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1.
Nanotechnology ; 31(2): 024001, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31550701

RESUMO

Nanostructured mesoporous carbon materials have been an attractive material for electrochemical energy storage in the recent decades. However, the controllable synthesis of two-dimensional mesoporous carbon with tunable thickness and desired pore structure is highly challenging. Here, a series of graphene@mesoporous nitrogen-doped carbon (denoted as G@mesoNC) core-shell structured nanosheets with tunable thicknesses have been fabricated via a sample hydrothermal method by using cellulose as the green and cheap carbon precursor. The resultant G@mesoNC nanosheets exhibit a distinct sandwich-like structure with tunable thicknesses (from 10 to 30 nm), a large surface area (562 m2 g-1), a narrow pore size distribution (2.3 nm) and a high nitrogen content (7.95%). Significantly, when being used as the electrode for supercapaciors, the resultant G@mesoNC nanosheets showcase a high specific capacitance of 264 F g-1. Most importantly, there is no substantial capacitance decay after 2500 cycles, indicating the perfect cyclic stability of G@mesoNC nanosheets. Our method paves a new way for synthesizing carbon electrodes for energy storage.

2.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117416, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31394389

RESUMO

In this work, density functional theory (DFT) and time density functional theory (TDDFT) methods were employed to investigate the nature of the double fluorescence emission of DEAHF in these three solvents. We analyzed the geometric structures, vibrational frequencies, frontier molecular orbitals (MOs), molecular electrostatic potential surface (MEPS), calculated absorption and fluorescence spectra and the potential-energy curves for DEAHF. All the results show that the intramolecular hydrogen bond of DEAHF is strengthened from S0 to S1 and the electron density redistribution occurs between the proton acceptor and donor, which can facilitate ESIPT. Moreover, the geometric structures, absorption and emission spectra, MEPS and potential-energy curve of DEAHF are identical. It reveals theoretically that ACN and PC can maintain the polarity of the solvent with 1:1 mixing, which is consistent with the experimental results.

3.
J Pharm Biomed Anal ; 177: 112837, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31493746

RESUMO

The ambiguity of dose-effect relationship of many traditional Chinese medicines (TCMs) has always influenced their rational use in TCM clinic. Rhubarb, a preferred representative of cathartic TCM, is currently widely used that results in a diversity of its dosage. The aim of this study was to use an integrated metabolomics strategy to simultaneously reveal dose-effect relationship and therapeutic mechanisms of different efficacy of rhubarb in constipation rats. Six doses of rhubarb (0.135, 0.27, 0.81, 1.35, 4.05, and 8.1 g/kg) were examined to elucidate the laxative and fire-purging effects by pathological sections and UPLC-Q-TOF/MSE. The results showed that there existed serious lesions in the stomach and colon of model rats. And conditions were basically improved to some extent in rhubarb-treated groups. Through relative distance calculation based on metabolomics score plots, it suggested that the effective dose threshold (EC20-EC80 range) of rhubarb was from 0.31 to 4.5 g/kg (corresponding to 3.44-50.00 g in the clinic) in rat serum and 0.29-2.1 g/kg (corresponding to 3.22-23.33 g in the clinic) in feces. Then, 33 potential biomarkers were identified in total. Functional pathway analysis revealed that the alterations of these biomarkers were associated with 15 metabolic pathways, mainly including arachidonic acid metabolism, glycerophospholipid metabolism, steroid biosynthesis, primary bile acid biosynthesis and sphingolipid metabolism. Of note, different doses of rhubarb could alleviate endogenous disorders to varying degrees through regulating multiple perturbed pathways to the normal state, which might be in a dose-dependent manner and involved in therapeutic mechanisms. To sum up, integrated serum and fecal metabolomics obtained that rhubarb ranging from 0.31 to 2.1 g/kg is safe and effective for constipation treatment. Also, our findings showed that the robust metabolomics techniques would be promising to be more accurately used in the dose-effect studies of complex TCM, and to clarify syndrome pathogenesis and action mechanisms in Chinese medicine.

