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VETERINARY PARASITOLOGY · 2020 · IF 2.157

Pharmacokinetics and anticoccidial activity of ethanamizuril in broiler chickens

Yikai Fu,Junwen Zhou,Lifang Zhang,Chenzhong Fei,Xiaoyang Wang,Mi Wang,Chunmei Wang,Keyu Zhang,Feiqun Xue,Yingchun Liu

The treatment effect of ethanamizuril (EZL) to broiler chickens experimentally infected with 8 × 10 4 Eimeria tenella was evaluated. On the third day after infection, the broiler chickens were treated with EZL by gavage at doses of 2, 4, and 8 mg/kg body weight (bw) for once. For double administration, the challenged broiler chickens were administered EZL at doses of 1, 2, 4, and 8 mg/kg bw by gavage continually on the third day and fourth day and once a day. Throughout the experimental period, performance parameters including body weight gain, mortality, cecal lesion score, bloody diarrhoea and oocyst output were recorded. The anticoccidial efficacy was evaluated using the anticoccidial index (ACI). Meanwhile, the concentrations of EZL in chicken cecal contents were measured, and the data were analyzed with a non-compartmental model. The results indicated that EZL showed good anticoccidial activity at single dose of 4 mg/kgbw, with the corresponding ACI of 175.73. When the challenged chickens were treated with EZL under double administration, the EZL showed a medium level of anticoccidial activity at a dose of 2 mg/kg bw, with the corresponding ACI of 162.48. The maximum concentrations (C max ) of EZL in content were 2.43 ± 1.16, 4.28 ± 1.56, and 8.57 ± 1.33 mg/kg after the chickens were administrated at doses of 2, 4, and 8 mg/kg bw, respectively. The respective areas under the curve were 36.93 ± 8.91, 96 ± 16.31, and 262.76 ± 51.52 mg/kg h. The respective half-lives (T 1/2 ) were 10.82 ± 2.02, 10.53 ± 2.23, and 10.60 ± 1.50 h. The results show that when the concentrations of EZL in chicken cecal contents reached 4.28 ± 1.56 mg/kg, there is a significant therapeutic effect on chicken coccidiosis.

CAS / MDL: 64-18-6
研究领域: 兽医学 · 药理学 · 寄生虫学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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RSC Advances · 2018 ·Vol. 8 ·期 26 ·14515-14526 · IF 2.936

Dual-sensitive chitosan derivative micelles for site-specific drug release in the treatment of chicken coccidiosis

Xin Zhang,Gujun Xu,Khalid Gadora,Hao Cheng,Jin Peng,Yong Ma,Yang Guo,Cheng Chi,Jianping Zhou,Yang Ding

Coccidiosis is a widespread and economic disease that deteriorates the growth of infected animals and largely affects our food safety. It has been proved that chitosan and its derivatives could offer outstanding antibacterial and hemostatic capabilities and help increase weight gain in the breeding of poultry. Herein, we put forward a novel strategy for the development of anti-coccidiosis drug formulations, aiming to synthesize 3-carboxyphenylboronic acid (CPBA) modified chitosan (CS) conjugates which could be self-assembled into polymeric micelles together with diclazuril (DIC), a poorly water-soluble coccidiostat drug, for site-specific drug release in the treatment of animal coccidiosis. The CPBA-modified micelles possessed specific glucose and pH dual-responsive capacity. The cumulative release of DIC reached the maximum of 85.0% at pH 6.8 and 50 mM glucose, while only 44.2% at pH 2.0 and no glucose, which allows drug to be released in the intestinal tract with neutral pH and glucose existence. 1H NMR and FTIR confirmed the successful synthesis of amphiphilic polymer; and the optimized DIC-loaded CS–CPBA micelles (DIC/CS–CPBA) shared nanoscale particle size of (118.9 ± 1.1) nm, drug loading of 8.97% and spherical shape. The pharmacokinetic results indicated that the AUC value of DIC/CS–CPBA micelles was 1.7 times than that of drug suspensions. The anti-coccidial efficacy demonstrated that DIC/CS–CPBA micelles improved the anticoccidial efficacy in vivo and reduced intestinal damage. These results indicated that phenylboronic acid-conjugated chitosan micelles provided a promising platform for specific-targeted drug release in the intestinal tract for the treatment of coccidiosis.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 兽医学 · 药剂学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Microorganisms · 2024 ·Vol. 12 ·期 3 ·601 · IF 4.1

Effects of Six Natural Compounds and Their Derivatives on the Control of Coccidiosis in Chickens

