyzed. Preoperative clinical and radiological records, preoperative observations, postoperative complications, and clinical responses were evaluated. RESULTS: The average age of 28 patients (F:13 M:19) was 44.7 (21-73). Fixation was performed with C1-C2 screw-rod system on the basis of the following diagnoses; type 2 odontoid fracture (16), basilar invagination (5), C1-C2 instability (5), and atlantoaxial subluxation secondary to rheumatoid arthritis (2). Lateral mass screws were inserted at C1 segment. C2 screws inserted were bilateral pedicle in 12 cases, bilateral pars in 4, bilateral laminar in 8 and one side pars, one side laminar in 4 cases. There was no screw malposition. Neither implant failure nor recurrent instability was observed during follow-up. Significant clinical improvement was reported according to the assessments done with JOA and VAS scores. CONCLUSION: C1-C2 screw fixation is regarded as a more successful and safe method than other fixation methods in surgical treatment of atlantoaxial instability considering complications, success in reduction, fusion and fixation strength. C2 laminar screw technique is as successful as the other alternatives in fixation and fusion.
28679512 Guillain-Barré syndrome in association with antitumour necrosis factor therapy: a case of 2017 Jul 5 Guillain-Barré syndrome (GBS) is an immune-mediated disease characterised by evolving ascending limb weakness, sensory loss and areflexia. Two-thirds of GBS cases are associated with preceding infection. However, GBS has also been described in association with antitumour necrosis factor (TNF) therapies including infliximab and adalimumab for chronic inflammatory disorders such as rheumatoid arthritis, ankylosing spondylitis and inflammatory bowel disease. We present the case of a patient who developed GBS while undergoing treatment with adalimumab in combination with azathioprine for severe fistulising Crohn's disease, and review the literature on neurological adverse events that occur in association with anti-TNF therapy. We also propose an approach to the optimal management of patients who develop debilitating neurological sequelae in the setting of anti-TNF therapy.
32309593 Drug repositioning: computational approaches and research examples classified according to 2017 Jun 30 Increasing need for novel drugs and their application for treating diseases are the main reasons for the development of bioinformatics platforms for drug repositioning. The use of existing approved drugs for treating other diseases reduces cost and time needed for a drug to come to clinical use. Different strategies for drug repositioning have been reported. The use of several omics types is becoming increasingly important in drug repositioning. Although there are several public databases intended for drug repositioning, not many successful cases of novel use of drugs have been reported in the literature and transferred to clinical use. Additionally, the study approaches in published literature are very heterogeneous. A classification scheme - Drug Repositioning Evidence Level (DREL) - for drug repositioning projects, according to the level of scientific evidence has been proposed previously. In the present study, we have reviewed main databases and bioinformatics approaches enabling drug repositioning studies. We also reviewed six published studies and evaluated them according to the DREL classification. The evaluated cases used drug repositioning approach for therapy of rheumatoid arthritis, cancer, coronary artery disease, diabetes, and gulf war illness. The drug repositioning study field could benefit from clearer definition in published articles therefore including drug repositioning DREL classification scheme could be included in published original and review studies. Novel bioinformatics approaches to improve prediction of drug-target interactions, continuous updating of the databases, and development of novel validation techniques are needed to facilitate the development of the drug repositioning field. Although there are still many challenges in drug repositioning and personalized medicine, stratification of patients based on their molecular signatures and testing of signature-targeting drugs should improve drug efficacy in clinical trials.
28528615 Chronic Tender Ulcers on the Calf and Both Forearms. 2017 An elderly woman presented with a 3-month history of nonhealing, tender ulcers involving the right calf and both forearms. She denied any history of similar lesions or trauma. Two trials of oral antibiotics had led to no improvement. Her medical history was significant for rheumatoid arthritis treated with methotrexate, hydroxychloroquine, and prednisone. A review of clinical manifestations was otherwise negative for disease. Physical examination of the patient's right calf revealed two punched-out ulcers with central necrotic black eschars, underlying retiform purpuric pattern, and mild fibrinopurulent drainage (Figure 1). Similar lesions were present on her forearms (Figures 2 and 3). No other remarkable skin changes were noted. The differential diagnosis included polyarteritis nodosa, cutaneous necrosis secondary to antiphospholipid syndrome, cryoglobulinemic vasculitis, and an atypical presentation of pyoderma gangernosum.