4.
J Pharm Biomed Anal ; 177: 112873, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31539711

RESUMO

A rapid, sensitive and convenient analytical method of ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (UPLC-QTRAP®/MS2) was proposed for the simultaneous determination of characteristic alkaline and acidic components covering many structure types including alkaloids, phenolic acids, phenylpropanoids and flavonoids in Leonurus japonicus Houtt. (LJ). The proposed method was first reported and validated by assessing the matrix effects, linearity, limit of detections, limit of quantifications, precision, repeatability, stability and recovery of target components. The developed UPLC-QTRAP®/MS2 was successfully applied to simultaneously determine all target compounds in 38 batches of LJ from 11 different producing regions in China and five organs (including root, caulis, branch, flower and leaf) of LJ from the same stand planting base in Jiangsu Province (China). The result showed that LJ in different regions with different geographical position would affect the accumulation of different compounds, and the significant discrepancies of some target compounds were also observed in different organs of LJ due to different biosynthetic pathway and enzymes in different organs. Furthermore, both hierarchical clustering analysis and principal components analysis were performed to classify the 38 batches of LJ samples from different producing regions on the basis of target compounds. As a result, the samples could be mainly clustered into different groups, which were similar with areas classification. Overall, the presented method would be helpful for the comprehensive utilization and development of LJ resources.

5.
J Ethnopharmacol ; 247: 112284, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31604137

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Herb pair, the most fundamental and simplest form of herb compatibility, serves as the basic building block of traditional Chinese medicine formulae. The Danshen-Honghua herb pair (DH), composed of Salviae Miltiorrhizae Radix et Rhizoma (Danshen in Chinese) and Carthami Flos (Honghua in Chinese), has remarkable clinical efficacy to cure cardio-cerebrovascular diseases. This study was designed to investigate the pharmacodynamics of DH in comparison with single herbs and pharmacokinetics of DH relative to Danshen in acute myocardial ischemic injury. MATERIALS AND METHODS: Sixty male Wistar rats were divided into control, model and drug treated groups. The acute myocardial ischemia rat model was induced by administering 85 mg/kg/d isoproterenol (ISO) subcutaneously for two consecutive days. For pharmacodynamic study, histopathological and biochemical analysis were performed to assess the anti-myocardial ischemic effects. While for pharmacokinetic study, a UPLC-MS/MS method was developed for determination of nine main active ingredients, namely danshensu, protocatechuic acid, protocatechualdehyde, caffeic acid, lithospermic acid, rosmarinic acid, salvianolic acid B, salvianolic acid A and salvianolic acid C in rat plasma. RESULTS: The histopathological and biochemical analysis revealed that DH exerted enhanced anti-myocardial ischemic effects against the ISO-induced myocardial ischemia compared with single herbs. The pharmacokinetic study indicated that DH could significantly increase the t1/2z of danshensu, Tmax, AUC0-∞ and MRT0-t of protocatechuic acid in comparison with Danshen alone in normal rats, but more importantly elevate systemic exposure level and prolong t1/2z of protocatechualdehyde, caffeic acid, Tmax of danshensu in acute myocardial ischemia rats. CONCLUSIONS: Our findings demonstrated the greater effects of DH after the compatibility in ISO-induced acute myocardial ischemia rats at pharmacodynamic and pharmacokinetic levels and provided valuable information for clinical application of herb pairs.

6.
J Nanosci Nanotechnol ; 20(4): 2114-2121, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492219

RESUMO

Organophosphorus pesticides (OPs) are an important class of common pesticides. However, due to the abuse of organophosphorus pesticides, pesticide residue problems have been highlighted. In this study, the colorimetric detection method for OPs residues was established based on the broadspectrum aptamer. Through optimization, isocarbophos and omethoate were analyzed to verify the performance of the colorimetric assay. Under optimal conditions, the method proved effective for detecting an isocarbophos range of 50-1000 ng/mL and an omethoate range of 100-500 ng/mL. The protective effects of broad-spectrum aptamers and the split (28-mer P1+26-mer P2) aptamers on gold nanoparticles (AuNPs) were also comparatively studied. The present results suggested that the colorimetric assay based on broad-spectrum aptamer could be applied for a preliminary screening of different kinds of OPs.

