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ID PMID Title PublicationDate abstract
30902137 Helminth therapy for autism under gut-brain axis- hypothesis. 2019 Apr Autism is a neurodevelopmental disease included within Autism Syndrome Disorder (ASD) spectrum. ASD has been linked to a series of genes that play a role in immune response function and patients with autism, commonly suffer from immune-related comorbidities. Despite the complex pathophysiology of autism, Gut-brain axis is gaining strength in the understanding of several neurological disorders. In addition, recent publications have shown the correlation between immune dysfunctions, gut microbiota and brain with the behavioral alterations and comorbid symptoms found in autism. Gut-brain axis acts as the "second brain", in a communication network established between neural, endocrine and the immunological systems. On the other hand, Hygiene Hypothesis suggests that the increase in the incidence of autoimmune diseases in the modern world can be attributed to the decrease of exposure to infectious agents, as parasitic nematodes. Helminths induce modulatory and protective effects against several inflammatory disorders, maintaining gastrointestinal homeostasis and modulating brain functions. Helminthic therapy has been previously performed in diseases such as ulcerative colitis, Crohn's disease, diabetes, multiple sclerosis, asthma, rheumatoid arthritis, and food allergies. Considering gut-brain axis, Hygiene Hypothesis, and the modulatory effects of helminths I hypothesized that a treatment with Trichuris suis soluble products represents a feasible holistic treatment for autism, and the key for the development of novel treatments. Preclinical studies are required to test this hypothesis.
30708140 Identification and characterization of differentially expressed genes in Type 2 Diabetes u 2019 Apr Diabetes mellitus is clinically characterized by hyperglycemia. Though many studies have been done to understand the mechanism of Type 2 Diabetes (T2D), however, the complete network of diabetes and its associated disorders through polygenic involvement is still under debate. The present study designed to re-analyze publicly available T2D related microarray raw datasets present in GEO database and T2D genes information present in GWAS catalog for screening out differentially expressed genes (DEGs) and identify key hub genes associated with T2D. T2D related microarray data downloaded from Gene Expression Omnibus (GEO) database and re-analysis performed with in house R packages scripts for background correction, normalization and identification of DEGs in T2D. Also retrieved T2D related DEGs information from GWAS catalog. Both DEGs lists were grouped after removal of overlapping genes. These screened DEGs were utilized further for identification and characterization of key hub genes in T2D and its associated diseases using STRING, WebGestalt and Panther databases. Computational analysis reveal that out of 99 identified key hub gene candidates from 348 DEGs, only four genes (CCL2, ELMO1, VEGFA and TCF7L2) along with FOS playing key role in causing T2D and its associated disorders, like nephropathy, neuropathy, rheumatoid arthritis and cancer via p53 or Wnt signaling pathways. MIR-29, and MAZ_Q6 are identified potential target microRNA and TF along with probable drugs alprostadil, collagenase and dinoprostone for the key hub gene candidates. The results suggest that identified key DEGs may play promising roles in prevention of diabetes.
30653140 Cutaneous vasculitis in a patient with ankylosing spondylitis: A case report. 2019 Jan RATIONALE: Cutaneous vasculitis is usually found in patients with rheumatoid arthritis (RA) as an extra-articular manifestation, but rare in patients with ankylosing spondylitis (AS). In this case, we describe an AS patient who developed large skin lesions, of which the histological findings were consistent with cutaneous vasculitis. PATIENT CONCERNS: A 22-year-old male who was diagnosed as HLA-27 positive AS for 5 years. However, in the last year, he suffered a recurrent skin lesion in both lower extremities especially the dorsum of feet, accompanying with intense pruritus. DIAGNOSIS: The originally diagnosis of the skin lessons was dermatitis, and then a skin biopsy pathology showed it was consistent with cutaneous vasculitis. INTERVENTION: At first he was treated with gentamycin and ethacridine for nearly 2 weeks, the symptoms were relieved. But then he suffered severe cutaneous lesions with swell at the ulcerous margin in his dorsum of right foot. The patient was treated with dexamethasone 10 mg intravenous drip daily for 2 weeks, and followed by methylprednisolone 160 mg oral administration daily after discharge. The skin lesions were gradually healed in several months OUTCOMES:: This patient was followed up at 1-month, 5-month, and 10-month after discharged, the skin lessons was gradually healed and never occurred. LESSONS: This case indicated that cutaneous vasculitis might be an extra-articular manifestation of AS in which IgA may plays a pathogenic part. All this may be associated with the damage of cytokines and autoantibodies to vascular endothelial wall caused by active inflammatory phase.