28502334 AP-1 Expression and its Clinical Relevance in Immune Disorders and Cancer. 2017 May The inflammatory response is known to have a significant role in certain autoimmune diseases and malignancies. We review current knowledge regarding the functions of activator protein 1 (AP-1) as an important modulator in several immune disorders and carcinomas. AP-1 is overexpressed in rheumatoid arthritis and in long-term allogeneic hematopoietic stem cell transplantation survivors; however, decreased expression of AP-1 has been observed in psoriasis, systematic lupus erythematosus and in patients who do not survive after hematopoietic stem cell transplantation. AP-1 also is implicated in the control of various cancer cells. Higher levels of AP-1 components are present in breast and endometrial carcinomas, colorectal cancer and in acute myeloid leukemia, Hodgkin׳s lymphoma and anaplastic large cell lymphoma, with downregulation in ovarian and gastric carcinomas and in patients with chronic myelogenous leukemia. AP-1 may enable the development of helpful markers to identify early-stage disease or to predict severity.
28372277 Mechanobiology of mesenchymal stem cells: Which interest for cell-based treatment? 2017 Thanks to their immune properties, the mesenchymal stem cells (MSC) are a promising source for cell therapy. Current clinical trials show that MSC administrated to patients can treat different diseases (graft-versus-host disease (GVHD), liver cirrhosis, systemic lupus, erythematosus, rheumatoid arthritis, type I diabetes…). In this case, the most common mode of cell administration is the intravenous injection, and the hemodynamic environment of cells induced by blood circulation could interfere on their behavior during the migration and homing towards the injured site. After a brief review of the mechanobiology concept, this paper will help in understanding how the mechanical environment could interact with MSC behavior once they are injected to patient in cell-based treatment.
28353409 What do we know about the role of regulatory B cells (Breg) during the course of infection 2017 May Parasitic diseases, such as malaria and leishmaniasis, are relevant public health problems worldwide. For both diseases, the alarming number of clinical cases and deaths reported annually has justified the incentives directed to better understanding of host's factors associated with susceptibility to infection or protection. In this context, over recent years, some studies have given special attention to B lymphocytes with a regulator phenotype, known as Breg cells. Essentially important in the maintenance of immunological tolerance, especially in autoimmune disease models such as rheumatoid arthritis and experimentally induced autoimmune encephalomyelitis, the function of these lymphocytes has so far been poorly explored during the course of diseases caused by parasites. As the activation of Breg cells has been proposed as a possible therapeutic or vaccine strategy against several diseases, here we reviewed studies focused on understanding the relation of parasite and Breg cells in malaria and leishmaniasis, and the possible implications of these strategies in the course of both infections.
27771479 Surgical Management for Destructive Atlantoaxial Spondyloarthropathy in Long-Term Hemodial 2017 Jan BACKGROUND: Atlantoaxial spondyloarthropathy most often results from rheumatoid arthritis, cancer metastasis, or basilar invagination. Dialysis-related spondyloarthropathy is a rare cause of spinal deformity and cervical myelopathy at the atlantoaxial joint. We report 2 patients on long-term hemodialysis who presented with atlantoaxial spondyloarthropathy. CASE DESCRIPTION: Two patients with end-stage renal failure presented with a history of progressively worsening neck pain, motion limitation, and gait disturbance. In both patients, radiologic findings showed a bone-destroying soft tissue mass lateral to C1 and C2, compressing the spinal cord and causing atlantoaxial instability. We performed a C1 laminectomy and C12 transarticular screw fixation and biopsied the osteolytic mass. The neck pain, hand numbness, and gait disturbance improved. CONCLUSIONS: Although the surgical management of these patients involves many challenges, appropriate decompression and fusion surgery is an effective treatment option.