7.
Nat Commun ; 10(1): 4953, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672991

RESUMO

The 1,2-diamine motif is widely present in natural products, pharmaceutical compounds, and catalysts used in asymmetric synthesis. The simultaneous introduction of two amino groups across an alkene feedstock is an appealing yet challenging approach for the synthesis of 1,2-diamines, primarily due to the inhibitory effect of the diamine products to transition metal catalysts and the difficulty in controlling reaction diastereoselectivity and regioselectivity. Herein we report a scalable electrocatalytic 1,2-diamination reaction that can be used to convert stable, easily available aryl alkenes and sulfamides to 1,2-diamines with excellent diastereoselectivity. Monosubstituted sulfamides react in a regioselective manner to afford 1,2-diamines bearing different substituents on the two amino groups. The combination of an organic redox catalyst and electricity not only obviates the use of any transition metal catalyst and oxidizing reagent, but also ensures broad reaction compatibility with a variety of electronically and sterically diverse substrates.

8.
Int J Infect Dis ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682959

RESUMO

OBJECTIVES: To determine the molecular characteristics of a sequence type 338 community-acquired methicillin-resistantStaphylococcus aureus (CA-MRSA) strain and the relationship among MRSA strains from various lineages and areas. METHODS: We performed whole genome sequencing, genomic comparison, antimicrobial susceptibility testing and haemolysis analysis to identify the resistance determinants and virulence factors of strain ZY05 and the relationships among CC59 clones. RESULTS: MRSA strain ZY05 was resistant to tetracycline, erythromycin and clindamycin, and the resistance genes erm(B) and tet(K) were detected in the genome. ZY05 harbours the genomic islands νSaα, νSaß, νSaγ and ΦSa2, the pathogenicity island νSa1, and virulence factors, such as Panton-Valentine leukocidin, phenol-soluble Modulins, alpha haemolysin, enterotoxin B, enterotoxin K, and enterotoxin Q, which were the same as those present in ST59 strains. In addition, the virulence potential of ST338 did not differ from that of ST59. This strain contains the staphylococcal cassette chromosome mec (SCCmec) type VT, a distinct SCCmec type previously reported from Taiwan. The results of cgMLST analysis showed that the gene distances between ST59 and ST338 were close among CC59 isolates, while strains from Taiwan were identical to isolates from the Chinese mainland with respect to these two STs. CONCLUSIONS: The ST338 strain ZY05, which has close genetic relationship with ST59 strains, is multi-drug resistant and highly virulent. Strains of two identical lineages, ST59 and ST338, from Taiwan and the Chinese mainland may have the same genetic background.

9.
Opt Express ; 27(21): 29854-29862, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684241

RESUMO

Monolithic integration of GaN-based phototransistors and light-emitting diodes (LEDs) is reported. Starting with an LED epitaxial wafer, selective Si diffusion was performed to produce an n-p-i-n structure for the phototransistor. A traditional AlGaN bulk electron-blocking layer (EBL) can block electron injection from an emitter to a collector, thereby hindering the photocurrent amplification process. We used an LED wafer with a superlattice EBL; blocking can be removed under a bias of approximately 7 V and above. External quantum efficiencies of more than 100% and 600% at approximately 380 nm and 330 nm, respectively, were achieved at room temperature and a bias of 11 V, corresponding to responsivities of 0.31 and 1.6 A/W, respectively, significantly higher than commercially available ultraviolet (UV) detectors. Furthermore, we demonstrated an integrated operation of the device. UV light was detected using a phototransistor that sent signals to drive an integrated LED as an indicator.

10.
Analyst ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31688860

RESUMO

In this paper, we present a novel method to improve the efficiency of single-cell transcriptome sequencing for analyzing valuable cell samples. The microfluidic device we designed integrates multiple single-cell isolation chambers with hydrodynamic traps and achieves a nearly 100% single-cell capture rate and minimal cell loss, making it particularly suitable for samples with limited numbers of cells. Single cells were encapsulated using a novel phase-switch method into picoliter-sized hydrogel droplets and easily recovered for subsequent reactions. Minimizing the reaction volume resulted in a high reverse transcription (RT) efficiency for RNA sequencing (RNA-Seq). With this novel microfluidic platform, we captured dozens of hESCs (H9) simultaneously and obtained live cells in individual picoliter volumes, thus allowing for the convenient construction of a high-quality library for deep single-cell RNA-Seq. Our single-cell RNA-Seq results confirmed that a spectrum of pluripotency existed within an H9 colony. This integrated microfluidic platform can be applied to various cell types for the investigation of rare cellular events, and the phase-switch single-cell processing strategy will improve the efficiency and accessibility of single-cell transcriptome sequencing analysis.

