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ID PMID Title PublicationDate abstract
27071377 Hypoxia-inducible factor 1 in autoimmune diseases. 2016 May Autoimmune disorders are a complicated and varied group of diseases arising from inappropriate immune responses. Recent studies have demonstrated that ongoing inflammatory and immune responses are associated with increased oxygen consumption, a process resulting in localized tissue hypoxia within inflammatory lesions ("inflammatory hypoxia"), in which hypoxia-inducible factor 1 (HIF-1), an oxygen-sensitive transcription factor that allows adaptation to hypoxia environments, has been shown to play an important function. HIF-1 is a regulator of angiogenesis and immune system. Besides, HIF-1-mediated metabolic shift and fibrosis may also play crucial roles in some autoimmune disorders. Firstly, we briefly summarize the role of HIF-1 in angiogenesis, immune responses and fibrosis. Secondly, we will show the major recent findings demonstrating a role for HIF-1 signaling in autoimmune disorders, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, systemic sclerosis and multiple sclerosis. The growing evidences may prompt HIF-1 to be a new target for treatment of autoimmune diseases.
27038546 CD147 promotes the formation of functional osteoclasts through NFATc1 signalling. 2016 Apr 29 CD147, a membrane glycoprotein of the immunoglobulin superfamily, is highly upregulated during dynamic cellular events including tissue remodelling. Elevated CD147 expression is present in the joint of rheumatoid arthritis patients. However, the role of CD147 in bone destruction remains unclear. To determine whether CD147 is involved in osteoclastogenesis, we studied its expression in mouse osteoclasts and its role in osteoclast differentiation and function. CD147 expression was markedly upregulated during osteoclast differentiation. To investigate the role of CD147 in receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis and bone resorption activity, osteoclast precursor cells were transfected with CD147 siRNA. Decreased CD147 expression inhibited osteoclast formation and bone resorption, inhibited RANKL-induced nuclear translocation of the nuclear factor of activated T cells (NFAT) c1 and decreased the expression of the d2 isoform of vacuolar ATPase Vo domain and cathepsin K. Therefore, CD147 plays a critical role in the differentiation and function of osteoclasts by upregulating NFATc1 through the autoamplification of its expression in osteoclastogenesis.
26919366 Sinomenine Attenuates Angiotensin II-Induced Autophagy via Inhibition of P47-Phox Transloc 2016 BACKGROUND/AIMS: Sinomenine, a pure alkaloid extracted from the Chinese medicinal plant Sinomenium acutum, and sinomenine hydrochloride (SN) has been successfully used for the therapy of rheumatoid arthritis (RA) and kidney diseases. Autophagy is a cytoprotective mechanism used by podocytes and other cells to alleviate the effects of oxidative stress, and angiotensin II (Ang II) significantly promotes podocyte autophagy. However, excessive autophagy may lead to cell death and podocyte depletion. The present study evaluated the effect of SN in podocytes induced by Ang II. METHODS: Podocytes were pretreated with graded concentrations (10(-8) M ∼ 10(-4) M) of SN and then stimulated with Ang II. The LC3B protein and the p47-phox membrane fraction were measured by Western blot. Autolysosomes were assessed by transmission electron microscopy. FACS was used to quantify the ROS produced by podocytes. The translocation of p47-phox to the membrane was investigated by immunofluorescence. RESULTS: The 10(-8) M ∼ 10(-4) M of SN alone did not effect ROS generation or podocyte autophagy. The 10(-8) M and 10(-6) M SN attenuated Ang II-induced autophagy in podocytes. Furthermore, SN decreased the level of ROS generation in Ang II-induced podocytes via inhibition of NOX subunit p47-phox translocation to the membrane. CONCLUSION: The appropriate concentration of SN attenuated Ang II-induced podocyte autophagy through ROS generation, at least in part, by regulating NOX subunit p47-phox translocation to the membrane.
