Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
23469987 Evaluation of mean platelet volume (MPV) levels in patients with synovitis associated with 2014 Platelet count, C-reactive protein (CRP) and neutrophile countings are markers those reflect the inflammatory response. Mean platelet volume (MPV) is a simple indicator of platelet size and has been known to be a marker of platelet activity. Some platelet markers, including MPV, have been investigated to have relation with inflammation. MPV is inversely correlated with inflammation in inflammatory bowel diseases, rheumatoid arthritis, and ankylosing spondylitis, as shown in the previous studies. In this study, we aimed to investigate the levels of MPV in patients with synovitis of knee osteoarthritis. 147 patients diagnosed with synovitis associated to osteoarthritis, 191 patients with knee osteoarthritis, and 121 patients between the same age range who did not have joint complaints (control group), totally 459 participants were included to our study. MPV results of these groups were compared. We found a significant difference between the patient group with synovitis associated with osteoarthritis of knee and patients with knee osteoarthritis in MPV blood level (p < 0.0001), similarly a significant difference was found between the patient group with synovitis associated with osteoarthritis of knee and the control group (p < 0.0001). There was no significant difference between the knee osteoarthritis patient group and the control group (p = 0.78). We found a significant relation between MPV and ESR in the patient group with synovitis of osteoarthritis (p = 0.004). According to the Pearson correlation, it is found that there is a negative relationship between CRP and MPV variables in those of knee osteoarthritis patients. This correlation coefficient is statistically significant at the 10% level (p = 0.058). We could not find a relation between CRP and MPV in patients with the osteoarthritis group, but we found negative correlation (p = 0.65). Significant relationship was not found between ESR and MPV variables at the 10% level; the p value is 0.34. In the control group no correlation was found between CRP-MPV (p = 0.69) and ESR-MPV (p = 0.798). MPV levels may be beneficial in osteoarthritis with synovitis patients. MPV levels may be considered as a marker of inflammation but further comprehensive prospective trials are needed in osteoarthritis associated with synovitis patients.
26237147 Cutaneous Cryptococcoma in a Patient on TNF-α Inhibition. 2013 Nov 22 An 87-year old Caucasian male with past medical history of rheumatoid arthritis (RA) and chronic kidney disease presents with left hand erythema, pain, tenderness, induration and edema. Clinically, these hand findings began proximal to the metacarpo-phalangeal joints and extended to the distal wrist. He was noted to have ipsilateral axillary lymph node enlargement but denied any constitutional signs or symptoms. Laboratory markers of inflammation were poor prognostic indicators due to relatively active RA, the use of chronic daily glucocorticoids and weekly adalimumab use. Oral antibiotics were administered with limited success leading to a skin biopsy which reported a hematogenously disseminated fungal panniculitis; cultures grew Cryptococcus neoformans, however, serum cryptococcal antigen was negative. With initial fluconazole treatment, skin findings and lymphadenopathy improved gradually over the next six months. However, the patient's improvement stagnated and his condition reverted back to the state of initial presentation.
23256773 Evaluation of anti-nuclear antibodies and kidney pathology in Lewis rats following exposur 2013 Oct The prevalence of anti-nuclear antibodies (ANA) and self-reported systemic autoimmune diseases were increased in residents of Libby, MT, as was the incidence of ANA in Lewis rats exposed to Libby amphibole (LA) asbestos. However, rats induced to develop rheumatoid arthritis (RA) did not develop autoantibodies associated with RA, nor was RA exacerbated by LA exposure, suggesting that increased ANA expression might be related to some other autoimmune process. Libby residents self-reported increased numbers of physician-diagnosed cases of systemic lupus erythematosus (SLE). Thus, the goal of this study was to determine if the increased incidence of ANA in Lewis rats exposed to LA is related to the development of SLE-like disease. Female Lewis rats were intratracheally instilled bi-weekly for 13 weeks with total doses of 0.15, 0.5, 1.5, or 5.0 mg of LA or 0.5 or 1.5 mg of a positive control fiber, amosite. ANA incidence was significantly increased in all asbestos dose groups, although no dose response was observed. The occurrence of proteinuria was increased in LA 0.5, LA 5.0, and amosite 0.5 dose groups; however, the microscopic appearance of the kidneys was normal, no binding of autoimmune complexes to glomerular surfaces was observed, and antibodies to double-stranded DNA were not elevated. Therefore, an increased prevalence of ANA in rats exposed to asbestos does not appear to correlate with disease markers typically observed in SLE. Analysis of ANA specificity for extractable nuclear antigens (ENA) determined that 98% of ENA(+) samples were specific for the Jo-1 antigen. Autoantibodies to Jo-1 have been reported in patients with interstitial lung disease, suggesting that autoantibodies to Jo-1 may be a biomarker for asbestos-related pulmonary disease.
