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ID PMID Title PublicationDate abstract
24346805 Emerging role of human basophil biology in health and disease. 2014 Jan Basophils have emerged in recent years as a small but potent subpopulation of leukocytes capable of bridging innate and adaptive immunity. They can be activated through IgE-dependent and IgE-independent mechanisms to release preformed mediators and to produce Th2 cytokines. In addition to their role in protective immunity to helminths, basophils are major participants in allergic reactions as diverse as anaphylaxis and immediate hypersensitivity reactions, late-phase hypersensitivity reactions, and delayed hypersensitivity reactions. Additionally, basophils have been implicated in the pathophysiology of autoimmune diseases such as lupus nephritis and rheumatoid arthritis, and the modulation of immune responses to bacterial infections, as well as being a feature of myelogenous leukemias. Distinct signals for activation, degranulation, transendothelial migration, and immune regulation are being defined, and demonstrate the important role of basophils in promoting a Th2 microenvironment. These mechanistic insights are driving innovative approaches for diagnostic testing and therapeutic targeting of basophils.
24302182 Thyroid autoimmunity in patients with Familial Mediterranean Fever: preliminary results. 2013 Nov AIM: We investigated whether there was a significant increase in thyroid autoimmunity in patients with Familial Mediterranean fever (FMF). PATIENTS AND METHODS: In total, 220 patients, consisting of 42 with FMF, 75 with rheumatoid arthritis (RA), and 103 healthy controls, were enrolled. Serum thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and thyroid autoantibodies (anti-thyroid peroxidase and anti-thyroglobulin) were measured in all participants. RESULTS: After adjustment for age, gender, and smoking status, statistically significant differences between serum levels of anti-thyroglobulin antibody, anti-thyroid peroxidase antibody, and fT3 were found between the groups (all p < 0.001). Serum TSH level did not differ between the groups (p > 0.05). The frequency of autoimmune thyroiditis in FMF group is higher than control group. However, this difference did not reached the level of statistical significance (p > 0.05). CONCLUSIONS: Although statistically not significant, thyroid autoimmunity was observed more frequently in patients with FMF than in healthy controls. Thyroid autoantibodies were significantly higher in patients with FMF. Studies with greater number of patients are required for evaluating the frequency of the autoimmune thyroiditis in patients with FMF.
24147601 Therapeutic potential of interleukin-17 in inflammation and autoimmune diseases. 2014 Jan INTRODUCTION: Interleukin-17 (IL-17) is a proinflammatory cytokine that mainly produced by T helper 17 (Th17) cells. In this article, we discussed the role of IL-17 in inflammation and autoimmune diseases, and the therapeutic strategies targeting IL-17. AREAS COVERED: In this article, we discussed the proinflammatory cytokine IL-17 and IL-17 receptors signals, and their regulation. IL-17 expression was abnormal in the bacterium, virus and fungus infection, and its higher level caused the tissue inflammation. IL-17 was involved in the pathological process of autoimmune diseases, such as systemic sclerosis, rheumatoid arthritis, ankylosing spondylitis and systemic lupus erythematosus, and IL-17 has been put as a therapeutic target in the clinic. EXPERT OPINION: IL-17/IL-17R signals and their application in inflammation process still need to be explored. Therapeutic strategies targeting IL-17 in autoimmune diseases ameliorated the inadequate response to anti-TNF-α therapy.
24142468 T-bet or not T-bet: taking the last bow on the autoimmunity stage. 2013 Nov The search for the encephalitogenic factor driving pathogenic T cells in autoimmune diseases such as rheumatoid arthritis, multiple sclerosis (MS), and psoriasis has proven to be a long and difficult mission, which is not yet completed. In this issue of the European Journal of Immunology, the importance of the transcription factor T-bet, previously shown to be essential for the induction of autoimmune disease in mice, is challenged. Two independent groups, O'Connor et al. [Eur. J. Immunol. 2013. 43:2818-2823] report] and Grifka-Walk et al. [Eur. J. Immunol. 2013. 43:2824-2831], report that T-bet is not mandatory for T cells to cause experimental autoimmune encephalomyelitis (EAE), which serves as a paradigmatic T-cell-mediated autoimmune disease. Both groups found that T-bet KO mice were fully susceptible to develop EAE, both after immunization with self-antigen and after adoptive transfer of IL-23-polarized autoaggressive T cells. T-bet deficiency mediated the loss of IFN-γ expression but retained or even enhanced GM-CSF and IL-17 production by central nervous system (CNS)-infiltrating T cells. These findings indicate that we have lost the last transcriptional regulator previously held to be required for the generation of autoimmune pathogenic T cells.
