INFLAMMATION
·
2020
·Vol. 43
·期 5
·1780-1788
·
IF 3.212
Zhang Liming,Huang Yang,Cui Xiaoxiao,Tan Xiao,Zhu Ying,Zhou Wenjun,Wang Chaokui,Yuan Gangxiang,Cao Qingfeng,Su Guannan,Kijlstra Aize,Yang Peizeng
Previous studies have pointed out that indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme initiating tryptophan metabolism, plays a role in the regulation of the immune system. This project was designed to investigate the potential role of IDO in monocyte-derived dendritic cells (moDCs) obtained from active Vogt-Koyanagi-Harada (VKH) disease patients. In this study, we found that the IDO mRNA expression and enzyme activity were increased in active VKH patients as compared with healthy controls and patients in remission. To investigate the role of IDO in immune regulation, an effective inhibitor 1-methyl-L-tryptophan (1-MT) was used to suppress its activity in DCs. The results showed that inhibition of IDO with 1-MT significantly decreased the expression of DC marker CD86. IDO inhibition did not affect the cytokine production of IL-6, IL-1β, TNF-α, IL-10, and TGF-β in DCs. Downregulation of IDO in DCs also led to the reduction of regulatory T (Treg) cells and an increased CD4 + T cell proliferation. Treatment with 1-MT did not affect the phosphorylation of the MAPK pathway in DCs. In general, our study suggests that IDO may play an important role in the pathogenesis of VKH disease by regulating DC and CD4 + T cell function. Tryptophan deficiency and kynurenine accumulation may account for the complicated effects of IDO. Further research is needed to study the precise tryptophan metabolites that may limit immune responses in VKH disease.
研究领域:
免疫学
·
眼科
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Targeted Oncology
·
2020
·Vol. 15
·期 3
·365-375
·
IF 4.036
Ding Shengnan,Mao Xia,Cao Yang,Wang Na,Xu Hao,Zhou Jianfeng
Background Although chimeric antigen receptor (CAR) T-cell therapy targeting antigens expressed in refractory and relapsed non-Hodgkin B-cell lymphoma, such as CD19 and CD22, has achieved encouraging clinical effects, some patients fail to attain remission, or relapse after CAR T-cell therapy, which has been ascribed to the loss of the target antigens. Objective To evaluate CD79b as an alternative target for CAR T-cell B-cell lymphoma therapy. Patient and methods The expression of CD79b in different B-cell lymphomas was determined. Anti-CD79b CAR T-cells expressing one of two different CARs were generated, and a series of in vitro and in vivo experiments were conducted to assess the CAR T-cell function. Results We found that CD79b was extensively expressed on the tumor cells of patients with various types of lymphoma regardless of stage, subtype, and cytogenetic and molecular features. Anti-CD79b CAR T-cells were highly specific and effective for the treatment of B-cell lymphomas. Conclusions Our data indicate that CD79b could be used as a target for CAR T-cell therapy of B-cell lymphomas, and further clinical development is warranted.
研究领域:
肿瘤学
·
免疫学
·
血液学
✓ 已验证
DOI
PubMed
高影响因子
Nature Communications
·
2018
·Vol. 9
·期 1
·1-10
·
IF 12.353
Li Xinchun,Zhai Tianyou,Gao Pengcheng,Cheng Hongli,Hou Ruizuo,Lou Xiaoding,Xia Fan
Nanochannels with functional elements have shown promise for DNA sequencing, single-molecule sensing, and ion gating. Ionic current measurement is currently a benchmark, but is focused solely on the contribution from nanochannels’ inner-wall functional elements (NIWFE); the attributes of functional elements at nanochannels’ outer surface (NOSFE) are nearly ignored, and remain elusive. Here we show that the role of NOSFE and NIWFE for ion gating can be distinguished by constructing DNA architectures using dual-current readout. The established molecular switches have continuously tunable and reversible ion-gating ability. We find that NOSFE exhibits negligible ion-gating behavior, but it can produce a synergistic effect in alliance with NIWFE. Moreover, the high-efficiency gating systems display more noticeable synergistic effect than the low-efficiency ones. We also reveal that the probe amount of NOSFE and NIWFE is almost equally distributed in our biomimetic nanochannels, which is potentially a premise for the synergistic ion-gating phenomena.
