BIOSENSORS & BIOELECTRONICS
·
2014
·
IF 6.451
Jianfei Xia,Daimin Song,Zonghua Wang,Feifei Zhang,Min Yang,Rijun Gui,Lin Xia,Sai Bi,Yanzhi Xia,Yanhui Li,Linhua Xia
Simultaneous detection of multiple biomarkers holds great promise for acute leukemia evaluation. Here, a novel biosensor is developed for simultaneous electrochemical detection of interferon gamma (IFN-γ) and lysozyme (Lys) based on aptamer recognition by coupling “signal-on” and “signal-off” modes. On one Au electrode, two kinds of signaling probes labeled by the thiolated ferrocene (Fc)- and methy blue (MB)- were designed to hybridize with IFN-γ and Lys aptamers respectively to form partial complementary DNA duplexes. In the presence of IFN-γ and Lys, the target–aptamer interaction led to the release of aptamer from duplex DNA structure . The single-stranded signaling probes thus suffered from the conformation changes, which resulted in the decreased (or increased) oxidation peak current of Fc (or MB) according to the “signal-off (or signal-on)” mode. Electrodes were characterized using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Under the optimized conditions, the signal changes were quantified using square wave voltammetry (SWV). This proposed biosensor for IFN-γ and Lys possessed linear detection range from 0.01 to 10 nM and 0.1 to 100 nM, with the detection limits of 1.14×10 −3 nM and 0.0164 nM, respectively. Moreover, this biosensor was readily regenerated and proved successful toward the practical analysis. The proposed strategy could provide more integrated and reliable information for acute leukemia evaluation.
研究领域:
生物医学工程
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2018
·
IF 4.556
Yijia Yin,Qian Hu,Chenfeng Xu,Qi Qiao,Xianya Qin,Qingle Song,Yang Peng,Yongdan Zhao,Zhiping Zhang
A dual-sensitive nanoparticle delivery system was constructed by incorporating an acid sensitive hydrazone linker into thermosensitive nanoparticles (TSNs) for co-encapsulating doxorubicin (DOX) and interferon γ (IFNγ) and to realize the co-delivery of chemotherapy and immunotherapy agents against melanoma. DOX, a chemotherapeutic drug, was conjugated to TSNs by a pH-sensitive chemical bond, and IFNγ, a potent immune-modulator, was absorbed into TSNs through the thermosensitivity and electrostatics of nanoparticles. Consequently, the dual sensitive drug-loaded TSN delivery systems were successfully built and showed an obvious core–shell structure, good encapsulation efficiency of drugs, sustained and sensitive drug release, prolonged circulation time, as well as excellent synergistic antitumor efficiency against B16F10 tumor bearing mice. Moreover, the combinational antitumor immune responses of hydrazone bearing DOX/IFNγ-TSN (hyd) were strengthened by activating Th1-type CD4+ T cells, cytotoxic T lymphocytes, and natural killer cells, downregulating the expression levels of immunosuppressive cytokines, such as IL10 and TGFβ, and upregulating the secretion of IL2 and TNFα. Taken together, the multifunctional TSNs system provides a promising strategy for multiple drugs co-delivery with distinct properties.
研究领域:
肿瘤学
·
药剂学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2019
·
IF 9.518
Huan Li,Shihao Song,Meiqi Wen,Ting Bao,Zhen Wu,Huayu Xiong,Xiuhua Zhang,Wei Wen,Shengfu Wang
In this paper, a novel label-free electrochemical impedance aptasensor for highly sensitive detection of IFN-γ based on target-induced exonuclease inhibition was constructed. For this purpose, we designed a DNA hairpin modified on the gold electrode whose loop was the aptamer of the IFN-γ, and the stem was 5′-thiol-modified. In the absence of IFN-γ, Exonuclease III (Exo III) and Exonuclease I (Exo I) digested the double-stranded and single-stranded strands of the hairpin DNA, respectively, causing smaller impedance value on the surface of the electrode. In the presence of IFN-γ, the function of Exo III was greatly inhibited by the binding of the aptamer with the target, and it stopped after cutting three bases of the hairpin DNA. Forming a major target-bound aptamer digestion product, it could not be digested by Exo I, so there was larger impedance on the electrode surface . The calibration curve for IFN-γ was linear in the range of 1 pM–50 nM with the detection limit (LOD) of 0.7 pM . The proposed aptasensor proved good selectivity and reproducibility, and low cost. In addition, the biosensor was able to detect IFN-γ in serum samples successfully, which is expected to provide an efficient method for TB diagnosis at early stages.