26861900 Disease prevalence in a rural Andean population of central Peru: a focus on autoimmune and 2016 Dec INTRODUCTION: The hygiene hypothesis, formulated to explain the increased incidence of allergic and autoimmune diseases observed in industrialized countries, remains controversial. We reflected upon this hypothesis during a medical mission to rural and impoverished villages of central Peru. MATERIALS AND METHODS: The mission was carried out in July 2015 to aid three Andean villages located near Cusco, and comprised 10 American physicians, 4 nurses, and 24 students. After recording the vital signs, patients were triaged by nurses based on the major complaint, visited by physicians, and prescribed medications. Physicians wrote their notes on a one-page form and established diagnoses purely on clinical grounds, without laboratory or imaging testing. Physician notes were then analyzed retrospectively in a de-identified and double-blinded fashion. RESULTS: A total of 1075 patients (357 men and 718 women) were visited during 5 consecutive clinic days, 840 being adults and 235 <18 years of age. The most common complaints were back pain, stomach pain, headache, and vision loss. Osteoarthritis, gastritis, visual disturbances, and parasitic infections dominated the diagnostic categories. Thirty-seven patients (3 %) were diagnosed with an allergic or autoimmune disease, mainly represented by asthma, rheumatoid arthritis, and Hashimoto's thyroiditis, a prevalence that was not significantly lower than that reported in industrialized countries. CONCLUSIONS: Although a study of this nature cannot definitively support or refute the hygiene hypothesis, it does provide a novel snapshot of disease prevalence in rural Andean villages of central Peru. The study could serve as a basis to implement basic public health interventions and prepare for future missions to the same or comparable regions.
26854400 Targeting FcγRs to treat antibody-dependent autoimmunity. 2016 Jun Self-reactive antibodies represent a significant force in autoimmune disease induction. In antibody-dependent autoimmune syndromes such as immune thrombocytopenia (ITP), systemic lupus erythematosus (SLE), myasthenia gravis and rheumatoid arthritis (RA), autoantibodies exert their inflammatory effect through FcγRs, a well-established class of cell surface receptors that interact with the Fc domain of IgG. Down-regulating FcγR functionality presents an attractive strategy to treat antibody-dependent autoimmune diseases. Various approaches, including nonspecific blocking of the IgG binding site as well as specific targeting using antagonistic monoclonal antibodies, have been explored to modulate the interaction between the Fc portion of IgG and FcγRs. The exquisite specificity and favorable pharmacokinetics of IgG make monoclonal antibodies a preferred choice. Indeed, the first antagonistic monoclonal antibody against the human FcγRIIIA had shown efficacy in refractory ITP patients; however, the practicality of using anti-FcγRIII antibody as a therapeutic was hindered by its associated adverse events, a phenomenon recapitulated in animal models. In this review, we discuss the role of FcγRs in autoimmune diseases, and focus on a novel monovalent approach to target FcγRs to resolve antibody-mediated autoimmunity.
26821815 Chemokine and chemokine receptors in autoimmunity: the case of primary biliary cholangitis 2016 Jun Chemokines represent a major mediator of innate immunity and play a key role in the selective recruitment of cells during localized inflammatory responses. Beyond critical extracellular mediators of leukocyte trafficking, chemokines and their cognate receptors are expressed by a variety of resident and infiltrating cells (monocytes, lymphocytes, NK cells, mast cells, and NKT cells). Chemokines represent ideal candidates for mechanistic studies (particularly in murine models) to better understand the pathogenesis of chronic inflammation and possibly become biomarkers of disease. Nonetheless, therapeutic approaches targeting chemokines have led to unsatisfactory results in rheumatoid arthritis, while biologics against pro-inflammatory cytokines are being used worldwide with success. In this comprehensive review we will discuss the evidence supporting the involvement of chemokines and their specific receptors in mediating the effector cell response, utilizing the autoimmune/primary biliary cholangitis setting as a paradigm.