研究领域:
生物物理学
·
纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2018
·Vol. 103
·期 2
·903-915
·
IF 3.34
Wang Hong,Chu Weihua,Ye Chao,Gaeta Bruno,Tao Huimin,Wang Min,Qiu Zheng
Quorum sensing (QS) is a cell-to-cell communication that is used by bacteria to regulate collective behaviors. Quorum sensing controls virulence factor production in many bacterial species and it is regarded as an attractive target to combat bacterial pathogenicity, especially against antibiotic-resistant bacteria. Chlorogenic acid (CA), abundant in fruits, vegetables, and Chinese herbs, processes multiple activities. In this research, we explored its quorum sensing quenching activity. In Pseudomonas aeruginosa , CA significantly inhibited the formation of biofilm, the ability of swarming, and virulence factors including protease and elastase activities and rhamnolipid and pyocyanin production. CA showed similar inhibitory effects in Chromobacterium violaceum on its biofilm formation, swarming motility, chitinolytic activity and violacein production. We examined the expression of QS-related genes in P.aeruginosa and found these genes were all downregulated by CA treatment. Computational modeling revealed that CA can form hydrogen bonds with all three QS receptors. Caenorhabditis elegans and mouse infection models were employed to explore the anti-virulence ability of CA and its effect on pathogenesis process in vivo . CA extended the survival period and reduced the quantity of P. aeruginosa in nematode gut, showing a moderate protective effect on C. elegans . In mice wound model, CA-treated groups showed an accelerating healing rate and the bacteria number in wound area was also decreased by CA treatment. It is suggested by our research that CA has potential to be used as an anti-virulence factor in P. aeruginosa infection.
研究领域:
微生物学
·
药理学
·
感染病学
✓ 已验证
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2017
·Vol. 184
·期 7
·2365-2373
·
IF 4.58
He Jincan,Li Gongke,Hu Yuling
The authors describe a fluorescence amplification strategy for selective and sensitive fluorescent assays based on aptamer-triggered directional hydrolysis and on the use of metal organic frameworks (MOFs) of type MIL-101. The method is implemented by mixing MIL-101, fluorescein-labeled DNA probes, exonuclease of type RecJf, and targets. A smart design of the three-adenine bulge on the DNA probe facilitates exonuclease-assisted directional hydrolysis, making the strategy universal for determination of both proteins and small molecules as well. Good selectivity is accomplished due to the use of MIL-101 protected aptamers, while high sensitivity resulted from exonuclease-assisted target-recycling signal amplification. The power of the method is demonstrated by analyzing the two model analytes thrombin (a fairly large protein) and oxytetracycline (OTC; a small molecule antibiotic). The limits of detection are 15 pM for thrombin and 4.2 nM for OTC. This is two orders of magnitude lower than that of conventional 1:1 homogeneous fluorescence assays. The strategy was successfully applied to the analysis of thrombin and OTC in real samples. In our perception, the strategy presented here has a wide scope for selective and sensitive detection of trace analytes for which appropriate DNA probes can be identified.
Schematic of an aptamer-triggered amplification strategy for sensitive bioassays based on fluorescence quenching of a MOF and 5′→3′ directional hydrolysis of RecJf exonuclease. The adenine-bulge on the DNA probe facilitates exonuclease hydrolysis, making the strategy universal for both proteins and small molecules detection.