11.
Kaohsiung J Med Sci ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31688991

RESUMO

MicroRNA-425-5p (miR-425-5p) has been reported to be involved in the tumorigenesis of several tumors, but its function in breast cancer is still unknown. In this study, miR-425-5p was found significantly upregulated in breast cancer cells, and predicted a poor prognosis for breast cancer patients. Overexpression of miR-425-5p could significantly promote breast cancer cell growth. Further studies showed that overexpression of miR-425-5p upregulated the protein levels of Cyclin D1, Cyclin D3, CDK4, and CDK6. However, inhibiting miR-425-5p downregulated their expression and induced cell cycle arrest at G0/G1 phase. In mechanism, overexpression of miR-425-5p increased the phosphorylation of PI3K p85 and AKT, but inhibiting miR-425-5p displayed opposite effects. Moreover, miR-425-5p bound to the 3'UTR of PTEN mRNA, and downregulated the expression levels of PTEN in both mRNA and protein levels in breast cancer cells. Collectively, the results above demonstrated that miR-425-5p was involved in the tumorigenesis of breast cancer by inducing PI3K/AKT signaling and indicated that miR-425-5p could be as a potential target for breast cancer therapy in the future.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31682205

RESUMO

Objectives: To investigate the effect of autologous blood transfusion (ABT) and Pringle maneuver (PM) on postoperative early liver function and short-term postoperative results following laparoscopic liver resection in patients with benign hepatic neoplasms. Materials and Methods: We retrospectively analyzed the clinical data for 125 consecutive patients who underwent laparoscopic segmental hepatectomy from January 2015 to May 2018 (68 in the ABT group versus 57 in the PM group). We compared patients' characteristics and intra- and postoperative short-term outcomes between the groups. Results: The 2 groups were well matched regarding patients' clinical characteristics, types of liver resection, operative time, and histopathological findings (P > .05). Median blood loss was significantly lower in the PM group versus the ABT group (200 mL versus 750 mL, respectively; P < .01), and overall complication rates were similar (n = 12 [17%] versus n = 9 [16%], respectively; P > .05). The ABT group had significantly lower mean levels of total bilirubin, indirect bilirubin, aspartate transaminase, and alanine aminotransferase on postoperative days 1 and 3 (P < .05). The ABT group had a shorter hospital stay compared with the PM group (5.8 days versus 7.7 days, respectively; P < .05) and lower hospitalization costs (55,400 ± 15,400 versus 667,000 ± 21,600 CN dollars, respectively; P < .05). Conclusions: Compared with Pringle's maneuver, laparoscopic hepatectomy with ABT promoted early recovery of liver function and reduced hospitalization costs in select patients with benign hepatic neoplasms.

13.
Sci Rep ; 9(1): 16056, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690780

RESUMO

Mesoporous silica nanoscale microsphere (MSNM), with a special morphology, high porosity, large pore volume and specific surface area, was successfully prepared and used as the matrix material of lauric acid (LA) to prepare a favorable shape-stabilized phase change material (LA/MSNM). The porous network structure of MSNM is effective to prevent the leakage and enhance the thermal stability of LA/MSNM. For comparison, shape-stabilized phase change material of LA/AC, which contained commercially purchased active carbon (AC) and LA, was prepared by the same method. Characterizations of LA/MSNM and LA/AC, such as chemical properties, structure, thermal properties and crystallization properties were studied. The mechanisms of interaction between LA molecules and MSNM or AC were explicated. The results of TGA test showed that the LA/MSNM and LA/AC had superior thermal stability, and however, the melting and solidification enthalpies of LA/MSNM were much higher than that of LA/AC, which was attributed that the loading capacity of MSNM was better than that of LA/AC. All of the study results demonstrated that the mesoporous silica nanoscale microspheres of MSNM synthesized in this study possessed the potential for practical applications as a suitable supporter of organic phase change materials.