30522694 CD84 cell surface signaling molecule: An emerging biomarker and target for cancer and auto 2019 Jul CD84 (SLAMF5) is a member of the SLAM family of cell-surface immunoreceptors. Broadly expressed on most immune cell subsets, CD84 functions as a homophilic adhesion molecule, whose signaling can activate or inhibit leukocyte function depending on the cell type and its stage of activation or differentiation. CD84-mediated signaling regulates diverse immunological processes, including T cell cytokine secretion, natural killer cell cytotoxicity, monocyte activation, autophagy, cognate T:B interactions, and B cell tolerance at the germinal center checkpoint. Recently, alterations in CD84 have been related to autoimmune and lymphoproliferative disorders. Specific allelic variations in CD84 are associated with autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. In chronic lymphocytic leukemia, CD84 mediates intrinsic and stroma-induced survival of malignant cells. In this review, we describe our current understanding of the structure and function of CD84 and its potential role as a therapeutic target and biomarker in inflammatory autoimmune disorders and cancer.
30527218 JAK-STAT inhibitors for the treatment of immunomediated diseases. 2019 May 3 The Janus kinase (JAK) pathway is implicated in the pathogenesis of many inflammatory and autoimmune diseases including rheumatoid arthritis (RA), psoriasis, and inflammatory bowel disease. There are a lot of proinflammatory cytokines involved in such diseases using this pathway to transduce intracellular signals. In the last years, JAK inhibitors (jakinibs) have appeared with a great success, showing that these kinds of drugs have a great applicability in clinical practice. Tofacitinib and baricitinib, the first jakinibs approved for the treatment of RA, are being investigated also for treating other autoimmune systemic diseases. Likewise, other jakinibs are in several phases of development. This review analyses the safety and clinical efficacy of the jakinibs, starting with the classics and continuing with next-generation jakinibs.
33455241 Polyelectrolyte-Based Platforms for the Delivery of Peptides and Proteins. 2019 Oct 14 The use of peptides and proteins in the pharmaceutical field has increased dramatically over recent years. They have been especially relevant to advances in the treatment of cancer, rheumatoid arthritis, leukemia, and cardiovascular, ophthalmological, metabolic, and infectious diseases. Despite the great potential of peptides and proteins, their use in pharmaceuticals has failed to reach its full potential because of some outstanding challenges. They are unstable under storage conditions and in biological milieus, and their high molecular weight limits permeation through biological membranes. A variety of delivery systems have been investigated to overcome these limitations. Polyelectrolytes (PEs) are molecules that bear multiple negative or positive charges. These molecules play an important role in various platforms relating to the delivery of peptide/protein-based drugs and subunit vaccines. The most commonly utilized PEs include chitosan, alginate, chondroitin sulfate, and poly(γ-glutamic acid). PE-based delivery systems, such as polyelectrolyte complexes (PECs), PE-coated nanocarriers, and PE multilayers, were designed to protect peptides and proteins from degradation and facilitate their absorption. These delivery systems are especially effective when administered orally or intranasally. This review emphasizes the important role of PEs and PE-based delivery vehicles in peptide/protein-based drugs and vaccines.
31588572 Chromogranin A and its fragments in cardiovascular, immunometabolic, and cancer regulation 2019 Nov Chromogranin A (CgA)-the index member of the chromogranin/secretogranin secretory protein family-is ubiquitously distributed in endocrine, neuroendocrine, and immune cells. Elevated levels of CgA-related polypeptides, consisting of full-length molecules and fragments, are detected in the blood of patients suffering from neuroendocrine tumors, heart failure, renal failure, hypertension, rheumatoid arthritis, and inflammatory bowel disease. Full-length CgA and various CgA-derived peptides, including vasostatin-1, pancreastatin, catestatin, and serpinin, are expressed at different relative levels in normal and pathological conditions and exert diverse, and sometime opposite, biological functions. For example, CgA is overexpressed in genetic hypertension, whereas catestatin is diminished. In rodents, the administration of catestatin decreases hypertension, cardiac contractility, obesity, atherosclerosis, and inflammation, and it improves insulin sensitivity. By contrast, pancreastatin is elevated in diabetic patients, and the administration of this peptide to obese mice decreases insulin sensitivity and increases inflammation. CgA and the N-terminal fragment of vasostatin-1 can enhance the endothelial barrier function, exert antiangiogenic effects, and inhibit tumor growth in animal models, whereas CgA fragments lacking the CgA C-terminal region promote angiogenesis and tumor growth. Overall, the CgA system, consisting of full-length CgA and its fragments, is emerging as an important and complex player in cardiovascular, immunometabolic, and cancer regulation.