研究领域:
生物化学
·
分析化学
·
分子生物学
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DOI
高影响因子
MICROCHIMICA ACTA
·
2017
·Vol. 184
·期 10
·3909-3917
·
IF 4.58
Wen Yi,Yuan Yali,Li Le,Ma Dandan,Liao Qi,Hou Shaoyan
The authors describe an ultrasensitive amperometric enzymatic assay for uranyl ion. It is based on the use of mesoporous silica nanoparticles (mesoSiNPs) loaded with Methylene Blue (MB) and functionalized with an UO 2 (II)-dependent DNAzyme. The electroactive label MB was sealed in the inner pores of the mesoSiNPs along with double stranded DNA (containing the DNAzyme and the substrate strand). In the presence of UO 2 (II), the DNAzyme is actived to cleave the substrate strands. This leads to the cleavage of the caps and the release of MB from the mesoSiNPs. The amount of released MB depends on the concentration of UO 2 (II) and can be determined amperometrically, best at a working voltage of −0.25 V (vs SCE), by using a chitosan coated carbon paste electrode. Response is linear in the 20 pM to 0.1 nM UO 2 (II) concentration range, and the detection limit is as low as 0.15 pM. Recoveries from spiked samples varied from 91.3 to 99.4%. The assay is highly specific, selective, and not interfered by other metal ions.
(a) Schematic representation of the synthesis, MB loading, and dsDNA Binding of the mesoSiNPs, as well as the release of MB from mesoSiNPs in the presence of UO 2
2+ . (b) Schematic illustration of the stepwise DNAzyme-based electrochemical sensor for uranium detection.
研究领域:
生物化学
·
环境科学
·
分析化学
✓ 已验证
DOI
高影响因子
BIOPROCESS AND BIOSYSTEMS ENGINEERING
·
2020
·Vol. 44
·期 1
·67-79
·
IF 2.419
Zhou Hai-Yan,Zhou Jian-Bao,Yi Xiao-Nan,Wang Yan-Mei,Xue Ya-Ping,Chen De-Shui,Cheng Xin-Ping,Li Mian,Wang Hong-Yan,Chen Kai-Qian,Liu Zhi-Qiang,Zheng Yu-Guo
To develop new cellulases for efficient utilization of the lignocellulose, an endoglucanase (CoCel5A) gene from Colletotrichum orchidophilum was synthesized and a recombinant Pichia pastoris GS115/pPIC9K/cocel5A was constructed for secretory expression of CoCel5A. After purification, the protein CoCel5A was biochemically characterized. The endoglucanase CoCel5A exhibited the optimal activity at 55–75 °C and high thermostability (about 85% residual activity) at the temperature of 55 °C after incubation for 3 h. The highest activity of CoCel5A was detected when 100 mM citric acid buffer (pH 4.0–5.0) was used and excellent pH stability (up to 95% residual activity) was observed after incubation in 100 mM citric acid buffer (pH 3.0–6.0) at 4 °C for 24 h. Carboxymethyl cellulose sodium salt ( n = approx. 500) (CMC) and β - d -glucan were the best substrates for CoCel5A among the tested substrates. The kinetic parameters V max , K m , and K cat / K m values against CMC were 290.70 U/mg, 2.65 mg/mL, and 75.67 mL/mg/s, respectively; and 228.31 U/mg, 2.06 mg/mL, and 76.45 mL/mg/s against β - d -glucan, respectively, suggesting that CoCel5A has high affinity and catalytic efficiency. These properties supported the potential application of CoCel5A in biotechnological and environmental fields.
