47 results on '"Yanjie Liu"'
Search Results
2. Effective and Targeted Human Orthotopic Glioblastoma Xenograft Therapy via a Multifunctional Biomimetic Nanomedicine
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Roger S. Chung, Dongya Zhang, Bingyang Shi, Meng Zheng, Zhipeng Yang, Xue Xue, Jia Geng, Yiqing Lu, Yan Zou, and Yanjie Liu
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Materials science ,Erythrocytes ,Cell Survival ,medicine.medical_treatment ,Multifunctional nanoparticles ,02 engineering and technology ,010402 general chemistry ,Blood–brain barrier ,01 natural sciences ,Mice ,Biomimetic Materials ,Cell Line, Tumor ,medicine ,Effective treatment ,Animals ,Humans ,Tumor growth ,Doxorubicin ,General Materials Science ,Chemotherapy ,Mechanical Engineering ,021001 nanoscience & nanotechnology ,medicine.disease ,0104 chemical sciences ,medicine.anatomical_structure ,Cell Transformation, Neoplastic ,Nanomedicine ,Mechanics of Materials ,Cancer research ,0210 nano-technology ,Glioblastoma ,Peptides ,medicine.drug - Abstract
Glioblastoma multiforme (GBM) is a fatal central nervous system tumor without effective treatment. Chemotherapeutic agents are mainstays in the treatment of glioblastoma. However, the effectiveness of these is seriously hindered by poor blood-brain-barrier (BBB) penetrance and tumor targeting, together with short biological half-life. Improved chemotherapy is thus urgently needed for GBM. Multifunctional nanoparticle delivery systems offer much promise in overcoming current limitations. Accordingly, a multifunctional biomimetic nanomedicine is developed by functionalizing the surface of red blood cell membranes (RBCms) with angiopep-2 and loading pH-sensitive nanoparticles (polymer, doxorubicin (Dox), and lexiscan (Lex)) using the functionalized cell membrane to generate the novel nanomedicine, Ang-RBCm@NM-(Dox/Lex). The studies toward orthotopic U87MG human glioblastoma tumor-bearing nude mice show that the Ang-RBCm@NM-(Dox/Lex) nanomedicine has much improved blood circulation time, superb BBB penetration, superior tumor accumulation and retention. Moreover, effective suppression of tumor growth and significantly improved medium survival time are also observed after Ang-RBCm@NM-(Dox/Lex) treatment. The results show that this biomimetic nanoplatform can serve as a flexible and powerful system for GBM treatment which can be readily adapted for the treatment of other central nervous system (CNS) disorders.
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- 2023
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3. The Matthew effect: Common species become more common and rare ones become more rare in response to artificial light at night
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Mark Van Kleunen, Yanjie Liu, Eva Knop, and Benedikt Speißer
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Global and Planetary Change ,Insecta ,Light Pollution ,Light ,Ecology ,ddc:570 ,Animals ,Environmental Chemistry ,Biomass ,Plants ,Introduced Species ,anthropocene, exotic, invasiveness, light pollution, non-native, plant-insect interaction, trophic level ,General Environmental Science - Abstract
Artificial light at night (ALAN) has been and still is rapidly spreading and has become an important component of global change. Although numerous studies have tested its potential biological and ecological impacts on animals, very few studies have tested whether it affects alien and native plants differently. Furthermore, common plant species, and particularly common alien species, are often found to benefit more from additional resources than rare native and rare alien species. Whether this is also the case with regard to increasing light due to ALAN is still unknown. Here, we tested how ALAN affected the performance of common and rare alien and native plant species in Germany directly, and indirectly via flying insects. We grew five common alien, six rare alien, five common native, and four rare native plant species under four combinations of two ALAN (no ALAN vs. ALAN) and two insect-exclusion (no exclusion vs. exclusion) treatments, and compared their biomass production. We found that common plant species, irrespective of their origin, produced significantly more biomass than rare species and that this was particularly true under ALAN. Furthermore, alien species tended to show a slightly stronger positive response to ALAN than native species did (p = .079). Our study shows that common plant species benefited more from ALAN than rare ones. This might lead to competitive exclusion of rare species, which could have cascading impacts on other trophic levels and thus have important community-wide consequences when ALAN becomes more widespread. In addition, the slightly more positive response of alien species indicates that ALAN might increase the risk of alien plant invasions. published
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- 2022
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4. Near infrared-activatable biomimetic nanogels enabling deep tumor drug penetration inhibit orthotopic glioblastoma
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Dongya Zhang, Sidan Tian, Yanjie Liu, Meng Zheng, Xiangliang Yang, Yan Zou, Bingyang Shi, and Liang Luo
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Indocyanine Green ,Mice ,Multidisciplinary ,Biomimetics ,Cell Line, Tumor ,Temozolomide ,Animals ,Nanogels ,General Physics and Astronomy ,General Chemistry ,Glioblastoma ,General Biochemistry, Genetics and Molecular Biology - Abstract
Glioblastoma multiforme (GBM) is one of the most fatal malignancies due to the existence of blood-brain barrier (BBB) and the difficulty to maintain an effective drug accumulation in deep GBM lesions. Here we present a biomimetic nanogel system that can be precisely activated by near infrared (NIR) irradiation to achieve BBB crossing and deep tumor penetration of drugs. Synthesized by crosslinking pullulan and poly(deca-4,6-diynedioic acid) (PDDA) and loaded with temozolomide and indocyanine green (ICG), the nanogels are inert to endogenous oxidative conditions but can be selectively disintegrated by ICG-generated reactive oxygen species upon NIR irradiation. Camouflaging the nanogels with apolipoprotein E peptide-decorated erythrocyte membrane further allows prolonged blood circulation and active tumor targeting. The precisely controlled NIR irradiation on tumor lesions excites ICG and deforms the cumulated nanogels to trigger burst drug release for facilitated BBB permeation and infiltration into distal tumor cells. These NIR-activatable biomimetic nanogels suppress the tumor growth in orthotopic GBM and GBM stem cells-bearing mouse models with significantly extended survival.
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- 2022
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5. Current Knowledge on Bee Innate Immunity Based on Genomics and Transcriptomics
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Xiaomeng Zhao and Yanjie Liu
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Organic Chemistry ,General Medicine ,Genomics ,Bees ,Catalysis ,Immunity, Innate ,Computer Science Applications ,Inorganic Chemistry ,Animals ,Physical and Theoretical Chemistry ,Pesticides ,Transcriptome ,Social Behavior ,Molecular Biology ,Spectroscopy ,Ecosystem - Abstract
As important pollinators, bees play a critical role in maintaining the balance of the ecosystem and improving the yield and quality of crops. However, in recent years, the bee population has significantly declined due to various pathogens and environmental stressors including viruses, bacteria, parasites, and increased pesticide application. The above threats trigger or suppress the innate immunity of bees, their only immune defense system, which is essential to maintaining individual health and that of the colony. In addition, bees can be divided into solitary and eusocial bees based on their life traits, and eusocial bees possess special social immunities, such as grooming behavior, which cooperate with innate immunity to maintain the health of the colony. The omics approach gives us an opportunity to recognize the distinctive innate immunity of bees. In this regard, we summarize innate bee immunity from a genomic and transcriptomic perspective. The genetic characteristics of innate immunity were revealed by the multiple genomes of bees with different kinds of sociality, including honeybees, bumblebees, wasps, leaf-cutter bees, and so on. Further substantial transcriptomic data of different tissues from diverse bees directly present the activation or suppression of immune genes under the infestation of pathogens or toxicity of pesticides.
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- 2022
6. Dietary supplementation of Aspergillus niger ‐expressed glucose oxidase ameliorates weaning stress and improves growth performance in weaning pigs
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Ningbo Chen, De Xin Dang, In Ho Kim, and Yanjie Liu
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Antioxidant ,Swine ,040301 veterinary sciences ,medicine.medical_treatment ,Sus scrofa ,Randomized block design ,Weaning ,medicine.disease_cause ,0403 veterinary science ,Glucose Oxidase ,chemistry.chemical_compound ,Animal science ,Food Animals ,medicine ,Animals ,chemistry.chemical_classification ,Meal ,biology ,Glutathione peroxidase ,Aspergillus niger ,0402 animal and dairy science ,04 agricultural and veterinary sciences ,Glutathione ,biology.organism_classification ,Animal Feed ,040201 dairy & animal science ,Diet ,chemistry ,Dietary Supplements ,Animal Nutritional Physiological Phenomena ,Digestion ,Animal Science and Zoology ,Oxidative stress - Abstract
Weaning is one of the most stressful events in the pig's life, which disrupts physiological balance and leads to oxidative stress. It is reported that glucose oxidase supplementation could alleviate oxidative stress in animals by increasing the concentration of antioxidant enzymes in vivo. The purpose of this study was to evaluate the effects of dietary supplementation of Aspergillus niger-expressed glucose oxidase (AN-GOX) on growth performance, nutrient digestibility, faecal microbiota, faecal gas emission and serum antioxidant enzyme parameters in weaning pigs. A total of 120 21-day-old weaning pigs [(Yorkshire ×Landrace) × Duroc] with an initial body weight of 6.54 ± 0.55 kg were used in a 21-day experiment (phase 1, days 1-7; phase 2, days 8-21) with a completely randomized block design. Pigs were randomly divided into 4 treatment groups with 6 replicate pens per treatment and 5 pigs per pen (2 barrows and 3 gilts). Dietary treatments were corn-soybean meal-based basal diet supplemented with 0, 0.01, 0.03 or 0.05% AN-GOX (1000 unit/g). The results of this study showed that average daily gain during days 1-7 and 1-21 and the concentrations of serum glutathione peroxidase and glutathione increased linearly at graduated doses of AN-GOX increased in the diet. However, dietary supplementation of AN-GOX had no effects on the apparent nutrient digestibility, faecal microbiota and faecal gas emission. In conclusion, supplementing AN-GOX to the diet of weaning pigs ameliorated weaning stress, which manifested as the increase in serum antioxidant enzyme levels, thus improving growth performance. The suitable dosage of AN-GOX used in the diet of weaning pigs was 0.05%.
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- 2021
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7. Brain Co-Delivery of Temozolomide and Cisplatin for Combinatorial Glioblastoma Chemotherapy
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Yan Zou, Yibin Wang, Sen Xu, Yanjie Liu, Jinlong Yin, David B. Lovejoy, Meng Zheng, Xing‐Jie Liang, Jong Bae Park, Yuri M. Efremov, Ilya Ulasov, and Bingyang Shi
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Mice ,Mechanics of Materials ,Blood-Brain Barrier ,Brain Neoplasms ,Drug Resistance, Neoplasm ,Mechanical Engineering ,Cell Line, Tumor ,Temozolomide ,Animals ,General Materials Science ,Cisplatin ,Glioblastoma ,Xenograft Model Antitumor Assays - Abstract
Glioblastoma (GBM) is an intractable malignancy with high recurrence and mortality. Combinatorial therapy based on temozolomide (TMZ) and cisplatin (CDDP) shows promising potential for GBM therapy in clinical trials. However, significant challenges include limited blood-brain-barrier (BBB) penetration, poor targeting of GBM tissue/cells, and systemic side effects, which hinder its efficacy in GBM therapy. To surmount these challenges, new GBM-cell membrane camouflaged and pH-sensitive biomimetic nanoparticles (MNPs) inspired by the fact that cancer cells readily pass the BBB and localize with homologous cells, are developed. This study's results show that MNPs can efficiently co-load TMZ and CDDP, transport these across the BBB to specifically target GBM. Incorporation of pH-sensitive polymer then allows for controlled release of drug cargos at GBM sites for combination drug therapy. Mice bearing orthotopic U87MG or drug-resistant U251
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- 2022
8. Study on the preparation and activity of intelligent response poly(lactic-co-glycolic acid)-ss-polyethylene glycol copolymer micelles
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Siying Wang, Lanlan Xie, Yanjie Liu, Qilei Yang, Wenqiang Jia, Dongmei Zhao, and Xiuhua Zhao
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Biomaterials ,Drug Carriers ,Mice ,Paclitaxel ,Polylactic Acid-Polyglycolic Acid Copolymer ,Cell Line, Tumor ,Biomedical Engineering ,Animals ,Micelles ,Zebrafish ,Polyethylene Glycols - Abstract
Amphiphilic polymer micellar carriers are the most commonly used nanocarriers for oral delivery of hydrophobic drugs because their hydrophilic shell can avoid the recognition of the reticuloendothelial system (RES), has excellent drug-carrying capacity, and protect the drug from inactivation in the gastrointestinal fluid. The polymer micelle shell can enter cancer cells by endocytosis, and autophagy in cells, degradation by lysosomal pathway, so as to release drugs, prolong the circulation time of drugs in vivo, and then achieve the effect of drug sustained release. In this study, the glutathione-responsive PLGA-ss-PEG loaded paclitaxel (PTX) micelles (PLGA-ss-PEG-PTX) were developed for anticancer therapy. With its long-term circulation and EPR (enhanced permeability and retention) effect, and the micelle had disulfide bond, which could be used as the recognition group of tumor microenvironment, so that the PLGA-ss-PEG-PTX could specifically accumulate at the tumor site, so as to produce better anti-tumor effect. The PLGA-ss-PEG-PTX was formulated by the emulsification method in this study. The drug loading was about 21.54%, the entrapment efficiency was about 94.2%, and the particle size range was about 90 nm with narrow particle size distribution. Cytotoxicity and embryonic toxicity experiments were carried out using mouse lung cancer cells (LLC) and zebrafish fertilized eggs. It was proved that the low concentration of blank micelles had little cytotoxicity, but high concentration of blank micelles had adverse effects on zebrafish embryonic development, resulting in embryonic malformation. The uptake of drugs by cancer cells was studied by a high connotation cell imaging analysis system. The experiments showed that the drug molecules encapsulated in micelles could achieve higher uptake by cells compared with free drug molecules. In addition, in the in vivo evaluation experiment of drugs, the PLGA-ss-PEG-PTX could significantly enhance the therapeutic effect of the PTX, improve its water solubility, and improve its oral bioavailability.
