Scientific Reports
·
2017
·Vol. 7
·期 1
·1-14
·
IF 4.259
Lu Jian,Shao Yanjiao,Qin Xuan,Liu Daozhi,Chen Ang,Li Dali,Liu Mingyao,Wang Xin
Cytochrome P450 (CYP) 3A accounts for nearly 30% of the total CYP enzymes in the human liver and participates in the metabolism of over 50% of clinical drugs. Moreover, CYP3A plays an important role in chemical metabolism, toxicity, and carcinogenicity. New animal models are needed to investigate CYP3A functions, especially for drug metabolism. In this report, Cyp3a1/2 double knockout (KO) rats were generated by CRISPR-Cas9 technology, and then were characterized for viability and physiological status. The Cyp3a1/2 double KO rats were viable and fertile, and had no obvious physiological abnormities. Compared with the wild-type (WT) rat, Cyp3a1/2 expression was completely absent in the liver of the KO rat. In vitro and in vivo metabolic studies of the CYP3A1/2 substrates indicated that CYP3A1/2 was functionally inactive in double KO rats. The Cyp3a1/2 double KO rat model was successfully generated and characterized. The Cyp3a1/2 KO rats are a novel rodent animal model that will be a powerful tool for the study of the physiological and pharmacological roles of CYP3A, especially in drug and chemical metabolism in vivo .
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Experimental and Therapeutic Medicine
·
2018
·Vol. 15
·期 4
·3265-3272
·
IF 1.41
Yuan‑Jun Xia,Hong Xia,Ling Chen,Qing‑Shui Ying,Xiang Yu,Li‑Hua Li,Jian‑Hua Wang,Ying Zhang
Bone morphogenetic protein‑2 (BMP‑2) serves an important role in the development of bone and cartilage. However, administration of BMP‑2 protein alone by intravenous delivery is not very effective. Sustained delivery of stabilized BMP‑2 by carriers has been proven necessary to improve the osteogenesis effect of BMP‑2. The present study constructed a novel drug delivery system using dextran sulfate (DS)‑chitosan (CS) microspheres and investigated the efficiency of the delivery system on recombinant human bone morphogenetic protein (rhBMP‑2). The microsphere morphology, optimal ratio of DS/CS/rhBMP‑2, and drug loading rate and entrapment efficiency of rhBMP‑2 CS nanoparticles were determined. L929 cells were used to evaluate the cytotoxicity and effect of DS/CS/rhBMP‑2 microspheres on cell proliferation. Differentiation study was conducted using bone marrow mesenchymal stem cells (BMSCs‑C57) cells treated with DS/CS/rhBMP‑2 microspheres or the control microspheres. The DS/CS/rhBMP‑2 microspheres delivery system was successfully established. Subsequent complexation of rhBMP‑2‑bound DS with polycations afforded well defined microspheres with a diameter of ~250 nm. High protein entrapment efficiency (85.6%) and loading ratio (47.245) µg/mg were achieved. Release of rhBMP‑2 from resultant microspheres persisted for over 20 days as determined by ELISA assay. The bioactivity of rhBMP‑2 encapsulated in the CS/DS microsphere was observed to be well preserved as evidenced by the alkaline phosphatase activity assay and calcium nodule formation of BMSCs‑C57 incubated with rhBMP‑2‑loaded microspheres. The results demonstrated that microspheres based on CS‑DS polyion complexes were a highly efficient vehicle for delivery of rhBMP‑2 protein. The present study may provide novel orientation for bone tissue engineering for repairing and regenerating bone defects.
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OncoTargets and Therapy
·
2023
·
IF 4
Liji Jiang,Gang Xu,Zihuang Li,Xiaowei Zeng,Zhuangling Li,Jingwen Liu,Lin Mei,Xianming Li
Although radiotherapy remains the most powerful as well as the primary treatment modality for nasopharyngeal carcinoma (NPC), approximately 20% of NPC patients still have local recurrence. Carbonic anhydrase IX (CAIX)-related signaling pathways that mediate radioresistance have been found in various kinds of cancer. However, the role of CAIX in NPC radioresistance is still unknown. In this study, we investigated the effect of CAIX silencing on sensitization to ionizing radiation in NPC by using Lipofectamine 2000, which delivers small interfering ribonucleic acid (siRNA) that targets CAIX. Results showed that Lipofectamine 2000 effectively delivered siRNA into the CNE-2 cells, which resulted in the decrease of CAIX expression and cell viability, decrease in cell proliferation and colony formation, and increase in the number of CNE-2 cells stuck in the G2/M phase of the cell cycle upon induction of ionizing radiation. Increased sensitivity of radiotherapy in CNE-2 cells under hypoxic conditions was correlated with the suppression of CAIX. Cells treated with irradiation in addition to CAIX-siRNA1 demonstrated reduced radiobiological parameters (survival fraction at 2 Gy [SF2]) compared with those treated with irradiation only, with a sensitization-enhancing ratio of 1.47. These findings suggest that CAIX can be a promising therapeutic target for the treatment of radioresistant human NPC.