23139073 Low-level laser therapy improves crescentic glomerulonephritis in rats. 2013 Jul Low-level laser therapy (LLLT) can reduce inflammation in a variety of clinical conditions, including trauma, postherpetic neuralgia, and rheumatoid arthritis. However, the effect of LLLT on internal organs has not been elucidated. The goal of the present study was to investigate the anti-inflammatory effect of daily external LLLT in an animal model of crescentic glomerulonephritis. Crescentic glomerulonephritis was induced in male Wister Kyoto rats by intravenous injection of antibody for glomerular basement membrane (GBM). The rats were irradiated with a low-reactive level diode laser with an infrared wavelength of 830 nm from the shaved skin surface once a day for 14 days (irradiation spot size on the skin surface, 2.27 cm(2); power intensity, 880 mW/cm(2); irradiation mode, continuous mode; irradiation time, 250 s; energy, 500 J; energy density, 220 J/cm(2)). After laser irradiation for 14 days, animals were killed, and the extent of inflammation was evaluated. Expression of gene for inflammatory cytokines including interleukin (IL)-1β and tumor necrosis factor alpha (TNF-α) was assessed by reverse transcription polymerase chain reaction. Crescent formation in glomeruli and infiltration of macrophages and lymphocytes were assessed by histochemical observation. Injection of anti-GBM antibody induced severe glomerulonephritis with crescent formation. Histological observations indicated that LLLT suppressed crescent formation and infiltration of ED1+ macrophages and CD8+ lymphocytes into the glomeruli. LLLT attenuated the levels of IL-1β and TNF-α messenger RNA in the renal cortex. Externally directed LLLT suppresses the activity of rat anti-GBM crescentic glomerulonephritis in rats. LLLT has the potential to be used for direct treatment of glomerulonephritis.
25294523 Hospital admissions greater than 30 days following bariatric surgery: patient and procedur 2015 Jun INTRODUCTION: Assessment of hospital admission in the 30-day period following bariatric surgery likely underestimates true hospital utilization. The purpose of this study is to assess hospital admissions for 2 years following bariatric surgery to identify potential differences by patient and procedure. METHODS: New York State Planning and Research Cooperative System (SPARCS) longitudinal administrative data were used to identify 22,139 adult patients who underwent a primary bariatric surgery from 2006 to 2008. Bariatric operations included laparoscopic gastric banding (LGB), laparoscopic Roux-en-y gastric bypass (RYGB), and laparoscopic sleeve gastrectomy (LSG). Patients were followed for 2 years after surgery to identify all-cause hospital admissions. Statistical correlation between postoperative hospital admission and patient demographics, comorbid conditions, and bariatric procedure was performed. RESULTS: Of the 22,139 patients, 5,718 (26 %) patients were admitted within 2 years of surgery for a total of 9,502 admissions. Thirty-day admission rate was 5 %. The number of admissions per patient ranged from 1 to 22. Assessing the number of admissions per patient demonstrated that 3,741 (17 %) patients had one, 1,575 (7 %) had 2-3, and 402 (2 %) patients had greater than 4 admissions. LSG had both the highest admission rate and percentage of patients with >4 admissions, followed by RYGB and then LGB (p < 0.001). Risk factors for admission included black race, female gender, age > 50, Medicaid/Medicare as payer, congestive heart failure, pulmonary disease, diabetes, rheumatoid arthritis, history of substance abuse, and psychoses/depression. CONCLUSION: One out of four bariatric patients will be admitted to the hospital within 2 years of surgery. While most patients are admitted only once, a subset of patients requiring numerous hospital admissions was identified. LSG is associated with both the highest rate as well as highest frequency of hospital admissions. Several patient factors were also identified that significantly increased admission risk. Consideration and attention to these factors are necessary for operative planning, preoperative patient education, and postoperative monitoring.