29998827 Survival and safety of infliximab bio-original and infliximab biosimilar (CT-P13) in usual 2019 Jan OBJECTIVES: Reports to-date indicate similarity between infliximab biosimilar (IB) and infliximab bio-original (IO) in clinical efficacy and safety. This study examines the survival of IB and IO using routinely collected data over a 2-year period. METHODS: Routinely collected clinical data inputted directly in an electronic database at a large rheumatology centre were analysed. Adult patients taking IO or IB for any rheumatological diagnosis were included. Kaplan-Meier survival analyses were used to examine IB and IO survival, with a sub-group analysis among those starting infliximab from 2008 onwards. RESULTS: Out of 395 patients analysed, 53% (n=209) were female; the majority had rheumatoid arthritis (31%) followed by spondyloarthritis (28%). Ninety-nine patients had IB as the first infliximab drug. Patients who started on IB vs. IO as their first infliximab product, had better survival over the first 2 years (log rank=0.001). Discontinuation due to inefficacy was much commoner in IO versus IB users (18 vs. 5%). In patients switching from IO to IB, drug survival was better versus those receiving IB as the first infliximab drug (log rank=0.073). CONCLUSIONS: IB was well-tolerated and comparable to IO, with no additional safety signals identified. The results suggest superior survival of IB over IO over the first 2 years.
31904333 Necrotizing Granulomatous Dermatitis and Panniculitis Masquerading as T Cell Lymphoma. 2019 A 51-year-old white woman with a past medical history significant for steroid-dependent ulcerative colitis, rheumatoid arthritis, and diabetes mellitus presented to the hospital with fever and painful, erythematous subcutaneous nodules on the medical aspects of both thighs. Histopathologic examination showed features suggestive of an abscess, but her condition failed to improve with intravenous broad-spectrum antibiotics. Molecular studies detected T cell receptor-β gene rearrangements. The lesions later exhibited signs of necrosis, requiring multiple debridements as well as therapy with hyperbaric oxygen. She was later referred to the MD Anderson Cancer Center for evaluation for possible subcutaneous panniculitis-like T cell lymphoma.
31849647 The Clinical Implications of Nocebo Effects for Biosimilar Therapy. 2019 Nocebo effects encompass negative responses to inert interventions in the research setting and negative outcomes with active treatments in the clinical research or practice settings, including new or worsening symptoms and adverse events, stemming from patients' negative expectations and not the pharmacologic action of the treatment itself. Numerous personality, psychosocial, neurobiological, and contextual/environmental factors contribute to the development of nocebo effects, which can impair quality of life and reduce adherence to treatment. Biologics are effective agents widely used in autoimmune disease, but their high cost may limit access for patients. Biosimilar products have gained regulatory approval based on quality, safety, and efficacy comparable to that of originator biologics in rigorous study programs. In this review, we identified gaps in patients' and healthcare professionals' awareness, understanding, and perceptions of biosimilars that may result in negative expectations and nocebo effects, and may diminish their acceptance and clinical benefits. We also examined features of nocebo effects with biosimilar treatment that inform research and clinical practices. Namely, when biosimilars are introduced to patients as possible treatment options, we recommend adoption of nocebo-reducing strategies to avoid negative expectations, including delivery of balanced information on risk-benefit profiles, framing information to focus on positive attributes, and promoting shared decision-making processes along with patient empowerment. Healthcare professionals confident in their knowledge of biosimilars and aware of bias-inducing factors may help reduce the risk of nocebo effects and improve patients' adherence in proposing biosimilars as treatment for autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease.