14.
J Cell Biochem ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31693255

RESUMO

Breast cancer (BC) and prostate cancer (PC) are the second most common malignant tumors in women and men in western countries, respectively. The risks of death are 14% for BC and 9% for PC. Abnormal estrogen and androgen levels are related to carcinogenesis of the breast and prostate. Estradiol stimulates cancer development in BC. The effect of estrogen on PC is concentration-dependent, and estrogen can regulate androgen production, further affecting PC. Estrogen can also increase the risk of androgen-induced PC. Androgen has dual effects on BC via different metabolic pathways, and the role of the androgen receptor (AR) in BC also depends on cell subtype and downstream target genes. Androgen and AR can stimulate both primary PC and castration-resistant PC. Understanding the mechanisms of the effects of estrogen and androgen on BC and PC may help us to improve curative BC and PC treatment strategies.

15.
Nurs Res ; 68(6): 433-438, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31693548

RESUMO

BACKGROUND: The relationship between an increasing elderly population and wide-ranging neurological conditions has led to heightened rates of cognitive function impairment. Some researchers have found that health literacy risk may be associated with cognitive impairment in older adults. OBJECTIVES: The purpose of this study was to delineate the difference in health literacy risk between older adults with mild cognitive impairment and those with normal cognitive function. METHODS: We conducted a survey study to explore the health literacy risk in older adults with and without mild cognitive impairment. Data were collected from 412 subjects between 60 and 91 years of age (260 without and 152 with mild cognitive impairment) between June and December 2016 in China. Cognitive function was measured using the Mini-Mental Status Examination, Montreal Cognitive Assessment, Global Deterioration Scale, Activities of Daily Living, and Hamilton Depression Rating Scale. Health literacy was measured using the Chinese Citizen Health Literacy Questionnaire. RESULTS: The scores of total health literacy and its three dimensions (basic health knowledge and mind, basic skills, and health lifestyle and behavior) were lower in those with mild cognitive impairment. Older adults with normal cognitive function had adequate or marginal health literacy levels, whereas those with mild cognitive impairment had marginal or inadequate health literacy levels. Using multiple logistic regression analysis, we found that health literacy risk, education level, age, marital status, and body mass index were independent risk factors for mild cognitive impairment. DISCUSSION: These results suggest that low health literacy may be a predictor of mild cognitive impairment. Screening for lower health literacy risk should be included in multidimensional geriatric evaluation.

16.
Bioresour Technol ; : 122252, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31669180

RESUMO

Biochar is traditionally used to improve soil properties in arable land and as adsorbent or precursor of activated carbon in wastewater treatment. Recent advances have shown biochar potentials in enhancing productions of biofuels and chemicals such as bio-ethanol, butanol, methane, hydrogen, bio-diesel, hydrocarbons and carboxylic acids. The properties of biochar such as high levels of porosity, functional groups, cation exchange capacity, pH buffering capacity, electron conductivity, and macro-/micro- nutrients (Na, K, Ca, Mg, P, S, Fe, etc.) provide appropriate conditions to relieve physicochemical stresses on microorganisms through pH buffering, detoxification, nutrients supply, serving as electron carrier and supportive microbial habitats. This paper critically reviewed biochar production and characteristics, biochar utilization in anaerobic digestion, composting, microbial fermentation, hydrolysate detoxification, catalysis in biomass refinery and biodiesel synthesis. This review provides novel vision of biochar application, which could guide future research towards cleaner and more economic production of renewable fuels and bio-based chemicals.

17.
Int J Pharm ; : 118769, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31669557

RESUMO

Bmi-1 is a gene related to malignant transformation in hepatocellular carcinoma (HCC). The liver cancer cells developed the ability to tolerate CDDP treatment with the elevation of Bmi-1. Bmi-1 is also an oncogene promoting malignance of tumor and an anti-cancer target in many studies. Herein, a biocompatible nanocarrier was designed in the study to deliver a chemotherapeutical agent CDDP and Bmi-1 siRNA to kill cancer cells and silence drug resistance related gene simultaneously. Calciumphosphate (CaP) was applied to coat both nanoplatin cores and siRNA as a shell for the purpose of delivering cargos to the cytosol of the tumor cells. Nanoplatin and siRNA co-loaded CaP nanoparticles (NPSC) enhanced cell uptake of CDDP and showed elevated drug accumulation in tumor. NPSC achieved considerable anti-cancer efficacy and counter-regulated drug tolerance, therefore, warranted a further investigation as a novel therapeutic nanosystem to improve cancer therapy.