25200589 TNF-like ligand 1A is associated with the pathogenesis of psoriasis vulgaris and contribut 2014 Dec TNF-like ligand 1A (TL1A), a newly identified member of the TNF superfamily, has been proved as an important mediator of inflammation and critically involved in the pathogenesis of rheumatoid arthritis and several other autoimmune diseases. The aim of our study was to determine the possible role of TL1A in the pathogenesis of psoriasis. In this study, serum levels of TL1A in patients with psoriasis vulgaris (PV) and atopic dermatitis (AD) were detected by enzyme-linked immunosorbent assay (ELISA). Then, peripheral blood mononuclear cells (PBMCs) from patients with PV were isolated, the mRNA expression of TL1A was measured by real-time quantitative PCR. The effects of TL1A on the production of T cell cytokines, such as IL-17, IFN-γ, IL-4 and IL-10 in PBMCs were determined. We demonstrated that serum TL1A levels were significantly elevated in patients with PV but not in patients with AD. Besides, the high serum TL1A levels in patients with PV decreased after treatment. PBMCs derived from psoriatic patients showed significantly increased TL1A mRNA levels. Soluble TL1A synergized with IL-23 to stimulate PBMCs from patients with PV to produce IL-17. Taken together, these findings strongly suggest that TL1A may play a role in the pathogenesis of PV.
25162741 Epstein-Barr virus in multiple sclerosis. 2014 Aug BACKGROUND/OBJECTIVES: Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system. Many diseases are associated with Epstein-Barr virus (EBV) infection, such as infectious mononucleosis and many types of malignancies, and it is thought to be related to some diseases of autoimmune origin, such as rheumatoid arthritis, systemic lupus erythematosis, and others. The present study aimed to assess EBV in patients with MS. PATIENTS AND METHODS: This case-control study was conducted from October 2012 to September 2013 on 75 MS patients and non-MS controls. Both were tested quantitatively for immunoglobulin G (IgG) antibodies against Epstein-Barr nuclear antigen-1 (EBNA1) and viral capsid antigen (VCA) using the enzyme linked immunosorbent assay technique. RESULTS: Seventy MS patients (93.3%) were positive for EBNA1 IgG compared with 68 controls (90.7%). In MS patients, the mean EBNA1 IgG serum level was 310.91 (±131.05) U/ml; meanwhile, among controls the mean serum EBNA IgG level was 177.81 (±104.98) U/ml.All patients with MS were positive for VCA IgG, whereas only 60 (80.0%) controls were positive. In the MS group, the VCA IgG mean level was 302.19 (±152.11) U/ml compared with 167.94 (±111.79) U/ml in controls. The differences in the serum levels of both markers between the two groups were statistically significant (P<0.001). CONCLUSION AND RECOMMENDATIONS: EBV proved to have a unique immunological pattern in MS patients when compared with non-MS controls. Further studies for more confirmation of the relation between EBV and MS on a large scale are recommended.
24696356 Leishmanial lipid suppresses the bacterial endotoxin-induced inflammatory response with at 2014 Aug The use of live, attenuated, or genetically modified microbes or their cellular component(s) or metabolites has begun to emerge as a potential new approach in medicinal research to deliver biologically active entities. Thus, advancing our knowledge of such microbe-mediated therapy may suggest new avenues for therapeutic intervention in many diseases. We had earlier reported that the total lipid of attenuated Leishmania donovani suppressed the inflammatory responses in rheumatoid arthritis patients. Our present study reveals that the pLLD, isolated from pathogenic L. donovani, decreases the inflammatory level of bacterial endotoxin in stimulated mouse macrophages, as also in the in vivo murine system. It exerts the activity by reducing the level of different mediators, such as cytokine-chemokine(s). It also suppresses the expression of the ubiquitous transcription factor NF-κBp65 in stimulated macrophage cells, improves the endotoxin-associated liver damage, reduces the vascular permeability factors, such as VEGF, and suppresses the expression of cell adhesion molecules, including ICAM-1, VCAM-1, PECAM-1, P-selectin, and E-selectin, in liver of septic mice. These findings indicate that pLLD may prove to be a potential anti-inflammatory agent and protect from endotoxin-induced sepsis in hepatic impairment.