31725283 Metabolic Activation of Tofacitinib Mediated by Myeloperoxidase in Vitro. 2019 Dec 16 Tofacitinib (TFT) is used for the treatment of moderately and severely active rheumatoid arthritis. Unfortunately, TFT was reported to induce leukopenia, and the underlying mechanisms remain unclear. The present study demonstrated that TFT was oxidized to a chemically reactive nitrenium ion by myeloperoxidase (MPO) occurring in neutrophils. The electrophilic ion showed chemical reactivity toward N-acetyl-cysteine (NAC) to produce two TFT-NAC conjugates (M1 and M2) in incubation of TFT with leucocytes in the presence of NAC. The generation of the nitrenium ion was verified by HClO-mediated oxidation of TFT. In addition, the nitrenium ion was found to react with sulfhydryl groups of cysteine residues of cellular protein in leucocytes after exposure to TFT. The study facilitates the understanding of the mechanisms of TFT toxic action.
31701573 Role of epigenetics in alveolar bone resorption and regeneration around periodontal and pe 2019 Dec Periodontitis and peri-implantitis are multifactorial diseases characterized by alveolar bone destruction mediated by the host response to a microbial challenge. Alveolar bone resorption mediated by epigenetics could be one of the mechanisms responsible for this destruction of alveolar bone. The relationship between epigenetic modifications and bone metabolism has been thoroughly investigated in bone remodeling, cancer, and rheumatoid arthritis, but evidence is low regarding the relationship between epigenetic modifications and alveolar bone loss related to periodontal and peri-implant diseases. Therefore, we conducted a review of the pertinent literature based on a priori-formulated focused questions and a screening strategy, in an attempt to comprehend the role of different epigenetic mechanisms in alveolar bone loss and to determine the current state with respect to their possible therapeutic applications in regenerative medicine. The review showed that the roles of DNA methylation, histone modifications, and non-coding RNAs in bone loss have been investigated. The results indicate that epigenetic mechanisms can participate in periodontal and peri-implant alveolar bone breakdown, suggesting their potential as therapeutic targets in alveolar bone regeneration. However, there is still only preliminary information regarding the possible therapeutic utility of these epigenetic mechanisms, suggesting a need for basic and translational research to assess the potential of such mechanisms in promoting alveolar bone regeneration.
31615077 Development of Aptamer-Based TID Assays Using Thermophoresis and Microarrays. 2019 Oct 14 Aptamers are single-stranded oligonucleotides which can be used as alternative recognition elements for protein detection, because aptamers bind their targets with a high affinity similar to antibodies. Due to the targetinduced conformational changes of aptamers, these oligonucleotides can be applied in various biosensing platforms. In this work, aptamers directed against the vascular endothelial growth factor (VEGF) were used as a model system. VEGF plays a key role in physiological angiogenesis and vasculogenesis. Furthermore, VEGF is involved in the development and growth of cancer and other diseases like agerelated macular degeneration, rheumatoid arthritis, diabetes mellitus, and neurodegenerative disorders. Detecting the protein biomarker VEGF is therefore of great importance for medical research and diagnostics. In this research, VEGFbinding aptamers were investigated for the systematic development of a targetinduced dissociation (TID) assay utilizing thermophoresis and microarrays. The established aptamer-microarray allowed for the detection of 0.1 nM of VEGF. Furthermore, the systematic development of the TID method using the VEGF model protein could help to develop further TID assays for the detection of various protein biomarkers.
31602897 [Research progress on chemical constituents and quality control of Tripterygium wilfordii 2019 Aug Tripterygium wilfordii preparations,with various biological activities such as immunosuppressive,anti-inflammatory and anti-cancer effects,are widely used in the treatment of autoimmune diseases such as rheumatoid arthritis,lupus erythematosus,and nephrotic syndrome. They have definite therapeutic effect,but often cause serious adverse reactions and result in damages to liver,kidney,blood,reproduction,and other systems due to their complex compositions,great toxicity,and narrow margin between the toxic and therapeutic dosages. At present,T. wilfordii preparations produced by different manufacturers exhibit large variations in clinical efficacy and side effects in account of their different chemical compositions and quality fluctuation due to differences in raw materials and production process. However,the existing quality standards are controversial in terms of index components and content limit,which cannot be effectively used for the overall quality control of the preparations. In this paper,the research progress on chemical constituents,quality standard and quality control methods of four T. wilfordii preparations including Tripterygium Tablets,Tripterygium Zongtie Tablets,Tripterygium Shuangceng Tablets and Tripterygium Glycosides Tablets was reviewed,in order to provide ideas and reference for the quality improvement of this type of preparations.