18.
Sci Rep ; 9(1): 16391, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31704981

RESUMO

Haemolymph microbiome was considered to be unique to healthy invertebrates and beneficial to the host against external pathogens, including disease resistance and maintenance of homeostasis. Here, we investigated the effects of elevated water temperature on infection of haemolymph microbiome of the hard-shelled mussel (Mytilus coruscus). Exposure to Vibrio. cyclitrophicus resulted in high mortality of mussels on day nine at 27 °C. The haemolymph was collected to determine the microbiota by 16 S rRNA gene sequencing. Exposure to waterborne V. cyclitrophicus increased the mortality of mussels that was associated with a reduction in the diversity of their microbial community. Principal coordinate analysis (PCoA) revealed that temperature was an essential factor in shaping microbial communities in mussel haemolymph. Vibrio exposure promoted the proliferation of opportunistic pathogens (e.g., Arcobacter and Francisella) at a lower temperature. A high abundance of Vibrio present in live and dead mussels, at 27 °C might contribute greatly to mortality, as indicated by linear discriminant analysis effect size (LEfSe). These data suggested that the dynamics of microbial community have unique biomarker species in mussel haemolymph that could be used as health indicators. An elevated temperature may reduce the ability of bacterial elimination function against infection in mussel haemolymph.

19.
Electrophoresis ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674686

RESUMO

A novel micro matrix solid phase dispersion method was successfully used for the extraction of quaternary alkaloids in Phellodendri chinensis cortex. The elution of target compounds was accomplished with sodium hexanesulfonate as the eluent solvent. A neutral ion pair was formed between ion-pairing reagent and positively charged alkaloids in this process, which was beneficial for selectively extraction of polar alkaloids. Several parameters were optimized and the optimal conditions were listed as follows: silica gel as the sorbent, silica to sample mass ratio of 1:1, the grinding time of 1 min, The exhaustive elution of targets was achieved by 200 µL methanol/water (9:1) containing 150 mM sodium hexane sulfonate at pH 4.5. The method validation covered linearity, recovery, precision of intra-day and inter-day, limits of detection, limits of quantitation and repeatability. This established method was rapid, simple, environmentally friendly and high sensitivity. This article is protected by copyright. All rights reserved.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31681622

RESUMO

As the first line defensive mediators against Mycobacterium tuberculosis (M.tb) infection, macrophages can be modulated by M.tb to influence innate and adaptive immunity. Recently, we have identified several potential immunodominant T-cell antigens from the region of deletion (RD) of M.tb H37Rv, including Rv1768 from RD14. In this study, we further determined that Rv1768 was highly conserved among virulent M.tb strains and mainly distributed as a secreted protein. Exposure to recombinant purified Rv1768 (rRv1768) induced apoptosis of bone marrow derived macrophages (BMDMs) but showed no dose-dependent manner. Regarding macrophage activation, significant higher levels of iNOS and pro-inflammatory cytokines (like IL-6 and TNF-α) were detected in rRv1768-challenged BMDMs, whereas arginase 1 (Arg1) expression was markedly decreased. Meanwhile, MHC-II expression and antigen presentation activity of BMDMs were also enhanced by rRv1768 stimulation, leading to significantly increased IFN-γ expression of CD4+ T cells isolated from H37Rv-infected mice. It is worthy to note that Rv1768-induced IFN-γ production of peripheral blood mononuclear cells (PBMCs) and Rv1768-specific immunoglobulins was specifically observed in H37Rv-infected mice, but not BCG-infected or normal mice. Analysis of clinical blood samples further revealed that Rv1768 had a higher sensitivity and specificity (91.38 and 96.83%) for tuberculosis diagnosis than the results obtained from clinical CFP10 and ESAT6 peptides (CE)-based enzyme-linked immunospot (ELISPOT) assay. The area under ROC curve of Rv1768 was 0.9618 (95% CI: 0.919-1.000) when cutoff value set as 7 spots. In addition, Rv1768-specific IgG and IgM also exhibited moderate diagnostic performance for tuberculosis compared with CE specific antibodies. Our data suggest that Rv1768 is an antigen that strongly activates macrophages and has potential to serve as a novel ELISPOT-based TB diagnostic agent.

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