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- 2022
9. Delivery of astragalus polysaccharide by ultrasound microbubbles attenuate doxorubicin-induced cardiomyopathy in rodent animals
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Yanjie Liu, Li Chen, Hao Wu, and Hebin Zhang
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Microbubbles ,Diabetic Cardiomyopathies ,Myocardium ,Body Weight ,Bioengineering ,Rodentia ,General Medicine ,AMP-Activated Protein Kinases ,Applied Microbiology and Biotechnology ,Fibrosis ,Rats ,Rats, Sprague-Dawley ,Doxorubicin ,Polysaccharides ,Animals ,Biotechnology - Abstract
The aim of this study was to investigate the cardioprotective effects and probable mechanism of ultrasound-targeted microbubble destruction (UTMD) combined with astragalus polysaccharide (APS) on diabetic cardiomyopathy (DCM) model rats. The DCM rats with diabetes and cardiomyopathy were induced via chronic treatment of doxorubicin and then randomly divided into the (1) DCM model group; (2) APS microbubble group; (3) UTMDgroup; and (4) APS microbubbles combined with UTMD group. After 4-week intervention, the fasting blood glucose levels, body weight, %HbA1c level and glucose tolerance of DCM rats received combination therapy were significantly improved as compared with those of UTMD or saline-treated ones. Moreover, the heart/body weight ratio, and myocardial contractility were all improved after receiving combination therapy groups compared with others. In addition, significantly upregulated activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as significantly downregulated malondialdehyde (MDA) levels were all observed in the ones received combined treatment compared to others. Furthermore, the lipid accumulation and the expression levels of inflammatory factors were all significantly down-regulated in those ones received combination therapy compared with others (all
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- 2022
10. Protective effect of glucagon-like peptide-1 mediated by ultrasound microbubbles on myocardial injury in rats with diabetic cardiomyopathy
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Yanjie Liu, Li Chen, Hao Wu, and Hebin Zhang
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Male ,Microbubbles ,Diabetic Cardiomyopathies ,Myocardium ,Ultrasonic Therapy ,glucagon-like peptide-1 receptor agonist ,Bioengineering ,General Medicine ,Applied Microbiology and Biotechnology ,combination therapy ,Rats ,Oxidative Stress ,Glucagon-Like Peptide 1 ,cardiovascular system ,diabetic cardiomyopathy ,Animals ,rat ,ultrasound microbubble ,TP248.13-248.65 ,Biotechnology - Abstract
Current study was performed to investigate the therapeutic effects of UTMD combined with Semaglutide, a GLP-1 R agonist, on DCM in GK rats. After 6-week intervention, all rats were examined by conventional echocardiography, and the indicators of papillary muscle horizontal wall were measured. At the end of experiment, the DCM rats were sacrificed, and then blood samples were taken to detect blood lipids and the activities of oxidative stress-related factors in myocardial tissues. Moreover, the myocardial tissues were also taken to observe histomorphological changes and myocardial fibrosis via H&E and Masson staining, respectively. Furthermore, the mRNA and protein levels of PPAR-γ and NF-κB in myocardial tissues were detected. As a result, the glycometabolism and the cardiac functions of DCM rats received combination therapy of GLP-1 R agonist and UTMD were improved. Significantly increased SOD and GSH-Px as well as significantly decreased MDA levels were also observed in rats of combined group compared with others. In addition, both mRNA and protein levels of PPAR-γ and NF-κB were significantly lower than those of the model control ones and Semaglutide microbubbles alone (all P
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- 2022
11. Allelopathy confers an invasive Wedelia higher resistance to generalist herbivore and pathogen enemies over its native congener
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Zhi-Cong Dai, Ling-Yun Wan, Daolin Du, Shan-Shan Qi, Justin S. H. Wan, Stephen P. Bonser, Rui-Ting Ju, and Yanjie Liu
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0106 biological sciences ,Larva ,Herbivore ,biology ,010604 marine biology & hydrobiology ,fungi ,food and beverages ,Asteraceae ,Generalist and specialist species ,biology.organism_classification ,010603 evolutionary biology ,01 natural sciences ,Invasive species ,Wedelia ,Congener ,Wedelia trilobata ,Botany ,Animals ,Herbivory ,Ecology, Evolution, Behavior and Systematics ,Allelopathy - Abstract
The Novel Defense Hypothesis predicts that introduced plants may possess novel allelochemicals which act as a defense against native generalist enemies. Here, we aim to test if the chemicals involved in allelopathy in the invasive plant Wedelia trilobata can contribute to higher resistance against generalist herbivore and pathogen enemies by comparing with its native congener W. chinensis in controlled laboratory conditions. The allelopathic effects of the leaf extract from W. trilobata on the generalist enemies were also assessed. We showed that the larvae of two moth species preferred W. chinensis over W. trilobata. The growth rate of larvae feeding on W. trilobata leaves was significantly lower than those feeding on W. chinensis leaves. When detached leaves were inoculated with phytopathogens, the infected leaf area of W. trilobata was significantly smaller than that of W. chinensis. In addition, the leaf extract of W. trilobata also effectively inhibited the growth of the larvae and the mycelial growth of the phytopathogens. Our results indicate that the defenses of invasive W. trilobata against generalist herbivore and pathogen enemies are stronger than that of its native congener, which may be attributed to the allelopathic effects. This study provides novel insights that can comprehensively link the Novel Defense, Behavioral Constraint and Enemy Release hypotheses. These combined hypotheses would explain how invasive plants escape from their natural specialist enemies, where their allelopathic chemicals may deter herbivorous insects and inhibit pathogen infection.
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- 2019
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12. Phloretin loaded porous starch (Ph-PS): Preparation, characterization, in vitro release and protective effect against oxidative stress in vivo zebrafish model
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Yanjie Liu, Lanlan Xie, Xiuhua Zhao, Shujun Li, Bolin Lian, Qian Zhang, Qilei Yang, and Yuanyuan Li
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Antioxidant ,Phloretin ,medicine.medical_treatment ,Absorption (skin) ,medicine.disease_cause ,Protective Agents ,Biochemistry ,Antioxidants ,Lipid peroxidation ,chemistry.chemical_compound ,Crystallinity ,Structural Biology ,In vivo ,medicine ,Animals ,Molecular Biology ,Zebrafish ,Chemistry ,Starch ,General Medicine ,In vitro ,Oxidative Stress ,Models, Animal ,Biophysics ,Lipid Peroxidation ,Reactive Oxygen Species ,Porosity ,Oxidative stress - Abstract
Phloretin loaded porous starch (Ph-PS) were prepared for its application in food. The effects of Ph-PS in vitro release and its ability against AAPH-induced oxidative stress in vivo zebrafish model were investigated. Ph-PS was prepared by absorption method, the physical and chemical characterization showed that PS decreased the crystallinity of Ph obviously. Ph-PS exhibited higher release amount and faster release rate of Ph compared to free Ph in vitro release study. What's more, the effect of Ph-PS reduced ROS generation and lipid peroxidation was better than that of free Ph in zebrafish model. These findings suggest Ph-PS is a new and simple strategy to improve dissolution rate and antioxidant ability of Ph.
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- 2021
13. An 'all-in-one' strategy based on the organic molecule DCN-4CQA for effective NIR-fluorescence-imaging-guided dual phototherapy
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Tianlei Zhou, Yanjie Liu, Yinshuai Bai, Tiedong Sun, Yue Wang, Xiuhua Zhao, Lu Li, Xiangzhen Liu, Shiying Zhang, and Tao Jia
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Materials science ,Biocompatibility ,Cell Survival ,Infrared Rays ,medicine.medical_treatment ,Biomedical Engineering ,Photodynamic therapy ,Antineoplastic Agents ,Photochemistry ,Heterocyclic Compounds, 4 or More Rings ,chemistry.chemical_compound ,Mice ,medicine ,Animals ,Humans ,General Materials Science ,Particle Size ,Density Functional Theory ,Fluorescent Dyes ,Photosensitizing Agents ,Molecular Structure ,Singlet oxygen ,Optical Imaging ,technology, industry, and agriculture ,Mammary Neoplasms, Experimental ,General Chemistry ,General Medicine ,Photothermal therapy ,Phototherapy ,Fluorescence ,Intersystem crossing ,chemistry ,Quinacridone ,Drug Screening Assays, Antitumor ,Drug carrier ,HeLa Cells - Abstract
Dual phototherapy combining photodynamic therapy (PDT) and photothermal therapy (PTT) is considered to be a more effective therapeutic method against cancer than single treatment. Therefore, the development of a single material with both near-infrared (NIR)-laser-triggered PDT and PTT abilities is highly desirable but remains a great challenge. A design philosophy for photosensitizers for integrated PDT and PTT treatment has been put forward: (1) a high molar extinction coefficient in the NIR region; (2) suitable LUMO and T1 energy levels to regulate intersystem crossing for effective singlet oxygen (1O2) generation for PDT; and (3) the suppression of fluorescence emission to enhance the process of nonradiative transition with appropriate chemical modifications. Herein, an “all-in-one” functional material, di-cyan substituted 5,12-dibutylquinacridone (DCN-4CQA), for diagnosis and therapy was obtained. DCN-4CQA possesses dual-functional phototherapeutic activity and NIR fluorescence and it was produced via a facile synthesis process from the classic organic photoelectric material quinacridone. We then prepared smart water-soluble nanoparticles (NPs), DCN-4CQA/F127, using Pluronic® 127 (F127) as a drug carrier. The NPs exhibited excellent biocompatibility, robust photostability, NIR fluorescence, a high photothermal conversion efficiency (η = 47.3%), and sufficient 1O2 generation (ΦΔ = 24.3%) under NIR laser irradiation. Remarkably, the DCN-4CQA/F127 NPs significantly inhibited tumor growth in mice subjected to NIR laser irradiation. This study provides a new route for the development of highly efficient, low-cytotoxicity photosensitizers for fluorescence-imaging-guided PTT/PDT.
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- 2021
14. pH-responsive delivery vehicle based on RGD-modified polydopamine-paclitaxel-loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) nanoparticles for targeted therapy in hepatocellular carcinoma
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Xiaoxue Zhang, Lingling Wang, Lu Wang, Chen Zhong, Yanjie Liu, Xiuhua Zhao, Qian Zhang, and Mingfang Wu
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Male ,lcsh:Medical technology ,Carcinoma, Hepatocellular ,Indoles ,Paclitaxel ,Biocompatibility ,Polymers ,lcsh:Biotechnology ,Dopamine ,Polyesters ,education ,Biomedical Engineering ,Mice, Nude ,Pharmaceutical Science ,Medicine (miscellaneous) ,Nanoparticle ,Bioengineering ,Applied Microbiology and Biotechnology ,Mice ,chemistry.chemical_compound ,Drug Delivery Systems ,In vivo ,lcsh:TP248.13-248.65 ,Animals ,Humans ,Fourier transform infrared spectroscopy ,Mice, Inbred BALB C ,PHBV ,Active targeting ,Research ,Liver Neoplasms ,pH-sensitive ,Hep G2 Cells ,RGD peptide ,Hydrogen-Ion Concentration ,Antineoplastic Agents, Phytogenic ,In vitro ,lcsh:R855-855.5 ,chemistry ,Delayed-Action Preparations ,Drug delivery ,Biophysics ,Nanoparticles ,Molecular Medicine ,Nanocarriers ,Oligopeptides - Abstract
A limitation of current anticancer nanocarriers is the contradiction between multiple functions and favorable biocompatibility. Thus, we aimed to develop a compatible drug delivery system loaded with paclitaxel (PTX) for hepatocellular carcinoma (HCC) therapy. A basic backbone, PTX-loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) PHBV nanoparticle (PHBV-PTX-NPs), was prepared by emulsion solvent evaporation. As a gatekeeper, the pH-sensitive coating was formed by self-polymerization of dopamine (PDA). The HCC-targeted arginine-glycine-aspartic acid (RGD)-peptide and PDA-coated nanoparticles (NPs) were combined through the Michael addition. Subsequently, the physicochemical properties of RGD-PDA-PHBV-PTX-NPs were characterized by dynamic light scattering-autosizer, transmission electron microscope, fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetry and X-ray spectroscopy. As expected, the RGD-PDA-PHBV-PTX-NPs showed robust anticancer efficacy in a xenograft mouse model. More importantly, they exhibited lower toxicity than PTX to normal hepatocytes and mouse in vitro and in vivo, respectively. Taken together, these results indicate that the RGD-PDA-PHBV-PTX-NPs are potentially beneficial for easing conflict between multifunction and biocompatible characters of nanocarriers.
