INTERNATIONAL JOURNAL FOR PARASITOLOGY
·
2021
·
IF 3.981
Wenfeng Li,Yi Zhang,Hui Peng,Ruonan Zhang,Zhengwei Wang,Zachary Y. Huang,Yan Ping Chen,Richou Han
Honey bees ( Apis ) are important pollinators for food crops and wild plants, but are facing great threats from pathogens and parasites, especially an obligate ectoparasitic mite, Varroa destructor . Cell invasion is a key step for V. destructor to reproduce, and the parasite displays remarkable host preference in this process. Varroa destructor made its host-shift from its original host, the Asian honey bee Apis cerana, to the new host, the European honey bee Apis mellifera several decades ago. However, it remains largely unstudied whether V. destructor shows a cell invasion preference between the two host species. Using cell invasion bioassays on a modified four-well arena, we showed that V. destructor significantly preferred to invade the worker and drone larvae of A. mellifera rather than A. cerana , suggesting that the new host is much more attractive to the parasite than the original one. Using gas chromatography-mass spectrometry (GC-MS), we revealed significant differences between the cuticular hydrocarbon (CHC) profiles of worker and drone larvae of the two bee hosts. The amounts of methyl-branched alkanes and alkenes (unsaturated CHCs), but not n -alkanes, were significantly different, and A. mellifera worker and drone larvae were found to express significantly higher amounts of methyl-alkanes, while A. cerana larvae produced higher amounts of alkenes. Cell invasion bioassays with glass dummies showed that the mites preferred the glass dummies coated with the CHCs of A. mellifera worker or drone larvae, which indicates a role of larval CHCs in mediating the preferential cell invasion of Varroa . The findings from this study extend our understanding of the host preference of V. destructor , and can potentially contribute to the development of effective strategies for mite control.
研究领域:
昆虫学
·
化学生态学
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DOI
PubMed
高影响因子
ACTA TROPICA
·
2025
·
IF 2.5
Haoshen Wen,Yawei Li,Jiayi Luo,Wenhe Zhu,Geoff Hide,Xianmin Feng,Zhao-Rong Lun,De-Hua Lai
Malaria is still one of the most important parasitic diseases with millions of cases reported globally every year. Combination therapies of artemisinin or its derivatives, with a partner drug, are the first-and second-line treatments for malaria. However, recently, artemisinin partial resistance or tolerance has emerged and emphasizes the need for new therapeutic approaches to malaria. For example, the encapsulation of artemisinin and its derivatives within nanoparticles offers a highly promising potential approach to improved therapeutic efficacy. In this study, we investigated the effects of this using artesunate, dihydroartemisinin and artemisinin. These drugs were captured in nanoparticles of zinc-based metal-organic frameworks (MOFs) and tested on Plasmodium berghei clearance in a heavy-parasite-load mouse model. Results showed that the dosage of 16 mg/kg artesunate nanoparticles, with three injections over a 24 hr interval, had a significantly improved effect on parasite clearance and combatting the occurrence of hyperparasitaemia (parasitaemia ≥ 5%). However, the same dosage regime, over a 12 hr interval, only delayed the occurrence of hyperparasitaemia. Using a 4-injection regime over 24 hr, both 10mg/kg dihydroartemisinin nanoparticles and artemisinin nanoparticles showed stronger parasite clearance than the control non-encapsulated artemisinin at the same dose. These findings not only pose opportunities for novel malaria therapeutic approaches against hyperparasitaemia but also indicate a bright future for using nanoparticles for drug development in parasitic protozoa.