Yue Hou,Bo Han,Zehua Lin,Qizheng Liu,Zhenhe Liu,Hongbin Si,Dandan Hu

Chicken coccidiosis costs the poultry industry over GBP 10 billion per year. The main method of preventing and controlling coccidiosis in chickens continues to be the use of drugs. Unfortunately, the prevalence of drug resistance in the field reduces or even eliminates the effectiveness of drugs, and drug residues in the food supply chain can also can be harmful to humans. Therefore, safe and effective anticoccidial drugs are urgently needed. Natural products have many advantages such as being safe, effective and inexpensive and are a sustainable way to control coccidiosis. In this study, the anticoccidial effects of six natural compounds were tested byEimeria tenellainfection. Oocyst production, cecum lesion, body weight gain, feed conversion ratio, and intestinal microbiota were measured. The results showed that nerolidol had a moderate effect on maintaining both body weight gain and feed conversion ratio. Silymarin and dihydroartemisinin showed significant anticoccidial effects by reducing total oocyst output. Dihydroartemisinin also significantly reduced the cecum lesion caused byEimeriainfection, but this compound may be toxic to the host at such informed doses because it decreases growth and survival rates. In addition, both silymarin and dihydroartemisinin partly restored the microbiota after challenge. This indicates that silymarin, dihydroartemisinin, and nerolidol are effective in the control of chicken coccidiosis. Our data provide basic knowledge about the anticoccidial effects of such natural compounds/derivates.

研究领域: 兽医学 · 寄生虫学 · 动物营养学
✓ 已验证 DOI PubMed 高影响因子
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VETERINARY RESEARCH · 2025 ·Vol. 56 ·期 1 ·1-14 · IF 3.5

Molecular mechanisms of surface antigen suppression by ApiAP2 and its implications for vaccine development

Li Peiyao,Su Rina,Ren Ganglin,Si Hongbin,Song Xingju,Hu Dandan

The apicomplexan parasite Eimeria is the causative agent of coccidiosis, which results in enteritis in animals and imposes a significant economic burden on the farming industry. Apicomplexan Apetala2/ERF (ApiAP2) transcription factors are known to play crucial roles in various processes of Apicomplexa parasites. However, little is understood regarding the role of ApiAP2s in Eimeria species. In this study, we performed a functional characterisation of ApiAP2 through CRISPR-Cas9-mediated knockout. Our results revealed that the parasite’s invasion efficiency, total oocyst output, and virulence were significantly impaired after EtAP2-S1 depletion. RNA sequencing (RNA-Seq) and Cleavage Under Targets and Tagmentation (CUT&Tag) analyses showed that EtAP2-S1 targets the promoters of numerous genes, and its knockout resulted in the up-regulation of 59 sag genes. Furthermore, the knockout strain exhibited significantly lower virulence while offering excellent immune protection, making it a promising candidate for a vaccine. This study demonstrates that EtAP2-S1 is a fitness-conferring gene that suppresses the expression of sag genes in E. tenella , which is the first step in developing gene-knockout vaccines to control coccidiosis.

CAS / MDL: 58-14-0
研究领域: 分子生物学 · 寄生虫学 · 免疫学 · 兽医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Immunology · 2022 · IF 8.786

Actin depolymerizing factor-based nanomaterials: A novel strategy to enhance E. mitis-specific immunity

ZhengQing Yu,LiXin Xu,Ke He,MingMin Lu,RuoFeng Yan,XiaoKai Song,XiangRui Li

The epidemic of avian coccidiosis seriously threatens the animals’ welfare and the economic gains of the poultry industry. Widespread in avian coccidiosis, Eimeria mitis ( E. mitis ) could obviously impair the production performance of the infected chickens. So far, few effective vaccines targeting E. mitis have been reported, and the nanovaccines composed of nanospheres captured our particular attention. At the present study, we construct two kinds of nanospheres carrying the recombinant E. mitis actin depolymerizing factor (rEmADF), then the characterization was then analyzed. After safety evaluation, the protective efficacy of rEmADF along with its nanospheres were investigated in chickens. The promoted secretions of antibodies and cytokines, as well as the enhanced percentages of CD4 + and CD8 + T cells were evaluated by the ELISA and flow cytometry assay. In addition, the absolute quantitative real-time PCR (qPCR) assay implied that vaccinations with rEmADF-entrapped nanospheres could significantly reduce the replications of E. mitis in feces. Compared with the rEmADF-loaded chitosan (EmADF-CS) nanospheres, the PLGA nanospheres carrying rEmADF (EmADF-PLGA nanosphers) were more effective in up-regulating weight efficiency of animals and generated equally ability in controlling E. mitis burdens in feces, suggesting the PLGA and CS nanospheres loaded with rEmADF were the satisfactory nanovaccines for E. mitis defense. Collectively, nanomaterials may be an effective antigen delivery system that could help recombinant E. mitis actin depolymerizing factor to enhance immunoprotections in chicken against the infections of E. mitis .