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- 2021
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15. Effects of thermostable phytase supplemented in diets on growth performance and nutrient utilization of broilers
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Zaibin Yang, Caiyun Yu, Tingting Song, Xu Zhao, Yanjie Liu, C Yang, and Fengliang Chen
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Male ,Hot Temperature ,Body weight ,03 medical and health sciences ,Animal science ,Nutrient ,Enzyme Stability ,Animals ,Organic matter ,Dry matter ,030304 developmental biology ,chemistry.chemical_classification ,6-Phytase ,0303 health sciences ,biology ,Body Weight ,Aspergillus niger ,0402 animal and dairy science ,Broiler ,Nutrients ,04 agricultural and veterinary sciences ,General Medicine ,biology.organism_classification ,Animal Feed ,040201 dairy & animal science ,Diet ,chemistry ,Phytase activity ,Dietary Supplements ,Animal Nutritional Physiological Phenomena ,Female ,Phytase ,Energy Metabolism ,General Agricultural and Biological Sciences ,Chickens - Abstract
Phytase is an enzyme that has the ability to release phosphorous (P) from phytate by hydrolyzing inositol-phosphate linkages. Recently, thermostable phytases have gained great consideration because the reduction in phytase activity was found when exposed to heat during feed pelleting. In this study, the effects of the granular thermostable phytase (Aspergillus niger) on growth performance and nutrient utilization of broilers were investigated. A total of 96 21-day-old Arbor Acres broilers were randomly distributed into six treatments including basal diet (control) and basal diet supplemented with 500, 1,000, 2,000, 4,000, 8,000 U of phytase/kg. In general, the metabolizable energy (ME) and the apparent and true availability of dry matter (DM), organic matter (OM), ether extract (EE), crude protein (CP), and amino acids (AA) showed both linearly (p
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- 2021
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16. Effects of housing systems and glucose oxidase on growth performance and intestinal health of Beijing You Chickens
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Yizhu Zhao, Yuming Guo, Dan Liu, Yanjie Liu, Peng Li, and Ningbo Chen
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Litter (animal) ,Firmicutes ,Ileum ,Biology ,Beijing You chicken ,Occludin ,Feed conversion ratio ,03 medical and health sciences ,Random Allocation ,Animal science ,RNA, Ribosomal, 16S ,IMMUNOLOGY, HEALTH AND DISEASE ,medicine ,Animals ,030304 developmental biology ,lcsh:SF1-1100 ,0303 health sciences ,0402 animal and dairy science ,Deep litter ,Bacteroidetes ,04 agricultural and veterinary sciences ,General Medicine ,biology.organism_classification ,040201 dairy & animal science ,Animal Feed ,glucose oxidase ,Diet ,medicine.anatomical_structure ,Beijing ,Dietary Supplements ,housing system ,Housing ,Animal Science and Zoology ,intestinal health ,lcsh:Animal culture ,Cage ,Chickens - Abstract
We investigated the effects of housing systems and dietary glucose oxidase (GOD) on the growth performance and intestinal health of Beijing You chickens (BYC). The experiment was designed as a factorial arrangement of 2 housing systems × 2 dietary treatments. Chickens were fed a basal diet or a diet with 200 U/kg GOD and were reared on the floor with deep litter or in the cages. Compared with the litter floor groups, the decreased average daily feed intake of 1 to 42 d, decreased feed conversion ratio (FCR), improved average daily gain of 42 to 77 d, and the whole period were identified in the cage rearing groups (P < 0.05). The FCR of 42 to 77 d and the whole period, the 42-d ileal pH, and 77-d jejunal and ileal pH decreased with the supplement of GOD (P < 0.05). Additionally, 16S rRNA gene of ileum contents was sequenced by high-throughput sequencing. Sequencing data indicated that the Firmicutes phylum of 42 d and the Bacteroidetes phylum were significantly higher in the litter group with GOD supplement (P < 0.05). The jejunal Occludin, Mucin-2 mRNA expression levels were higher in the litter floor groups than those in the cage rearing groups on 42 d (P < 0.05). The Mucin-2 and TNF-α mRNA expression levels increased with cage rearing on 77 d (P < 0.05). The Occludin and TLR-4 mRNA expression levels increased with the supplementation of GOD on 77 d (P < 0.05). Moreover, the upregulation effects of Occludin and ZO-1 mRNA expression levels were more obvious in the litter floor group fed with GOD diet on 77 d (P < 0.05). The serum endotoxin content of 42-day-old cage rearing groups were higher than that of the litter floor groups, and the serum endotoxin content significantly decreased with the supplement of GOD on 77 d. The results indicated that the litter floor systems were beneficial to the development of intestinal barrier junction in the early stage, but the cage systems were more conducive to the growth performance of BYC. The dietary GOD could inhibit the harmful bacteria and promote the beneficial bacteria, which might be related to the improvement of the growth performance and intestinal barrier function.
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- 2020
17. The Combination of CD8αα and Peptide-MHC-I in a Face-to-Face Mode Promotes Chicken γδT Cells Response
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Yanjie Liu, Rong Chen, Ruiying Liang, Beibei Sun, Yanan Wu, Lijie Zhang, Jim Kaufman, Chun Xia, and Apollo - University of Cambridge Repository
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Models, Molecular ,lcsh:Immunologic diseases. Allergy ,chicken γδT cells response ,T cell ,CD8 Antigens ,Immunology ,chemical and pharmacologic phenomena ,Evolution, Molecular ,Species Specificity ,Immunity ,medicine ,Immunology and Allergy ,Cytotoxic T cell ,Animals ,Protein Interaction Domains and Motifs ,Allele ,CD8/pMHC-I interaction ,Intraepithelial Lymphocytes ,Thymic T cell selection ,Original Research ,cCD8αα/pBF2*0401 ,Binding Sites ,Chemistry ,T-cell receptor ,Histocompatibility Antigens Class I ,Cell biology ,CTL ,medicine.anatomical_structure ,Multiprotein Complexes ,Protein Multimerization ,lcsh:RC581-607 ,Chickens ,CD8 ,face-to-face mode ,cCD8αα/pBF2*1501 ,Protein Binding - Abstract
The CD8αα homodimer is crucial to both thymic T cell selection and the antigen recognition of cytotoxic T cells. The CD8-pMHC-I interaction can enhance CTL immunity via stabilizing the TCR-pMHC-I interaction and optimizing the cross-reactivity and Ag sensitivity of CD8+ T cells at various stages of development. To date, only human and mouse CD8-pMHC-I complexes have been determined. Here, we resolved the pBF2*1501 complex and the cCD8αα/pBF2*1501 and cCD8αα/pBF2*0401 complexes in nonmammals for the first time. Remarkably, cCD8αα/pBF2*1501 and the cCD8αα/pBF2*0401 complex both exhibited two binding modes, including an “antibody-like” mode similar to that of the known mammal CD8/pMHC-I complexes and a “face-to-face” mode that has been observed only in chickens to date. Compared to the “antibody-like” mode, the “face-to-face” binding mode changes the binding orientation of the cCD8αα homodimer to pMHC-I, which might facilitate abundant γδT cells to bind diverse peptides presented by limited BF2 alleles in chicken. Moreover, the forces involving in the interaction of cCD8αα/pBF2*1501 and the cCD8αα/pBF2*0401 are different in this two binding model, which might change the strength of the CD8-pMHC-I interaction, amplifying T cell cross-reactivity in chickens. The coreceptor CD8αα of TCR has evolved two peptide-MHC-I binding patterns in chickens, which might enhance the T cell response to major or emerging pathogens, including chicken-derived pathogens that are relevant to human health, such as high-pathogenicity influenza viruses.
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- 2020
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18. Structural and Functional Analysis of PGRP-LC Indicates Exclusive Dap-Type PGN Binding in Bumblebees
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Yanjie Liu, Huiyue Zhao, Minming Chen, Jiandong An, and Nanhui Ye
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0106 biological sciences ,0301 basic medicine ,Protein Conformation ,Insect ,medicine.disease_cause ,01 natural sciences ,Defensins ,lcsh:Chemistry ,chemistry.chemical_compound ,Bombus lantschouensis ,Drosophila Proteins ,Protein Isoforms ,Defensin ,lcsh:QH301-705.5 ,Spectroscopy ,media_common ,biology ,Chemistry ,Pattern recognition receptor ,General Medicine ,bumblebee ,Bees ,Computer Science Applications ,Cell biology ,Drosophila melanogaster ,Insect Proteins ,innate immune ,Protein Binding ,Dap-type PGNs ,media_common.quotation_subject ,Peptidoglycan ,Gram-Positive Bacteria ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Gram-Negative Bacteria ,medicine ,Escherichia coli ,Animals ,Amino Acid Sequence ,Physical and Theoretical Chemistry ,Molecular Biology ,Innate immune system ,Sequence Homology, Amino Acid ,Organic Chemistry ,Mutagenesis ,fungi ,biology.organism_classification ,010602 entomology ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,PGRP-LC ,Carrier Proteins ,Antimicrobial Cationic Peptides - Abstract
Peptidoglycan recognition proteins (PGRPs) play an important role in the defense against invading microbes via the recognition of the immunogenic substance peptidoglycan (PGN). Bees possess fewer PGRPs than Drosophila melanogaster and Anopheles gambiae but retain two important immune pathways, the Toll pathway and the Imd pathway, which can be triggered by the recognition of Dap-type PGN by PGRP-LCx with the assistance of PGRP-LCa in Drosophila. There are three isoforms of PGRP-LC including PGRP-LCx, PGRP-LCa and PGRP-LCy in Drosophila. Our previous study showed that a single PGRP-LC exists in bumblebees. In this present study, we prove that the bumblebee Bombus lantschouensis PGRP-LC (Bl-PGRP-LC) can respond to an infection with Gram-negative bacterium Escherichia coli through binding to the Dap-type PGNs directly, and that E. coli infection induces the quick and strong upregulation of PGRP-LC, abaecin and defensin. Moreover, the Bl-PGRP-LC exhibits a very strong affinity for the Dap-type PGN, much stronger than the affinity exhibited by the PGRP-LC from the more eusocial honeybee Apis mellifera (Am-PGRP-LC). In addition, mutagenesis experiments showed that the residue His390 is the anchor residue for the binding to the Dap-type PGN and forms a hydrogen bond with MurNAc rather than meso-Dap, which interacts with the anchor residue Arg413 of PGRP-LCx in Drosophila. Therefore, bumblebee PGRP-LC possesses exclusive characteristics for the immune response among insect PGRPs.
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- 2020
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19. Improved water dispersion and bioavailability of coenzyme Q10 by bacterial cellulose nanofibers
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Qian Zhang, Qilei Yang, Yanjie Liu, Bingxue Liu, Shujun Li, Yuanyuan Li, and Xiuhua Zhao
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Thermogravimetric analysis ,Polymers and Plastics ,Ubiquinone ,Scanning electron microscope ,Nanofibers ,Administration, Oral ,Biological Availability ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Crystallinity ,Differential scanning calorimetry ,Suspensions ,X-Ray Diffraction ,Spectroscopy, Fourier Transform Infrared ,Materials Chemistry ,Zeta potential ,Animals ,Cellulose ,Calorimetry, Differential Scanning ,Gluconacetobacter xylinus ,Chemistry ,Polysaccharides, Bacterial ,Organic Chemistry ,Water ,Rats ,Bioavailability ,Solubility ,Bacterial cellulose ,Nanofiber ,Thermogravimetry ,Microscopy, Electron, Scanning ,Solvents ,Nuclear chemistry - Abstract
The purpose of this study was to investigate the potential of bacterial cellulose nanofiber suspension (BCNs) as stabilizer in anti-solvent precipitation and its effect on improving bioavailability of coenzyme Q10. Bacterial cellulose (BC) was hydrolyzed by sulfuric acid followed by the oxidation with hydrogen peroxide to prepare BCNs. The suspension of BCNs-loaded CoQ10 (CoQ10-BCNs) were prepared by antisolvent precipitation. The zeta potential of CoQ10-BCNs was about −36.01 mV. The properties of CoQ10, BCNs and CoQ10-BCNs were studied by scanning electron microscopy, transmission electron microscope, Fourier-transform infrared spectroscopy, X–ray diffraction, differential scanning calorimetry and thermo gravimetric analysis. The crystallinity of CoQ10 decreased in CoQ10-BCNs compared with the raw CoQ10, and CoQ10-BCNs have good physicochemical stability. In oral bioavailability studies, the area under curve (AUC) of CoQ10-BCNs was about 3.62 times higher than the raw CoQ10 in rats.
