Microorganisms
·
2025
·Vol. 13
·期 6
·1203
·
IF 4.2
Zhenhe Liu,Haolong Qiu,Yucong Jiang,Yuxi Mo,Linlin Lu,Yan Wang,Dandan Hu,Xingju Song
Toxoplasma gondii, an obligate intracellular protozoan parasite infecting nucleated cells of warm-blooded vertebrates, causes severe complications in immunocompromised hosts. Current therapies remain limited by suboptimal efficacy and toxicity, necessitating novel anti-toxoplasmic agents. Piceatannol (PIC), a natural stilbenoid, demonstrates multifaceted bioactivity including antimicrobial and anti-parasitic effects, suggesting therapeutic potential againstT. gondii. Our previous study revealed PIC’s potent anti-parasitic activity, selectively inhibitingT. gondiiproliferation and altering parasite morphology without host cytotoxicity. In this study, mechanistic analyses indicated that PIC disrupts mitochondrial integrity in tachyzoites, reducing mitochondrial membrane potential and ATP production while elevating ROS levels. Transcriptomic profiling identified significant suppression of oxidative phosphorylation-related genes, consistent with mitochondrial dysfunction. These findings establish PIC as a promising candidate targetingT. gondiithrough the mechanism of mitochondrial impairment.
研究领域:
寄生虫学
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药理学
·
细胞生物学
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DOI
PubMed
高影响因子
EXPERIMENTAL PARASITOLOGY
·
2016
·
IF 1.623
Xiaochuan Zhang,Lili Jin,Zhe Cui,Changhao Zhang,Xue Wu,Hyun Park,Hongmei Quan,Chunmei Jin
Toxoplasma gondii ( T . gondii ) is an important pathogen which can causes serious public health problems. Since the current therapeutic drugs for toxoplasmosis present serious host toxicity, research on effective and new substances of relatively low toxicity is urgently needed. This study was carried out to evaluate the anti-parasitic effect of oxymatrine (OM) and matrine (ME) against T . gondii in vitro and in vivo . In our study, the anti- T . gondii activities of ME and OM were evaluated in vitro using cell counting kit-8 assay, morphological observation and trypan blue exclusion assay. In vivo , mice were sacrificed four days post-infection and ascites were drawn out to determine the extent of tachyzoite proliferation. Viscera indexes and liver biochemical parameters, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione (GSH) and malondialdehyde (MDA), were examined to evaluate the toxicity of compounds to mice. As a result, OM and ME showed anti- T . gondii activity but low selectivity toxicity to HeLa cells. Both compounds also significantly decreased the number of tachyzoites in peritoneal cavity and recovered the levels of ALT, AST, GSH and MDA in liver. Moreover, the mice treated with OM or ME achieved better results in viscera index and survival rate than that of spiramycin. These results suggest that OM and ME are likely the sources of new drugs for toxoplasmosis, and further studies will be necessary to compare the efficacy of drug combination, as well as identify its action of mechanism.
研究领域:
寄生虫学
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药理学
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传染病学
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产品关联
DOI
PubMed
高影响因子
Metabolites
·
2023
·Vol. 13
·期 4
·476
·
IF 4.1
Qiong Xu,Yin-Yan Duan,Ming Pan,Qi-Wang Jin,Jian-Ping Tao,Si-Yang Huang
Due to the limited effectiveness of existing drugs for the treatment of toxoplasmosis, there is a dire need for the discovery of new therapeutic options. Artemether is an important drug for malaria and several studies have indicated that it also exhibits anti-T. gondiiactivity. However, its specific effect and mechanisms are still not clear. To elucidate its specific role and potential mechanism, we first evaluated its cytotoxicity and anti-Toxoplasmaeffect on human foreskin fibroblast cells, and then analyzed its inhibitory activity duringT. gondiiinvasion and intracellular proliferation. Finally, we examined its effect on mitochondrial membrane potential and reactive oxygen species (ROS) inT. gondii. The CC50value of artemether was found to be 866.4 μM, and IC50was 9.035 μM. It exhibited anti-T. gondiiactivity and inhibited the growth ofT. gondiiin a dose-dependent manner. We also found that the inhibition occurred primarily in intracellular proliferation, achieved by reducing the mitochondrial membrane integrity ofT. gondiiand stimulating ROS production. These findings suggest that the mechanism of artemether againstT. gondiiis related to a change in the mitochondrial membrane and the increase in ROS production, which may provide a theoretical basis for optimizing artemether derivatives and further improving their anti-Toxoplasmaefficacy.Keywords:Toxoplasma gondii;artemether;mitochondria;mechanism;in vitro