25436575 Role of nuclear IκBs in inflammation regulation. 2013 Apr A wide variety of environmental cues, including inflammatory cytokines, ligands for pattern recognition receptors and endogenous danger signals, activate the inducible transcription factor nuclear factor-κB (NF-κB), which is a central regulator of inflammatory and immune responses. Excessive activation of NF-κB results in the development of severe diseases, such as chronic inflammatory disorders, autoimmune diseases and cancer. Therefore, the transcriptional activity of NF-κB is tightly regulated at multiple steps. One mechanism is mediated by the inhibitor of κB (IκB), a well-defined regulator of NF-κB that resides in the cytoplasm and prevents NF-κB from nuclear entry by sequestration. Recently, several atypical IκBs that reside in the nucleus were identified: Bcl-3, IκBζ, IκBNS and IκBη. In contrast to conventional IκBs, these atypical IκBs positively and negatively modulate NF-κB-mediated transcription. The function of atypical IκBs is independent of the prevention of NF-κB nuclear entry. Therefore, atypical IκBs are considered distinct from conventional IκBs and have been termed 'nuclear IκBs.' In addition to these members, our recent study indicated that IκBL, originally reported as a susceptibility gene for rheumatoid arthritis, also serves as a nuclear IκB. Biological and genetic studies strongly suggest that nuclear IκBs play important roles in the pathogenesis of inflammatory and autoimmune diseases via the regulation of both innate and adaptive immunity. In this review, we discuss the recent advances in our understanding of nuclear IκBs in the context of NF-κB-mediated transcriptional regulation and inflammatory responses.
27231402 Ultrasensitive impedimetric lectin based biosensor for glycoproteins containing sialic aci 2013 Jan We report on an ultrasensitive label-free lectin-based impedimetric biosensor for the determination of the sialylated glycoproteins fetuin and asialofetuin. A sialic acid binding agglutinin from Sambucus nigra I was covalently immobilised on a mixed self-assembled monolayer (SAM) consisting of 11-mercaptoundecanoic acid and 6-mercaptohexanol. Poly(vinyl alcohol) was used as a blocking agent. The sensor layer was characterised by atomic force microscopy, electrochemical impedance spectroscopy and X-ray photoelectron spectroscopy. The biosensor exhibits a linear range that spans 7 orders of magnitude for both glycoproteins, with a detection limit as low as 0.33 fM for fetuin and 0.54 fM for asialofetuin. We also show, by making control experiments with oxidised asialofetuin, that the biosensor is capable of quantitatively detecting changes in the fraction of sialic acid on glycoproteins. We conclude that this work lays a solid foundation for future applications of such a biosensor in terms of the diagnosis of diseases such as chronic inflammatory rheumatoid arthritis, genetic disorders and cancer, all of which are associated with aberrant glycosylation of protein biomarkers.
25519054 MiR-223-3p targeting SEPT6 promotes the biological behavior of prostate cancer. 2014 Dec 18 MicroRNAs (miRNAs) present frequently altered expression in urologic cancers including prostate, bladder, and kidney cancer. The altered expression of miR-223 has been reported in cancers and other diseases in recent researches. MiR-223 is up-regulated in systemic lupus erythematosus and rheumatoid arthritis. In neoplastic diseases, miR-223 is proved to be up-expressed in plasma or serum and cancer tissues compared with normal tissues in pancreatic cancer, gastric cancer, et al. However, whether altered expression of miR-223 is associated with prostate cancer (PCa) and what it is potential functions in PCa remained unveiled. In this study, we firstly found miR-223-3p were up-regulated in prostate cancer tissues and then we study functional role of miR-223-3p in PCa using DU145, PC3 and LNCaP cell lines. Our data suggested that miR-223-3p might target gene SEPT6 and promoted the biological behavior of prostate cancer. Notably, we found increasing SEPT6 expression might reverse the biological activity induced by miR-223-3p, which might be a potential therapeutic target for PCa.