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ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Ruijin Zeng,Minghao Qiu,Qing Wan,Zhisheng Huang,Xiaolong Liu,Dianping Tang,Dietmar Knopp
Large-scale, rapid, and inexpensive serological diagnoses of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) are of great interest in reducing virus transmission at the population level; however, their development is greatly plagued by the lack of available point-of-care methods, leading to low detection efficiency. Herein, an ultrasensitive smartphone-based electrochemical immunoassay is reported for rapid (less than 5 min), low-cost, easy-to-implement detection of the SARS-CoV-2 nucleocapsid protein (SARS-CoV-2 N protein). Specifically, the electrochemical immunoassay was fabricated on a screen-printed carbon electrode coated with electrodeposited gold nanoparticles, followed by incubation of anti-N antibody (Ab) and bovine serum albumin as the working electrode. Accompanied by the antigen–antibody reaction between the SARS-CoV-2 N protein and the Ab, the electron transfer between the electroactive species [Fe(CN)6]3–/4– and the electrode surface is disturbed, resulting in reduced square-wave voltammetry currents at 0.075 V versus the Ag/AgCl reference electrode. The proposed immunoassay provided a good linear range with SARS-CoV-2 N protein concentrations within the scope of 0.01–1000 ng/mL (R2 = 0.9992) and the limit of detection down to 2.6 pg/mL. Moreover, the detection data are wirelessly transmitted to the interface of the smartphone, and the corresponding SARS-CoV-2 N protein concentration value is calculated and displayed. Therefore, the proposed portable detection mode offers great potential for self-differential diagnosis of residents, which will greatly facilitate the effective control and large-scale screening of virus transmission in resource-limited areas.
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POLYMER TESTING
·
2021
·
IF 4.282
Jing Zhang,Pai Peng,Lingdong Chen,Liping Zhao,Jie Feng
In recent years, hydrogels with antifouling properties and good biocompatibility have attracted great attention in bio-devices, but most of them are lack of eminent mechanical properties that limit their practical application greatly. In this work, a newly hybrid ion-covalent cross-linked double network (DN) hydrogels with excellent antifouling as well as mechanical properties were prepared by a simple one-pot method based on sodium alginate and a kind of antifouling material, N -hydroxyethyl acrylamide (HEAA). The DN hydrogel have excellent mechanical properties, including high tensile strength (1.32 MPa), high elastic modulus (0.31 MPa) and preeminent fatigue resistance. Besides, the DN hydrogel have good antifouling properties suggested by protein adsorption and cell adhesion experiments. In addition, they also exhibit highly in vitro compatibility. These properties make the DN hydrogels suitable for application in different fields, such as tissue scaffolds, implantable devices and so on.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Ji Wang,Yanhao Zhang,Shuo Dong,Wenhui Zha,Chao Liu,Yang Wang,Yuhao Jiang,Hanlei Xing,Xinsong Li
Lipid nanoparticles (LNPs)-based mRNA vaccines have shown great potential in the fight against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. However, it remains still a challenge to improve the delivery efficiency of LNPs and the long-term stability of their mediated mRNA vaccines. Herein, a novel ionizable lipid 2-hexyldecyl 6-(ethyl(3-((2-hexyldecyl)oxy)-2-hydroxypropyl)amino)hexanoate (HEAH) derived LNPs were developed for delivering the receptor binding domain (RBD) mRNAs. In vitro cell assays confirmed that the ionizable lipid HEAH with one ether bond and one ester bond derived LNPs possessed higher mRNA delivery efficiency compared with the approved ALC-0315 with two ester bonds used in the BNT162b2 vaccine. Notably, the HEAH-derived LNPs powder lyophilized did not significantly change for 30 days after storage at 37 °C indicating good thermostability. After two RBD mRNAs of Delta and Omicron variants were encapsulated into the HEAH-derived LNPs, a bivalent mRNA vaccine was obtained as a nanoparticle formulation. Importantly, the bivalent mRNA vaccine not only resisted Delta and Omicron and also generated protective antibodies against ancestral SARS-CoV-2. The HEAH-mediated bivalent vaccine induced stronger humoral and cellular immunity than those of the ALC-0315 group. Taken together, the ionizable lipid HEAH-derived LNPs show outstanding potential in improving the delivery efficiency of mRNA and the stability of mRNA vaccine.