研究领域:
生物传感技术
·
医学诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Reports Medicine
·
2024
·
IF 11.7
Yaozhang Yang,Yuanyuan Wang,Fengyi Zeng,Yuhao Chen,Zhiyi Chen,Fei Yan
Our previous work developed acoustic response bacteria, which enable the precise tuning of transgene expression through ultrasound. However, it is still difficult to visualize these bacteria in order to guide the sound wave to precisely irradiate them. Here, we develop ultrasound-visible engineered bacteria and chemically modify them with doxorubicin (DOX) on their surfaces. These engineered bacteria (Ec@DIG-GVs) can produce gas vesicles (GVs), providing a real-time imaging guide for remote hyperthermia high-intensity focused ultrasound (hHIFU) to induce the expression of the interferon (IFN)-γ gene. The production of IFN-γ can kill tumor cells, induce macrophage polarization from the M2 to the M1 phenotype, and promote the maturation of dendritic cells. DOX can be released in the acidic tumor microenvironment, resulting in immunogenic cell death of tumor cells. The concurrent effects of IFN-γ and DOX activate a tumor-specific T cell response, producing the synergistic anti-tumor efficacy. Our study provides a promising strategy for bacteria-mediated tumor chemo-immunotherapy.
研究领域:
医学
·
生物技术
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Xinchen Zhao,Liyan Qiu
Triple-negative breast cancer (TNBC) is associated with high invasiveness and mortality, with current immunotherapies offering limited clinical benefits. Reduced tumor immunogenicity and dendritic cell (DC) dysfunction are major contributors to tumor immune evasion. Herein, an alkaline phosphatase (ALP)-responsive nanovesicle system (P-DOX/IFN-γ), based on lipid-like polyphosphonitrile (PEBP), was developed for the co-delivery of doxorubicin hydrochloride (DOX) and interferon-γ (IFN-γ), aiming to enhance the therapeutic efficacy against TNBC. The phosphate ester structure facilitates nanovesicle formation and enables multiple interactions with both drugs, thereby efficiently achieving the synchronous encapsulation of DOX within the membrane and IFN-γ in the aqueous cavity. P-DOX/IFN-γ exhibits enhanced tumor targeting and ALP-responsive drug release within the tumor microenvironment. Mechanistically, DOX induces immunogenic cell death in tumor cells, while IFN-γ induces cell cycle arrest and upregulates major histocompatibility complex class I (MHC I) expression, synergistically enhancing tumor immunogenicity and promoting DC activation. As a result, P-DOX/IFN-γ significantly amplifies antitumor immunity and reduces long-term postoperative metastasis in the orthotopic 4T1 tumor model. Overall, this study provides a versatile nanoplatform and a promising immunotherapeutic strategy for TNBC and other poorly immunogenic tumors.
研究领域:
肿瘤学
·
药剂学
·
免疫学
✓ 已验证
产品关联
DOI
高影响因子
MICROCHIMICA ACTA
·
2019
·Vol. 186
·期 6
·1-8
·
IF 5.479
Wang Jing,Li Bingzhi,Lu Qiaoyun,Li Xiaoyun,Weng Chenyuan,Yan Xiaoqiang,Hong Junli,Zhou Xuemin
The authors describe a versatile aptasensing scheme based on the use of polypyrrole nanoparticles (PPyNPs) and DNA-silver nanoclusters (DNA-AgNCs) for multiple target detection. The DNA-AgNCs consist of two functional domains, viz. (a) a nucleation domain for attaching the metal core of the nanoclusters, and (b) a recognition domain which consists of a single-stranded aptamer. In the absence of analytes, the single-strand recognition domain will be absorbed onto the surface of the PPyNPs through π stacking and hydrophobic interactions. As a result, the red fluorescence of the DNA-AgNCs (with excitation/emission peaks at 535/625 nm) is quenched by the PPyNPs. On introducing the analytes, the DNA-AgNCs will bind them. This leads to the desorption of DNA-AgNCs and the recovery of the red fluorescence. Based on the above strategy, a versatile, sensitive and selective aptasensor was established for detection of adenosine, thrombin and interferon-gamma. The method was applied to the detection of the above targets in (spiked) serum samples and gave satisfactory results, with detection limit of 0.58 nM for IFN-γ, 0.39 nM for adenosine, and 2.2 nM for thrombin. The use of PPyNPs results in uniquely low non-specific absorption and in improved analytical results in case of real-sample analysis when compared to previously reported methods.