25524576 Leishmanial sphingolipid induces apoptosis in Sarcoma 180 cancer cells through regulation 2015 Apr Sphingolipids are membrane and intracellular lipids that typically modulate cellular processes to cause cell death. Exogenous administration of sphingolipids may cause restriction of tumour growth and several alternative strategies are being used to control the cell growth. The microbes, their cellular component(s) or metabolites like DHA, EPA and also FTY720 have been employed as new therapeutic entities to regulate the disease condition. The therapeutic efficacy of lipids from Leishmania donovani in rheumatoid arthritis and also in sepsis condition associated with inflammatory diseases is well established. In this study, we explored the apoptotic effect of LSPL-1 (leishmanial sphingolipid-1) in Sarcoma 180 cells towards the regulation of tumour growth. The study using a panel of cancer cell lines revealed that LSPL-1 induces cell death in Sarcoma 180. The apoptotic changes were assessed by annexin exposure and DNA content analysis using flow cytometry. LSPL-1 appears to activate several pro- and anti-apoptotic molecules through reactive oxygen species (ROS) generation and also caspase activation, as determined by Western blot and ELISA analyses. Simultaneously, it may improve the survival rate of mice bearing tumour induced by Sarcoma 180 cells, with pathological changes. LSPL-1 may also suppress the cancer-associated inflammatory responses with the expression of matrix metalloproteinase having inhibitory role. It may regulate several angiogenic factors including VEGF, Ang-2 and CD34 in angiogenic events generated in Sarcoma 180 cell-induced tumour. These studies underline the significance of anti-neoplastic potential of LSPL-1 through apoptosis induction and abrogation of angiogenic responses in Sarcoma 180 cell-associated tumour.
25434398 The influences of aconitine, an active/toxic alkaloid from aconitum, on the oral pharmacok 2014 Aconitine (AC), an active/toxic alkaloid from Aconitum species, is commonly present in Traditional Chinese Medicine (TCM) prescriptions because of the great effectiveness of Aconitum for the treatment of rheumatoid arthritis, cardiovascular diseases, and tumors in clinic. Buspirone (BP) is a sensitive CYP3A probe drug that is administered through oral/intravenous routes as recommended by the U.S. Food and Drug Administration. This study aims to investigate the influences of AC (0.125 mg/kg, oral) on first-pass (intestinal and hepatic) CYP3A activity by using oral BP as the probe in rats. The pharmacokinetics of oral buspirone hydrochloride at different doses (12.5, 25, and 50 mg/kg) were conducted. The pharmacokinetics of oral BP in rats pretreated with single dose or multiple doses (7-day) of AC were investigated. The plasma concentrations of BP and its major metabolites [1-(2-pyrimidinyl)piperazine (1-PP) and 6'-hydroxybuspirone (6'-OH-BP)] were determined. The formation ratios of 1-PP and 6'-OH-BP from BP (AUC0-∞ of 1-PP/AUC0-∞ of BP and AUC0-∞ of 6'-OH-BP/AUC0-∞ of BP values) showed no alternation when the dose of BP changed. Single dose of AC decreased the AUC0-∞ of BP by 53% but increased the formation ratio of 6'-OH-BP by 74% (P<0.05). Multiple AC exposure increased the AUC0-∞ of BP by 110%, and the formation ratios of 1-PP and 6'-OH-BP from BP were increased by 229% and decreased by 95%, respectively (P<0.05). Conclusively, single/multiple AC exposure did not alter the first-pass CYP3A activity when using oral BP as probe in rats. Nevertheless, multiple AC exposure had markedly changed the production of BP metabolites.