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JOURNAL OF APPLIED ENTOMOLOGY
·
2022
·Vol. 146
·期 6
·760-772
·
IF 2.183
Ya Xing,Fang Niu,Xiao-Mei Wang,Huan-Wen Chen,De-Fu Chi
Dioryctria abietella is a major pest of conifer cones that can initiate specific behaviours (locating hosts, finding mates and selecting oviposition sites) through sensitive olfactory systems. General odorant-binding proteins are involved in the first step in odorant perception in insects, but their specific functional roles in D . abietella chemoreception have not been fully elucidated. In this study, quantitative real-time polymerase chain reaction (PCR) examinations showed that DabiGOBP2 is predominantly expressed in the antennae of female adults. Western blot experiments further confirmed that these proteins show biased expression in the tissues. Binding property analysis demonstrated that DabiGOBP2 exhibited ligand specificity to terpenes, especially myrcene ( K i = 8.19 ± 0.05). Electroantennogram (EAG) and Y-tube assays showed that three plant volatiles elicited high EAG responses, but only dodecanal showed a strong attraction to females. However, myrcene and isobutyl benzoate were significantly repellent to males at high doses in the behaviour test. In conclusion, exploring the functions of DabiGOBP2 can help in better understanding the mechanism of the olfactory system of D . abietella and developing novel strategies to control this pest.
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Journal of Environmental Chemical Engineering
·
2021
·
IF 5.909
Liying Jiang,Zhiwei Yao,Pengju Wang,Jianmeng Chen,Yufen Zhang,Wu Huang,Xiang Cao,Yufeng Xu
Plasma-catalytic removal of chlorobenzene (CB) was conducted in a dielectric barrier discharge (DBD) reactor over two manganese-based catalysts, LaMnO 3 and cryptomelane-type octahedral molecular sieve (OMS-2). The physicochemical properties of two catalysts were characterized by XRD , SEM, TEM , BET, XPS and H 2 -TPR. It was shown that OMS-2 catalyst had larger surface area, smaller particle size, better redox properties, higher ratio of Mn 4+ /Mn 3+ and higher content of surface-adsorbed oxygen (O ads ). The introduction of manganese-based catalysts enhanced CB removal, increased the CO 2 selectivity , and inhibited ozone (O 3 ) and NO x formation. OMS-2 exhibited a better degradation, mineralization and energy yield, with 89.5% of CB degradation, 57.6% of CO 2 selectivity and 0.54 g kWh −1 at discharge voltage of 6 kV, than LaMnO 3 in the NTP-catalytic reactor and this was ascribed to more active sites, more O ads , higher redox property and better O 3 decomposition ability on OMS catalyst surface. The two manganese-based catalysts were stable in the NTP-catalysis system although some intermediate byproducts were deposited on the catalyst surface during the 24-h activity cycling tests. Moreover, the intermediate byproducts were analyzed by GC/MS, and then the possible degradation pathways of CB decomposition in the plasma-catalysis system were suggested.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2018
·
IF 3.412
Fei Zhou,Weisu Huang,Maiquan Li,Yongheng Zhong,Mengmeng Wang,Baiyi Lu
Acteoside and salidroside are major phenylethanoid glycosides (PhGs) in Osmanthus fragrans Lour. flowers with extensive pharmacological activities and poor oral bioavailability. The absorption mechanisms of these two compounds remain unclear. This study aimed to investigate the bioaccessibility of these compounds using an in vitro gastrointestinal digestion model and to examine the absorption and transport mechanisms of PhGs using the Caco-2 cell model. The in vitro digestion model revealed that the bioaccessibility of salidroside (98.7 ± 1.35%) was higher than that of acteoside (50.1 ± 3.04%), and the superior bioaccessibility of salidroside can be attributed to its stability. The absorption percentages of total phenylethanoid glycoside, salidroside, and acteoside were 1.42–1.54%, 2.10–2.68%, and 0.461–0.698% in the Caco-2 model, respectively. Salidroside permeated Caco-2 cell monolayers through passive diffusion. At the concentration of 200 μg/mL, the apparent permeability (Papp) of salidroside in the basolateral (BL)-to-apical (AP) direction was 23.7 ± 1.33 × 10–7 cm/s, which was 1.09-fold of that in the AP-to-BL direction (21.7 ± 1.38 × 10–7 cm/s). Acteoside was poorly absorbed with low Papp (AP to BL) (4.75 ± 0.251 × 10–7 cm/s), and its permeation mechanism was passive diffusion with active efflux mediated by P-glycoprotein (P-gp). This study clarified the bioaccessibility, absorption, and transport mechanisms of PhGs. It also demonstrated that the low bioavailability of acteoside might be attributed to its poor bioaccessibility, low absorption, and P-gp efflux transporter.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2020