研究领域:
寄生虫学
·
药理学
·
纳米技术
·
传染病学
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
AQUACULTURE
·
2025
·
IF 3.9
Shenye Qu,Yihang Liu,Kaiyuan Lu,Yunlong Qin,Jiacheng Qin,Jietao Liu,Xiaohu Wu,Gaoxue Wang,Fei Ling
Ichthyophthirius multifiliis infections constitute a critical challenge demanding urgent resolution in global aquaculture systems. Although over 20 chemicals and natural products have demonstrated efficacy against I. multifiliis in the past two decades, the translation of these findings into clinically viable antiparasitic agents has progressed slowly, with the development of novel potent therapeutics remaining a major challenge. In this study, six novel magnolol-derived compounds were rationally designed through structural optimization of the magnolol scaffold. All synthesized compounds exhibited potent antiparasitic activity against both theront and tomont stages of I. multifiliis . Compound C1 showed superior efficacy to magnolol, with 18-fold and 26-fold lower EC 50 values against theronts (0.035 mg/L) and tomonts (0.024 mg/L) in vitro, respectively. Notably, these activity surpassed the potency of malachite green. Moreover, compound C1 showed lower toxicity than malachite green. ADMET and Density functional theory (DFT) calculations revealed that compound C1 had a favorable electrostatic potential (ESP) distribution and a lower energy gap between Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO), indicating good druggability. Integrated in silico strategy identified Mapk3 (mitogen-activated protein kinase 3) as the primary therapeutic target mediating C1's antiparasitic effects. Protein-Protein Interaction (PPI) network analysis, along with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, suggested that compound C1 might disrupt lipid metabolism and lipoxygenases pathways by modulating Mapk3 expression, thereby exerting potent antiparasitic effects. These findings establish compound C1 as the most potent anti- I. multifiliis agent reported to date. Its potential application in aquaculture may provide valuable insights for addressing this critical bottleneck issue.
研究领域:
药理学
·
水产养殖学
·
计算化学
✓ 已验证
DOI
高影响因子
AQUACULTURE
·
2023
·
IF 4.5
Jietao Liu,Shenye Qu,Tao Wang,Bin Yang,Xiang Liu,Gaoxue Wang,Pengfei Li,Qing Yu,Fei Ling
Natural products have gained recognition as a valuable resource and have significant implications in the field of aquaculture. Nevertheless, the limited water solubility of drugs, leading to compromised bioavailability, has been a persistent challenge in the realm of pharmaceutical research. Magnolol as a natural product, the low solubility leads to limited activity against Ichthyophthirius multifiliis , which severely limits the application of magnolol. Nanosuspensions are considered to be an important strategy to improve the solubility and bioavailability of insoluble drugs. The purpose of this study is to fabricate nanosuspensions that can effectively improve the solubility and antiparasitic activity of magnolol. Magnolol nanosuspensions (MNs) containg Pluronic F68 as a stabilizer was prepared by the solvent-antisolvent precipitation method. The results of TEM , DSC and FTIR analysis showed that the surfactant attached to the surface of magnolol, and the nanosuspensions process significantly reduced the crystallinity and improved the solubility and dissolution rate of magnolol. The Central Composite Design was adopted to investigate the effects of independent variables viz. amount of temperature (A), the ratio of pluronic F68 to magnolol ( w /w) (B), and churning time (C) on particle size (Y), obtaining optimum nanosuspensions with a size of 32.03 nm. Compared with free magnolol, the release rate of magnolol in 119 nm and 35 nm MNs was significantly improved, and the release rate of magnolol was increased from 28.13% to 58.45% and 85.70% within 60 min. Further, the antiparasitic activity of MNs was measured. The results showed the reduction in drug particle size leads to an enhancement in the insecticidal activity of magnolol. Altogether, this study proposes a promising strategy to enhance activity by increasing the solubility of natural products.
研究领域:
水产养殖
·
药剂学
·
天然产物研究
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产品关联
DOI
高影响因子
Frontiers in Veterinary Science
·
2022
·
IF 3.471
Jiang Yucong,Shi Yuehong,Hu Dandan,Song Xingju
Toxoplasma gondii is an obligate intracellular protozoan that infects the nucleated cells of warm-blooded animals and causes life-threatening disease in immunocompromised patients. Due to the limited effectiveness and prominent side effects of existing drugs, there is an urgent need to develop new therapeutic options against T. gondii. Piceatannol is a natural plant compound with multiple functions such as antibacterial, antileukemic and antiparasitic activities. In the present study, the anti-T. gondii activity of piceatannol was evaluated. Piceatannol potently inhibited Toxoplasma with a half-maximal effective concentration (EC50) of 28.10 μM. Piceatannol showed a significant inhibitory effect on intracellular proliferation, inhibiting intracellular parasites at a rate of 98.9% when treatment with 100 μM piceatannol. However, the invasion ability of tachyzoites was not affected by piceatannol. By immunofluorescence assay, we noted that the parasite showed abnormalities in cell division after exposure to piceatannol. To determine the in vivo effect of piceatannol on acute infection, a model was established by infecting BALB/c mice with the virulent RH strain of T. gondii. Mice infected with 500 tachyzoites showed a significant therapeutic effect when treated with 15 mg/kg of piceatannol. These results suggest that piceatannol is a promising drug for the treatment of T. gondii.