26813112 Macrophage migration inhibitory factor enhances lipopolysaccharide-induced fibroblast prol 2016 Jan 26 BACKGROUND: Fibroblast proliferation is a common manifestation of chronic inflammatory diseases, including rheumatoid arthritis (RA), Crohn's disease and ulcerative colitis, etc. To alleviate patient suffering, the mechanism underlying fibroblast proliferation should be elucidated. METHODS: CCK-8 assay was used to assess the stimulatory effect of LPS and macrophage migration inhibitory factor (MIF) on fibroblast proliferation. Then, TLR4 expression on fibroblast cell membrane was carried out by confocal scanning microscopy. Finally, real-time fluorescent quantitative PCR and flow cytometry were applied to determine the expression of TLR4 after MIF challenge. RESULTS: LPS alone directly stimulated the fibroblast proliferation. In addition, MIF showed co-stimulatory effect on LPS-induced fibroblast proliferation. Interestingly, fibroblast overtly expressed TLR4 without stimulation. After MIF stimulation, real-time PCR showed TLR4 mRNA levels were increased by about 33% in the fibroblasts; in agreement, TLR4 expression on the fibroblast membrane was increased by about 20%, as shown by flow cytometry. CONCLUSIONS: These findings indicated MIF elevates TLR4 expression in fibroblast, enhancing LPS-induced cell proliferation.
26807898 Randomized Trial Comparing Amniotic Membrane Transplantation with Lamellar Corneal Graft f 2016 Apr PURPOSE: There are few studies comparing different surgical procedures for the treatment of corneal thinning. Lamellar corneal transplantation (LCT) has been reported to be efficient, but its results can be jeopardized by allograft rejection, opacification, or high astigmatism. Amniotic membrane transplantation (AMT) has been considered a good alternative, but it is not as resistant as LCT and the tissue can be reabsorbed after surgery. METHODS: A prospective, randomized, interventional, and comparative study of consecutive patients with corneal thinning over 6 months was performed. Ophthalmological examination was performed before transplant surgery and then repeated 1, 7, 15, 30, 90, and 180 days after surgery and ultrasound biomicroscopy was performed before and then 30, 90, and 180 days after surgery to assess corneal thinning. RESULTS: Herpes simplex infection was the main cause of corneal thinning (9 eyes), followed by surgery (cataract, glaucoma, 5 cases), rheumatoid arthritis (1), chemical burn (1), perforating trauma (1), previous band keratopathy treatment (1), and Stevens-Johnson syndrome (1). Although all patients showed significant increase in final thickness in the area of thinning, it was higher in those submitted to LCT at 180 days postoperatively. Regardless of the surgical technique, all patients showed epithelialization. Patients undergoing AMT showed an 89% decrease in neovascularization. Final corrected distance visual acuity was better in patients submitted to AMT. CONCLUSIONS: LCT proved to be the best option for treating corneal thinning. AMT represents an alternative that allows good visual recovery but does not restore corneal thickness as efficiently as LCT.
26778692 Identification of inflammatory factor TNFα inhibitor from medicinal herbs. 2016 Apr The inflammatory response is one of the first defenses our body has to fight against potential endangerments. It plays a critical role in host defense, clearing and slowing the infection in the case of microbial invasion. During an inflammatory response, a variety of cytokines are produced by cells and trigger or enhance the specific inflammation response. TNFα, one of these factors, plays a crucial role in many immune and inflammatory processes, such as proliferation, apoptosis, necrosis, and cell survival. It acts in orchestrating the cytokine cascade and the major regulator of inflammatory cytokine production. Abnormality of TNFα signaling leads to many diseases, including rheumatoid arthritis, psoriasis, Crohn's disease, atherosclerosis, and cancer. Due to the importance of TNFα, regulating TNFα activity is a key to treat the related diseases. There is a long history of using medicinal herbs to treat diseases related to inflammation. We searched for an ingredient that has the ability to inhibit TNFα, we examined AO herbal extract, containing 10 individual herbs and most of these herbs have anti-inflammatory activity within humans. We have tested the anti-inflammatory ability of AO herbal extract on mice. Furthermore, we used macrophage cell from young mice and found that AO extract has the ability to reduce the inflammation by inhibiting TNFα level.