27719647 Cardiovascular Toxicity of Cyclooxygenase Inhibitors and Promising Natur a l Substitutes. 2017 Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of drugs which are used for a wide variety of diseases including pain and inflammatory conditions such as osteoarthritis, rheumatoid arthritis, musculoskeletal disorders, and other comorbid complications. However, this group of drugs have undesirable effects such as peptic ulcer, bleeding and renal failure. Some of these side effects are associated with or caused by generation of oxidative stress. Following the withdrawal of a cyclo-oxygenase-2 (COX-2) inhibitor drug, rofecoxib (VIOXX®) due to cardiovascular complications, scientists suggested that natural COX-2 inhibitors might provide valuable alternatives to COX inhibitors. Although, most of medicinal plants reduce pain and inflammation in a similar manner to synthetic medications, however, they often have fewer side effects and are better tolerated. The present review other than focusing on cardiovascular and some other complications of NSAIDs, is trying to introduce the natural alternative remedies for these medications.
29422815 The role of regulatory T cells and genes involved in their differentiation in pathogenesis 2017 Dec Regulatory T cells (Tregs) represent a cell type that promotes immune tolerance to autologous components and maintains immune system homeostasis. The abnormal function of Tregs is relevant to the pathogenesis of several skin diseases like psoriasis, atopic dermatitis, systemic lupus erythematosus, cutaneous T-cell lymphomas, and skin cancer and is also important in rheumatoid arthritis, diabetes and other autoimmune diseases. In this review, we will summarize the role of mutations and/or polymorphisms of genes involved in Tregs development, and functions in the pathogenesis of selected skin diseases.
29290695 Systematic review of the role of rituximab in treatment of antineutrophil cytoplasmic auto 2017 Rituximab (RTX) is established for the treatment of rheumatoid arthritis. This systematic review of the literature since 2006 summarizes evidence for the use of RTX in the treatment of additional rheumatological diseases: antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV), hepatitis C virus-related cryoglobulinemic vasculitis, Henoch-Schönlein purpura, ankylosing spondylitis, and Raynaud's phenomenon. Data from randomized controlled trials are available only for AAV, confirming efficacy for remission induction, including in disease resistant to conventional treatment, and maintenance of remission. Further studies are required to confirm optimal maintenance regimens in AAV, important questions needing to be addressed including protocol administration versus treatment in response to clinical relapse and the importance of maintaining B-cell depletion. Sufficient data are available in other diseases to suggest RTX to be useful and that randomized controlled trials should be conducted.
29183642 Tick-borne diseases and autoimmunity: A comprehensive review. 2018 Mar Tick-borne diseases (TBDs) are emerging and reemerging diseases transmitted by ticks, which portray wide heterogeneity and global distribution. TBDs may present acute clinical pictures that resemble those of autoimmune diseases (i.e., musculoskeletal symptoms, cutaneous involvement, neurologic impairment, renal failure, etc.), and in some cases infection is considered a triggering factor for autoimmunity (e.g., rheumatoid arthritis, autoimmune thyroid disease, vasculitides). The clinician should consider TBDs among the differential diagnoses when approaching autoimmune-like signs in areas of tick infestation. Epidemiological setting (e.g., endemic areas, seasons) and an accurate diagnostic approach (i.e., clinical history, physical examination and laboratory tests) are necessary to confirm TBDs. Further, control and prevention of TBDs is warranted. Research in the fields of ticks microbiome and vaccination (i.e., wildlife and humans) are ahead to control vector transmission and bacterial infection. This review offers a comprehensive update on TBDs and their relationship with autoimmunity.