研究领域:
寄生虫学
·
药理学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE WORLD AQUACULTURE SOCIETY
·
2022
·Vol. 53
·期 6
·1084-1100
·
IF 3.402
Wei-Wei Mao,Zi-Chen Zhao,Gui-Hua Li,Wei-Liang Guo,Ze-Hao Ding,Shi-Feng Wang,Yun Sun,Zhen-Jie Cao,Jian-Long Li,Yong-Can Zhou
Cryptocaryon irritans , one of the most devastating holotrichous ciliated protozoans, causes massive economic losses in the pompano, Trachinotus ovatus , mariculture industries. Considering the many advantages of phytochemicals, such as low cost, low residuals, and low pollution, they can be a good alternative for the prevention and control of C. irritans infestations. In this study, 14 phytochemicals were evaluated for their antiparasitic activity against the theront of C. irritans , and nine showed significant antiparasitic activity. Nerolidol was the most promising compound, causing 100% mortality of theronts with 30-min exposure at a concentration of 10.0 μl/L. The half-maximal inhibitory concentrations ( IC 50 s) of nerolidol on C. irritans theronts, protomonts, and tomonts were 2.1, 13.3, and 7.1 μl/L, respectively. Abnormal morphologies of the theronts, trophonts, and tomonts were observed after exposure to 10.0, 30.0, and 10.0 μl/L nerolidol solution for 15 min, 30 min, and 480 min, respectively. A diet supplemented with 2.3 ml/kg of nerolidol reduced the number of trophonts on the gills of pompano by 95.7% decrease compared with the control groups and the theront chemotaxis to pompano mucus and sera, while increased the survival rate of infected pompanos by 24.44%, and had no significant effect on pompano hindgut and serum myeloperoxidase. These results suggest that nerolidol is a new potential drug for controlling fish cryptocaryonosis.
研究领域:
水产养殖学
·
寄生虫学
·
药理学
✓ 已验证
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Shenye Qu,Yihang Liu,Jietao Liu,Xiaohu Wu,Pengfei Li,Qing Yu,Gaoxue Wang,Fei Ling
Aquaculture is a rapidly growing sector of global food production, playing a vital role in poverty alleviation, food security, and income generation. However, it faces substantial challenges, particularly due to infections caused by the protozoan Ichthyophthirius multifiliis, leading to reduced yields and economic losses. In this study, two classes of magnolol derivatives (M1–M26) were synthesized and evaluated for their parasiticidal activity against I. multifiliis theronts and tomonts. Based on the determined EC50 values, two significant convolutional neural networks (CNNs) and pharmacophore models were developed, guiding the design and synthesis of three new compounds. Among these, compound new-1 exhibited superior parasiticidal efficacy both in vitro and in vivo compared to magnolol and the commercial parasiticide methylene blue, with EC50 values of 0.197 and 0.252 mg/L, respectively. Toxicity assays demonstrated that compound new-1 showed no significant harmful effects on goldfish and zebrafish embryos at effective concentrations. Further, in silico and experimental analyses identified CDK2 as a molecular target for compound new-1, which disrupted the reproduction and exerts parasiticidal activity against I. multifiliis. Additionally, compound new-1 exhibited antifungal activity against Aspergillus flavus with a MIC of ∼0.8 mg/mL, suggesting its potential application in food preservation. This study provides valuable insights into the development of magnolol-based agents for aquaculture.
研究领域:
水产养殖
·
药物化学
·
计算生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
PARASITOLOGY RESEARCH
·
2023
·Vol. 123
·期 1
·1-6
·
IF 2
Wang Bingxiang,Zhao Ningning,Sun Lingyu,Tan Qianqian,Xiao Qianqian,Chen Junpeng,Li Jinxuan,Zhang Xiao,Zhao Xiaomin
Difficulties of in vitro culture and genetic manipulation of Eimeria tenella have hindered the screening of virulence factors in this parasite. In this study, the E. tenella rhoptry protein 30 (EtROP30) was expressed in Toxoplasma gondii (RH∆Ku80-EtROP30), and its effect on the proliferation and virulence of parasites was investigated. The results revealed that the expression of EtROP30 had no impact on the invasion and egress processes. However, the RH∆Ku80-EtROP30 strain formed larger plaques compared to the RH∆Ku80, indicating that the EtROP30 expression promotes T. gondii proliferation. Furthermore, the RH∆Ku80-EtROP30 strain exhibited greater pathogenicity, resulting in earlier mortality and shorter overall survival time compared to RH∆Ku80. These results imply that EtROP30 expression facilitates parasite intracellular proliferation and virulence in mice, suggesting that EtROP30 might be a candidate virulence factor of E. tenella.