Schematic illustration of DNA-silver nanoclusters and polypyrrole nanoparticles in an aptasensor for detection of multiple targets.
研究领域:
分析化学
·
生物传感器
·
分子诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF INFECTIOUS DISEASES
·
2008
·Vol. 197
·期 1
·117-125
·
IF 6.035
Michaëlsson Jakob,Long Brian R.,Loo Christopher P.,Lanier Lewis L.,Spotts Gerald,Hecht Frederick M.,Nixon Douglas F.
Natural killer (NK) cells are believed to play a role in human immunodeficiency virus type 1 (HIV-1) disease progression, and NK cell levels are reduced in individuals with chronic HIV-1 infection. Interleukin (IL)-2 therapy results in an expansion of CD4+ T cells as well as NK cells; however, little is known about the detailed effects of IL-2 therapy on NKcells in HIV-1 infection in general and in early infection in particular. Here, we investigated the effects of combined IL-2 therapy and antiretroviral therapy (ART) on the number, frequency, phenotype, and interferon (IFN)-γ production of NK cells in individuals with early HIV-1 infection. Patients randomized to receive combined ART and IL-2 therapy predominantly expanded CD56dim NK cells, and the expansion was greater than in patients randomized to receive ART alone. Importantly, NK cell receptor expression and IFN-γ production were maintained over time. This reconstitution ofNKcells may be useful in helping contain viremia if patients discontinue therapy or develop drug resistance.
研究领域:
免疫学
·
病毒学
·
传染病学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Yufeng Deng,Qi hu,Zhiying Song,Mengyuan Nie,Zhiguo Wu,Yongrong Lei,Meng Liu,Dujuan Zhan,Baogang Xie
Objective Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality. Targeted therapies like lenvatinib face limitations due to resistance and immunosuppression. d -Glucaro-1,4-lactone (1,4-GL), a bioactive natural compound with anti-HCC activity, holds unexplored synergistic potential with lenvatinib. This study investigates the combinatorial efficacy of 1,4-GL and lenvatinib against HCC and elucidates the underlying mechanisms. Methods Efficacy was evaluated in H22 tumor-bearing mice treated with lenvatinib (20 mg/kg/day) ± 1,4-GL (25, 50, 100 mg/kg/day). Tumor inhibition, serum cytokines (TNF-α, IFN-γ, AFP), oxidative stress markers (MDA, SOD), liver enzymes (ALT, AST), and splenic T-cell subsets (flow cytometry) were assessed. Histopathology was analyzed via H&E staining. Lenvatinib pharmacokinetics (serum, liver, tumor) with/without 1,4-GL was determined in mice and SD rats using UPLC-MS/MS. In vitro, combinatorial effects on proliferation (CCK-8), migration (scratch assay), and clonogenicity (colony formation) were tested in Huh7 and HepG2 cells. STAT3 phosphorylation and PD-L1 expression (protein: Western blot; mRNA: RT-qPCR) were analyzed. PD-L1 induction was achieved using IFN-γ (20 ng/ml). Results The medium-dose combination (LMGL) achieved 89.97% tumor inhibition in H22 mice, significantly reducing tumor mass by 75% vs. lenvatinib alone (0.21±0.18 g vs. 0.84±0.79 g, p < 0.01). H&E staining revealed extensive necrosis in combination groups. Serum TNF-α and IFN-γ levels significantly increased ( p < 0.001), while AFP approached baseline. Flow cytometry showed an elevated CD4⁺/CD8⁺ T-cell ratio. Oxidative stress was modulated (reduced MDA and elevated SOD, p < 0.01). Pharmacokinetic studies revealed no significant differences in lenvatinib exposure or steady-state concentrations ( p > 0.05) with 1,4-GL co-administration. In vitro, 1,4-GL significantly reduced lenvatinib's IC 50 (Huh7: 18.54 μmol/l; HepG2: 30.34 μmol/l). Combinatorial treatment markedly downregulated PD-L1 protein/mRNA and inhibited STAT3 phosphorylation ( p < 0.05). Scratch and colony formation assays indicated synergy stemmed from immunomodulation and signaling inhibition, not enhanced anti-migration/proliferation. Conclusion 1,4-GL potently synergizes with lenvatinib against HCC by enhancing oxidative stress, reconstituting antitumor immunity, and suppressing the STAT3/PD-L1 signaling axis, without perturbing lenvatinib pharmacokinetics. This defines a novel phytochemical-based combinatorial strategy with significant clinical translation potential for HCC therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2021
·Vol. 22
·期 2
·1-11
·
IF 2.447
Jingli Zhang,Lingling Zhu,Hong Shi,Huizhe Zheng
Previous studies have demonstrated that microRNAs (miRNAs/miRs) serve a vital role in the pathogenesis of Sjögren's syndrome (SS). The present study aimed to investigate the role of miR‑155‑5p in SS and determine its underlying molecular mechanism. An inflammatory lesion model was established by stimulating salivary gland epithelial cells (SGECs) with interferon‑γ (IFN‑γ). The apoptosis of SGECs was measured by using flow cytometry. Levels of proinflammatory factors were detected by reverse transcription‑quantitative PCR and ELISA, respectively. Immunofluorescence was used for p65 staining. Dual‑luciferase reporter assay was performed to verify the interaction between miR‑155‑5p and arrestin β2 (ARRB2). The protein levels in the NF‑κB signaling pathway were assessed by western blotting. The results of the present study demonstrated that treatment with IFN‑γ increased miR‑155‑5p expression, in addition to inducing apoptosis and inflammation in SGECs. Furthermore, overexpression of miR‑155‑5p promoted IFN‑γ‑induced apoptosis and inflammation in SGECs. Overexpression of miR‑155‑5p also increased Bax protein expression, enzyme activities of caspase 3 and caspase 9, release of inflammatory cytokines interleukin‑6 and tumor necrosis factor‑α, and decreased Bcl‑2 protein expression in IFN‑γ‑treated SGECs. By contrast, all of the effects aforementioned were reversed following miR‑155‑5p knockdown. These results demonstrated that miR‑155‑5p activated the NF‑κB signaling pathway, where treatment with the NF‑κB inhibitor, pyrrolidine dithiocarbamate, reversed the effects of miR‑155‑5p overexpression on the inflammatory factors in IFN‑γ‑induced SGECs. miR‑155‑5p was demonstrated to target ARRB2 and negatively regulated its expression levels, such that overexpression of ARRB2 reversed the effects of miR‑155‑5p overexpression on the inflammatory response, apoptosis and the NF‑κB signaling pathway in IFN‑γ‑treated SGECs. Collectively, results from the present study suggest that miR‑155‑5p may activate the NF‑κB signaling pathway by negatively regulating ARRB2 to promote salivary gland damage during SS pathogenesis. This suggests that miR‑155‑5p may serve to be a potential target for the treatment of SS.