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- 2022
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20. Effects of dietary glucose oxidase on growth performance and intestinal health of AA broilers challenged by Clostridium perfringens
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Jiahuan Fu, Yuming Guo, Dan Liu, Yizhu Zhao, Yanjie Liu, Peng Li, and Ningbo Chen
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Clostridium perfringens ,Crypt ,broiler ,necrotic enteritis ,Occludin ,medicine.disease_cause ,SF1-1100 ,digestive system ,Lesion ,Glucose Oxidase ,Basal (phylogenetics) ,Animal science ,IMMUNOLOGY, HEALTH AND DISEASE ,medicine ,Animals ,Glucose oxidase ,biology ,Broiler ,General Medicine ,Animal culture ,Diet ,Gastrointestinal Microbiome ,biology.protein ,intestinal health ,Animal Science and Zoology ,Composition (visual arts) ,medicine.symptom ,Chickens - Abstract
Arbor Acre (AA) broilers were used as the research object to investigate whether glucose oxidase (GOD) has preventive and relieving effects on necrotic enteritis. The experiment was designed as a factorial arrangement of 2 dietary treatments × 2 infection states. Chickens were fed a basal diet or a diet with 150 U/kg GOD, and were challenged with Clostridium perfringens (Cp) or sterile culture medium. In our study, Cp challenge led to intestinal injury, as evidenced by reducing the average daily gain and the average daily feed intake of AA broilers of 14 to 21 d (P < 0.05), increasing the intestinal jejunal lesion score (P < 0.05), reducing the jejunal villi height and villi height/crypt depth (P < 0.05), upregulating the mRNA expression levels jejunal IFN-γ (P < 0.05). The dietary GOD had no significant effects on the growth performance of each growth period, but significantly decreased the ileal pH, increased the height of villi and the ratio of villi height to crypt depth (P < 0.05) and the expression levels of Occludin and Zonula occludens-1 (ZO-1) at d 21. Moreover, dietary GOD and the Cp challenge significantly altered the composition of 21-d ileal microbiota. The Cp challenge decreased the relative abundance of genus Lactobacillus (P = 0.057), and increased the relative abundance of genus Romboutsia (P < 0.05) and genus Veillonella (P = 0.088). The dietary GOD tended to increase the relative abundance of genus Helicobacter (P = 0.066) and decrease the relative abundance of genus Streptococcus (P = 0.071). This study has shown that the supplementation of GOD could promote the integrity of intestinal barrier and the balance of ileal microbiota, but the effects of GOD on NE broilers and its application in actual production need to be further confirmed.
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- 2022
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21. Long non-coding RNA HOTAIR promotes cervical cancer progression through regulating BCL2 via targeting miR-143-3p
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Mingzhu Liu, Chunfang Wang, Xinjie Wang, Yanjie Liu, Jinying Jia, and Ruitai Fan
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0301 basic medicine ,Cancer Research ,Mice, Nude ,Uterine Cervical Neoplasms ,Biology ,Transfection ,Flow cytometry ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Pharmacology ,Mice, Inbred BALB C ,Gene knockdown ,medicine.diagnostic_test ,Cell growth ,HOTAIR ,Long non-coding RNA ,MicroRNAs ,030104 developmental biology ,Proto-Oncogene Proteins c-bcl-2 ,Oncology ,Apoptosis ,Cell culture ,030220 oncology & carcinogenesis ,Disease Progression ,Cancer research ,Heterografts ,Molecular Medicine ,Female ,RNA, Long Noncoding ,HOX Transcript Antisense RNA ,HeLa Cells ,Research Paper - Abstract
Background: HOX transcript antisense RNA (HOTAIR) is a long non-coding RNA (lncRNA) widely involved in the progression of numerous malignancies. Whereas, the potential molecular mechanism of HOTAIR involved in cervical cancer progression is still needed to be elaborated. Methods: The expression of HOTAIR and miR-143-3p were detected in cervical cancer tissues and cells by qRT-PCR. MTT and flow cytometry analysis were performed to measure cell proliferation and apoptosis. Bioinformatics, Dual-Luciferase reporter and RIP were used to analyze the possible correlation between HOTAIR, miR-143-3p and BCL2. The expression of Bax and BCL2 was detected by western blot. Mice xenograft model was established to confirm the role of HOTAIR on tumor growth in vivo. Results: HOTAIR expression was elevated while miR-143-3p expression was reduced in cervical cancer tissues and cell lines. HOTAIR knockdown suppressed proliferation and enhanced apoptosis in cervical cancer cells. Moreover, HOTAIR could function as a sponge for miR-143-3p. The inhibitory effect of HOTAIR knockdown on cervical cancer cells growth was abolished following decrease of miR-143-3p expression. Furthermore, HOTAIR promoted BCL2 expression by modulating miR-143-3p. BCL2 overexpression attenuated the tumor-suppressive effect of miR-143-3p in cervical cancer. Finally, the carcinogenicity of HOTAIR was validated in mice. Conclusions: HOTAIR promoted cervical cancer cell growth by modulating BCL2 via miR-143-3p, hinting a novel regulatory mechanism and potential therapeutic target in cervical cancer.
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- 2018
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22. Therapeutic effect of icariin combined with stem cells on postmenopausal osteoporosis in rats
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Yanjie Liu, Zhengguang Wang, Dao Tang, Fei Xu, Dongbo Wang, and Cuiling Ju
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medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Osteocalcin ,Osteoporosis ,Kidney ,Bone tissue ,Bone and Bones ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,Absorptiometry, Photon ,0302 clinical medicine ,Endocrinology ,Osteoprotegerin ,Bone Density ,Internal medicine ,Animals ,Humans ,Medicine ,Orthopedics and Sports Medicine ,Femur ,030212 general & internal medicine ,Osteoporosis, Postmenopausal ,Flavonoids ,Bone mineral ,Tartrate-Resistant Acid Phosphatase ,business.industry ,Stem Cells ,Body Weight ,General Medicine ,Alkaline Phosphatase ,medicine.disease ,Biomechanical Phenomena ,Transplantation ,medicine.anatomical_structure ,Adipose Tissue ,Liver ,chemistry ,030220 oncology & carcinogenesis ,Alkaline phosphatase ,Female ,Stem cell ,business ,Icariin ,Stem Cell Transplantation - Abstract
Osteoporosis is characterized by skeletal fragility and microarchitectural deterioration. The side effects of drugs to treat osteoporosis will negatively affect the health of patients. This study aimed to investigate the therapeutic effects of icariin combined with adipose-derived stem cells on osteoporosis in a postmenopausal osteoporosis model after ovariectomy in rats. After ovariectomy the rats were treated with icariin combined with adipose-derived stem cell transplantation. The levels of alkaline phosphatase, tartrate-resistant acid phosphatase, osteoprotegerin, and bone γ-carboxyglutamate protein in serum were determined by ELISA. The bone mineral density was measured by dual-energy X-ray absorptiometry. The mechanical properties were determined by a three-point bending test. The kidney functions were evaluated by an automatic analyzer and a diagnostic kit. Icariin combined with stem cells significantly reduced body weight gain caused by ovariectomy, significantly decreased alkaline phosphatase, tartrate-resistant acid phosphatase, and bone γ-carboxyglutamate protein content in serum, significantly increased osteoprotegerin content, significantly elevated bone mineral density of the lumbar spine, left femur, and right femur, and enhanced bone biomechanical properties of the femur, including maximum bending load, bending rigidity, and fracture energy, in osteoporotic rats. In addition, icariin combined with stem cells substantially decreased the damage to the liver and kidney in osteoporotic rats. Icariin combined with stem cells can not only ameliorate reduction of bone mass and disruption of the microarchitectural structure of bone tissue caused by osteoporosis in a rat model but can also have a beneficial effect on organ functions, such as those of the liver and kidney.
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- 2017
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23. Melatonin-loaded silica coated with hydroxypropyl methylcellulose phthalate for enhanced oral bioavailability: Preparation, and in vitro-in vivo evaluation
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Lingling Wang, Yuangang Zu, Yuanyuan Li, Weiwei Wu, Chang Zu, Xiuhua Zhao, Yiping Deng, and Yanjie Liu
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Male ,Thermogravimetric analysis ,Administration, Oral ,Biological Availability ,Pharmaceutical Science ,02 engineering and technology ,In Vitro Techniques ,Methylcellulose ,010402 general chemistry ,01 natural sciences ,Rats, Sprague-Dawley ,Differential scanning calorimetry ,Microscopy, Electron, Transmission ,X-Ray Diffraction ,In vivo ,Spectroscopy, Fourier Transform Infrared ,medicine ,Animals ,Solubility ,Melatonin ,Chromatography ,Calorimetry, Differential Scanning ,Chemistry ,General Medicine ,Silicon Dioxide ,021001 nanoscience & nanotechnology ,Biopharmaceutics Classification System ,Controlled release ,Enteric coating ,Rats ,0104 chemical sciences ,Bioavailability ,Thermogravimetry ,0210 nano-technology ,Biotechnology ,medicine.drug - Abstract
Melatonin (MLT) is a small molecule with low water solubility and high permeability. According to the Biopharmaceutics Classification System, MLT is a class II drug exhibiting a very short half-life and minimal and variable bioavailability. This work aimed to establish a delivery system composed of an enteric MLT nanosphere with favorably controlled and sustained release characteristics superior to those of raw MLT. The nanosphere was composed of hydroxypropyl methylcellulose phthalate (HP55) and silica (SiO2) with MLT. As a carrier, SiO2 contains numerous surface pores with high adsorption capacity advantageous for permeability and slow release. HP55 is a good enteric coating material. MLT-loaded SiO2 was obtained through adsorption in acetone solution. A MLT-loaded SiO2 coated with HP55 (MLT-SiO2-HP55) nanosphere was prepared via desolvation. The characteristics of this nanosphere were analyzed through transmission electron microscopy, Brunauer-Emmett-Teller surface area analysis, diffuse reflectance infrared Fourier transform spectroscopy, X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. Results show that MLT was loaded mostly in the pores of SiO2. HP55 was coated on a large portion of MLT-SiO2. In vitro release studies revealed that the release rate of MLT from MLT-SiO2 was higher than that of raw MLT in simulated gastric fluid (SGF). The amount of MLT released from MLT-SiO2-HP55 in SGF was lower than that released from simulated intestinal fluid because of HP55 coated on MLT-SiO2. In vivo evaluation demonstrated the controlled drug release of MLT-SiO2-HP55 in rats. Compared with raw MLT, MLT-SiO2-HP55 prolonged peak time (Tmax) from 15min to 30min and increased peak concentration (Cmax) from 168.86ng/mL to 383.71ng/mL. The corresponding area under the curve (AUC) of MLT-SiO2-HP55 was 3.5 times higher than that of raw MLT. This finding illustrated the sustained release of MLT-SiO2-HP55. Our in vitro release and in vivo absorption studies indicated that the proposed preparation of MLT-SiO2-HP55 is an effective method to facilitate the controlled and sustained release of MLT with enhanced bioavailability.
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- 2017
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24. Charge Conversional Biomimetic Nanocomplexes as a Multifunctional Platform for Boosting Orthotopic Glioblastoma RNAi Therapy
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Jinlong Yin, Wei Tao, Yan Zou, Yanjie Liu, Roger S. Chung, Meng Zheng, Bingyang Shi, Chan Feng, Helen Rizos, Jong Bea Park, Omid C. Farokhzad, and Albert Lee
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Biocompatibility ,Mice, Nude ,Bioengineering ,02 engineering and technology ,Blood–brain barrier ,Mice ,RNA interference ,Biomimetic Materials ,Lysosome ,Cell Line, Tumor ,medicine ,Gene silencing ,Animals ,General Materials Science ,RNA, Small Interfering ,Chemistry ,Brain Neoplasms ,Mechanical Engineering ,General Chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,medicine.disease ,Xenograft Model Antitumor Assays ,medicine.anatomical_structure ,Transcytosis ,Blood-Brain Barrier ,Blood circulation ,Cancer research ,RNA Interference ,0210 nano-technology ,Glioblastoma - Abstract
Nanotechnology-based RNA interference (RNAi) has shown great promise in overcoming the limitations of traditional clinical treatments for glioblastoma (GBM). However, because of the complexity of brain physiology, simple blood-brain barrier (BBB) penetration or tumor-targeting strategies cannot entirely meet the demanding requirements of different therapeutic delivery stages. Herein, we developed a charge conversional biomimetic nanoplatform with a three-layer core-shell structure to programmatically overcome persistent obstacles in siRNA delivery to GBM. The resulting nanocomplex presents good biocompatibility, prolonged blood circulation, high BBB transcytosis, effective tumor accumulation, and specific uptake by tumor cells in the brain. Moreover, red blood cell membrane (RBCm) disruption and effective siRNA release can be further triggered elegantly by charge conversion from negative to positive in the endo/lysosome (pH 5.0-6.5) of tumor cells, leading to highly potent target-gene silencing with a strong anti-GBM effect. Our study provides an intelligent biomimetic nanoplatform tailored for systemically siRNA delivery to GBM, leveraging Angiopep-2 peptide-modified, immune-free RBCm and charge conversional components. Improved therapeutic efficacy, higher survival rates, and minimized systemic side effects were achieved in orthotopic U87MG-luc human glioblastoma tumor-bearing nude mice.