26754991 Coexistence of autoimmune diseases and autoantibodies in patients with myasthenia gravis. 2016 Jan BACKGROUND: In this study, we assessed 75 patients with myasthenia gravis (MG) for coexistent autoimmune diseases (ADs) and for the characteristic autoantibodies that are associated with the most relevant forms of ADs. METHODS: The demographic and clinical characteristics of the patients were recorded. In all patients, thyroid function tests, thyroid autoantibodies, and other autoantibodies were studied. The diagnosis of autoimmune thyroid disease (AITD) was made based on the clinical features, physical examination, and laboratory findings. The diagnoses of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were made in accordance with the revised criteria of American College of Rheumatology. The presence of other ADs were also recorded which was based on whether or not the patient already had a diagnosis of ADs; or, whether it was detected during the period of the study based on clinical findings and/or laboratory abnormalities. RESULTS: Thirty-nine patients (52%) had autoantibody positivity in their sera. Thyroid autoantibodies and antinuclear antibodies were the main autoantibodies detected. In twenty one of these patients, a diagnosis of AD could not be confirmed. Eighteen patients (24%) had a confirmed diagnosis of a coexisting AD. These ADs included AITD (16%), RA (4%), SLE (2.6%), and Lambert-Eaton myasthenic syndrome (1.3%). In ten patients, the diagnosis of ADs had been established before the development of MG; 8 of the patients included those who were newly diagnosed with ADs in the course of the management of MG. CONCLUSIONS: MG has an increased frequency of coexisting ADs. Autoantibodies that are characteristic for ADs can be found in the patients without the presence of any of the clinical findings of ADs. Clinical attention towards the management of ADs is especially needed during the follow-up of patients with MG.
26615427 Semantic annotation of 3D anatomical models to support diagnosis and follow-up analysis of 2016 May PURPOSE: While 3D patient-specific digital models are currently available, thanks to advanced medical acquisition devices, there is still a long way to go before these models can be used in clinical practice. The goal of this paper is to demonstrate how 3D patient-specific models of anatomical parts can be analysed and documented accurately with morphological information extracted automatically from the data. Part-based semantic annotation of 3D anatomical models is discussed as a basic approach for sharing and reusing knowledge among clinicians for next-generation CAD-assisted diagnosis and treatments. METHODS: We have developed (1) basic services for the analysis of 3D anatomical models and (2) a methodology for the enrichment of such models with relevant descriptions and attributes, which reflect the parameters of interest for medical investigations. The proposed semantic annotation is ontology-driven and includes both descriptive and quantitative labelling. Most importantly, the developed methodology permits to identify and annotate also parts-of-relevance of anatomical entities. RESULTS: The computational tools for the automatic computation of qualitative and quantitative parameters have been integrated in a prototype system, the SemAnatomy3D framework, which demonstrates the functionalities needed to support effective annotation of 3D patient-specific models. From the first evaluation, SemAnatomy3D appears as an effective tool for clinical data analysis and opens new ways to support clinical diagnosis. CONCLUSIONS: The SemAnatomy3D framework integrates several functionalities for 3D part-based annotation. The idea has been presented and discussed for the case study of rheumatoid arthritis of carpal bones; however, the framework can be extended to support similar annotations in different clinical applications.
26556950 Complexation Hydrogels as Oral Delivery Vehicles of Therapeutic Antibodies: An in Vitro an 2015 Oct 28 Oral administration of monoclonal antibodies (mAbs) may enable the localized treatment of infections or other conditions in the gastrointestinal tract (GI) as well as systemic diseases. As with the development of oral protein biotherapeutics, one of the most challenging tasks in antibody therapies is the loss of biological activity due to physical and chemical instabilities. New families of complexation hydrogels with pH-responsive properties have demonstrated to be excellent transmucosal delivery vehicles. This contribution focuses on the design and evaluation of hydrogel carriers that will minimize the degradation and maximize the in vivo activity of anti-TNF-α, a mAb used for the treatment of inflammatory bowel disease (IBD) in the GI tract and systemically for the treatment of rheumatoid arthritis. P(MAA-g-EG) and P(MAA-co-NVP) hydrogels systems were optimized to achieve adequate swelling behavior, which translated into improved protein loading and release at neutral pH simulating the small intestine conditions. Additionally, these hydrogel systems preserve antibody bioactivity upon release resulting in the systemic circulation of an antibody capable of effectively performing its biological function. The compatibility if these hydrogels for mAb bioactivity preservation and release makes them candidates for use as oral delivery systems for therapeutic antibodies.