CAS / MDL: 7758-29-4
研究领域: 兽医学 · 免疫学 · 纳米技术 · 微生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food Analytical Methods · 2017 ·Vol. 10 ·期 9 ·3042-3051 · IF 2.038

An Enzyme-Linked Immunosorbent Assay to Detect Salinomycin Residues Based on Immunomagnetic Bead Clean-up

Tian Wenhao,Zhang Xiaoxiao,Song Meirong,Jiang Haiyang,Ding Shuangyang,Shen Jianzhong,Li Jiancheng

Polyether antibiotics have been widely used for the treatment and prevention of coccidiosis in chicken farming. In the present study, an efficient, simple and inexpensive competitive indirect enzyme-linked immunosorbent assay (ciELISA) method based on immunomagnetic sample clean up was developed for salinomycin. Monoclonal antibodies were immobilized on the surface of carboxylic acid magnetic beads (2.8 μm in diameter). After a simple extraction, residues in sample extracts were specifically adsorbed and the supernatant removed by magnetic separation. Analytes retained on the beads were then released by elution prior to ciELISA. The limit of detection for salinomycin in chicken muscle and liver was 22 and 18 ng mL −1 , respectively, and the linear quantitative range was 47–653 ng mL −1 . Intra-assay recoveries ranged from 86.00 to 99.32%, and inter-assay recoveries were between 85.68 and 96.34%. The inhibition efficiency and sensitivity of this method was improved compared with traditional hydrophilic-lipophilic balance column clean up ciELISA. Furthermore, the convenience and repeatability of the immunomagnetic cleanup renders the new method of high value for the analysis of drug residues in complex matrices. The test method of schematic diagram

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 兽医学 · 分析化学 · 食品安全
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VETERINARY RESEARCH · 2022 ·Vol. 53 ·期 1 ·1-21 · IF 3.829

A multiepitope vaccine encoding four Eimeria epitopes with PLGA nanospheres: a novel vaccine candidate against coccidiosis in laying chickens

Yu ZhengQing,Chen SiYing,Huang JianMei,Ding WenXi,Chen YuFeng,Su JunZhi,Yan RuoFeng,Xu LiXin,Song XiaoKai,Li XiangRui

With a worldwide distribution, Eimeria spp. could result in serious economic losses to the poultry industry. Due to drug resistance and residues, there are no ideal drugs and vaccines against Eimeria spp. in food animals. In the current study, a bioinformatics approach was employed to design a multiepitope antigen, named NSLC protein, encoding antigenic epitopes of E. necatrix NA4, E. tenella SAG1, E. acervulina LDH, and E. maxima CDPK. Thereafter, the protective immunity of NSLC protein along with five adjuvants and two nanospheres in laying chickens was evaluated. Based on the humoral immunity, cellular immunity, oocyst burden, and the coefficient of growth, the optimum adjuvant was evaluated. Furthermore, the optimum immune route and dosage were also investigated according to the oocyst burden and coefficient of growth. Accompanied by promoted secretion of antibodies and enhanced CD4+ and CD8+ T lymphocyte proportions, NSLC proteins entrapped in PLGA nanospheres were more effective in stimulating protective immunity than other adjuvants or nanospheres, indicating that PLGA nanospheres were the optimum adjuvant for NSLC protein. In addition, a significantly inhibited oocyst burden and growth coefficient promotion were also observed in animals vaccinated with NSLC proteins entrapped in PLGA nanospheres, indicating that the optimum adjuvant for NSLC proteins was PLGA nanospheres. The results also suggested that the intramucosal route with PLGA nanospheres containing 300 μg of NSLC protein was the most efficient approach to induce protective immunity against the four Eimeria species. Collectively, PLGA nanospheres loaded with NSLC antigens are potential vaccine candidates against avian coccidiosis.

研究领域: 兽医学 · 免疫学 · 纳米技术 · 家禽健康
✓ 已验证 产品关联 DOI PubMed 高影响因子
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AAPS PHARMSCITECH · 2019 ·Vol. 20 ·期 2 ·1-15 · IF 2.608

Formulation and Evaluation of a Novel Oral Oil-Based Suspension Using Micro-environmental pH-Modifying Solid Dispersion

Zhang Shudong,Wan Qiang,Xing Yidan,Ding Jiafeng,Yang Shizhuang,Sun Weiwei,Lu Mengmeng,Pan Baoliang

Drugs with pH-dependent solubility that have poor water solubility can be identified in the drug discovery pipeline. Some of them have poor oral absorption, which can result in insufficient efficacy. Micro-environmental pH-modifying solid dispersion (micro pHm SD) is a promising approach to overcome the poor oral absorption of these drugs. In the present study, toltrazuril (TOL), a weakly acidic drug with poor aqueous and pH-dependent solubility, was used as a model drug. Using micro pHm SD, a novel oral oil-based suspension of TOL SD (TSDS) was developed, and the stability of this formulation was evaluated based on particle size, settling volume ratio, redispersibility, thermal stability, and drug content. The optimized soybean oil-based TSDS (S-TSDS) had high physicochemical stability and good histocompatibility with common inflammatory reactions. The results of the in vitro dissolution analysis showed that S-TSDS rapidly and markedly released the drug and provided higher efficacy and longer persistence against coccidiosis (above 90.9%) in rabbits. This technique could increase the oral absorption and bioavailability of new drug candidates.

CAS / MDL: 10191-41-0 25013-16-5
研究领域: 药剂学 · 药物递送系统 · 药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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