[Role of BCG-depleted immunodominant antigens derived from M. tuberculosis in serological test for tuberculosis].

OBJECTIVE: To explore the roles of BCG-depleted immunodominant antigens derived from M. tuberculosis in serological tests for tuberculosis (TB). METHODS: Four different combinations of current mainstream antigens used for serological diagnosis of TB were selected: Reagent A [Mycobacterium TB immunoglobulin G (IgG) antibody assay kit]; Reagent B (Mycobacterium TB detection kit); Reagent C (M. tuberculosis-specific antibody detection kit); Reagent D [Active TB antibody detection enzyme-linked immunosorbent assay (ELISA) system]. Immunological methods of Western blot, colloidal gold and ELISA were developed to test the antibodies in 109 patients with active tuberculosis (TB) and 97 healthy populations. They were divided into purified protein derivative of tuberculin (PPD) positive and negative groups. Bayesian statistical analysis was used to analyze the influences of variable combinations of different antigens on the detection accuracy of TB. RESULTS: For Reagent A, B, C, D, the detection rates of IgG antibodies in the patients with active TB were 80.0%, 66.7%, 80.7%, 56.0% versus 23.9%, 8.9%, 6.6% and 1.0% respectively in healthy populations. The TB antibody detection rates in four TB patient populations were all higher than that in healthy populations (χ(2) = 47.53, 51.59, 90.48, 69.68, all P < 0.01). The TB antibody detection rates of Reagents A and B increased with the intensity of positive reaction to PPD in healthy populations (χ(2) = 2.124, 2.220, all P < 0.05) while those of Reagents C, D in healthy populations were irrelevant to PPD reaction. (χ(2) = 0.122, 0.479, all P > 0.05). Reagent D has the highest accuracy. The immunoglobulin M (IgM) antibody detection rate of Reagent D was only 2.1% in the patients with active TB. CONCLUSIONS: The detecting sensitivity of TB IgG antibodies is associated with antigen selection. And it is also positively correlated with the number of combined antigens. High-sensitivity detection is often accompanied by a loss of specificity. With the BCG-depleted antigens derived from M. tuberculosis, the specificity of serological test for TB may significantly improve.

Impacts of anti-inflammatory phosphodiesterase inhibitors on a murine model of chronic pulmonary inflammation.

Chronic obstructive pulmonary disease (COPD) often tends to respond poorly to glucocorticoid (GC) therapy. Reduced Histone deacetylase-2 (HDAC-2) activity is an important mechanism behind this GC insensitivity. In this study, we investigated the effects of three phosphodiesterase inhibitors (PDEIs), with an anti-inflammatory propensity, on cigarette smoke (CS)-induced pulmonary inflammation and HDAC-2 activity. Male C57BL/6 mice were exposed to cigarette smoke (CS) over the course of 30 weeks. Administration of the PDEIs commenced from the 29th week and followed a schedule of once daily treatments, 5 days a week, for 2 weeks. Roflumilast (ROF) was administered intragastrically (5 mg·kg-1 ), while pentoxifylline (PTX) (10 mg·kg-1 ) and theophylline (THEO) (10 mg·kg-1 ) were administered intraperitoneally, either alone or in combination with a GC (triamcinolone acetonide or TRI, 5 mg·kg-1 , i.m., single injection). Lung morphometry, as well as the activity of HDAC-2, pro-inflammatory cytokines and reactive oxygen species (ROS) were assessed at the end of the 30-week course. CS exposure was associated with a reduction in HDAC-2 activity and the up-regulation of ROS expression. PTX, ROF, and THEO administration led to the partial restoration of HDAC-2 activity, which was favorably associated with the reduction of ROS expression. However, combining TRI to any of these PDEIs did not synergistically augment HDAC-2 activity. Inactivation of HDAC-2 due to long-term CS exposure is closely related to exaggerated oxidative stress, and this reduced HDAC-2 activity could partially be restored through the use of PDEIs. This finding provides a potential novel approach for further clinical research.

Effect of neutrophil CD64 for diagnosing sepsis in emergency department.

BACKGROUND: The aim of this study is to investigate the diagnostic and prognostic value of neutrophil CD64 (nCD64) as a novel biomarker in sepsis patients. METHODS: One hundred fifty-one adult patients diagnosed with sepsis and 20 age-matched healthy controls were enrolled in the study. Patients with sepsis were further subdivided into a sepsis group and a septic shock group. nCD64 expression, serum procalcitonin (PCT) level, C-reactive protein (CRP) level, and white blood cell (WBC) count were obtained for each patient, and Sequential Organ Failure Assessment (SOFA) scores were calculated. RESULTS: nCD64 expression was higher in the sepsis group with confirmed infection than in the control group. The receiver operating characteristic (ROC) curve of nCD64 was higher than those of SOFA score, PCT, CRP and WBC for diagnosing infection. The area under the curve (AUC) of nCD64 combined with SOFA score was the highest for all parameters. The AUC of nCD64 for predicting 28-day mortality in sepsis was significantly higher than those of PCT, CRP, and WBC, but slightly lower than that of SOFA score. The AUC of nCD64 or PCT combined with SOFA score was significantly higher than that of any single parameter for predicting 28-day mortality. CONCLUSION: nCD64 expression and SOFA score are valuable parameters for early diagnosis of infection and prognostic evaluation of sepsis patients.