25470136 Novel insights into Tim-4 function in autoimmune diseases. 2015 Jun T-cell immunoglobulin domain and mucin domain-4 (Tim-4) was first recognized as a costimulatory molecule regulating T-cell activation. Dysregulation of Tim-4 has been found in some autoimmune conditions, particularly in the immune cells. Recently, Tim-4 was found to be critical for regulating T cells, with the ability of inhibiting naïve CD4(+) T cells and Th17 cells, increasing Th2 cell development. Tim-4 can also enhance T cell expansion via linker for activation of T cells, extracellular signal-regulated kinase (ERK) and Protein kinase B (PKB, also known as Akt) signaling pathways. Moreover, the Tim-4 signaling pathway may affect multiple molecular processes in autoimmune diseases. A number of previous studies have demonstrated that Tim-4 influences chronic autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus. In addition, an association between Tim-4 polymorphisms and susceptibility to several autoimmune diseases have been identified, such as RA. Taken together, recent works have indicated that Tim-4 may represent a novel target for the treatment of autoimmune diseases. In this article, we will discuss the Tim-4 function and the therapeutic potential of modulating the Tim-4 in autoimmune diseases.
25159724 In vitro inhibitory effect of crab shell extract on human umbilical vein endothelial cell. 2015 Jan Angiogenesis plays an important role in the tissue repair, rheumatoid arthritis, retinopathies, and growth and metastasis of cancer. Endothelial cell proliferation has been introduced as a model of angiogenesis. Crab sell was suggested for cancer treatment in traditional medicine. The aim of the present study was to investigate the in vitro effect of crab shell hydroethanolic extract on the human umbilical vein endothelial cell (HUVEC) proliferation. Crab sell extract was prepared and the effect of its various concentrations (0, 100, 200, 400, 800, 1000 μg/ml) on HUVECs were surveyed in three periods of 24, 48 and 72 h. HUVEC viability, Nitric oxide (NO) secretion and apoptosis were assessed by MTT, Griess and Tunnel methods, respectively. Data were compared by one-way ANOVA. In this study we found HUVECs viability was reduced in dose and time depended manner significantly and HUVECs NO production decreased significantly, too. Apoptosis index was increased significantly. These findings reveal that high concentrations of crab shell extract have anti-proliferative effects on HUVECs and can be used for cancer treatment.
24079661 Inhibitors of cathepsin G: a patent review (2005 to present). 2013 Dec INTRODUCTION: Cathepsin G (CatG) is a neutral proteinase originating from human neutrophils. It displays a unique dual specificity (trypsin- and chymotrypsin-like); thus, its enzymatic activity is difficult to control. CatG is involved in the pathophysiology of several serious human diseases, such as chronic obstructive pulmonary disease (COPD), Crohn's disease, rheumatoid arthritis, cystic fibrosis and other conditions clinically manifested by excessive inflammatory reactions. For mentioned reasons, CatG was considered as good molecular target for the development of novel drugs. However, none of them have yet entered the market as novel therapeutic agents. AREAS COVERED: This article presents an in-depth and detailed analysis of the therapeutic potential of CatG inhibitors based on a review of patent applications and academic publishing disclosed in patents and patent applications (1991 - 2012), with several exceptions for inhibitors retrieved from academic articles. EXPERT OPINION: Among the discussed inhibitors of CatG, examples corresponding to derivatives of β-ketophosphonic acids, aminoalkylphosphonic esters and boswellic acids (BAs) could be regarded as the most promising. The most promising one seems to be analogues of compounds of Nature's origin (peptidic and BA derivates). Nevertheless, nothing is currently known about the clinical disposition of any of the CatG inhibitors discovered so far. This latter point suggests that there is still a lot of work to do in the design of stable, pharmacologically active compounds able to specifically regulate the in vivo activity of cathepsin G.