研究领域:
免疫学
·
分子生物学
·
细胞生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Analysis and Testing
·
2023
·Vol. 7
·期 3
·295-303
·
IF 4.7
Xia Yanping,Chen Hui,Liu Ruixin,Shi Feng,Ren Chuanli,Li Juan,Zhao Jie,Chen Xiang,Yang Zhanjun
Interferon-γ is a kind of protein with a wide range of biological activities, which can regulate the immune function of the body, and can be used as an important marker to detect and treat bovine tuberculosis diseases. Here, a picogram-level bovine interferon-γ (BoIFN-γ) electrochemical impedance immunosensor was constructed for the first time using mesoporous silica nanospheres (MSNs) to immobilize specific monoclonal BoIFN-γ antibodies. The MSNs and BoIFN-γ immunosensors were characterized using scanning electron microscopy, transmission electron microscope, nitrogen adsorption experiment, X-ray photoelectron spectra, and contact angle measurements. MSNs possess a substantial specific surface area and significant hydrophilicity, and can immobilize many antibody molecules, thereby improving detection sensitivity. The immunosensor has a linear detection range from 0.001 to 10.0 ng/mL with an exceptionally low detection limit of 0.62 pg/mL. Compared to the traditional BoIFN-γ analysis method, BoIFN-γ immunosensor presents superiorities in sensitivity, wide linear range as well as short processing time. More importantly, the BoIFN-γ sensor exhibits high selectivity, reliable repeatability as well as stability, providing a promising application prospect for the early diagnosis of Mycobacterium bovis infection.
研究领域:
生物医学工程
·
免疫学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
TALANTA
·
2025
·
IF 6.1
Yan Hao,Chuling Wu,Ying Zhou,Zelin Zheng,Bin Zhou
A multiplex electrochemiluminescence (ECL) biosensing platform utilizing a potential-resolved pattern was constructed for precise evaluation of dual tuberculosis (TB) biomarkers, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). In the study, the synthesized carbon quantum dot (CQD) and gold nanocluster (AuNC) were successively combined on gold nanoparticle (AuNP) and magnetic bead (MB) to construct signal-amplifying and potential-resolved ECL complex probes. Primary antibody (Ab1) to IFN-γ and TNF-α was modified onto double distinct regions of patterned indium tin oxide electrodes for capturing TB biomarkers. Then, the captured IFN-γ and TNF-α was recognized by corresponding secondary antibody (Ab2)-functionalized ECL complex probes. The binding events generated two distinct and well-resolved ECL peaks in a single potential scan. The intensity of ECL peaks correlated linearly with IFN-γ and TNF-α concentrations over the range of 0.01–1500 pg mL −1 . The multiplex biosensing platform enabled simultaneous and precise evaluation of dual TB biomarkers in serum, potentially establishing a faster and more reliable TB diagnostic technology.
研究领域:
生物医学工程
·
分子诊断
·
免疫学
·
纳米医学
·
临床检验医学
·
转化医学
✓ 已验证
DOI
PubMed
高影响因子
MEDICAL SCIENCE MONITOR
·
2019
·
IF 1.98
Liang Chen,Hanfei Huang,Weixin Zhang,Feifan Ding,Zhenlei Fan,Zhong Zeng
Background CD8 + cytotoxic T lymphocytes (CTLs) have been proved to exert crucial roles in immunological rejection. Exosomes (EXOs) secreted by CD4 + CD25 + regulatory T (Treg) cells is believed to be deeply involved in immune regulation. Nevertheless, whether immunomodulatory effect of CD4 + CD25 + Treg cells on CD8 + CTL depends on EXOs remains unknown and needs to be explored. Material/Methods We purified CD4 + CD25 + Treg cells followed by in vitro amplification. EXOs in culture supernatants of Treg cells was separated and identified. The effect of CD4 + CD25 + Treg cells and CD4 + CD25 + Treg cells-derived EXOs on CD8 + CTL viability, proliferation, cell cycle mRNA, intracellular cytokines, and protein expression were investigated. Results We successfully obtained EXOs from CD4 + CD25 + Treg cells. The inhibition effect of EXOs on CD8 + CTL was concentration-dependent. In addition, the inhibition effect of CD4 + CD25 + Treg cells could be reversed by GW4869, an EXOs inhibitor. The inhibition effect was associated with the regulation of IFN-γ and perforin. Our in vivo experiments proved that natural CD4 + CD25 + Treg cells-released EXOs can prolong liver allograft survival. Conclusions CD4 + CD25 + Treg cells-derived EXOs could become an alternative tool for manipulating the immune system to discover novel underlying immunomodulatory mechanisms.
研究领域:
免疫学
·
移植医学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）