·
IF 4.872
Ruifen Kang,Aneela Perveen,Chunmei Li
T-2 toxin is a kind of group A trichothecenes mycotoxins , frequently detected in various foods and feeds, having high toxic effects on both humans and animals. The present study aims to investigate the toxic effects of T-2 toxin exposure to ICR mice during pregnancy and lactation on liver glycolipid metabolism of young mice. The pregnant mice were given 0, 0.005 and 0.05 mg of T-2 toxin/kg bw daily through oral gavage from late gestation (GD 14) to the lactation (LD 21). Liver and serum samples of the young mice were collected on postnatal day 21 (PND 21), PND 28 and PND 56. The results showed that T-2 toxin increased the contents of triglycerides (TG), total cholesterol (T-CHO) and glucose in serum of young mice on PND 21 and PND 28. In addition, obvious lipid droplets of liver in T-2 toxin treatment groups were observed, especially in 0.05 mg group of PND 21and PND 28. Compared with the control group, T-2 treatment also increased the expressions of genes associated with liver glycolipid metabolism, such as PEPCK , Glut2 , Fas , Acox1 , Hmgcr , PPARα , Srebp1 and CD36 . These results demonstrated T-2 toxin exposure to pregnant mice could cause liver glycolipid metabolism disruption in the young mice and the toxic effects weakened on PND 56.
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MICROCHIMICA ACTA
·
2022
·Vol. 189
·期 8
·1-10
·
IF 6.408
Zhao Tingting,Yan Weizhen,Dong Fengqi,Hu Xinlong,Xu Yanli,Wang Zhenyu,Shen Yating,Wang Wanrong,Zhao Ye,Wei Wenmei
COVID-19 necessitates the development of reliable and convenient diagnostic tools. In this work, a facile 3D-printed smartphone platform was constructed that achieved reliable visual detection of SARS-CoV-2 by eliminating the effect of ambient light and fixing the camera position relative to the sample. The oligonucleotide probe is modified with orange-red-emitting TAMRA working as an internal standard and green-emitting FAM serving as a sensitive sensing agent. Under 365-nm UV excitation, the emission wavelengths of TAMRA and FAM are 580 nm and 518 nm, respectively. When the probes interact with the targets, the green fluorescence gradually restores while the orange-red fluorescence remains stable. Thus, a striking color transition from orange-red to green could be observed by the naked eye. The detection limit of SARS-CoV-2 nucleic acid is 0.23 nM, and the entire process of color change could be completed in 25 min. Furthermore, the RGB value analysis of the sample solution was conducted using a smartphone for reliable and reproducible discrimination of SARS-CoV-2. The proposed smartphone platform might establish a general method for visual detection of SARS-CoV-2 nucleic acid as well as other virus-related diseases. Graphical abstract
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MATERIALS LETTERS
·
2012
·
IF 2.307
Chang Gao,Yurong Cai,Xiangdong Kong,Guoxiang Han,Juming Yao
The injectable chitosan/β-glycerophosphate (CS/GP) hydrogels were prepared with dexamethasone (Dex)/recombinant human bone morphogenetic protein (rhBMP-2) loaded hydroxyapatite nanoparticles (nHAP). The obtained samples were characterized by TEM, SEM, XRD and nitrogen adsorption tests, and the effect of Dex and rhBMP-2 on the mesenchymal stem cells (MSCs) was evaluated. The results showed that nHAP could be dispersed homogeneously in the matrix of injectable CS/GP hydrogels and the combination of Dex and rhBMP-2 could promote the proliferation and osteoblastic differentiation of MSCs, indicating that the prepared injectable CS/GP hydrogels with Dex and rhBMP-2 loaded nHAP have great potential in different orthopedic regenerative applications.
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危险品化学品经营许可证（带存储）