24027590 The use of (18)F-FDG-PET/CT for diagnosis and treatment monitoring of inflammatory and inf 2013 FDG-PET, combined with CT, is nowadays getting more and more relevant for the diagnosis of several infectious and inflammatory diseases and particularly for therapy monitoring. Thus, this paper gives special attention to the role of FDG-PET/CT in the diagnosis and therapy monitoring of infectious and inflammatory diseases. Enough evidence in the literature already exists about the usefulness of FDG-PET/CT in the diagnosis, management, and followup of patients with sarcoidosis, spondylodiscitis, and vasculitis. For other diseases, such as inflammatory bowel diseases, rheumatoid arthritis, autoimmune pancreatitis, and fungal infections, hard evidence is lacking, but studies also point out that FDG-PET/CT could be useful. It is of invaluable importance to have large prospective multicenter studies in this field to provide clear answers, not only for the status of nuclear medicine in general but also to reduce high costs of treatment.
24004059 The role of cytokines in inflammatory bone loss. 2013 Chronic inflammatory processes close to bone often lead to loss of bone in diseases such as rheumatoid arthritis, periodontitis, loosened joint prosthesis and tooth implants. This is mainly due to local formation of bone resorbing osteoclasts which degrade bone without any subsequent coupling to new bone formation. Crucial for osteoclastogenesis is stimulation of mononuclear osteoclast progenitors by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) which induces their differentiation along the osteoclastic lineage and the fusion to mature, multinucleated osteoclasts. M-CSF and RANKL are produced by osteoblasts/osteocytes and by synovial and periodontal fibroblasts and the expression is regulated by pro- and anti-inflammatory cytokines. These cytokines also regulate osteoclastic differentiation by direct effects on the progenitor cells. In the present overview, we introduce the basic concepts of osteoclast progenitor cell differentiation and summarize the current knowledge on cytokines stimulating and inhibiting osteoclastogenesis by direct and indirect mechanisms.
23994797 Syk inhibitors. 2013 Non-receptor type of protein-tyrosine kinase Syk (spleen tyrosine kinase) was isolated in University of Fukui in 1991. Syk is most highly expressed by haemopoietic cells and known to play crucial roles in the signal transduction through various immunoreceptors of the adaptive immune response. However, recent reports demonstrate that Syk also mediates other biological functions, such as innate immune response, osteoclast maturation, platelet activation and cellular adhesion. Moreover, ectopic expression of Syk by epigenetic changes is reported to cause retinoblastoma. Because of its critical roles on the cellular functions, the development of Syk inhibitors for clinical use has been desired. Although many candidate compounds were produced, none of them had progressed to clinical trials. However, novel Syk inhibitors were finally developed and its usefulness has been evaluated in the treatment of allergic rhinitis, rheumatoid arthritis and idiopathic thrombocytopenic purpura. In this review, we will summarize the history, structure and function of Syk, and then the novel Syk inhibitors and their current status. In addition, we will introduce our research focused on the functions of Syk on Dectin-1-mediated mast cell activation.
23937231 Molecular recognition of tachykinin receptor selective agonists: insights from structural 2013 Dec This Review deals essentially with the elucidation of structural features of Tachykinin family of neuropeptides, which are known to interact through three distinct GPCR subtypes, namely NK1 (Neurokinin 1), NK2 (Neurokinin 2) and NK3 (Neurokinin 3) receptors. In mammals, Tachykinins have been shown to elicit a wide array of activities such as powerful vasodilatation, hypertensive action and stimulation of extravascular smooth muscle and are known to be involved in a variety of clinical conditions including chronic pain, Parkinson's disease, Alzheimer's disease, depression, rheumatoid arthritis, irritable bowel syndrome and asthma. This broad spectrum of action of Tachykinins is attributed to the lack of selectivity of tachykinins to their receptors. All tachykinins interact with all the three-receptor subtypes with SP preferring NK1, NKA preferring NK2 and NKB preferring NK3. This lack of specificity can be accounted for by the conformational flexibility of these short, linear peptides. Hence, identification of structural features of the agonists important for receptor binding and biological activity is of great significance in unraveling the molecular mechanisms involved in tachykinin receptor activation and also in rational design of novel therapeutic agents. Understanding structure of the ligand-receptor complex and analysis of topography of the binding pocket of the tachykinin receptor is also crucial in rational design of drugs.