MicroRNA­192 acts as a tumor suppressor in colon cancer and simvastatin activates miR­192 to inhibit cancer cell growth.

Colon cancer is one of the most common malignant tumors worldwide. Understanding the underlying molecular mechanisms is crucial for the development of therapeutic strategies for the treatment of patients with colon cancer. In the present study, a novel tumor suppressive microRNA, miR­192, was demonstrated to be markedly downregulated in colon cancer cells compared with normal colon cells. By overexpressing miR­192 in colon cancer HCT­116 cells, the results of the present study revealed that miR­192 inhibits cell proliferation, migration and invasion. Bioinformatics were used to determine the target gene of miR­192 and Ras­related protein Rab­2A (RAB2A) was identified as a downstream target of miR­192. Following the determination of the role of the miR­192­RAB2A pathway in colon cancer, small molecules that may regulate miR­192 were screened and the results demonstrated that simvastatin is an activator of miR­192. Furthermore, simvastatin upregulated miR­192 and inhibited the expression of downstream targets of miR­192, which subsequently led to suppressed proliferation, migration and invasion of colon cancer cells. In conclusion, the present study identified a novel colon cancer cell suppressor, as well as a small­molecule activator of the tumor suppressor miR­192, which may represent a therapeutic strategy for the treatment of patients with colon cancer.

Efficacy of cytokine-induced killer cell-based immunotherapy for hepatocellular carcinoma.

In attempts to delay tumor progression after surgery or minimally invasive local treatments, multidisciplinary strategies have been broadly studied in patients with hepatocellular carcinoma (HCC). The objective of this present study was to evaluate the efficacy of autologous transplantations of cytokine-induced killer (CIK) cells as an adjuvant therapy for patients with HCC. A total of 264 patients with HCC were enrolled in this retrospective study. Of these patients, 165 received either CIK cell therapy alone or as adjuvant therapy to surgery, transcatheter arterial chemoembolization (TACE), or TACE-based comprehensive treatments (CT). The remaining 99 patients received only surgery or TACE. Kaplan-Meier analysis and the Chi-squared test were used to analyze the overall survival (OS), progression-free survival (PFS), and clinical characteristics of the patients in the different treatment subgroups. Kaplan-Meier analysis suggested that patients in the Surgery+CIK group had a significantly improved OS compared with those in the other three groups (P < 0.001). Furthermore, patients who developed a fever after the CIK cell treatments manifested a likely better OS (P = 0.028). Subgroup analysis indicated that patients in the Surgery+CIK group likely had an improved PFS but a similar OS compared with the patients in the Surgery-alone group (P = 0.055 for PFS, and P = 0.746 for OS). Further subgroup analysis showed that the OS in both the TACE+CIK and CT+CIK groups was prolonged significantly compared with that in the TACE-alone group (P = 0.015 and P = 0.018, respectively). However, similar OS was observed between the TACE+CIK and CT+CIK groups (P = 0.686). Autologous transplantation of CIK cells as an adjuvant therapy was associated with better survival for patients with HCC, especially for those who had also undergone TACE. A fever reaction might be a potential event for assessing the curative effect of the CIK treatment.

Fluorescence Resonance Energy Transfer-based Biosensor Composed of Nitrogen-doped Carbon Dots and Gold Nanoparticles for the Highly Sensitive Detection of Organophosphorus Pesticides.

The present article reports a novel biosensor for organophosphorus pesticides based on fluorescence resonance energy transfer (FRET) between nitrogen-doped carbon dots (NC-dots) and gold nanoparticles (AuNPs). The effective NC-dots/AuNPs assembly through the Au-N interaction results in good fluorescence quenching. Active acetylcholinesterase (AChE) catalyzes the hydrolysis of acetylthiocholine into -SH containing thiocholine to replace the NC-dots and trigger the aggregation of AuNPs. In the presence of paraoxon, the activity of AChE is inhibited, and thus preventing the generation of thiocholine, causing fewer NC-dots to be replaced. As a consequence, the fluorescence intensity gradually decreases with increasing amount of paraoxon. This biosensor does not require any complex synthesis or modification, and the results show a wide detection range of from 10(-4) to 10(-9) g/L with a detection limit of 1.0 × 10(-9) g/L (3.6 × 10(-12) mol/L). Two linear response regions have been reported with a turning point at about 10(-6) g/L and three different factors that would influence the response behavior. These phenomena discussed in detail so as to explain the special response mechanism.