研究领域:
寄生虫学
·
分子生物学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FISH DISEASES
·
2025
·
IF 2.2
Jing Dong,Liwei Xia,Yongtao Liu,Qiuhong Yang,Ning Xu,Xiaohui Ai,Shun Zhou
Monogeneans are ectoparasitic flatworms causing significant economic losses in aquaculture. This study aimed to identify potential anthelmintic agents against these parasites by integrating computer-aided drug design (CADD) and in vivo evaluation. The β-tubulin gene, a well-established anthelmintic target, was cloned from Gyrodactylus kobayashii and its three-dimensional structure was generated using homology modelling. Virtual screening of 2319 FDA-approved drugs and nine common benzimidazoles against the modelled β-tubulin identified several promising compounds with low binding energy. Subsequent in vivo anthelmintic efficacy and acute toxicity assays in goldfish revealed etravirine as a potent candidate with an EC 50 value of 0.55 mg/L and a therapeutic index (TI) greater than 18.18. This favourable safety profile highlights etravirine's potential for controlling monogenean infections in aquaculture. Flubendazole and mebendazole also demonstrated potent anthelmintic activity, with EC 50 values of 0.022 and 0.023 mg/L and therapeutic indices exceeding 45.45 and 43.48, respectively. Molecular dynamics simulations confirmed stable binding modes for flubendazole and mebendazole with β-tubulin, providing mechanistic insights into their anthelmintic activity. Overall, this study demonstrated the utility of CADD in identifying potential therapeutic agents against monogenean and underscored the importance of β-tubulin as a key target for anthelmintic therapy, contributing to the development of sustainable aquaculture practices.
研究领域:
水产养殖
·
药理学
·
生物信息学
✓ 已验证
DOI
PubMed
高影响因子
PLoS Pathogens
·
2025
·Vol. 21
·期 8
·e1013446
·
IF 4.9
Fanyan Chen,Bingkuan Zhu,Yu Fang,Zilüe Li,Zhigang Lei,Zechao Xue,Tao Shen,Sha Zhou,Xiaojun Chen,Lei Xu,Yalin Li,Jifeng Zhu,Wei Hu,Chuan Su
Background
Schistosomiasis is an important neglected tropical disease necessitating focus. Cercarial proteases are essential for schistosome invasion. Leishmanolysin has been identified as the most predominant protease in Schistosoma japonicum ( S. japonicum ) cercariae, but the role and mechanism of leishmanolysin in host skin invasion by S. japonicum cercariae remain unclear.
Methodology/principal findings
Our bioinformatic analysis revealed the classification of S. japonicum leishmanolysin within the M8 matrix metalloprotease family. We then expressed recombinant S. japonicum leishmanolysin-like peptidase isoform 1 (SjLLPi1) and verified its hydrolytic enzyme activity. Western blotting analysis confirmed high level of SjLLPi1 protein in S. japonicum cercariae. Immunofluorescence staining revealed SjLLPi1 is predominantly present in the acetabular glands and their ducts in the cercarial head. Infection of mice with anti-SjLLPi1 monoclonal antibody treated S. japonicum cercariae significantly reduced worm and egg burden in mice 42 days post-infection. Infection of mice with anti-SjLLPi1 monoclonal antibody treated S. japonicum cercariae also significantly reduced parasite number in mice 7 days post-infection. In addition, treatment of mouse macrophages with SjLLPi1 prompted notable macrophage activation and substantial parasiticidal NO release. Finally, mice infected with anti-SjLLPi1 monoclonal antibody treated cercariae demonstrated a marked reduction in skin-invading parasite numbers as early as 30 min post-infection.
Conclusions/significance
Our study indicates that SjLLPi1 aids S. japonicum cercariae penetration into the definitive host by hydrolyzing skin components, thereby facilitating parasite migration and transition to adult worms within the host. These results may provide valuable guidance for vaccine development and control strategy formulation against schistosome infection.