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- 2020
25. Structures of the MHC-I molecule BF2*1501 disclose the preferred presentation of an H5N1 virus-derived epitope
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Lijie Zhang, Xiaoying Li, Nianzhi Zhang, Lizhen Ma, Yanjie Liu, and Chun Xia
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0301 basic medicine ,animal diseases ,Immunology ,Receptors, Antigen, T-Cell ,chemical and pharmacologic phenomena ,medicine.disease_cause ,Biochemistry ,Epitope ,03 medical and health sciences ,Epitopes ,MHC class I ,medicine ,Cytotoxic T cell ,Animals ,Molecular Biology ,Conserved Sequence ,030102 biochemistry & molecular biology ,biology ,Influenza A Virus, H5N1 Subtype ,Histocompatibility Antigens Class I ,virus diseases ,Cell Biology ,Virology ,Influenza A virus subtype H5N1 ,Vaccination ,CTL ,030104 developmental biology ,Epitope mapping ,biology.protein ,Chickens ,CD8 ,Epitope Mapping - Abstract
Lethal infections by strains of the highly-pathogenic avian influenza virus (HPAIV) H5N1 pose serious threats to both the poultry industry and public health worldwide. A lack of confirmed HPAIV epitopes recognized by cytotoxic T lymphocytes (CTLs) has hindered the utilization of CD8(+) T-cell–mediated immunity and has precluded the development of effectively diversified epitope-based vaccination approaches. In particular, an HPAIV H5N1 CTL-recognized epitope based on the peptide MHC-I–β2m (pMHC-I) complex has not yet been designed. Here, screening a collection of selected peptides of several HPAIV strains against a specific pathogen-free pMHC-I (pBF2*1501), we identified a highly-conserved HPAIV H5N1 CTL epitope, named HPAIV–PA(123–130). We determined the structure of the BF2*1501–PA(123–130) complex at 2.1 Å resolution to elucidate the molecular mechanisms of a preferential presentation of the highly-conserved PA(123–130) epitope in the chicken B15 lineage. Conformational characteristics of the PA(123–130) epitope with a protruding Tyr-7 residue indicated that this epitope has great potential to be recognized by specific TCRs. Moreover, significantly increased numbers of CD8(+) T cells specific for the HPAIV–PA(123–130) epitope in peptide-immunized chickens indicated that a repertoire of CD8(+) T cells can specifically respond to this epitope. We anticipate that the identification and structural characterization of the PA(123–130) epitope reported here could enable further studies of CTL immunity against HPAIV H5N1. Such studies may aid in the development of vaccine development strategies using well-conserved internal viral antigens in chickens.
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- 2020
26. Single siRNA Nanocapsules for Effective siRNA Brain Delivery and Glioblastoma Treatment
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Chengnan Yan, Yibin Wang, Yan Zou, Xinhong Sun, Dongya Zhang, Bingyang Shi, Jia Li, Meng Zheng, Roger S. Chung, and Yanjie Liu
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Small interfering RNA ,Materials science ,Intracellular Space ,02 engineering and technology ,010402 general chemistry ,Blood–brain barrier ,01 natural sciences ,Nanocapsules ,chemistry.chemical_compound ,Mice ,RNA interference ,Cell Line, Tumor ,medicine ,Animals ,Humans ,General Materials Science ,RNA, Small Interfering ,Drug Carriers ,Mechanical Engineering ,Brain ,021001 nanoscience & nanotechnology ,medicine.disease ,0104 chemical sciences ,Drug Liberation ,medicine.anatomical_structure ,Cell Transformation, Neoplastic ,chemistry ,Mechanics of Materials ,Blood-Brain Barrier ,Cancer research ,Fatal disease ,Growth inhibition ,0210 nano-technology ,Glioblastoma ,Peptides ,Intracellular - Abstract
Small interfering RNA (siRNA) has been considered as a highly promising therapeutic agent for human cancer treatment including glioblastoma (GBM), which is a fatal disease without effective therapy methods. However, siRNA-based GBM therapy is seriously hampered by a number of challenges in siRNA brain delivery including poor stability, short blood circulation, low blood-brain barrier (BBB) penetration, and tumor accumulation, as well as inefficient siRNA intracellular release. Herein, an Angiopep-2 (Ang) functionalized intracellular-environment-responsive siRNA nanocapsule (Ang-NCss (siRNA)) is successfully developed as a safe and efficient RNAi agent to boost siRNA-based GBM therapy. The experimental results demonstrate that the developed Ang-NCss (siRNA) displays long circulation in plasma, efficient BBB penetration capability, and GBM accumulation and retention, as well as responsive intracellular siRNA release due to the unique design of small size (25 nm) with polymeric shell for siRNA protection, Ang functionalization for BBB crossing and GBM targeting, and disulfide bond as a linker for intracellular-environment-responsive siRNA release. Such superior properties of Ang-NCss (siRNA) result in outstanding growth inhibition of orthotopic U87MG xenografts without causing adverse effects, achieving remarkably improved survival benefits. The developed siRNA nanocapsules provide a new strategy for RNAi therapy of GBM and beyond.
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- 2020
27. Diagnostic indicators of wild pollinators for biodiversity monitoring in long-term conservation
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Zhiyong Zhou, Muhammad Naeem, Guiling Ding, Hong Zhang, Shiwen Zhang, Jiaxing Huang, Jiandong An, Shudong Luo, Qihua Luo, and Yanjie Liu
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China ,Environmental Engineering ,Plateau ,geography.geographical_feature_category ,010504 meteorology & atmospheric sciences ,biology ,Ecology ,Biodiversity ,Breviceps ,010501 environmental sciences ,Bees ,biology.organism_classification ,01 natural sciences ,Pollution ,Geography ,Pollinator ,Canonical correspondence analysis ,Indicator species ,Environmental Chemistry ,Animals ,Waste Management and Disposal ,Bumblebee ,0105 earth and related environmental sciences - Abstract
For the conservation of wild pollinators, instead of surveying the whole community, one or more indicator species can be used as monitoring targets for long-term conservation. China, the richest country in terms of bumblebee species with 125 species, was selected here to investigate the indicator species of the different biogeographic regions of bumblebees. Four principal biogeographic regions of bumblebee species, i.e., South China, North-Northeast China (North China), the Mongolian Plateau and surrounding mountains (Mongolian Plateau) and the Tibetan Plateau and surrounding mountains (Tibetan Plateau), were revealed by Ward's agglomerative cluster analysis. The role of climatic factors in defining the biogeographic regions was found to be greater than those of topographical factors and their joint effects. We found that 14, 13, 12 and 12 species were associated with the regions of South China, North China, the Mongolian Plateau and the Tibetan Plateau, respectively. In addition, among these species, seven (Bombus atripes, B. bicoloratus, B. breviceps, B. eximius, B. flavescens, B. montivagus and B. trifasciatus), five (B. deuteronymus, B. patagiatus, B. pseudobaicalensis, B. tricornis and B. ussurensis), ten (B. armeniacus, B. confusus, B. cryptarum, B. cullumanus, B. hortorum, B. muscorum, B. ruderarius, B. soroeensis, B. subterraneus and B. terrestris) and four species (B. kashmirensis, B. personatus, B. rufofasciatus and B. waltoni) were identified as important indicator species for South China, North China, the Mongolian Plateau and the Tibetan Plateau, respectively. Furthermore, we identified specific areas for targeted bumblebee diversity monitoring in each region. This study highlights the bioregionalization and the identification of indicator species of bumblebee pollinators for long-term monitoring in conservation.
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- 2019
28. Liquid antisolvent precipitation: an effective method for ocular targeting of lutein esters
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Mingfang, Wu, Ziqi, Feng, Yiping, Deng, Chen, Zhong, Yanjie, Liu, Jiaying, Liu, Xiuhua, Zhao, and Yujie, Fu
- Subjects
nanotechnology ,solubility ,Lutein ,Administration, Oral ,Biological Availability ,Administration, Ophthalmic ,Esters ,Antioxidants ,Rats, Sprague-Dawley ,Mice ,Drug Delivery Systems ,International Journal of Nanomedicine ,Solvents ,ocular pharmacokinetics ,Animals ,Chemical Precipitation ,Nanoparticles ,drug delivery system ,Tissue Distribution ,Particle Size ,bioavailability ,Original Research - Abstract
Mingfang Wu,1,* Ziqi Feng,1,* Yiping Deng,1 Chen Zhong,2 Yanjie Liu,1 Jiaying Liu,1 Xiuhua Zhao,1 Yujie Fu1 1Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, Heilongjiang, China; 2State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China *These authors contributed equally to this work Background: Lutein ester (LE) is an important carotenoid fatty acid ester. It is a form in which lutein is present in nature and is produced by free non-esterification and fatty acid esterification. LE is one of the safe sources of lutein. Increasing lutein intake can prevent and treat age-related macular degeneration. In addition, it can effectively inhibit gastric cancer, breast cancer, and esophageal cancer. However, the poor aqueous solubility of LE has impeded its clinical applications.Objective: The objective of this study was to prepare lutein ester nanoparticles (LE-NPs) by liquid antisolvent precipitation techniques to improve the bioavailability of LE in vivo and improve eye delivery efficiency.Materials and methods: The physical characterization of LE-NPs was performed, and their in vitro dissolution rate, in vitro antioxidant capacity, in vivo bioavailability, tissue distribution, and ocular pharmacokinetics were studied and evaluated.Results: The LE freeze-dried powder obtained under the optimal conditions possessed a particle size of ~164.1±4.3 nm. The physical characterization analysis indicated the amorphous form of LE-NPs. In addition, the solubility and dissolution rate of LE-NPs in artificial gastric juice were 12.75 and 9.65 times that of the raw LE, respectively. The bioavailability of LE-NPs increased by 1.41 times compared with that of the raw LE. The antioxidant capacity of LE-NPs was also superior to the raw LE. The concentration of lutein in the main organs of rats treated with the LE-NPs was higher than that in rats treated with the raw LE. The bioavailability of LE-NPs in rat eyeballs was found to be 2.34 times that of the original drug.Conclusion: LE-NPs have potential application as a new oral pharmaceutical formulation and could be a promising eye-targeted drug delivery system. Keywords: solubility, nanotechnology, drug delivery system, bioavailability, ocular pharmacokinetics
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- 2019
29. Structural and Biochemical Analyses of Swine Major Histocompatibility Complex Class I Complexes and Prediction of the Epitope Map of Important Influenza A Virus Strains
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Wenzhong Zhou, Nianzhi Zhang, Yanan Wu, Bo Jiang, Song Wang, Zhenbao Wang, Ruiying Liang, Chun Xia, Yanjie Liu, and Shuhua Fan
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Models, Molecular ,0301 basic medicine ,Protein Conformation ,Swine ,Immunology ,Antigen presentation ,Epitopes, T-Lymphocyte ,Human leukocyte antigen ,Biology ,Crystallography, X-Ray ,medicine.disease_cause ,Major histocompatibility complex ,Microbiology ,Epitope ,03 medical and health sciences ,0302 clinical medicine ,Protein structure ,Orthomyxoviridae Infections ,Virology ,Influenza A virus ,medicine ,Animals ,Amino Acid Sequence ,Peptide sequence ,Genetics ,Antigen Presentation ,Sequence Homology, Amino Acid ,Protein Stability ,Circular Dichroism ,Structure and Assembly ,Histocompatibility Antigens Class I ,fungi ,Histocompatibility Antigens Class II ,Alanine scanning ,Peptide Fragments ,030104 developmental biology ,Insect Science ,biology.protein ,Protein Binding ,T-Lymphocytes, Cytotoxic ,030215 immunology - Abstract
The lack of a peptide-swine leukocyte antigen class I (pSLA I) complex structure presents difficulties for the study of swine cytotoxic T lymphocyte (CTL) immunity and molecule vaccine development to eliminate important swine viral diseases, such as influenza A virus (IAV). Here, after cloning and comparing 28 SLA I allelic genes from Chinese Heishan pigs, pSLA-3*hs0202 was crystalized and solved. SLA-3*hs0202 binding with sβ2m and a KMNTQFTAV (hemagglutinin [HA]-KMN9) peptide from the 2009 pandemic swine H1N1 strain clearly displayed two distinct conformations with HA-KMN9 peptides in the structures, which are believed to be beneficial to stimulate a broad spectrum of CTL immune responses. Notably, we found that different HA-KMN9 conformations are caused, not only by the flexibility of the side chains of residues in the peptide-binding groove (PBG), but also by the skewing of α1 and α2 helixes forming the PBG. In addition, alanine scanning and circular-dichroism (CD) spectra confirmed that the B, D, and F pockets play critical biochemical roles in determining the peptide-binding motif of SLA-3*hs0202. Based on biochemical parameters and comparisons to similar pockets in other known major histocompatibility complex class I (MHC-I) structures, the fundamental motif for SLA-3*hs0202 was determined to be X-(M/A/R)-(N/Q/R/F)-X-X-X-X-X-(V/I) by refolding in vitro and multiple mutant peptides. Finally, 28 SLA-3*hs0202-restricted epitope candidates were identified from important IAV strains, and two of them have been found in humans as HLA-A*0201-specific IAV epitopes. Structural and biochemical illumination of pSLA-3*hs0202 can benefit vaccine development to control IAV in swine. IMPORTANCE We crystalized and solved the first SLA-3 structure, SLA-3*hs0202, and found that it could present the same IAV peptide with two distinct conformations. Unlike previous findings showing that variable peptide conformations are caused only by the flexibility of the side chains in the groove, the skewing of the α1 and α2 helixes is important in the different peptide conformations in SLA-3*hs0202. We also determined the fundamental motif for SLA-3*hs0202 to be X-(M/A/R)-(N/Q/R/F)-X-X-X-X-X-(V/I) based on a series of structural and biochemical analyses, and 28 SLA-3*hs0202-restricted epitope candidates were identified from important IAV strains. We believe our structure and analyses of pSLA-3*hs0202 can benefit vaccine development to control IAV in swine.