31578802 Insights into IL-29: Emerging role in inflammatory autoimmune diseases. 2019 Dec Interleukin-29 (IL-29) is a newly discovered member of type III interferon. It mediates signal transduction via binding to its receptor complex and activates downstream signalling pathways, and therefore induces the generation of inflammatory components. Recent studies reported that expression of IL-29 is dysregulated in inflammatory autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, Sjögren's syndrome, psoriasis and systemic sclerosis. Furthermore, functional analysis revealed that IL-29 may involve in the pathogenesis of the inflammatory autoimmune disorders. In this review, we will systematically review the current knowledge about IL-29. The information collected revealed the regulatory role of IL-29 and may give important implications for its potential in clinical treatment.
31548746 The use of surface electromyography in rehabilitating rheumatic patients after knee arthro 2019 OBJECTIVES: The aim of the conducted research was to assess muscle performance in rheumatic patients qualified for knee arthroplasty before and after surgical treatment. MATERIAL AND METHODS: Patients with the diagnosis of rheumatoid arthritis or a degenerative joint disease qualified for surgical treatment were examined. Three groups were analysed: 1) a control group, 2) a group of patients qualified for knee arthroplasty (G1), 3) a group of patients with one knee joint endoprosthesis qualified for the second surgery (G2). The study was carried out through a portable surface electromyography system from Noraxon U.S.A. INC., Clinical DTS and using surface electrodes. The surface electromyography (sEMG) examination was conducted twice: before and on the 10th day after the surgery. The study concerned the quadriceps femoris muscle, i.e. its straight and medial head in both lower limbs during isometric tension and active movement. RESULTS: The comparison of the examined muscles' activity in the control group revealed greatly increased activity during isometric tension than during active movement in both muscles. In the G1 group, the comparison of the average values of isometric tension of the examined muscles before the surgery showed slight differences between the healthy limb and the one qualified for the surgical treatment. After the surgery, significant asymmetry between the average values achieved by the healthy and the operated limb could be identified in both muscles. In the G2 group, muscle activity within the currently operated limb revealed only slight differences between the limbs before the surgery. After the surgery, there was an increase in muscle activity within the previously operated limb. CONCLUSIONS: Considerably higher average values of muscle activity during the isometric tension, when compared to the active movement in a sitting position, indicate the necessity of more widespread use of isometric tension in rehabilitating patients after knee arthroplasty.
31493201 Pathogenesis, Diagnosis and Management of Polymyalgia Rheumatica. 2019 Nov Polymyalgia rheumatica is an inflammatory rheumatic disease of the elderly characterised by pain and stiffness in the neck and pelvic girdle, and is the second most common inflammatory rheumatic condition in this age group, after rheumatoid arthritis. Polymyalgia rheumatica can occur independently or in association with giant cell arteritis, which is the most common form of primary vasculitis. The diagnosis of polymyalgia rheumatica is usually based on clinical presentation and increase of inflammatory markers. There are no pathognomonic findings that can confirm the diagnosis. However, different imaging techniques, especially ultrasonography, can assist in the identification of polymyalgia rheumatica. Glucocorticoids are the cornerstone of the treatment of polymyalgia rheumatica, but they might be associated with different adverse events. A subgroup of patients presents with a refractory disease course and, in these cases, adding methotrexate as a steroid-sparing agent could be useful. In this review, we summarise the latest findings regarding the pathogenesis, diagnosis and management of polymyalgia rheumatica and try to highlight the possible pitfalls, especially in elderly patients.