Schistosomiasis, affecting over 200 million individuals globally, remains a significant neglected tropical disease. The cercaria stage of schistosomes is the only phase capable of infecting humans, with proteases from the acetabular glands of cercariae aiding in skin invasion. Leishmanolysin, which is the most predominant protease expressed by S. japonicum cercariae, has an unclear role in human skin invasion by S. japonicum cercariae. Bioinformatic analysis revealed that S. japonicum leishmanolysin belongs to the M8 matrix metalloprotease family, potentially with hydrolytic activity. We expressed recombinant S. japonicum leishmanolysin-like peptidase isoform 1 (SjLLPi1) and confirmed its enzymatic activity. Then we prepared the anti-SjLLPi1 monoclonal antibody. Treatment of S. japonicum cercariae with anti-SjLLPi1 monoclonal antibody reduced worm and egg burden in mice by preventing skin invasion, offering insights for vaccine development and control strategies.
研究领域:
寄生虫学
·
分子生物学
·
免疫学
·
感染性疾病
·
蛋白质组学
·
疫苗研发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
eLife
·
2025
·
IF 0
Yi Li,Long Gong,Jing Wu,Wesley Hung,Mei Zhen,Shangbang Gao
Resistance to anthelmintics, particularly the macrocyclic lactone ivermectin (IVM), presents a substantial global challenge for parasite control. We found that the functional loss of an evolutionarily conserved E3 ubiquitin ligase, UBR-1, leads to IVM resistance in Caenorhabditis elegans. Multiple IVM-inhibiting activities, including viability, body size, pharyngeal pumping, and locomotion, were significantly ameliorated in various ubr-1 mutants. Interestingly, exogenous application of glutamate induces IVM resistance in wild-type animals. The sensitivity of all IVM-affected phenotypes of ubr-1 is restored by eliminating proteins associated with glutamate metabolism or signaling: GOT-1, a transaminase that converts aspartate to glutamate, and EAT-4, a vesicular glutamate transporter. We demonstrated that IVM-targeted GluCls (glutamate-gated chloride channels) are downregulated and that the IVM-mediated inhibition of serotonin-activated pharynx Ca2+ activity is diminished in ubr-1. Additionally, enhancing glutamate uptake in ubr-1 mutants through ceftriaxone completely restored their IVM sensitivity. Therefore, UBR-1 deficiency-mediated aberrant glutamate signaling leads to ivermectin resistance in C. elegans.
研究领域:
寄生虫学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
PARASITOLOGY RESEARCH
·
2022
·Vol. 121
·期 5
·1507-1516
·
IF 2.383
Bingxiang Wang,Ningning Zhao,Yakun Wang,Lingyu Sun,Hongmei Li,Zhang Xiao,Zhao Xiaomin
Rhoptry proteins (ROPs), secreted by specific rhoptry organelles of apicomplexan parasites, are determinants of parasite pathogenesis and sources of vaccine candidates. Twenty-eight ROPs of Eimeria tenella have been predicted by genomic approaches, and in the present study, E. tenella rhoptry protein 30 (EtROP30) was characterized. Subcellular localizations of EtROP30 in sporozoites and merozoites were in the apical complex and rhoptry-like bulb, suggesting that EtROP30 is a member of ROPs in E. tenella . Sequence analysis showed that EtROP30 contained an N-terminal secretory signal, a protein kinase domain with eight E. tenella -specific rhoptry kinase 1 subfamily (ROPK-Eten1) motifs, and a C-terminal nuclear localization sequence (NLS), making EtROP30 the only ROP that contains both a secretory signal and an NLS in E. tenella . Subsequent experiments showed that EtROP30 was a secreted protein in the sporozoite stage, relying on NLS for migration to the host nucleus. In addition, EtROP30 showed significantly higher expression levels in the parasite merozoite stage, indicating that EtROP30 plays a critical role during parasite reinvasion and development and may be a viable option as a vaccine candidate for anti-parasitic infection. The immunization protection efficacies of EtROP30 were evaluated. Significant improvements in mean body weight gain, reduction of cecum lesion score, and number of oocysts excreted were observed, indicating that EtROP30 has good immunogenicity against E. tenella . In the present study, a ROP of E. tenella with secretory and nuclear localization characteristics has been identified, and proved to be an effective vaccine candidate against this parasite.
研究领域:
寄生虫学
·
免疫学
·
分子生物学
·
疫苗学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）