25391768 Soluble overexpression and purification of bioactive human CCL2 in E. coli by maltose-bind 2015 Mar Human chemokine (C-C motif) ligand 2 (hCCL2) is a small cytokine in the CC chemokine family that attracts monocytes, memory T lymphocytes, and natural killer cells to the site of tissue injury- or infection-induced inflammation. hCCL2 has been implicated in the pathogeneses of diseases characterized by monocytic infiltrates, including psoriasis, rheumatoid arthritis, atherosclerosis, multiple sclerosis, and insulin-resistant diabetes. The prokaryotic overexpression of hCCL2 has been investigated previously in an attempt to develop biomedical applications for this factor, but this has been hampered by protein misfolding and aggregation into inclusion bodies. In our present study, we screened 7 protein tags-Trx, GST, MBP, NusA, His8, PDI, and PDIb'a'-for their ability to allow the soluble overexpression of hCCL2. Three tags-MBP, His8, and PDI-solubilized more than half of the expressed hCCL2 fusion proteins. Lowering the expression temperature to 18 °C significantly further improved the solubility of all fusion proteins. MBP was chosen for further study based on its solubility, expression level, ease of purification, and tag size. MBP-CCL2 was purified using conventional chromatography and cleaved using TEV or Factor Xa proteases. Biological activity was assessed using luciferase and cell migration assays. Factor Xa-cleaved hCCL2 was found to be active and TEV-cleaved hCCL2 showed relatively less activity. This is probably because the additional glycine residues present at the N-terminus of hCCL2 following TEV digestion interfere with the binding of hCCL2 to its receptor.
25339672 Human IgA Fc receptor FcαRI (CD89) triggers different forms of neutrophil death depending 2014 Dec 1 FcαRI (CD89), the human Fc receptor for IgA, is highly expressed on neutrophil granulocytes. In this study, we show that FcαRI induces different forms of neutrophil death, depending on the inflammatory microenvironment. The susceptibility of inflammatory neutrophils from sepsis or rheumatoid arthritis toward death induced by specific mAb, or soluble IgA at high concentrations, was enhanced. Although unstimulated cells experienced apoptosis following anti-FcαRI mAb stimulation, preactivation with cytokines or TLR agonists in vitro enhanced FcαRI-mediated death by additional recruitment of caspase-independent pathways, but this required PI3K class IA and MAPK signaling. Transmission electron microscopy of FcαRI-stimulated cells revealed cytoplasmic changes with vacuolization and mitochondrial swelling, nuclear condensation, and sustained plasma membrane. Coculture experiments with macrophages revealed anti-inflammatory effects of the partially caspase-independent death of primed cells following FcαRI engagement. Our data suggest that FcαRI has the ability to regulate neutrophil viability and to induce different forms of neutrophils depending on the inflammatory microenvironment and specific characteristics of the ligand-receptor interactions. Furthermore, these findings have potential implications for FcαRI-targeted strategies to treat neutrophil-associated inflammatory diseases.
25045124 Leptin induces ADAMTS-4, ADAMTS-5, and ADAMTS-9 genes expression by mitogen-activated prot 2015 Jan Elucidation of the causes of inflammation has vital importance in the development of new approaches for the treatment of arthritic diseases. The degradation of aggrecan by upregulated disintegrin and metalloproteinase with trombospondin motifs (ADAMTSs) is the key event in the development of both rheumatoid arthritis (RA) and osteoarthritis (OA). Increased levels of leptin in both RA and OA have been demonstrated, thus linking leptin to arthritic diseases, but the mechanism has not been clarified. This study investigated the putative role of signaling pathways (p38, JNK, MEK1, NF-ĸB, and PI3) involved in leptin-induced cartilage destruction. Normal human articular chondrocytes were cultured with recombinant human leptin at 100, 250, 500, and 1000 ng/mL doses for 6, 12, 24, and 48 h, after which ADAMTS-4, -5, and -9 genes expression were determined by real time-polymerase chain reaction (RT-PCR) and Western Blot methods. The signaling pathways involved in leptin-induced ADAMTSs upregulation were also investigated by using inhibitors of signaling pathways. It was demonstrated that ADAMTSs expression level was peaked at 1000 ng/mL doses for 48 hours, and MAPKs (p38, JNK, and MEK) and NF-ĸB signaling pathways involving in leptin triggered ADAMTSs upregulation. Obesity as a risk for RA and OA may contribute to the inflammation of both RA and OA diseases by secreting adipokines like leptin. We hypothesize that leptin is involved in the development of RA and OA accompanied with obesity by increasing ADAMTS-4, -5, and -9 genes expression via MAPKs and NF-ĸB signaling pathways.
