Current Issue : October - December Volume : 2017 Issue Number : 4 Articles : 6 Articles
Background: We found recently that baseline signal transducer and activator of transcription 3 phosphorylation in\nperipheral blood CD4+ T cells of patients with early rheumatoid arthritis (RA) is associated with treatment response\nto synthetic disease-modifying antirheumatic drugs (DMARDs). This prompted us to study the baseline\nphosphorylation profiles of Janus kinases (JAKs) in blood leukocytes with respect to treatment response in early RA.\nMethods: Thirty-five DMARD-na�¯ve patients with early RA provided blood samples for whole blood flow cytometric\ndetermination of phosphorylation of JAKs in CD4+ and CD8+ T cells, CD19+ B cells, and CD14+ monocytes.\nTreatment response was determined after 1 year of treatment with synthetic DMARDs, with remission defined as\nabsence of tender and swollen joints and normal erythrocyte sedimentation rate. Exact logistic regression was used\nto investigate the association of baseline variables with treatment response. Ninety-five percent CIs of means were\nestimated by bias-corrected bootstrapping.\nResults: High JAK3 phosphorylation in CD4+ and CD8+ T cells, CD19+ B cells, and CD14+ monocytes and low JAK2\nphosphorylation in CD14+ monocytes were significantly associated with remission following treatment with\nsynthetic DMARDs.\nConclusions: Baseline JAK phosphorylation profile in peripheral blood leukocytes may provide a means to predict\ntreatment response achieved by synthetic DMARDs among patients with early RA....
Background: T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain\n(TIGIT) and programmed cell death protein 1 (PD-1) are important inhibitory receptors that associate with\nT cell exhaustion in acute myeloid leukemia (AML). In this study, we aimed to determine the underlying\ntranscriptional mechanisms regulating these inhibitory pathways. Specifically, we investigated the role of\ntranscription factor B lymphocyte-induced maturation protein 1 (Blimp-1) in T cell response and transcriptional\nregulation of TIGIT and PD-1 in AML.\nMethods: Peripheral blood samples collected from patients with AML were used in this study. Blimp-1 expression\nwas examined by flow cytometry. The correlation of Blimp-1 expression to clinical characteristics of AML patients was\nanalyzed. Phenotypic and functional studies of Blimp-1-expressing T cells were performed using flow cytometry-based\nassays. Luciferase reporter assays and ChIP assays were applied to assess direct binding and transcription activity of\nBlimp-1. Using siRNA to silence Blimp-1, we further elucidated the regulatory role of Blimp-1 in the TIGIT and PD-1\nexpression and T cell immune response.\nResults: Blimp-1 expression is elevated in T cells from AML patients. Consistent with exhaustion, Blimp-1+ T cells\nupregulate multiple inhibitory receptors including PD-1 and TIGIT. In addition, they are functionally impaired\nmanifested by low cytokine production and decreased cytotoxicity capacity. Importantly, the functional defect is\nreversed by inhibition of Blimp-1 via siRNA knockdown. Furthermore, Blimp-1 binds to the promoters of PD-1 and\nTIGIT and positively regulates their expression.\nConclusions: Our study demonstrates an important inhibitory effect of Blimp-1 on T cell response in AML; thus,\ntargeting Blimp-1 and its regulated molecules to improve the immune response may provide effective leukemia\ntherapeutics....
Background: Advanced stages of liver cirrhosis lead to a dramatically increased mortality. For valid identification of\nthese patients suitable biomarkers are essential. The most important biomarkers for liver function are bilirubin and\nprothrombin time expressed as International Normalized Ratio (INR). However, the influence of several anticoagulants\non the prothrombin time limits its diagnostic value.\nAim of this study was the evaluation of cholesterol esterification (CE) fraction (esterified cholesterol vs. total cholesterol)\nas an alternative biomarker for liver synthesis and mortality prediction. Under physiological conditions the CE fraction\nin blood is closely regulated by lecithin-cholesterol acyltransferase (LCAT) which is produced in the liver.\nMethods: One hundred forty-two patients with liver disease clinically considered for orthotopic liver transplant for\ndifferent indications were enrolled in the study. One patient was excluded because of the intake of a direct oral factor\nXa inhibitor which has a strong impact on prothrombin time.\nResults: Results of CE fraction were in good agreement with INR (R2 = 0.73; p < 0.001). In patients who died or\nsurvived within three months mean CE fraction was 56% vs. 74% (p < 0.001) and mean INR was 2.0 vs. 1.3 (p < 0.001),\nrespectively. The predictive value of CE fraction for three-month mortality risk was higher compared to INR (p = 0.04).\nResults for one-year mortality were comparable.\nConclusions: The cholesterol esterification fraction is a valid biomarker for liver synthesis and allows reliable prediction\nof mortality. In contrast to INR, it is independent of anticoagulation and other analytical limitations of coagulation tests....