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- 2016
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30. Melatonin loaded with bacterial cellulose nanofiber by Pickering-emulsion solvent evaporation for enhanced dissolution and bioavailability
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Lingling Wang, Weiwei Wu, Yanjie Liu, Qilei Yang, Yuanyuan Li, Bingxue Liu, Qian Zhang, Yang Jianhang, and Xiuhua Zhao
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Nanofibers ,Pharmaceutical Science ,Administration, Oral ,Biological Availability ,02 engineering and technology ,030226 pharmacology & pharmacy ,Rats, Sprague-Dawley ,03 medical and health sciences ,Hydrolysis ,chemistry.chemical_compound ,0302 clinical medicine ,Differential scanning calorimetry ,Suspensions ,X-Ray Diffraction ,Spectroscopy, Fourier Transform Infrared ,Animals ,Solubility ,Cellulose ,Dissolution ,Melatonin ,Bacteria ,Calorimetry, Differential Scanning ,021001 nanoscience & nanotechnology ,Pickering emulsion ,Bioavailability ,Rats ,chemistry ,Bacterial cellulose ,Nanofiber ,Microscopy, Electron, Scanning ,Solvents ,Emulsions ,0210 nano-technology ,Nuclear chemistry - Abstract
The objective of the present work aimed to explore the potential of bacterial cellulose (BC) for oral delivery of melatonin (MLT), a natural hormone that faces problems of low solubility and oral bioavailability. BC was hydrolyzed by sulfuric acid followed by the oxidation to prepare bacterial cellulose nanofiber suspension (BCNs). Melatonin-loaded bacterial cellulose nanofiber suspension (MLT-BCNs) was prepared by emulsion solvent evaporation method. The properties of freeze-dried BCs and MLT-BCNs were studied by Fluorescence microscopy (FM), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and thermo gravimetric (TG). The results indicated that the fibers in BCNs became short and thin compared with BC, MLT in MLT-BCNs was uniformly distributed, both BCNs and MLT-BCNs have good thermodynamic stability. The MLT-BCNs showed more rapid dissolution MLT rates compared to the commercially available MLT in SGF and SIF, the dissolution of the cumulative release rate was about 2.1 times of the commercially available MLT. The oral bioavailability of MLT-BCNs in rat was about 2.4 times higher than the commercially available MLT. Thus, MLT-BCNs could act as promising delivery with enhanced dissolution and bioavailability for MLT after oral administration.
- Published
- 2018
31. Structural Insights into the Preferential Binding of PGRP-SAs from Bumblebees and Honeybees to Dap-Type Peptidoglycans Rather than Lys-Type Peptidoglycans
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Jiaxing Huang, Yanjie Liu, Xiaomeng Zhao, Minming Chen, and Jiandong An
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0106 biological sciences ,0301 basic medicine ,Bombus ignitus ,In silico ,Immunology ,Sequence Homology ,Bacillus subtilis ,Hymenoptera ,Plasma protein binding ,Peptidoglycan ,Crystallography, X-Ray ,010603 evolutionary biology ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,Structure-Activity Relationship ,Phylogenetics ,Immunology and Allergy ,Animals ,Protein Interaction Domains and Motifs ,Phylogeny ,Binding Sites ,biology ,Bees ,biology.organism_classification ,Biological Evolution ,Micrococcus luteus ,030104 developmental biology ,chemistry ,Biochemistry ,Models, Chemical ,Insect Proteins ,Drosophila ,Carrier Proteins ,Protein Binding - Abstract
The peptidoglycan recognition protein SAs (PGRP-SAs) from Bombus ignitus (Bi-PGRP-SA), Apis mellifera (Am-PGRP-SA), and Megachile rotundata PGRP-SA (Mr-PGRP-SA) exhibit an intrinsic ability to preferentially bind to Dap-type peptidoglycan (PGN) from Bacillus subtilis rather than Lys-type PGN from Micrococcus luteus. This ability is more analogous to the binding exhibited by PGRP-LCx and PGRP-SD than to that exhibited by PGRP-SA in Drosophila. Moreover, Bi-PGRP-SA and Am-PGRP-SA share greater sequence identity with Drosophila PGRP-LCx than with PGRP-SD and retain several conserved contact residues, including His37/His38, His60/His61, Trp66/Trp67, Ala150/Ala151, and Thr151/Thr152. However, the corresponding contact residue Arg85 is not a major anchor residue in bees (e.g., bumblebees, honeybees, and leaf-cutting bees), and an in silico analysis indicated that the residues Thr151/Thr152 and Ser153/Ser154 of Bi-PGRP-SA and Am-PGRP-SA are deduced to be anchor residues. In addition, the nonconserved residues Asp67 in Bi-PGRP-SA and Mr-PGRP-SA and His68 in Am-PGRP-SA are deduced to be involved in the binding to Dap-type PGNs in bumblebees, honeybees, and leaf-cutting bees. We conclude that the structures and specificities of PGRP-SAs in bees are more analogous to those of PGRP-LCx than to those of Drosophila PGRP-SA. This phenomenon might be explained by the fact that the evolutionary clade of Hymenoptera is more ancient than that of Diptera.
- Published
- 2018
32. Major Histocompatibility Complex Class I (FLA-E*01801) Molecular Structure in Domestic Cats Demonstrates Species-Specific Characteristics in Presenting Viral Antigen Peptides
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Yanan Wu, Nianzhi Zhang, Zibin Li, Junya Wang, Lijie Zhang, Chun Xia, Zehui Qu, Ruiying Liang, Lizhen Ma, Nan Zhang, Yanjie Liu, Yaping Sun, and Xiaohui Wei
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0301 basic medicine ,Feline immunodeficiency virus ,Amino Acid Motifs ,Immunology ,Antigen presentation ,Gene Products, gag ,Peptide binding ,Peptide ,Immunodeficiency Virus, Feline ,Crystallography, X-Ray ,Major histocompatibility complex ,Microbiology ,Epitope ,03 medical and health sciences ,0302 clinical medicine ,Virology ,MHC class I ,Animals ,Humans ,AIDS Vaccines ,chemistry.chemical_classification ,Antigen Presentation ,Binding Sites ,biology ,Histocompatibility Antigens Class I ,biology.organism_classification ,030104 developmental biology ,chemistry ,Insect Science ,Lentivirus ,Cats ,HIV-1 ,biology.protein ,Pathogenesis and Immunity ,Peptides ,030215 immunology - Abstract
Feline immunodeficiency virus (FIV) infection in domestic cats is the smallest usable natural model for lentiviral infection studies. FLA-E*01801 was applied to FIV AIDS vaccine research. We determined the crystal structure of FLA-E*01801 complexed with a peptide derived from FIV (gag positions 40 to 48; RMANVSTGR [RMA9]). The A pocket of the FLA-E*01801 complex plays a valuable restrictive role in peptide binding. Mutation experiments and circular-dichroism (CD) spectroscopy revealed that peptides with Asp at the first position (P1) could not bind to FLA-E*01801. The crystal structure and in vitro refolding of the mutant FLA-E*01801 complex demonstrated that Glu 63 and Trp 167 in the A pocket play important roles in restricting P1D. The B pocket of the FLA-E*01801 complex accommodates M/T/A/V/I/L/S residues, whereas the negatively charged F pocket prefers R/K residues. Based on the peptide binding motif, 125 FLA-E*01801-restricted FIV nonapeptides (San Diego isolate) were identified. Our results provide the structural basis for peptide presentation by the FLA-E*01801 molecule, especially A pocket restriction on peptide binding, and identify the potential cytotoxic T lymphocyte (CTL) epitope peptides of FIV presented by FLA-E*01801. These results will benefit both the reasonable design of FLA-E*01801-restricted CTL epitopes and the further development of the AIDS vaccine. IMPORTANCE Feline immunodeficiency virus (FIV) is a viral pathogen in cats, and this infection is the smallest usable natural model for lentivirus infection studies. To examine how FLA I presents FIV epitope peptides, we crystallized and solved the first classic feline major histocompatibility complex class I (MHC-I) molecular structure. Surprisingly, pocket A restricts peptide binding. Trp 167 blocks the left side of pocket A, causing P1D to conflict with Glu 63 . We also identified the FLA-E*01801 binding motif X (except D)-(M/T/A/V/I/L/S)-X-X-X-X-X-X-(R/K) based on structural and biochemical experiments. We identified 125 FLA-E*01801-restricted nonapeptides from FIV. These results are valuable for developing peptide-based FIV and human immunodeficiency virus (HIV) vaccines and for studying how MHC-I molecules present peptides.
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- 2018
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33. Structural Illumination of Equine MHC Class I Molecules Highlights Unconventional Epitope Presentation Manner That Is Evolved in Equine Leukocyte Antigen Alleles
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Shugang Yao, Rong Chen, Junya Wang, Chun Xia, Yanjie Liu, Jianxun Qi, Nianzhi Zhang, George F. Gao, Yanan Wu, and Jun Liu
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0301 basic medicine ,viruses ,Molecular Sequence Data ,Immunology ,Antigen presentation ,Epitopes, T-Lymphocyte ,Human leukocyte antigen ,Crystallography, X-Ray ,Lymphocyte Activation ,Epitope ,Equine infectious anemia ,03 medical and health sciences ,0302 clinical medicine ,MHC class I ,Animals ,Immunology and Allergy ,Amino Acid Sequence ,Horses ,Antigens, Viral ,Peptide sequence ,Alleles ,Genetics ,Antigen Presentation ,biology ,Linear epitope ,Histocompatibility Antigens Class I ,MHC restriction ,biology.organism_classification ,Virology ,Equine Infectious Anemia ,030104 developmental biology ,biology.protein ,Infectious Anemia Virus, Equine ,T-Lymphocytes, Cytotoxic ,030215 immunology - Abstract
MHC class I (MHC I)–restricted virus-specific CTLs are implicated as critical components in the control of this naturally occurring lentivirus and in the protective immune response to the successfully applied attenuated equine infectious anemia virus vaccine in the horse. Nevertheless, the structural basis for how the equine MHC I presents epitope peptides remains unknown. In this study, we investigated the binding of several equine infectious anemia virus–derived epitope peptides by the ability to refold recombinant molecules and by thermal stability, and then by determining the x-ray structure of five peptide–MHC I complexes: equine MHC class I allele (Eqca)-N*00602/Env-RW12, Eqca-N*00602/Gag-GW12, Eqca-N*00602/Rev-QW11, Eqca-N*00602/Gag-CF9, and Eqca-N*00601/Gag-GW12. Although Eqca-N*00601 and Eqca-N*00602 differ by a single amino acid, Eqca-N*00601 exhibited a drastically different peptide presentation when binding a similar CTL epitope, Gag-GW12; the result makes the previously reported function clear to be non–cross-recognition between these two alleles. The structures plus Eqca-N*00602 complexed with a 9-mer peptide are particularly noteworthy in that we illuminated differences in apparent flexibility in the center of the epitope peptides for the complexes with Gag-GW12 as compared with Env-RW12, and a strict selection of epitope peptides with normal length. The featured preferences and unconventional presentations of long peptides by equine MHC I molecules provide structural bases to explain the exceptional anti-lentivirus immunity in the horse. We think that the beneficial reference points could serve as an initial platform for other human or animal lentiviruses.
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- 2016
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34. Salvianolic Acid Y: A New Protector of PC12 Cells against Hydrogen Peroxide-Induced Injury from Salvia officinalis
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Meizhen Song, Aichun Ju, Wei Zhou, Dekun Li, Gong Jun, Li Li, Ying He, Zhengliang Ye, Dazheng Zhou, Wanli Geng, Wang Yunhua, Yanjie Liu, Li Bing, and Rui-Chao Lin
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Circular dichroism ,Stereochemistry ,Proton Magnetic Resonance Spectroscopy ,Salvia officinalis ,Pharmaceutical Science ,Salvianolic acid Y ,Alkenes ,Article ,Analytical Chemistry ,lcsh:QD241-441 ,chemistry.chemical_compound ,food ,lcsh:Organic chemistry ,Biosynthesis ,Drug Discovery ,circular dichroism (CD) ,Animals ,Viability assay ,Physical and Theoretical Chemistry ,Hydrogen peroxide ,Benzofurans ,Chemistry ,Organic Chemistry ,PC12 cells ,Polyphenols ,Phenolic acid ,Hydrogen Peroxide ,In vitro ,food.food ,Rats ,Neuroprotective Agents ,Chemistry (miscellaneous) ,Cytoprotection ,Molecular Medicine ,Drugs, Chinese Herbal - Abstract
Salvianolic acid Y (TSL 1), a new phenolic acid with the same planar structure as salvianolic acid B, was isolated from Salvia officinalis. The structural elucidation and stereochemistry determination were achieved by spectroscopic and chemical methods, including 1D, 2D-NMR (1H-1H COSY, HMQC and HMBC) and circular dichroism (CD) experiments. The biosynthesis pathway of salvianolic acid B and salvianolic acid Y (TSL 1) was proposed based on structural analysis. The protection of PC12 cells from injury induced by H2O2 was assessed in vitro using a cell viability assay. Salvianolic acid Y (TSL 1) protected cells from injury by 54.2%, which was significantly higher than salvianolic acid B (35.2%).