24992422 The safety and efficacy of bariatric surgery for obese, wheelchair bound patients. 2014 Jul INTRODUCTION: The aim of this study was to evaluate outcomes of bariatric surgery performed in order to improve mobility in patients with severe mobility limitations. METHODS: Patients with severe mobility impairment (wheelchair bound) who underwent laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic adjustable gastric banding (LAGB) surgery to improve their mobility were included in this study. Patients were identified between July 2009 and October 2011 using an electronic prospective bariatric database. Mobility was assessed by questionnaire during clinic follow-up appointments. RESULTS: Fifteen patients (11 female, 4 male) with a mean age of 48 years (range: 26-71 years) and a mean body mass index of 46 kg/m(2) (range: 33-54 kg/m(2)) were included. Seven patients (47%) underwent LAGB and eight (53%) LRYGB. The aetiologies of mobility impairment included advanced osteoarthritis (n=6), spinal conditions (n=4), severe bilateral leg oedema and ulceration (n=2), advanced rheumatoid arthritis (n=2) and traumatic paraplegia (n=1). The mean length of hospital stay was 3.8 days. There was no mortality. One patient was lost to follow-up. Of the remaining 14 patients, the mean excess weight loss percentage at a mean of 18.5 months postoperatively was 48% (68% for LRYGB, 20 months; 29% for LAGB, 17 months). Ten patients reported improved mobility. Reduced pain, improved independence and ability to transfer were most commonly cited. Four patients reported no improvement in mobility (three LAGB patients, one LRYGB patient). CONCLUSIONS: Bariatric surgery can safely improve mobility and quality of life in obese patients with severe mobility impairment. Our paper supports the idea that severe mobility impairment should be considered an indication for bariatric surgery in selected patients. LRYGB demonstrated better weight loss and mobility improvement than LAGB. Larger studies are required to establish robust selection criteria for surgery in this group.
24954358 A novel role for interferon regulatory factor 1 (IRF1) in regulation of bone metabolism. 2014 Aug Increased risk of bone fractures is observed in patients with chronic inflammatory conditions, such as inflammatory bowel disease and rheumatoid arthritis. Members of the Interferon Response Factor family of transcriptional regulators, IRF1 and IRF8, have been identified as genetic risk factors for several chronic inflammatory and autoimmune diseases. We have investigated a potential role for the Irf1 gene in bone metabolism. Here, we report that Irf1(-/-) mutant mice show altered bone morphology in association with altered trabecular bone architecture and increased cortical thickness and cellularity. Ex vivo studies on cells derived from bone marrow stimulated with Rank ligand revealed an increase in size and resorptive activity of tartrate-resistant acid-positive cells from Irf1(-/-) mutant mice compared with wild-type control mice. Irf1 deficiency was also associated with decreased proliferation of bone marrow-derived osteoblast precursors ex vivo, concomitant with increased mineralization activity compared with control cells. We show that Irf1 plays a role in bone metabolism and suggest that Irf1 regulates the maturation and activity of osteoclasts and osteoblasts. The altered bone phenotype of Irf1(-/-) mutants is strikingly similar to that of Stat1(-/-) mice, suggesting that the two interacting proteins play a critical enabling role in the common regulation of these two cell lineages.