研究领域:
生物化学
·
生物技术
·
酶学
·
微生物学
✓ 已验证
DOI
PubMed
高影响因子
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
·
2015
·Vol. 176
·期 7
·2039-2052
·
IF 1.735
Feng Tingting,Liu Haitao,Xu Qinggang,Sun Jianzhong,Shi Haifeng
Coptotermes formosanus is a well-known wood-feeding termite that can degrade lignocellulose polysaccharides efficiently with its unique multi-enzyme catalysis system. β-glucosidase (BG) is one of the important cellulases in its enzyme system. However, there may present multiple endogenous BGs in termite digestive system for various properties and functions. This study aims to characterize two BG homologs and reveal their potential coordinative effect. In this study, two endogenous BG homologs (CfGlu1B and CfGlu1C) from C. formosanus showed different substrate specificity. CfGlu1B favors cellobiose while CfGlu1C favors sucrose. Besides, CfGlu1C exhibited higher alkali resistance than CfGlu1B. Kinetic analysis revealed that CfGlu1B enzyme’s activity toward p -NP-β-D-glucopyranoside ( p -NPG) was higher than that of CfGlu1C, and the difference mainly attributes to the turnover number ( K
cat ). In addition, the activity assay showed significant synergistic action of CfGlu1B and CfGlu1C in degrading D-lactosum. For effect of metals, Cu 2+ inhibited both enzymes and Ca 2+ increased the activity of CfGlu1C but not CfGlu1B. Site-directed mutagenesis analysis indicated that both enzymes lost activities when residues E190 of CfGlu1B and E168 of CfGlu1C were mutated to alanine, respectively, which were essential active centers of the GHF1 enzymes. Moreover, mutation H252N increased the activity of enzyme CfGlu1C by 2.1-fold. This study implies interesting possibilities for better practical biotechnological use in green energy production.
研究领域:
酶学
·
生物化学
·
分子生物学
·
生物技术
✓ 已验证
DOI
PubMed
高影响因子
Nano Research
·
2020
·Vol. 14
·期 1
·222-231
·
IF 8.183
Zhu Huimin,Cao Guodong,Fu Yike,Fang Chao,Chu Qiang,Li Xiang,Wu Yulian,Han Gaorong
Multidrug resistance (MDR) restricts chemotherapy efficacy due to P-glycoprotein (P-gp) mediated drug efflux, whereas current approaches to suppressing P-gp expression suffer from intrinsic challenges, such as low transfection, high toxicity and poor specificity. Here, hollow ferric-tannic acid complex nanocapsules (HFe-TA), which can be effectively degraded by the reaction with adenosine triphosphate (ATP), are synthesized for the delivery of glucose oxidase (GOx) and doxorubicin (DOX) for tumor treatment. The findings indicate that the intracellular ATP is significantly decreased due to the combined effect of HFe-TA degradation and GOx-mediated glucose consumption. Along with this ATP down-regulation, P-gp expression of tumor cells is suppressed remarkably, which in turn promotes the intracellular accumulation and anticancer efficacy of DOX. In addition, the production of OH by Fe ions released from HFe-TA is promoted by the by-products of the oxidation of glucose process by GOx. In consequence, HFe-TA nanocapsules loaded with DOX and GOx enable significant inhibition effect to tumors both in vitro and in vivo due to the synergistic effect of cascade reactions. This study has therefore provided an alternative therapeutic platform for effective tumor inhibition with the potential in overcoming intrinsic MDR.
研究领域:
纳米技术
·
药学
·
癌症研究
·
生物医学工程
✓ 已验证
DOI
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2016
·Vol. 409
·期 7
·1797-1803
·
IF 3.125
He Meng-Qi,Wang Kun,Wang Jin,Yu Yong-Liang,He Rong-Huan
To specifically and sensitively identify bisphenol A (BPA) with a simple and rapid method is very important for food safety. Using an anti-BPA aptamer and Mo 2 C nanotubes, we developed a label-free and low-background signal biosensor for BPA detection. The anti-BPA aptamer drastically increased the fluorescence signal of N -methylmesoporphyrin IX under an assistance of Help-DNA. Additionally, BPA can interact with the anti-BPA aptamer and switch its conformation to prevent the formation of a G-quadruplex, resulting in fluorescence quenching. Simultaneously, Mo 2 C nanotubes can reduce the background signals due to the adsorption of Help-DNA on their surface. This method shows a linear range of 2–20 nM with a detection limit of 2 nM for detecting BPA. This label-free BPA aptasensor with low background signal is inexpensive, easy to use, and can be applied to determine BPA in real water samples.