29137206 Ancient Food Habits Dictate that Food Can Be Medicine but Medicine Cannot Be "Food"!! 2017 Nov 13 Background: Extensive surveys of several population settlements in different parts of India-covering plains, mountains, valleys, river banks and deeper areas of forests at different altitudes-between 1968 and 2016 demonstrated that the basic vital need of hunger is being fulfilled since antiquity by plants in the wild. Methods: Based on collections, consultations with local population personnel and literature searches, this paper presents many plants that are commonly used as food and focuses on their products, which are rich in alkaloids, polysaccharides, steroids, terpenoids, flavonoids, aminoacids, fatty acids and antibiotics etc. These complex organic compounds are suitable for the production of drugs for many ailments/diseases, including the prevention of cancers. Results: There are more than 100 families including several hundred plant taxa from various plant groups like angiosperms, bryophytes, pteridophytes, gymnosperms and even fleshy fungi, which have offered essential food items to ever-growing human populations since antiquity. Phytochemicals functioning as antioxidants are exceedingly beneficial to the human body but excess consumption of these compounds, adding higher levels of antioxidants, may even be responsible for chronic diseases including aging, cancer, cardiovascular diseases, rheumatoid arthritis, atherosclerosis, etc. These medicines can obviously be taken in small and prescribed quantities but can never be consumed as "food items."
31966412 Serum proteomics study reveals candidate biomarkers for systemic lupus erythematosus. 2017 Systemic lupus erythematosus (SLE) is an autoimmune disease which is characterized by the presence of autoantibodies. It will be helpful if specific serum biomarkers can be used for monitoring the disease activity as well as differentiating SLE from other diseases. For this purpose, we used a label free-based two dimensional liquid chromatography mass spectrometry platform to analyze serum samples from SLE patients in active or inactivestage. Significant differences were found for 42 serum proteins implicated in pathways including complement and coagulation cascades. Further gene set enrichment analysis revealed that gene sets including formation of fibrin clot, ECM glycoproteins and innate immune system were highly correlated with the SLE disease activity. To further assess the validity of these findings, thrombospondin-4 was selected for subsequent ELISA assays. We also explored the autoantibody of three candidate biomarkers in larger cohorts including SLE, Rheumatoid arthritis, Sjogrensyndrome patients and normal controls. Our findings provided valuable information on the proteomic changes in the serum of different SLE disease activity. Serum properdin, collectin-11 and thrombospondin-4 were valuable in monitoring the disease activity of SLE, and the autoantibodies to them may be valuable in differentiating SLE from other diseases for clinical diagnosis in the future.
28914372 The role of gut microbiota in the pathogenesis of rheumatic diseases. 2018 Jan Rheumatic diseases refer to many diseases with a loss of immune self-tolerance, leading to a chronic inflammation, degeneration, or metabolic derangement in multiple organs or tissues. The cause of rheumatic diseases remains to be elucidated, though both environmental and genetic factors are required for the development of rheumatic diseases. Over the past decades, emerging studies suggested that alteration of intestinal microbiota, known as gut dysbiosis, contributed to the occurrence or development of a range of rheumatic diseases, including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, systemic sclerosis, and Sjogren's syndrome, through profoundly affecting the balance between pro- and anti-inflammatory immune responses. In this article, we discussed the role of gut microbiota in the pathogenesis of rheumatic diseases based on a large number of experimental and clinical materials, thereby providing a new insight for microbiota-targeted therapies to prevent or cure rheumatic diseases.
28889730 Anti-inflammatory and immunomodulatory activities of Inula cappa roots (Compositae). 2017 Mar 18 Background The medicinal properties of Inula cappa, a perennial shrub, are ascribed to its roots. In this article, we study the anti-inflammatory and immunomodulatory activities of I. cappa root extracts based on its utilization in traditional medicine-treatment of rheumatoid arthritis, menoxenia, fever, jaundice and many others. Methods Anti-inflammatory and immunomodulatory activities of I. cappa extracts were studied. The anti-inflammatory activity was determined by carrageenan-induced rat paw edema and cotton pellet-induced granulation method while the immunomodulatory activity was estimated by phagocytic assay method, hemagglutinating antibody (HA) titer assay, delayed-type hypersensitivity assay method, plaque forming cell assay and determination of immunoprophylatic activity. Results The methanolic extract showed maximum reduction in the rat paw edema and showed significant inhibition of the cotton pellet-induced granulomas in rats. The methanolic extract also showed potential immunomodulatory activity in all the assays performed. Two sesquiterpenes, isoalantolactone and germacranolide were also isolated from the methanolic extract. Conclusions The present study supports the evidence that the roots of I. cappa can be used as a potent anti-inflammatory and immunomodulatory agent.