- Published
- 2015
35. Structural Definition of Duck Major Histocompatibility Complex Class I Molecules That Might Explain Efficient Cytotoxic T Lymphocyte Immunity to Influenza A Virus
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Yanan Wu, Nianzhi Zhang, Shuhua Fan, Jianhua Zhang, Ruiying Liang, Rong Chen, Hongyu Yuan, Junya Wang, Chun Xia, and Yanjie Liu
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Models, Molecular ,0301 basic medicine ,crystal structure ,duck ,Protein Conformation ,Immunology ,Peptide binding ,Biology ,Crystallography, X-Ray ,medicine.disease_cause ,Major histocompatibility complex ,Microbiology ,Virus ,Epitope ,03 medical and health sciences ,Virology ,MHC class I ,Influenza A virus ,medicine ,influenza A virus ,Animals ,Cytotoxic T cell ,Antigens, Viral ,Influenza A Virus, H5N1 Subtype ,Structure and Assembly ,Histocompatibility Antigens Class I ,CTL ,Ducks ,030104 developmental biology ,Influenza in Birds ,Insect Science ,biology.protein ,disulfide bond ,beta 2-Microglobulin ,Oligopeptides ,Protein Binding ,T-Lymphocytes, Cytotoxic - Abstract
A single dominantly expressed allele of major histocompatibility complex class I (MHC I) may be responsible for the duck's high tolerance to highly pathogenic influenza A virus (HP-IAV) compared to the chicken's lower tolerance. In this study, the crystal structures of duck MHC I ( Anpl -UAA*01) and duck β2-microglobulin (β2m) with two peptides from the H5N1 strains were determined. Two remarkable features were found to distinguish the Anpl -UAA*01 complex from other known MHC I structures. A disulfide bond formed by Cys 95 and Cys 112 and connecting the β5 and β6 sheets at the bottom of peptide binding groove (PBG) in Anpl -UAA*01 complex, which can enhance IAV peptide binding, was identified. Moreover, the interface area between duck MHC I and β2m was found to be larger than in other species. In addition, the two IAV peptides that display distinctive conformations in the PBG, B, and F pockets act as the primary anchor sites. Thirty-one IAV peptides were used to verify the peptide binding motif of Anpl -UAA*01, and the results confirmed that the peptide binding motif is similar to that of HLA-A*0201. Based on this motif, approximately 600 peptides from the IAV strains were partially verified as the candidate epitope peptides for Anpl -UAA*01, which is a far greater number than those for chicken BF2*2101 and BF2*0401 molecules. Extensive IAV peptide binding should allow for ducks with this Anpl -UAA*01 haplotype to resist IAV infection. IMPORTANCE Ducks are natural reservoirs of influenza A virus (IAV) and are more resistant to the IAV than chickens. Both ducks and chickens express only one dominant MHC I locus providing resistance to the virus. To investigate how MHC I provides IAV resistance, crystal structures of the dominantly expressed duck MHC class I (p Anpl -UAA*01) with two IAV peptides were determined. A disulfide bond was identified in the peptide binding groove that can facilitate Anpl -UAA*01 binding to IAV peptides. Anpl -UAA*01 has a much wider recognition spectrum of IAV epitope peptides than do chickens. The IAV peptides bound by Anpl -UAA*01 display distinctive conformations that can help induce an extensive cytotoxic T lymphocyte (CTL) response. In addition, the interface area between the duck MHC I and β2m is larger than in other species. These results indicate that HP-IAV resistance in ducks is due to extensive CTL responses induced by MHC I.
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- 2017
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36. Myricetin suppresses breast cancer metastasis through down-regulating the activity of matrix metalloproteinase (MMP)-2/9
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Yingqian Ci, Jianhua Cao, Mei Han, Shuai Lu, Zongyu Huang, Yubo Zhang, Huajun Li, Jing Zhang, Xudong Zhu, Yanjie Liu, and Jin Gao
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0301 basic medicine ,Down-Regulation ,Breast Neoplasms ,Matrix metalloproteinase ,Metastasis ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Breast cancer ,Western blot ,In vivo ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Viability assay ,Neoplasm Metastasis ,Pharmacology ,Flavonoids ,Mice, Inbred BALB C ,medicine.diagnostic_test ,Cell migration ,medicine.disease ,030104 developmental biology ,chemistry ,Matrix Metalloproteinase 9 ,030220 oncology & carcinogenesis ,Cancer research ,Matrix Metalloproteinase 2 ,Myricetin ,Female - Abstract
Tumour metastasis is the major cause of breast cancer mortality. Myricetin, a natural polyphenol, is found in teas, wines, and berries. The pharmacodynamic action and molecular mechanism of myricetin on breast cancer metastasis remain unknown. Here, we investigated the effect of myricetin on MDA-Mb-231Br cell viability, migration, invasion, and 4T1 mouse lung metastasis mouse models. MMP-2/9 protein expression and ST6GALNAC5 expression were analysed using western blot assays and quantitative real-time polymerase chain reaction, respectively. Cell migration and invasion were detected by wound-healing and Boyden transwell assays. The antimetastatic effect in vivo was evaluated by lung metastasis model. Myricetin significantly decreased the activities of MMP-2/9 and mRNA levels of ST6GALNAC5. In addition, the migration, invasion, and adhesion were effectively inhibited in a concentration-dependent manner. On the other hand, mice treated with myricetin exhibited smaller tumour nodules compared with the vehicle mice, with only 17.78 ± 15.41% after treatment with 50 mg/kg myricetin. In conclusion, myricetin could significantly block invasion of MDA-Mb-231Br cells through suppressing the protein expression of MMP-2/9 and the expression of ST6GALNAC5, as well as lung metastasis in a mouse model, which suggests that myricetin should be developed as a potential therapeutic candidate for breast cancer.
- Published
- 2017
37. Crystallization and preliminary X-ray diffraction analysis of a single variable domain of the immunoglobulin superfamily in amphioxus,Amphi-IgSF-V
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Bo Jiang, Zhenbao Wang, Rong Chen, Yanjie Liu, Mansoor Tariq, and Chun Xia
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Human immunoglobulins ,Genetics ,Single variable ,biology ,Stereochemistry ,Resolution (electron density) ,Biophysics ,Immunoglobulins ,Condensed Matter Physics ,Biochemistry ,law.invention ,X-Ray Diffraction ,Crystallization Communications ,Structural Biology ,law ,Domain (ring theory) ,X-ray crystallography ,biology.protein ,Animals ,Immunoglobulin superfamily ,Crystallization ,Antibody ,Lancelets - Abstract
Amphioxus is regarded as an essential animal model for the study of immune evolution. Discovery of new molecules with the immunoglobulin superfamily (IgSF) variable (V) domain in amphioxus would help in studying the evolution of IgSF V molecules in the immune system. A protein was found which just contains only one IgSF V domain in amphioxus, termedAmphi-IgSF-V; it has over 30% sequence identity to the V domains of human immunoglobulins and mammalian T-cell receptors. In order to clarify the three-dimensional structure of this new molecule in amphioxus,Amphi-IgSF-V was expressed, purified and crystallized, and diffraction data were collected to a resolution of 1.95 Å. The crystal belonged to space groupP3221, with unit-cell parametersa=b= 53.9,c= 135.5 Å. The Matthews coefficient and solvent content were calculated to be 2.58 Å3 Da−1and 52.38%, respectively. The results will provide structural information to study the evolution of IgSF V molecules in the immune system.
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- 2014
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38. Phosphinic acid-based inhibitors of tubulin polyglutamylases
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Yanjie Liu, Martin E. Tanner, Christopher P. Garnham, and Antonina Roll-Mecak
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Microtubule-associated protein ,Clinical Biochemistry ,Pharmaceutical Science ,Plasma protein binding ,Biochemistry ,Article ,Mice ,Drug Discovery ,Animals ,Enzyme Inhibitors ,Peptide Synthases ,Molecular Biology ,Polyglutamylation ,chemistry.chemical_classification ,DNA ligase ,biology ,Organic Chemistry ,Glutamate receptor ,Phosphinic Acids ,Enzyme ,Tubulin ,chemistry ,biology.protein ,Molecular Medicine ,Function (biology) ,Protein Binding - Abstract
Tubulin is subject to a reversible post-translational modification involving polyglutamylation and deglutamylation of glutamate residues in its C-terminal tail. This process plays key roles in regulating the function of microtubule associated proteins, neuronal development, and metastatic progression. This study describes the synthesis and testing of three phosphinic acid-based inhibitors that have been designed to inhibit both the glutamylating and deglutamylating enzymes. The compounds were tested against the polyglutamylase TTLL7 using tail peptides as substrates (100 µM) and the most potent inhibitor displayed an IC50 value of 150 µM. The incorporation of these compounds into tubulin C-terminal tail peptides may lead to more potent TTLL inhibitors.
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- 2013
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39. Crystal structure of zebrafish complement 1qA globular domain
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Hongyu, Yuan, Rong, Chen, Mansoor, Tariq, Yanjie, Liu, Yaping, Sun, and Chun, Xia
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Evolution, Molecular ,Protein Domains ,Complement C1 ,Animals ,Humans ,Zebrafish Proteins ,Crystallography, X-Ray ,Protein Structure Reports ,Zebrafish - Abstract
C1q contains three globular domains (C1qgD) that are the key functional component of the classical complement system. C1qgD can interact with important immune molecules, including IgG and C‐reactive protein (CRP) to form defense systems to protect animals. Here, the first non‐mammalian structure, zebrafish C1qA globular domain (Dare‐C1qAgD) was solved. Although the overall architecture of Dare‐C1qAgD is similar to human C1qA, residues involved in C1qBgD, C1qCgD, and CRP binding are somewhat different while residues involved in IgG binding are not present in zebrafish. The structure gives insight into how human and fish C1qA evolved from an ancestral protein.
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- 2016
40. The structural basis of chicken, swine and bovine CD8αα dimers provides insight into the co-evolution with MHC I in endotherm species
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Yanjie Liu, Xin Li, Nianzhi Zhang, Jianxun Qi, and Chun Xia
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0301 basic medicine ,Stereochemistry ,Swine ,Dimer ,CD8 Antigens ,Sequence alignment ,Plasma protein binding ,Biology ,Major histocompatibility complex ,Crystallography, X-Ray ,Receptors for Activated C Kinase ,Article ,Evolution, Molecular ,03 medical and health sciences ,chemistry.chemical_compound ,MHC class I ,Molecule ,Animals ,Protein Structure, Quaternary ,Multidisciplinary ,Base Sequence ,Hydrogen bond ,Intermolecular force ,Histocompatibility Antigens Class I ,Hydrogen Bonding ,030104 developmental biology ,chemistry ,biology.protein ,Cattle ,Peptides ,Chickens ,Dimerization ,Sequence Alignment ,Protein Binding - Abstract
It is unclear how the pivotal molecules of the adaptive immune system (AIS) maintain their inherent characteristics and relationships with their co-receptors over the course of co-evolution. CD8α, a fundamental but simple AIS component with only one immunoglobulin variable (IgV) domain, is a good example with which to explore this question because it can fold correctly to form homodimers (CD8αα) and interact with peptide-MHC I (p/MHC I) with low sequence identities between different species. Hereby, we resolved the crystal structures of chicken, swine and bovine CD8αα. They are typical homodimers consisting of two symmetric IgV domains with distinct species specificities. The CD8αα structures indicated that a few highly conserved residues are important in CD8 dimerization and in interacting with p/MHC I. The dimerization of CD8αα mainly depends on the pivotal residues on the dimer interface; in particular, four aromatic residues provide many intermolecular forces and contact areas. Three residues on the surface of CD8α connecting cavities that formed most of the hydrogen bonds with p/MHC I were also completely conserved. Our data propose that a few key conserved residues are able to ensure the CD8α own structural characteristics despite the great sequence variation that occurs during evolution in endotherms.
- Published
- 2016
41. Narrow Groove and Restricted Anchors of MHC Class I Molecule BF2*0401 Plus Peptide Transporter Restriction Can Explain Disease Susceptibility of B4 Chickens
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Xuyu Zhou, Yanjie Liu, Jianxun Qi, James C. Kaufman, Jianhua Zhang, George F. Gao, Chun Xia, Feng Gao, Yong Chen, and Jun Liu
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Immunology ,Peptide ,Crystallography, X-Ray ,Major histocompatibility complex ,Article ,Epitope ,Immune system ,MHC class I ,Marek Disease ,Animals ,Immunology and Allergy ,Genetic Predisposition to Disease ,Genetics ,chemistry.chemical_classification ,Antigen Presentation ,biology ,Histocompatibility Antigens Class I ,Haplotype ,MHC restriction ,Peptide Fragments ,In vitro ,Protein Transport ,Haplotypes ,chemistry ,biology.protein ,Chickens ,Protein Binding - Abstract
The major histocompatibility complex (MHC) has genetic associations with many diseases, often due to differences in presentation of antigenic peptides by polymorphic MHC molecules to T lymphocytes of the immune system. In chickens, only a single classical class I molecule in each MHC haplotype is expressed well due to co-evolution with the polymorphic transporters associated with antigen presentation (TAPs), which means that resistance and susceptibility to infectious pathogens are particularly easy to observe. Previously, structures of chicken MHC class I molecule BF2*2101 from B21 haplotype showed an unusually large peptide-binding groove that accommodates a broad spectrum of peptides to present as epitopes to cytotoxic T lymphocytes (CTL), explaining the MHC-determined resistance of B21 chickens to Marek's disease. Here, we report the crystal structure of BF2*0401 from the B4 (also known as B13) haplotype, showing a highly positively-charged surface hitherto unobserved in other MHC molecules, as well as a remarkably narrow groove due to the allele-specific residues with bulky side chains. Together, these properties limit the number of epitope peptides that can bind this class I molecule. However, peptide-binding assays show that in vitro BF2*0401 can bind a wider variety of peptides than are found on the surface of B4 cells. Thus, a combination of the specificities of the polymorphic TAP transporter and the MHC results in a very limited set of BF2*0401 peptides with negatively charged anchors to be presented to T lymphocytes.