A low-background and label-free biosensor was designed based on Mo 2 C nanotubes and aptamer for BPA detection.
研究领域:
分析化学
·
环境科学
·
食品安全
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL GEOCHEMISTRY AND HEALTH
·
2017
·Vol. 40
·期 2
·763-776
·
IF 2.616
Wang Lanjun,Wang Jinhua,Zhu Lusheng,Wang Jun
The production of commercial livestock and poultry often involves using with antibiotics and feed additives, such as oxytetracycline (OTC) and copper (Cu). These are often excreted into the soil by animal feces; hence, combined pollutants may contaminate the soil. To evaluate single and combined toxic effects of OTC and Cu on the soil ecology, changes in quantities of bacteria, fungi, and actinomycetes in the soil were studied over a 28-d incubation period by a plate count method, microbes numbers counted on days 7, 14, 21, and 28. Abundances of ammonia monooxygenase ( amoA ) gene expression by ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) in soil samples also were tested by real-time polymerase chain reactions (RT-PCRs) on day 21. The results revealed that the numbers of bacteria, fungi and actinomycetes and amoA genes copies of AOA and AOB were reduced seriously by exposure to Cu (1.60 mmol/kg). Similarly, the combined pollution treatments (mole ratios of OTC: Cu was 1:2, 1:8, and 1:32) also had inhibitory effect on bacteria, fungi, and actinomycetes numbers and amoA gene copies of AOA and AOB; the inhibitory rate was on obvious growth trend with the increasing mole ratios. Effects from single OTC pollution were found on bacteria (days 7 and 14), fungi (days 7, 14, 21, and 28), and AOA- amoA gene copies (day 21), with promotion at a low concentration (0.05 mmol/kg) and suppression at higher concentrations (0.2 and 0.8 mmol/kg). Also, numbers of bacteria, fungi, and actinomycetes decreased with longer culture times. Combining OTC and Cu led to a higher inhibition of soil microbes than when either chemical was used alone. However, there was no significant relationship between single and combined toxic chemicals because of their complicated interactions, either antagonistic or synergistic. The results also indicated the sensitivity of bacteria, fungi, actinomycetes on toxic chemicals existed difference and that the AOA were more tolerant than the AOB to these chemicals.
研究领域:
环境科学
·
微生物学
·
土壤生态学
✓ 已验证
DOI
PubMed
高影响因子
Food Analytical Methods
·
2021
·Vol. 14
·期 5
·957-967
·
IF 3.366
Sha Junyi,Lin Hong,Timira Vaileth,Sui Jianxin
To detect enrofloxacin (ENR) and ciprofloxacin (CIP) residues in fishery foods, a computer simulation was used to predict and analyze the binding sites existing aptamer specific to ENR and CIP. A new aptamer (SEQ.3) that can recognize ENR and CIP was screened and evaluated, and the dissociation constants (K d ) of SEQ.3 from ENR and CIP were determined to be 210.955 nM and 887.49 nM which are higher than other aptamers SEQ.4 and SEQ.5 by microscale thermophoresis (MST). Colorimetric detection method based on gold nanoparticles (AuNPs) was developed through optimization of temperature, incubation time, aptamer concentration, and other conditions. The results showed that the limit of defection (LOD) of the new aptamer to ENR and CIP were 1.89 nM and 6.84 nM, respectively, which were similar to that of the original aptamer. The recovery rate of the colorimetric method was between 87.8~102.18%. All the results implied that the developed colorimetric aptamer sensor has broad application prospects in food safety detection and environmental monitoring.
研究领域:
食品安全
·
环境监测
·
分子生物学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）