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Biomedical subjects

Ting Deng

Publications and source records attributed to Ting Deng.

11 recordsLinked to original sources

The mRNA export pathway licenses viral mimicry response and antitumor immunity by actively exporting nuclear retroelement transcripts.

Nuclear retroelement transcripts (RTs), which can be elicited both transcriptionally and posttranscriptionally, form double-stranded RNA (dsRNA) in cytosol to trigger the viral mimicry response (VMR) and antitumor immunity. However, the strength of the induced VMR varies tremendously across tumor types, and the underlying mechanisms remain poorly understood. Here, we demonstrate that the mRNA export pathway modulates the VMR through actively exporting nuclear RTs for cytosolic dsRNA formation after their induction. Tumor cells hijack this process for immune evasion through aberrant coactivator-associated arginine methyltransferase 1 (CARM1) expression. Mechanistically, we show that the cytoplasmic transportation of RTs by the mRNA export pathway is counteracted by the RNA exosome, which cleaves multiple transcripts within this pathway, including those encoding the essential DExD-box helicase 39A (DDX39A) and the adaptor protein ALYREF. CARM1 enhances the RNA exosome activity to attenuate the nuclear export of RTs by the mRNA export pathway through two synergistic mechanisms: (i) transcriptionally activating several RNA exosome components and (ii) posttranslationally methylating arginine 6 of the RNA exosome subunit EXOSC1, which protects it from proteasome-mediated degradation. Collectively, our study highlights the critical active regulatory role of the mRNA export pathway in transporting nuclear RTs into the cytosol for triggering the VMR and tumor immunity. Furthermore, we propose that enhancing the mRNA export pathway activity, either through CARM1 inhibition or RNA exosome modulation, could reinforce the therapeutic agent-induced VMR, thus holding the promise for overcoming tumor immune evasion and immunotherapy resistance.

Humans↗

Anti-hyperlipidemic properties of CM108 (a flavone derivative) in vitro and in vivo.

Peroxisome proliferator-activated receptors (PPARs) and liver X receptor alpha are ligand-activated transcription factors that belong to nuclear receptors superfamily and are involved in the regulation of lipid metabolism. PPAR, especially PPAR-alpha, PPAR-gamma agonists and liver X receptor alpha agonists can regulate the expression or biosynthesis of some factors involved in the formation and function of HDL, such as apolipoprotein (apo) A-I and ATP binding cassette transporter A1 (ABCA1). It is well known that HDL plays an important role in the treatment of hyperlipidemia as the carrier of reverse cholesterol transport. In the present study, the anti-hyperlipidemic properties of CM108, a derivative of flavone, 9-Hydroxy-2-mercapto-6-phenyl-2-thioxo-1,3,5-trioxa-2lambda(5)-phospha-cyclopenta[b]naphthalen-8-one, were studied. Through the transactivation assays of in vitro study, it was discovered that CM108 could activate PPAR-alpha PPAR-gamma and liver X receptor alpha at 40-150 microg/ml, which subsequently resulted in activating ABCA1 promoter and enhancing apoA-I and apoA-II production, whereas reducing apoC-III production significantly. Furthermore, after in vivo study that the hyperlipidemic rats were treated with CM108 for 4 weeks, a significant increase was found in HDL cholesterol levels (26.7%, P<0.05) and a significant decrease was also noticed in triglyceride levels (26.3%, P<0.01) at 100 mg/kg CM108 group compared with that of control animals. Meanwhile, the atherogenicity index, represented by total cholesterol/HDL ratio, was significantly reduced (P<0.01). In conclusion, CM108 can effectively elevate HDL levels and lower triglyceride levels in hyperlipidemic rats maybe by regulating a series of genes, receptors and proteins related to HDL.

ATP Binding Cassette Transporter 1↗

A novel piezoelectric immunoagglutination assay technique with antibody-modified liposome.

A simple rapid piezoelectric immunoagglutination assay (PEIA) technique with antibody-modified liposome has been developed for direct quantitative detection of human immunoglobulin G (hIgG). This technique is based on specific agglutination of antibody-coated liposome particles in the presence of the corresponding antigen, which can be monitored by the frequency shift of a piezoelectric device. Compared with conventional piezoelectric assays, this liposome-based PEIA does not require the immobilization of antigen or antibody on the quartz crystal surface, making the developed technique especially useful for rapid and renewable immunochemical determination. To alleviate non-specific adsorption of serum proteins, modification of the quartz crystal surface by different protocols and the composition of the assay medium have been investigated. The results indicate that the background interference can be substantially minimized through modifying the quartz crystal surface with a bovine serum albumin (BSA) layer and introducing an appropriate amount of BSA in the assay medium. The effects of the liposome composition, the liposome concentration and the concentration of poly(ethylene glycol) (PEG) in the assay medium, have also been investigated. The frequency responses of the liposome-based PEIA are linearly correlated to hIgG concentration in the range of 0.05-6 microg mL(-1) with a detection limit of 50 ng mL(-1).