24922195 Elevated serum levels of calprotectin (myeloid-related protein 8/14) in patients with anky 2014 Aug BACKGROUND: Calprotectin is one of the major leukocyte S100 proteins showing both calcium binding and antimicrobial characteristics. The serum level of calprotectin is markedly elevated in patients with inflammatory bowel disease, rheumatoid arthritis, as well as systemic lupus erythematosus and has been suggested to play a prominent role in both progression and pathogenesis of these diseases. AIM: The purpose of this study was to investigate the serum level of calprotectin in patients with ankylosing spondylitis (AS) and its association with disease activity and other clinical characteristics of AS. MATERIALS AND METHODS: Thirty-one patients who met the modified New York criteria for AS and 45 healthy controls were included in this study. Both Bath AS disease activity index and AS disease activity score were applied on the patients with AS for the assessment of disease activity; Bath AS functional index, for the assessment of functional activity; Bath AS radiology index, for the assessment of radiological damage; and the AS quality of life questionnaire for the assessment of disease-related life status. Spinal and hip measurements were performed using Bath AS metrology index. The serum level of calprotectin was determined using enzyme-linked immunosorbent assay kit. RESULTS: Mean serum level of calprotectin was significantly higher in the patients with AS compared with healthy controls (P = 0.003). Serum levels of calprotectin did not correlate with Bath AS disease activity index, AS disease activity score, Bath AS functional index, Bath AS radiology index, Bath AS metrology index, modified Schober, chest expansion, AS quality of life questionnaire, erythrocyte sedimentation rate, and C-reactive protein values (P > 0.05). CONCLUSIONS: Our results suggest that calprotectin might play an important role in the pathogenetic mechanisms of AS; however, the calprotectin levels did not correlate with the measurements of disease activity, functional abilities, radiological damage, and the quality of life in these patients. Further insight into this area of research might provide opportunities to develop novel treatment strategies, which take into account the role of these peptides in the pathogenetic mechanisms of AS.
24872622 Immunolocalization of Ki-67 in different periodontal conditions. 2014 Mar BACKGROUND: Ki-67 which is a non-histone nuclear protein which is expressed in proliferating cells, during all the active phases of the cell cycle. Increased Ki-67 expression has been seen in several inflammatory and malignant conditions like diabetes, rheumatoid arthritis, atherosclerosis, pancreatitis and squamous cell carcinoma. AIM: The aim of the present study is to analyze the expression of Ki-67 in gingival tissues by immunohistochemistry in smokers and non-smokers with healthy gingiva and chronic periodontitis. MATERIALS AND METHODS: Gingival biopsies (n = 32) were obtained from smokers who had clinically healthy gingiva (n = 8), smokers with periodontitis (n = 8), chronic periodontitis (n = 8) and healthy gingiva (n = 8). The expression of Ki-67 was evaluated immunohistochemically. STATISTICAL ANALYSIS USED: Mean and standard deviation were estimated for the gingival tissue extract sample for each study group. Mean values were compared between different study groups by, one way ANOVA, post hoc analysis. In this study P < 0.05 was considered as the level of significance. RESULTS: The mean number of Ki-67 positive cells/field was higher in the smokers with periodontitis group. When the mean Ki-67 positive cells were compared between different groups, statistical significant difference was observed between healthy and both the periodontitis groups (P = 0.000) and between smokers group (P = 0.001). CONCLUSIONS: Ki-67 was maximally expressed in smoker with periodontitis followed by chronic periodontitis patients, healthy smokers and healthy control patients which shed light on the toxic effects of tobacco in dysregulating the cell cycle and cellular proliferation. The findings of this study also help us to understand the role of the cell cycle in resolution of periodontal inflammation which is a salient feature in the pathogenesis of chronic periodontitis.