26246896 Granzyme B mediated function of Parvovirus B19-specific CD4(+) T cells. 2015 Jul A novel conception of CD4(+) T cells with cytolytic potential (CD4(+) CTL) is emerging. These cells appear to have a part in controlling malignancies and chronic infections. Human parvovirus B19 can cause a persistent infection, yet no data exist on the presence of B19-specific CD4(+) CTLs. Such cells could have a role in the pathogenesis of some autoimmune disorders reported to be associated with B19. We explored the cytolytic potential of human parvovirus B19-specific T cells by stimulating peripheral blood mononuclear cell (PBMC) with recombinant B19-VP2 virus-like particles. The cytolytic potential was determined by enzyme immunoassay-based quantitation of granzyme B (GrB) and perforin from the tissue culture supernatants, by intracellular cytokine staining (ICS) and by detecting direct cytotoxicity. GrB and perforin responses with the B19 antigen were readily detectable in B19-seropositive individuals. T-cell depletion, HLA blocking and ICS experiments showed GrB and perforin to be secreted by CD4(+) T cells. CD4(+) T cells with strong GrB responses were found to exhibit direct cytotoxicity. As anticipated, ICS of B19-specific CD4(+) T cells showed expected co-expression of GrB, perforin and interferon gamma (IFN-γ). Unexpectedly, also a strong co-expression of GrB and interleukin 17 (IL-17) was detected. These cells expressed natural killer (NK) cell surface marker CD56, together with the CD4 surface marker. To our knowledge, this is the first report on virus-specific CD4(+) CTLs co-expressing CD56 antigen. Our results suggest a role for CD4(+) CTL in B19 immunity. Such cells could function within both immune regulation and triggering of autoimmune phenomena such as systemic lupus erythematosus (SLE) or rheumatoid arthritis.
26242703 Anti-infective immunoadhesins from plants. 2015 Oct Immunoadhesins are recombinant proteins that combine the ligand-binding region of a receptor or adhesion molecule with immunoglobulin constant domains. All FDA-approved immunoadhesins are designed to modulate the interaction of a human receptor with its normal ligand, such as Etanercept (Enbrel(®) ), which interferes with the binding of tumour necrosis factor (TNF) to the TNF-alpha receptor and is used to treat inflammatory diseases such as rheumatoid arthritis. Like antibodies, immunoadhesins have long circulating half-lives, are readily purified by affinity-based methods and have the avidity advantages conferred by bivalency. Immunoadhesins that incorporate normal cellular receptors for viruses or bacterial toxins hold great, but as yet unrealized, potential for treating infectious disease. As decoy receptors, immunoadhesins have potential advantages over pathogen-targeted monoclonal antibodies. Planet Biotechnology has specialized in developing anti-infective immunoadhesins using plant expression systems. An immunoadhesin incorporating the cellular receptor for anthrax toxin, CMG2, potently blocks toxin activity in vitro and protects animals against inhalational anthrax. An immunoadhesin based on the receptor for human rhinovirus, ICAM-1, potently blocks infection of human cells by one of the major causes of the common cold. An immunoadhesin targeting the MERS coronavirus is in an early stage of development. We describe here the unique challenges involved in designing and developing immunoadhesins targeting infectious diseases in the hope of inspiring further research into this promising class of drugs.