31323799 Optimization of Aceclofenac Proniosomes by Using Different Carriers, Part 1: Development a 2019 Jul 18 In the contemporary medical model world, the proniosomal system has been serving as a new drug delivery system that is considered to significantly enhance the bioavailability of drugs with low water solubility. The application of this system can improve the bioavailability of aceclofenac that is used for the relief of pain and inflammation in osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. The present study is intended to develop an optimized proniosomal aceclofenac formula by the use of different carriers. Aceclofenac proniosomes have been prepared by slurry method, and different carriers such as maltodextrin, mannitol, and glucose were tried. Prepared proniosomes characterized by differential scanning calorimetry (DSC) analysis and Fourier transform infrared (FTIR) analysis revealed the compatibility of the drug chosen with the ingredient added, powder X-ray diffractometry (XRD) confirmed the amorphous phase of the prepared proniosomes, and finally, the surfactant layer was observed by scanning electron microscopy (SEM). Aceclofenac physical state transformations were confirmed with all formulas but maltodextrin proniosomes exhibited solubility more than other formulations. HPLC method has been used to analyze the niosomes derived from proniosomes in terms of their entrapment capability and drug content. The obtained results revealed that aceclofenac proniosomes can be successfully prepared by using different carriers.
31057544 Understanding Fc Receptor Involvement in Inflammatory Diseases: From Mechanisms to New The 2019 Fc receptors (FcRs) belong to the ITAM-associated receptor family. FcRs control the humoral and innate immunity which are essential for appropriate responses to infections and prevention of chronic inflammation or auto-immune diseases. Following their crosslinking by immune complexes, FcRs play various roles such as modulation of the immune response by released cytokines or of phagocytosis. Here, we review FcR involvement in pathologies leading notably to altered intracellular signaling with functionally relevant consequences to the host, and targeting of Fc receptors as therapeutic approaches. Special emphasis will be given to some FcRs, such as the FcαRI, the FcγRIIA and the FcγRIIIA, which behave like the ancient god Janus depending on the ITAM motif to inhibit or activate immune responses depending on their targeting by monomeric/dimeric immunoglobulins or by immune complexes. This ITAM duality has been recently defined as inhibitory or activating ITAM (ITAMi or ITAMa) which are controlled by Src family kinases. Involvement of various ITAM-bearing FcRs observed during infectious or autoimmune diseases is associated with allelic variants, changes in ligand binding ability responsible for host defense perturbation. During auto-immune diseases such as rheumatoid arthritis, lupus or immune thrombocytopenia, the autoantibodies and immune complexes lead to inflammation through FcR aggregation. We will discuss the role of FcRs in autoimmune diseases, and focus on novel approaches to target FcRs for resolution of antibody-mediated autoimmunity. We will finally also discuss the down-regulation of FcR functionality as a therapeutic approach for autoimmune diseases.
30713550 Conserved Disease Modules Extracted From Multilayer Heterogeneous Disease and Gene Network 2018 Disease relationship studies for understanding the pathogenesis of complex diseases, diagnosis, prognosis, and drug development are important. Traditional approaches consider one type of disease data or aggregating multiple types of disease data into a single network, which results in important temporal- or context-related information loss and may distort the actual organization. Therefore, it is necessary to apply multilayer network model to consider multiple types of relationships between diseases and the important interplays between different relationships. Further, modules extracted from multilayer networks are smaller and have more overlap that better capture the actual organization. Here, we constructed a weighted four-layer disease-disease similarity network to characterize the associations at different levels between diseases. Then, a tensor-based computational framework was used to extract Conserved Disease Modules (CDMs) from the four-layer disease network. After filtering, nine significant CDMs were reserved. The statistical significance test proved the significance of the nine CDMs. Comparing with modules got from four single layer networks, CMDs are smaller, better represent the actual relationships, and contain potential disease-disease relationships. KEGG pathways enrichment analysis and literature mining further contributed to confirm that these CDMs are highly reliable. Furthermore, the CDMs can be applied to predict potential drugs for diseases. The molecular docking techniques were used to provide the direct evidence for drugs to treat related disease. Taking Rheumatoid Arthritis (RA) as a case, we found its three potential drugs Carvedilol, Metoprolol, and Ramipril. And many studies have pointed out that Carvedilol and Ramipril have an effect on RA. Overall, the CMDs extracted from multilayer networks provide us with an impressive understanding disease mechanisms from the perspective of multi-layer network and also provide an effective way to predict potential drugs for diseases based on its neighbors in a same CDM.