24819773 Efficient neutrophil extracellular trap induction requires mobilization of both intracellu 2014 Excessive or aberrant generation of neutrophil extracellular traps (NETs) has recently become implicated in the underlying aetiology of a number of human pathologies including preeclampsia, systemic lupus erythromatosus, rheumatoid arthritis, auto-antibody induced small vessel vasculitis, coagulopathies such as deep vein thrombosis or pulmonary complications. These results imply that effective pharmacological therapeutic strategies will need to be developed to counter overt NETosis in these and other inflammatory disorders. As calcium flux is implicated in the generation of reactive oxygen species and histone citrullination, two key events in NETosis, we analysed the roles of both extra- and intracellular calcium pools and their modulation by pharmacological agents in the NETotic process in detail. Interleukin-8 (IL-8) was used as a physiological stimulus of NETosis. Our data demonstrate that efficient induction of NETosis requires mobilisation of both extracellular and intracellular calcium pools. Since modulation of the calcineurin pathway by cyclosporine A has been described in neutrophils, we investigated its influence on NETosis. Our data indicate that IL-8 induced NETosis is reduced by ascomycin and cyclosporine A, antagonists of the calcineurin pathway, but not following treatment with rapamycin, which utilizes the mTOR pathway. The action of the G protein coupled receptor phospholipase C pathway appears to be essential for the induction of NETs by IL-8, as NETosis was diminished by treatment with either pertussis toxin, a G-protein inhibitor, the phospholipase C inhibitor, U73122, or staurosporine, an inhibitor of protein kinase C. The data regarding the calcineurin antagonists, ascomycin and cyclosporine A, open the possibility to therapeutically suppress or modulate NETosis. They also provide new insight into the mechanism whereby such immune suppressive drugs render transplant patients susceptible to opportunistic fungal infections.
24728598 RORs in autoimmune disease. 2014 The retinoic acid receptor-related orphan receptor (ROR) subfamily of nuclear receptors are transcription factors involved in the maintenance of circadian rhythm and are essential for proper immune function. The T cell-specific isoform, RORγt, is required for T helper 17 cells (TH17) development and it has been implicated in the pathogenesis of autoimmune diseases including multiple sclerosis and rheumatoid arthritis. Thus, pharmacological repression of RORγt may provide a strategy for therapeutic intervention in autoimmune disorders. This chapter provides a summary of the current status for target validation and development of new chemical entities targeting RORγt.
24685647 Comparative proteomic analysis of anti-cancer mechanism by periplocin treatment in lung ca 2014 BACKGROUND: Periplocin is used for treatment of rheumatoid arthritis, reinforcement of bones and tendons, palpitations or shortness of breath and lower extremity edema in traditional medicine. Our previous findings suggested that periplocin could inhibit the growth of lung cancer both in vitro and in vivo. But the biological processes and molecular pathways by which periplocin induces these beneficial effects remain largely undefined. METHODS: To explore the molecular mechanisms of periplocin involved in anti-cancer activity, in the present study the protein profile changes of human lung cancer cell lines A549 in response to periplocin treatment were investigated using the proteomics approaches (2-DE combined with MS/MS). Western blot was employed to verify the changed proteins. Interactions between changed proteins were analyzed by STRING. RESULTS: 29 down-regulated protein species named GTP-binding nuclear protein Ran (RAN), Rho GDP-dissociation inhibitor 1 (ARHGDIA), eukaryotic translation initiation factor 5A-1 (EIF5A) and Profilin-1(PFN1), and 10 up-regulated protein species named Heat shock cognate 71 kDa protein (HSPA8),10 kDa heat shock protein (HSPE1), and Cofilin-1(CFL-1) were identified. Among them, GTP-binding nuclear protein Ran (RAN) and Rho GDP-dissociation inhibitor 1 (ARHGDIA) were the most significantly changed (over tenfold). The proteasome subunit beta type-6 (PSMB6), ATP synthase ecto-α-subunit (ATP5A1), Aldehyde dehydrogenase 1 (ALDH1) and EIF5A were verified by immunoblot assays to be dramatically down-regulated. By STRING bioinformatics analysis revealing interactions and signaling networks it became apparent that the proteins changed they are primarily involved in transcription and proteolysis. CONCLUSION: Periplocin inhibited growth of lung cancer by down-regulating proteins, such as ATP5A1, EIF5A, ALDH1 and PSMB6. These findings may improve our understanding of the molecular mechanisms underlying the anti-cancer effects of periplocin on lung cancer cells.