26212387 Human autoimmune diseases: a comprehensive update. 2015 Oct There have been significant advances in our understanding of human autoimmunity that have led to improvements in classification and diagnosis and, most importantly, research advances in new therapies. The importance of autoimmunity and the mechanisms that lead to clinical disease were first recognized about 50 years ago following the pioneering studies of Macfarlane Burnett and his Nobel Prize-winning hypothesis of the 'forbidden clone'. Such pioneering efforts led to a better understanding not only of autoimmunity, but also of lymphoid cell development, thymic education, apoptosis and deletion of autoreactive cells. Contemporary theories suggest that the development of an autoimmune disease requires a genetic predisposition and environmental factors that trigger the immune pathways that lead, ultimately, to tissue destruction. Despite extensive research, there are no genetic tools that can be used clinically to predict the risk of autoimmune disease. Indeed, the concordance of autoimmune disease in identical twins is 12-67%, highlighting not only a role for environmental factors, but also the potential importance of stochastic or epigenetic phenomena. On the other hand, the identification of cytokines and chemokines, and their cognate receptors, has led to novel therapies that block pathological inflammatory responses within the target organ and have greatly improved the therapeutic effect in patients with autoimmune disease, particularly rheumatoid arthritis. Further advances involving the use of multiplex platforms for diagnosis and identification of new therapeutic agents should lead to major breakthroughs within the next decade.
26100340 Reality of a Vaccine in the Prevention and Treatment of Atherosclerosis. 2015 Jul Atherosclerosis together with multiple sclerosis, psoriasis and rheumatoid arthritis can be used as examples of chronic inflammatory diseases associated with multifactorial components that evolve over the years. Nevertheless, an important difference between these diseases relies on the fact that atherosclerosis develops from early ages where inflammation dominates the very beginning of the disease. This review highlights the inflammatory nature of atherosclerosis and the role the immune system plays in the process of atherogenesis. Although treatment of atherosclerosis has been for years based on lipid-lowering therapies reducing a series of risk factors, the degree of success has been only limited because cardiovascular complications related to the evolution of atherosclerotic lesions continue to appear in the population worldwide. In this sense, alternative treatments for atherosclerosis have come into play where both innate and adaptive immunity have been proposed to modulate atherosclerosis-associated inflammatory phenomena. When tested for their atheroprotective properties, several immunogens have been studied through passive and active immunization with good results and, therefore, the strategy through vaccination to control the disease has been made possible. Many experimental pre-clinical studies demonstrating proof of concept that vaccination using DNA and protein with an effective use of adjuvants and the optimal route of administration now provide a tangible new therapeutic approach that sets the stage for several of these vaccines to be tested in large, randomized, long-term clinical studies. A vaccine ready for human use will only be accomplished through the close association between academia, regulatory government organizations and private industry, allowing the reality of a simple and successful therapy to reduce atherosclerosis and its severe clinical complications.
25876705 Leukocyte adhesion deficiency-I with a novel intronic mutation presenting with pyoderma ga 2015 May Pyoderma gangrenosum (PG) is an uncommon noninfectious neutrophilic dermatosis characterized by recurrent, sterile, necrotic skin ulcers. It is commonly associated with underlying systemic disease like inflammatory bowel disease, rheumatoid arthritis and hematological malignancies. Pathogenesis of PG remains unclear though aberrant immune responses have been implicated. The diagnosis of PG is of exclusion and management is empirical with local or systemic immunosuppressive therapy. LAD-I is a rare form of autosomal recessive disorders caused by mutations of the gene ITGB2, clinically characterized by recurrent severe bacterial infection, impaired pus formation, poor wound healing and persistent neutrophilia. Though skin ulcerations are common, predominant clinical presentation as PG is unusual in LAD-I. Here we present four Indian patients with LAD-I from three unrelated families initially diagnosed as PG due to chronic recurrent skin ulcerations requiring steroids and antibiotics for healing, associated with atrophic scar formation. All these four patients had persistent neutrophilia without history of delayed cord separation and showed moderate expression of CD18 (19 to 68%) on neutrophils. Sequencing of the entire coding region and intronic splice sites of the ITGB2 gene from the genomic DNA of these patients revealed a novel common mutation IVS10+4A>G. LAD-I should be kept in mind while evaluating patients with PG especially those with persistent neutrophila in the absence of other rheumatological disorders. Diagnosis of LAD-I in these cases is extremely important for management as treating these patients without adequate antibiotic cover may prove fatal and these patients often require hematopoietic stem cell transplantation for permanent cure.