23840156 Azathioprine-induced fever in autoimmune hepatitis. 2013 Jul 7 Underdiagnosis of drug-induced fever leads to extensive investigation and prolongation of hospitalization, and may lead to multiple unnecessary invasive procedures and a wrong diagnosis. Azathioprine is a widely used immunosuppressive drug. We report a case of a 53-year-old female patient diagnosed with autoimmune hepatitis treated with azathioprine, who presented to the emergency room with a 6-wk history of fever and chills without other associated symptoms. Since the patient's fever was of unknown origin, she was hospitalized. All treatment was stopped and an extensive workup to explore the source of fever and chills was performed. Results of chest X-ray, viral, urine, and blood cultures, autoimmune serology, transthoracic and transesophageal echocardiography, and abdominal ultrasound revealed no source of infection. A rechallenge test of azathioprine was performed and the fever and chills returned within a few hours. Azathioprine was established as the definite cause following rechallenge. Fever as an adverse drug reaction is often unrecognized. Azathioprine has been reported to cause drug-induced fever in patients with inflammatory bowel disease, rheumatoid arthritis, and sarcoidosis. To the best of our knowledge there have been no previous reports documenting azathioprine-induced fever in patients with autoimmune hepatitis. The occurrence of fever following the readministration of azathioprine suggests the diagnosis of drug-induced fever, particularly after the exclusion of other causes. A careful rechallenge is recommended to confirm the diagnosis.
23814989 [Kinking of the endotracheal tube in a prone patient associated with the inadequate withdr 2013 Jun We report a case of intraoperative kinking of an endotracheal tube (ETT) in a prone patient during spine surgery. We postulate that one of the risk factors involved with kinking was the inadequate withdrawal maneuver of Pentax-AWS Airway Scope (AWS). Patient was a 69-year-old woman with hypertension, diabetes mellitus, and rheumatoid arthritis, undergoing C4-6 laminoplasty under general anesthesia in the prone position. A 7.0-mm polyvinyl endotracheal tube (Paker Flex-Tip Tube) was placed to 21 cm at the right angle of the mouse without difficulty using the AWS. Both peak inspiratory pressure (PIP) and partial pressure of end-tidal carbon dioxide began to rise gradually from 24 to 28 cmH2O and 38 to 44 mmHg, respectively. Although over 30 cmH2O in PIP repeatedly appeared after that, we did not find any remarkable change of ventilation except for weak breath sound. Thereafter, when we checked the tube with a flexible fiberoptic bronchoscope, it could not pass through the tube. At first, we asked the surgeon to release neck flexion as much as possible. This procedure could not correct the kink completely but allowed the passage of bronchoscope in the ETT. Then, we tried to reposition the ETT by inserting the bronchoscope beyond the point of kinking for maintaining luminal patency and adequate ventilation. The subsequent anesthetic course was uneventful. Kinking of the ETT in the oral cavity is an uncommon problem but we must keep in mind as one of the differential diagnoses. When using the AWS for endotracheal intubation, we recommend the confirmation of the position of the ETT to be normal in the oral cavity by direct laryngoscopy.
23814679 Acute eosinophilic pneumonia leading to acute respiratory failure in a current systemic co 2013 Jul A 69-year-old female patient visited the emergency room with fever (38.3℃) and dyspnea. She had been taking prednisolone (5 mg once per day) and methotrexate (2.5 mg once per week) for rheumatoid arthritis for 2 years. Chest computed tomography (CT) showed bilateral, multifocal ground glass opacity with interlobular septal thickening. Peripheral blood leukocyte count was 6,520/mm(3) (neutrophils, 77.4%; eosinophils, 12.1%). During the night, mechanical ventilation was initiated due to the development of severe hypoxemia. Bronchoalveolar lavage fluid showed a high proportion of eosinophils (49%). Her symptoms improved dramatically after commencement of intravenous methylprednisolone therapy. This is the first report of idiopathic acute eosinophilic pneumonia developing in a current user of systemic corticosteroids.