Agglutination Tests↗

[Pharmacokinetics and tissue distribution of atractylenolide III in rats].

OBJECTIVE: [corrected] To establish an HPLC method for the analysis of pharmacokinetics and tissue distribution of atractylenolide III in rats. METHODS: The biological samples were extracted with ether. The chromatographic conditions were as follows: Hypersil ODS column (150 mm x 4.6 mm, 5 microm) was used. The mobile phase was methnol/warter (67 : 33) with a flow rate of 1.0 ml/min under the column temperature of 25 degrees C, and the detection wavelength was set at 220 nm. RESULTS: The recovery of the method was 85.12% (RSD = 5.57%). The linear range was 0.2 microg/ml - 18.5 microg/ml (r = 0.9996) in rat plasma. The Lowest Limit of detection was 0.10 microg/ ml (S/N > 3). The within-day and between-day precision were from 0.98% to 6.19% and 12.95% to 15.48%, respectively. After oral administration of atractylenolide III (100 mg/kg), the concentration-time profiles of atractylenonlide III fit a two compartment model. In main effect tissues, the atractylenolide III concentration was followed as in order C(lung) > C(cerebellum) > C(heart) > C(cerebrum), and that was C(spleen) > C(liver) > C(kidney) in eliminated tissues. CONCLUSION: The method is accurate, stable and reliable, and can be used for the investigation of atractylenolide III in plasma and tissues of rats.

Animals↗

Quartz crystal microbalance bioaffinity sensor for biotin based on mixed self-assembled monolayers and metastable molecular complex receptor.

A quartz crystal microbalance (QCM) sensor was proposed for the detection of small molecule biotin based on the mixed self-assembled monolayer (SAM) of thiols on gold substrate and the bioaffinity difference between an analyte (biotin) and an analogue compound (HABA) in binding avidin. Avidin formed a metastable complex with 2-[(4-hydroxyphenyl)azo]benzoic acid (HABA) immobilized on the crystal surface. When the sensor contacts a sample solution containing biotin, the avidin was released from the sensor surface to form a more stable complex with biotin in solution. The frequency change recorded is proportional to the desorbed mass of avidin, and there is a clear mathematic relationship between the frequency change and the biotin concentration. The use of mixed SAMs allows the stable attachment of bioreceptor molecules on the QCM, and enhances the amount of the immobilized molecules on the QCM, as a longer "space arm" in the mixed SAMs makes this monolayer membrane more accessible to capture the immobilized molecules. The proposed bioaffinity sensor has nice response to biotin in the range of 0.017-1.67 microg/mL. The sensor could be regenerated under very mild conditions simply by reimmersion of the sensor into a biotin solution to desorb the surplus avidin.

Azo Compounds↗

A sensitive immunoassay based on electropolymerized films by capacitance measurements for direct detection of immunospecies.

Fabrication of a capacitive immunosensor based on electropolymerized polytyramine (Pty) film for the direct detection of human serum albumin (HSA) without any labeling is described. The capacitance change of the heterostructures, Pty films/covalently bonded antibodies/buffered medium, is utilized for monitoring the specific antibody-antigen interaction. The Pty films are ultrathin and the HSA assay is nearly specific. Experimental parameters affecting antibody immobilization and the sensing of HSA are investigated in detail and optimized. This capacitive sensor prepared with the present method can provide high sensitivity. Under the optimized experimental conditions, a linear calibration curve in the concentration range 1.84-368.6 ng/ml when plotted vs the logarithm of the antigen concentration is obtained and the detection limit (S/N=3) is 1.60 ng/ml. After an acidic washing the present system can be used again. The applicability and reliability of the sensor are also demonstrated.

Animals↗

[Relationship between CD8+ T-cell CD28 expression and TCM differentiation type in patients with chronic aplastic anemia].

OBJECTIVE: To explore the relationship between CD8+ T-cell CD28 molecular expression in peripheral blood and TCM type in patients with chronic aplastic anemia (CAA). METHODS: Using flow cytometry to detect the CD28 expression in 45 in-patients or out-patients and 24 healthy subjects for control. And the relation with TCM type was analyzed from the immunological aspect. RESULTS: (1) The levels of CD8, CD28, CD8+ CD28+ expression and CD8+ CD28+/CD8+ CD28- were all higher in the CAA patients than those in the healthy subjects (P < 0.05 or P < 0.01). (2) The levels of CD28, CD8+ CD28+ expression and CD8+ CD28+/CD8+ CD28- were all higher in the CAA patients of Shen-Yin deficiency type than those in the CAA patients of Shen-Yang deficiency type (P < 0.05 or P < 0.01). CONCLUSION: (1) The abnormal high expression of peripheral blood co-stimulatory molecules CD28 suggested CD28 disorder may play an important role in immuno-pathogenesis of CAA. (2) The levels of peripheral CD28, CD8+ CD28+ expression and CD8+ CD28+/CD8+ CD28- can be taken as an objective indexes for TCM typing of CAA, which was disordered more severe in patients of Shen-Yin deficiency type than in those of Shen-Yang deficiency type.