25575769 Risk factors for periprosthetic joint infection after total joint arthroplasty: a systemat 2015 Feb Many of the mooted risk factors associated with periprosthetic joint infection (PJI) after total joint arthroplasty (TJA) remain controversial and are not well characterized. Online and manual searches were performed using Medline, Embase, Chinese National Knowledge Infrastructure and the Cochrane Central Database from January 1980 to March 2014). For inclusion, studies had to meet the quality assessment criteria of the CONSORT statement, and be concerned with evaluation of risk factors for PJI after TJA. Two reviewers extracted the relevant data independently and any disagreements were resolved by consensus. Fourteen studies were included in this meta-analysis. The following significant risk factors for PJI were identified: body mass index (both continuous and dichotomous variables); diabetes mellitus; corticosteroid therapy; hypoalbuminaemia; history of rheumatoid arthritis; blood transfusion; presence of a wound drain; wound dehiscence; superficial surgical site infection; coagulopathy; malignancy, immunodepression; National Nosocomial Infections Surveillance Score ≥2; other nosocomial infection; prolonged operative time; and previous surgery. Factors that were not significantly associated with PJI were: cirrhosis; hypothyroidism; urinary tract infection; illicit drug abuse; alcohol abuse; hypercholesterolaemia; hypertension, ischaemic heart disease; peptic ulcer disease; hemiplegia or paraplegia; dementia; and operation performed by a staff surgeon (vs a trainee). Strategies to prevent PJI after TJA should focus, in particular, on those patients at greatest risk of infection according to their individual risk factors.
25572286 Receptor activator of nuclear factor-κB ligand (RANKL)/RANK/osteoprotegerin system in bon 2015 May The receptor activator of nuclear factor‑κB ligand (RANKL)/RANK/osteoprotegerin (OPG) system was identified in the late 1990s, ending the search for the specific factors expressed by osteoblasts and stromal cells in order to regulate osteoclastogenesis. The identification of the RANKL/RANK/OPG system was a breakthrough in bone biology; however, the system not only works as a dominant mediator in osteoclast activation, formation and survival, but also functions in other tissues, including the mammary glands, brain and lymph nodes. Evidence has indicated that the existence of the RANKL/RANK/OPG system in these tissues suggests that it may have specific functions beyond those in bone. Disorders of the RANKL/RANK/OPG system are associated with certain human diseases, including postmenopausal osteoporosis, rheumatoid arthritis (RA), bone tumors and certain bone metastatic tumors. Genetic studies have indicated that the RANKL/RANK/OPG system may be a key regulator in the formation of lymph nodes and in the autoimmune disease RA, which further suggests that the immune system may interact with the RANKL/RANK/OPG system. The present review aimed to provide an overview of the role of the RANKL/RANK/OPG system in osteoclastogenesis, bone disease and tissues beyond bone.
25483364 Inhibition of 5-lipoxygenase triggers apoptosis in pancreatic cancer cells. 2015 Feb The 5-lipoxygenase (5-LOX) pathway has been associated with a variety of inflammatory diseases including asthma, atherosclerosis, rheumatoid arthritis, cancer and liver fibrosis. Several classes of 5-LOX inhibitors have been identified, but only one drug, zileuton, a redox inhibitor of 5-LOX, has been approved for clinical use. In the present study, 5-LOX was found to be overexpressed not only in pancreatic cancer cell lines but also in tissue samples of patients suffering from pancreatic adenocarcinoma. There was a close correlation between the tumor expression levels of 5-LOX mRNA and protein and the clinicopathological patient characteristics including lymph node metastasis and TNM stage. Zileuton suppressed the proliferation of SW1990 cells in a concentration- and time‑dependent manner. In addition, zileuton induced SW1990 cells to undergo apoptosis and significantly decreased 5-LOX expression. The number of apoptotic cells, estimated by flow cytometry, Annexin V/PI assay, TUNEL staining and sub‑diploid population was significantly higher than that of the control. These results suggest that the level of 5-LOX expression was increased in pancreatic cancer tissues and may be related to lymph node metastasis and TNM stage.