23813914 Automated image analysis of in vitro angiogenesis assay. 2013 Oct Angiogenesis is the biological process of generating new capillary blood vessels. It is a fundamental component of a number of normal (reproduction and wound healing) and pathological processes (diabetic retinopathy, rheumatoid arthritis, tumor growth, and metastasis). In vitro angiogenesis assays provide a platform for evaluating the effects of pro- or antiangiogenic compounds. One of the most informative assays is the endothelial cells capillary tube formation assay performed on a biological matrix. This assay is based on quantification of the stimulatory and inhibitory effects of various agents, which is estimated through the measurement of the pseudo-tubules network length. This standard measurement is usually carried out manually by trained operators but requires time, attention, and dedication to achieve a reasonable degree of accuracy. Moreover, the screening is operator dependent. In this article, we propose an automated procedure to evaluate the pseudo-tubule network lengths. We propose a series of image analysis procedures developed using a freely available image analysis software library. More than 800 images from 12 experiments were analyzed automatically and manually, and their results were compared to improve and validate the proposed image analysis procedure. The resulting image analysis software is currently running on a dedicated server, with comparable accuracy to manual measurements. Using this new automated procedure, we are able to treat 540 images, or three complete assays per hour.
23810024 Better reporting and greater homogeneity in outcome measures are seen in randomized trial 2013 Aug OBJECTIVE: Outcome Measures in Rheumatology promotes standardized outcome measures. No such organization exists for nephrology. We compared the reporting and homogeneity of outcome measures in registered protocols of randomized trials in rheumatology and nephrology. STUDY DESIGN AND SETTING: Data were extracted from protocols for rheumatoid arthritis or nephroprotection registered in ClinicalTrials.gov. We rated five outcome items (domain, specific measurement, specific metric, method of aggregating data, and time frame) to obtain a 5-point score. We split outcomes into clusters that could be pooled for meta-analysis, and assessed the proportion of trials and patients by cluster. RESULTS: We selected 75 protocols for rheumatology and 66 for nephrology. A high adjusted score for outcomes was associated with rheumatology protocols (odds ratio, 4.2; 95% confidence interval, 2.39, 7.39). We retained 13 clusters of outcomes for rheumatology, and one of one outcome (American College Rheumatology Criteria) could pool 87.1% of trials and 92.8% of patients. We retained eight clusters for nephrology, and one of four outcomes (assessing proteinuria) could pool 83.1% of trials and 44.7% of patients. CONCLUSIONS: The reporting and homogeneity of outcomes is better in registered protocols of rheumatology than nephrology. The presence of international guidelines on outcome measurement may explain the differences.
23783459 Natural products as a source of anti-inflammatory agents associated with inflammatory bowe 2013 Jun 19 Accumulating epidemiological and clinical study indicates that inflammation is a significant risk factor to develop various human diseases such as inflammatory bowel disease (IBD), chronic asthma, rheumatoid arthritis, multiple sclerosis, and psoriasis. Suppressing inflammation is therefore important to control or prevent various diseases. Among them, IBD is one of the major problems affecting people worldwide. IBD affects at least one in a thousand persons in many Western countries. Various natural products have been shown to safely suppress pro-inflammatory pathway and control IBD. In vivo and/or in vitro studies indicate that anti-IBD effects of natural products occur by inhibition of the expression of pro-inflammatory cytokines (for example, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule expression and pro-inflammatory mediators (such as inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2), master transcription factors (such as nuclear factor-κB (NF-κB)), reactive oxygen species (ROS) and by improving the antioxidant activity. In this review, we summarize recent research focused on IBD and the effects that natural products have on IBD factors.