Adult↗

Piezoelectric immunoassay for complement C4 based on a Nafion-modified interface for antibody immobilization.

A piezoelectric immunosensor based on a Nafion membrane interface with a simple immobilization procedure has been developed for the determination of complement C4 in human serum. The polyanionic perfluorosulfonated Nafion polymer was used to modify the electrode surface of quartz-crystal microbalance (QCM) as a platform for the immobilization of complement C4 antibodies. The surface morphology of QCM modified with Nafion membrane was investigated using scanning electron microscopy. The system was optimized with regard to the parameters involved in the preparation of the immunosensor and the assay process. The proposed immunosensor responds well to C4 in the range of 0.08-1.6 microg/ml with a relative standard deviation of <5.3%. Moreover, the proposed immunosensor has advantages in terms of the speed and simplicity of the immobilization procedure as well as the simple and advantageous regeneration process. The experimental results obtained with regard to nonspecific adsorption and recovery indicate that the proposed immunosensor offers a promising alternative tool for the clinical diagnosis of complement C4.

Antibodies↗

A plasma-polymerized film for capacitance immunosensing.

A capacitance immunosensor based on a plasma-polymerized ethylenediamine film (PPEF) has been developed. The resulting PPEF is studied with scanning electrode micrograph (SEM), IR reflection spectrum and cyclic voltammetry. SEM and IR reflection spectrum showed that the plasma-polymerized film (PPF) formed on the gold electrode surface is quite homogeneous, flat, nonporous and contains plenty of free-reacted -NH2. Moreover, cyclic voltammetry showed that the hexacyanoferrate redox reactions were blocked well by the formed PPF, that is to say, the formed PPF has excellent insulating characteristics. To investigate its applicability for capacitive immunosensing, goat-anti-human IgG antibody (IgGAb) was coupled to the PPF-coated gold electrode surface via glutaraldehyde (GA) to form an immunoglobulin G (IgG) probe. Alternating current (ac) impedance and capacitance measurement were used in the immunoassay. The experiment results show that the PPEF is applicable to form insulating layer of capacitive immunosensors.

Biosensing Techniques↗

Immunophenotyping of acute leukemia using an integrated piezoelectric immunosensor array.

Immunophenotyping evaluation is of particular importance for the clinical diagnosis, therapy, and prognosis of acute leukemia. In this paper, an integrated piezoelectric immunosensor array has been developed for the first time to detect the differentiated leukocyte antigens for immunophenotyping of acute leukemia. The probes (crystals) of the array were fabricated with plasma-polymerized n-butylamine film and nanometer-sized gold particles on which the Fab'-SH fragments obtained by the reduction of leukemic lineage-associated monoclonal antibodies (markers) were subsequently immobilized. Investigation results showed that the developed immunosensor array could rapidly identify normal cells from leukemic blasts and define the leukemic blasts within certain phenotypic groups (lineages) by only one analysis of the sample purified or unpurified. It permits the detection of unpurified leukocytes in the dynamic concentration range of 2 orders of magnitude (10(4)-10(6) cells mL(-1)). Up to 17 successive assay cycles with retentive sensitivity were achieved for the probes regenerated with 8 M urea. Moreover, the piezoelectric immunoassay system was applied to evaluate a number of practical specimens with immunophenotyping results in acceptable agreement with those clinically classified. The newly proposed multiparameter analysis technique provides a rapid, simple, and direct alternative tool for clinical immunophenotyping of acute leukemia.

Acute Disease↗

A protein A-based orientation-controlled immobilization strategy for antibodies using nanometer-sized gold particles and plasma-polymerized film.

A novel protein A (PA)-based strategy for the orientation-controlled immobilization of antibodies using nanometer-sized gold (Nano-gold) particles and an amine-terminated plasma-polymerized film (PPF) has been proposed. A quartz crystal microbalance was fabricated, accordingly, coupling with haptoglobin (HP) antibody followed by HP immunoassay, as a model test system. The crystal was modified with plasma-polymerized n-butyl amine film to deposit Nano-gold particles and PA, on which HP antibodies were immobilized. The surface topology of the as-prepared crystal was characterized by use of scanning electron microscopy. In contrast to the traditional flat gold surface, the assembled Nano-gold particle monolayer could allow PA molecules bound with higher bioactivity and loading amount (density), achieving better antibody-binding capabilities. Results indicate that immunosensors prepared using the developed PPF-Nano-gold-PA binding procedure exhibit increased analytical performance compared with those produced using the direct PA binding procedure and the PPF-based glutaraldehyde cross-linking procedure. A HP serum concentration as low as 0.41 nM can be determined by this new system. Regenerated simply by rinsing in the acid buffer, the proposed sensor can achieve up to 11 assay cycles without significant loss of sensitivity.

Animals↗