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- 2012
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42. De novo transcriptomic analysis of peripheral blood lymphocytes from the Chinese goose: gene discovery and immune system pathway description
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Junya Wang, Chun Xia, Hongyu Yuan, Yanan Wu, Mansoor Tariq, Yanjie Liu, and Rong Chen
- Subjects
China ,biology.animal_breed ,lcsh:Medicine ,Genome ,Transcriptome ,Goose ,Immune system ,Chinese goose ,Immunity ,biology.animal ,Geese ,Animals ,Lymphocytes ,RNA, Messenger ,lcsh:Science ,Gene ,Genetics ,Multidisciplinary ,biology ,Gene Expression Profiling ,lcsh:R ,High-Throughput Nucleotide Sequencing ,Sequence Analysis, DNA ,Gene expression profiling ,Gene Ontology ,lcsh:Q ,Research Article - Abstract
Background The Chinese goose is one of the most economically important poultry birds and is a natural reservoir for many avian viruses. However, the nature and regulation of the innate and adaptive immune systems of this waterfowl species are not completely understood due to limited information on the goose genome. Recently, transcriptome sequencing technology was applied in the genomic studies focused on novel gene discovery. Thus, this study described the transcriptome of the goose peripheral blood lymphocytes to identify immunity relevant genes. Principal Findings De novo transcriptome assembly of the goose peripheral blood lymphocytes was sequenced by Illumina-Solexa technology. In total, 211,198 unigenes were assembled from the 69.36 million cleaned reads. The average length, N50 size and the maximum length of the assembled unigenes were 687 bp, 1,298 bp and 18,992 bp, respectively. A total of 36,854 unigenes showed similarity by BLAST search against the NCBI non-redundant (Nr) protein database. For functional classification, 163,161 unigenes were comprised of three Gene Ontology (Go) categories and 67 subcategories. A total of 15,334 unigenes were annotated into 25 eukaryotic orthologous groups (KOGs) categories. Kyoto Encyclopedia of Genes and Genomes (KEGG) database annotated 39,585 unigenes into six biological functional groups and 308 pathways. Among the 2,757 unigenes that participated in the 15 immune system KEGG pathways, 125 of the most important immune relevant genes were summarized and analyzed by STRING analysis to identify gene interactions and relationships. Moreover, 10 genes were confirmed by PCR and analyzed. Of these 125 unigenes, 109 unigenes, approximately 87%, were not previously identified in the goose. Conclusion This de novo transcriptome analysis could provide important Chinese goose sequence information and highlights the value of new gene discovery, pathways investigation and immune system gene identification, and comparison with other avian species as useful tools to understand the goose immune system.
- Published
- 2015
43. Formula optimization of the Jiashitang scar removal ointment and antiinflammatory compounds screening by NF-κB bioactivity-guided dual-luciferase reporter assay system
- Author
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Jie, Gao, Jin, Tao, Nannan, Zhang, Yanjie, Liu, Min, Jiang, Yuanyuan, Hou, Qian, Wang, and Gang, Bai
- Subjects
Ointments ,Cicatrix ,Mice ,Molecular Structure ,Plant Extracts ,Anti-Inflammatory Agents ,NF-kappa B ,Animals ,Rats, Wistar ,Luciferases ,Mass Spectrometry ,Chromatography, Liquid ,Drugs, Chinese Herbal - Abstract
Inflammation plays a role in scar formation; therefore, decreasing inflammation benefits scar removal. Jiashitang scar removal ointment (JST) is a commercially available traditional Chinese medicinal formulation. It is composed of extracts from Carthamus tinctorius L. (Car), Rheum officinale Baill. (Rhe), Salvia miltiorrhiza Beg. (Sal), and Panax notoginseng (Burk.) F. H. Chen (Pan), which are all herbs with potent antiinflammatory activities. Our aims are to optimize the formula of JST and to elucidate its antiinflammatory active components. Response surface methodology was applied to optimize proportions of the four herb extracts. The antiinflammatory effects were evaluated using in vitro and in vivo models. To screen for active components in this formula, a bioactivity-based ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry analysis was performed. After optimization, the antiinflammatory effects of the new formula were significantly superior to the original one. Screening identified 13 active ingredients: a series of saffiomin, emodin, salvianolic acid, tanshinone, and triterpenoid saponin derivatives. These active ingredients were predicted to exert nuclear factor-κB inhibiting effects through MAPK, PI3K/AKT, and NIK-IKK pathways. In conclusion, the original formula was successfully optimized with more potent antiinflammatory activity. These methods can be applied to researches of other formulas.
- Published
- 2014
44. Crystallization and preliminary crystallographic studies of the complement 1qA globular domain from zebrafish, Dare-C1qAgD
- Author
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Yaping Sun, Rong Chen, Hongyu Yuan, Yanjie Liu, Mansoor Tariq, and Chun Xia
- Subjects
Signal peptide ,Protein subunit ,Biophysics ,Gene Expression ,Biology ,Crystallography, X-Ray ,Biochemistry ,Classical complement pathway ,Structural Biology ,Genetics ,Escherichia coli ,Animals ,Cloning, Molecular ,Zebrafish ,Complement C1q ,Zebrafish Proteins ,Condensed Matter Physics ,biology.organism_classification ,Recombinant Proteins ,Complement (complexity) ,Complement system ,Molecular Weight ,Crystallography ,Protein Subunits ,Crystallization Communications ,Orthorhombic crystal system ,Protein Multimerization ,Crystallization - Abstract
Complement 1q (C1q) is the first component of the complement system which can initiate the classical complement pathway. In human, C1q is composed of 18 polypeptide chains: six C1qA chains, six C1qB chains and six C1qC chains. Each chain has a signal peptide and is comprised of a collagen-like region and a C-terminal C1q globular domain (C1qgD), which is organized as a heterotrimer. C1qgD can recognize antigen–antibody complexes containing IgG and IgM or can bind directly to the C-reactive protein. Although the classical complement pathway is found from fish to mammals, only the human C1qgD structure has been determined. Compared with that of mammals, fish C1q exhibits similar immune functions and genome arrangement. In order to illustrate the structure of C1qgD in fish, zebrafish (Danio rerio) C1qA globular domain (Dare-C1qAgD) was expressed, purified and crystallized. X-ray diffraction data were collected from a crystal to a resolution of 2.05 Å; the crystal belonged to the orthorhombic space groupP212121, with unit-cell parametersa= 50.347,b= 85.059,c= 95.560 Å. It contained three molecules in the asymmetric unit. The Matthews coefficient valueVMwas 2.31 Å3 Da−1, with a calculated solvent content of 46.7%. The data will help to give insight into the structural basis of C1qA in fish species.
- Published
- 2014
45. Complex assembly, crystallization and preliminary X-ray crystallographic analysis of the chicken CD8αα-BF2*0401 complex
- Author
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Yanjie Liu, Mansoor Tariq, Chun Xia, and Rong Chen
- Subjects
animal structures ,Protein Conformation ,CD8 Antigens ,Antigen presentation ,Molecular Sequence Data ,Biophysics ,Crystallography, X-Ray ,Biochemistry ,law.invention ,Crystal ,Structural Biology ,law ,MHC class I ,Genetics ,Cytotoxic T cell ,Animals ,Amino Acid Sequence ,Crystallization ,DNA Primers ,Molecular mass ,biology ,Base Sequence ,Chemistry ,Resolution (electron density) ,Condensed Matter Physics ,Solvent ,Crystallography ,Crystallization Communications ,biology.protein ,Electrophoresis, Polyacrylamide Gel ,Chickens ,Oligopeptides - Abstract
In the process of antigen presentation, the MHCI–CD8 complex is important for immune signal transduction by the activation of cytotoxic T cells. Here, the expression, purification, crystallization and X-ray analysis of the complex of the chicken MHC class I molecule BF2*0401 and CD8αα (CD8αα–BF2*0401) are reported. This complex was verified by SDS–PAGE analysis of a CD8αα–BF2*0401 crystal, which showed three bands corresponding to the molecular weights of BF2*0401,β2-microglobulin and CD8α, respectively. The crystal of CD8αα–BF2*0401 diffracted to 2.8 Å resolution and belonged to space groupP21, with unit-cell parametersa= 90.6,b= 90.8,c= 94.9 Å,β= 98°. The Matthews coefficient and solvent content were calculated to be 2.88 Å3 Da−1and ∼57.3%, respectively.
- Published
- 2014
46. Membrane fusion triggers rapid degradation of two gamete-specific, fusion-essential proteins in a membrane block to polygamy in Chlamydomonas
- Author
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William J. Snell, Yanjie Liu, and Michael J. Misamore
- Subjects
Immunoblotting ,Membrane Fusion ,Cell membrane ,medicine ,Animals ,Molecular Biology ,Research Articles ,Genetics ,Zygote ,biology ,Chlamydomonas ,Algal Proteins ,Cell Membrane ,Lipid bilayer fusion ,biology.organism_classification ,Cell biology ,Membrane ,medicine.anatomical_structure ,Germ Cells ,Membrane protein ,Microscopy, Fluorescence ,Fertilization ,Gamete ,Fusion mechanism ,Developmental Biology - Abstract
The plasma membranes of gametes are specialized for fusion, yet, once fusion occurs, in many organisms the new zygote becomes incapable of further membrane fusion reactions. The molecular mechanisms that underlie this loss of fusion capacity (block to polygamy) remain unknown. During fertilization in the green alga Chlamydomonas, the plus gamete-specific membrane protein FUS1 is required for adhesion between the apically localized sites on the plasma membranes of plus and minus gametes that are specialized for fusion, and the minus-specific membrane protein HAP2 is essential for completion of the membrane fusion reaction. HAP2 (GCS1) family members are also required for fertilization in Arabidopsis, and for the membrane fusion reaction in the malaria organism Plasmodium berghei. Here, we tested whether Chlamydomonas gamete fusion triggers alterations in FUS1 and HAP2 and renders the plasma membranes of the cells incapable of subsequent fusion. We find that, even though the fusogenic sites support multi-cell adhesions, triploid zygotes are rare, indicating a fusion-triggered block to the membrane fusion reaction. Consistent with the extinction of fusogenic capacity, both FUS1 and HAP2 are degraded upon fusion. The rapid, fusion-triggered cleavage of HAP2 in zygotes is distinct from degradation occurring during constitutive turnover in gametes. Thus, gamete fusion triggers specific degradation of fusion-essential proteins and renders the zygote incapable of fusion. Our results provide the first molecular explanation for a membrane block to polygamy in any organism.
- Published
- 2010
47. The conserved plant sterility gene HAP2 functions after attachment of fusogenic membranes in Chlamydomonas and Plasmodium gametes
- Author
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Sara Garbom, Jue Ning, Andrew M. Blagborough, Yanjie Liu, William J. Snell, Jimin Pei, Robert E. Sinden, Nick V. Grishin, Robert Steele, Rita Tewari, and Oliver Billker
- Subjects
Male ,Plasmodium berghei ,Mutant ,Protozoan Proteins ,Plasmodium ,Membrane Fusion ,Arabidopsis ,parasitic diseases ,Genetics ,medicine ,Animals ,Gene ,Sperm-Ovum Interactions ,biology ,Chlamydomonas ,Algal Proteins ,Lipid bilayer fusion ,biology.organism_classification ,medicine.anatomical_structure ,Germ Cells ,Gamete ,Female ,Developmental Biology ,Research Paper - Abstract
The cellular and molecular mechanisms that underlie species-specific membrane fusion between male and female gametes remain largely unknown. Here, by use of gene discovery methods in the green alga Chlamydomonas, gene disruption in the rodent malaria parasite Plasmodium berghei, and distinctive features of fertilization in both organisms, we report discovery of a mechanism that accounts for a conserved protein required for gamete fusion. A screen for fusion mutants in Chlamydomonas identified a homolog of HAP2, an Arabidopsis sterility gene. Moreover, HAP2 disruption in Plasmodium blocked fertilization and thereby mosquito transmission of malaria. HAP2 localizes at the fusion site of Chlamydomonas minus gametes, yet Chlamydomonas minus and Plasmodium hap2 male gametes retain the ability, using other, species-limited proteins, to form tight prefusion membrane attachments with their respective gamete partners. Membrane dye experiments show that HAP2 is essential for membrane merger. Thus, in two distantly related eukaryotes, species-limited proteins govern access to a conserved protein essential for membrane fusion.
- Published
- 2008
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