Background: The blood urea nitrogen to creatinine ratio (BCR) has been used since the early 1940s to help clinicians\ndifferentiate between prerenal acute kidney injury (PR AKI) and intrinsic AKI (I AKI). This ratio is simple to use and often\nput forward as a reliable diagnostic tool even though little scientific evidence supports this. The aim of this study was\nto determine whether BCR is a reliable tool for distinguishing PR AKI from I AKI.\nMethods: We conducted a retrospective observational study over a 13 months period, in the Emergency Department\n(ED) of Nantes University Hospital. Eligible for inclusion were all adult patients consecutively admitted to the ED with a\ncreatinine >133 �¼mol/L (1.5 mg/dL).\nResults: Sixty thousand one hundred sixty patients were consecutively admitted to the ED. 2756 patients had plasma\ncreatinine levels in excess of 133 �¼mol/L, 1653 were excluded, leaving 1103 patients for definitive inclusion.\nMean age was 75.7 �± 14.8 years old, 498 (45%) patients had PR AKI and 605 (55%) I AKI. BCR was 90.55 �± 39.32 and 91.\n29 �± 39.79 in PR AKI and I AKI groups respectively. There was no statistical difference between mean BCR of the PR AKI\nand I AKI groups, p = 0.758. The area under the ROC curve was 0.5 indicating that BCR had no capacity to discriminate\nbetween PR AKI and I AKI.\nConclusions: Our study is the largest to investigate the diagnostic performance of BCR. BCR is not a reliable parameter\nfor distinguishing prerenal AKI from intrinsic AKI....
Background: Oral squamous cell carcinoma (OSCC) is becoming more common across the globe. The prognosis of\nOSCC is largely dependent on the early detection. But the routine oral cavity examination may delay the diagnosis\nbecause the early oral malignant lesions may be clinically indistinguishable from benign or inflammatory diseases.\nIn this study, the new diagnostic method is developed by using the surface enhanced Raman spectroscopy (SERS)\nto detect the serum samples from the cancer patients.\nMethod: The blood serum samples were collected from the OSCC patients, MEC patients and the volunteers\nwithout OSCC or MEC. Gold nanoparticles(NPs) were then mixed in the serum samples to obtain the high quality\nSERS spectra. There were totally 135 spectra of OSCC, 90 spectra of mucoepidermoid carcinoma (MEC) and 145\nspectra of normal control group, which were captured by SERS successfully. Compared with the normal control\ngroup, the Raman spectral differences exhibited in the spectra of OSCC and MEC groups, which were assigned to\nthe nucleic acids, proteins and lipids. Based on these spectral differences and features, the algorithms of principal\ncomponent analysis(PCA) and linear discriminant analysis (LDA) were employed to analyze and classify the Raman\nspectra of different groups.\nResults: Compared with the normal groups, the major increased peaks in the OSCC and MEC groups were\nassigned to the molecular structures of the nucleic acids and proteins. And these different major peaks between\nthe OSCC and MEC groups were assigned to the special molecular structures of the carotenoids and lipids. The\nPCA-LDA results demonstrated that OSCC could be discriminated successfully from the normal control groups with\na sensitivity of 80.7% and a specificity of 84.1%. The process of the cross validation proved the results analyzed by\nPCA-LDA were reliable.\nConclusion: The gold NPs were appropriate substances to capture the high-quality SERS spectra of the OSCC, MEC\nand normal serum samples. The results of this study confirm that SERS combined PCA-LDA had a giant capability to\ndetect and diagnosis OSCC through the serum sample successfully....
Background: Despite numerous studies on cardioprotective effects of omega-3 polyunsaturated fatty acids (n-3\nPUFAs), there is limited evidence for n-3 PUFA-mediated effects, especially at its higher dose, on cardiovascular risk in\npatients with type 2 diabetes (DM2) and established atherosclerosis.\nPurpose: To investigate the effect of daily treatment with a higher dose (2 g) of n-3 PUFAs on platelet function,\ncoagulation parameters, fibrin clot properties, markers of systemic inflammation and metabolic status, in patients\nwith atherosclerotic vascular disease and DM2 who receive optimal medical therapy.\nMethods: We conducted a prospective, double-blind, placebo-controlled, randomized, double-center study, in\nwhich thrombin generation (plasma thrombogenic potential from automated thrombogram), fibrin clot properties\n(plasma fibrin clot permeability; lysis time), platelet aggregation (light transmission aggregometry with adenosine\ndiphosphate and arachidonic acid used as agonists), HbA1c, insulin level, lipid profiles, leptin and adiponectin levels,\nas well as markers of systemic inflammation (i.e., hsCRP, IL-6, TNF-�±, ICAM-1, VCAM-1, and myeloperoxidase) were\ndetermined at baseline and at 3 months after treatment with 2 g/day of n-3 PUFAs (n = 36) or placebo (n = 38).\nMoreover, we assessed serum fatty acids of the phospholipid fraction by gas chromatography both at baseline and at\nthe end of the study.\nResults: Majority of patients were treated with optimal medical therapy and achieved recommended treatment\ntargets. Despite higher serum levels of eicosapentaenoic acid (EPA) (by 204%; p < 0.001) and docosahexaenoic acid\n(DHA) (by 62%; p < 0.0001) in n-3 PUFA group at the end of treatment no changes in platelet aggregation, thrombin\ngeneration, fibrin clot properties or markers of systemic inflammation were observed. No intergroup differences in the\ninsulin, HbA1c and lipid levels were found at the end of the study. There was no change in adiponectin and leptin in\ninterventional group, however leptin increased in control group (p = 0.01), therefore after study period leptin levels\nwere lower in the interventional group (p = 0.01). Additionally, resolvin D1 did not differ between interventional and\ncontrol group.Conclusions: In conclusion, our study demonstrated that in patients with long-standing, well-controlled DM2 and\natherosclerotic disease the treatment with a high dose of n-3 PUFAs (namely, 1 g/day of EPA and 1 g/day of DHA for\n3 months) does not improve coagulation, metabolic, and inflammatory status when measured with the specified\ntests....
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