研究领域:
药理学
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寄生虫学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 5
·2493
·
IF 4.9
Zhu Ying,Meng Yin,Zifu Zhu,Zheng Shang,Yanqun Pei,Jing Liu,Qun Liu
Iron is an indispensable nutrient for the survival ofToxoplasma gondii; however, excessive amounts can lead to toxicity. The parasite must overcome the host’s “nutritional immunity” barrier and compete with the host for iron. SinceT. gondiican infect most nucleated cells, it encounters increased iron stress during parasitism. This study assessed the impact of iron stress, encompassing both iron depletion and iron accumulation, on the growth ofT. gondii. Iron accumulation disrupted the redox balance ofT. gondiiwhile enhancing the parasite’s ability to adhere in high-iron environments. Conversely, iron depletion promoted the differentiation of tachyzoites into bradyzoites. Proteomic analysis further revealed proteins affected by iron depletion and identified the involvement of phosphotyrosyl phosphatase activator proteins in bradyzoite formation.Keywords:Toxoplasma gondii;iron depletion;iron accumulation;bradyzoite differentiation
研究领域:
寄生虫学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2021
·
IF 7.561
Yu Zhengqing,Cao Wandi,Gao Xuchen,Aleem Muhammad Tahir,Liu Junlong,Luo Jianxun,Yan Ruofeng,Xu Lixin,Song Xiaokai,Li Xiangrui
Toxoplasma gondii (T. gondii) is an intracellular parasitic protozoan that can cause serious public health problems. However, there is no effectively preventive or therapeutic strategy available for human and animals. In the present study, we developed a DNA vaccine encoding T. gondii oxidoreductase from short-chain dehydrogenase/reductase family (TgSDRO-pVAX1) and then entrapped in chitosan and poly lactic-co-glycolic acid (PLGA) to improve the efficacy. When encapsulated in chitosan (TgSDRO-pVAX1/CS nanospheres) and PLGA (TgSDRO-pVAX1/PLGA nanospheres), adequate plasmids were loaded and released stably. Before animal immunizations, the DNA vaccine was transfected into HEK 293-T cells and examined by western blotting and laser confocal microscopy. Th1/Th2 cellular and humoral immunity was induced in immunized mice, accompanied by modulated secretion of antibodies and cytokines, promoted the maturation and MHC expression of dendritic cells, and enhanced the percentages of CD4+ and CD8+ T lymphocytes. Immunization with TgSDRO-pVAX1/CS and TgSDRO-pVAX1/PLGA nanospheres conferred significant immunity with lower parasite burden in the mice model of acute toxoplasmosis. Furthermore, our results also lent credit to the idea that TgSDRO-pVAX1/CS and TgSDRO-pVAX1/PLGA nanospheres are substitutes for each other. In general, the current study proposed that TgSDRO-pVAX1 with chitosan or PLGA as the delivery vehicle is a promising vaccine candidate against acute toxoplasmosis.
研究领域:
免疫学
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分子生物学
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寄生虫学
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疫苗学
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生物技术
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产品关联
DOI
PubMed
高影响因子
Microbial Biotechnology
·
2024
·Vol. 17
·期 4
·e14455
·
IF 4.8
Xuke Yang,Jichao Yang,Mengyu Lyu,Yaqiong Li,Anqi Liu,Bang Shen
Toxoplasma gondii is a zoonotic parasite infecting humans and nearly all warm-blooded animals. Successful parasitism in diverse hosts at various developmental stages requires the parasites to fine tune their metabolism according to environmental cues and the parasite's needs. By manipulating the β and γ subunits, we have previously shown that AMP-activated protein kinase (AMPK) has critical roles in regulating the metabolic and developmental programmes. However, the biological functions of the α catalytic subunit have not been established. T. gondii encodes a canonical AMPKα, as well as a KIN kinase whose kinase domain has high sequence similarities to those of classic AMPKα proteins. Here, we found that Tg KIN is dispensable for tachyzoite growth, whereas Tg AMPKα is essential. Depletion of Tg AMPKα expression resulted in decreased ATP levels and reduced metabolic flux in glycolysis and the tricarboxylic acid cycle, confirming that Tg AMPK is involved in metabolic regulation and energy homeostasis in the parasite. Sequential truncations at the C-terminus found an α-helix that is key for the function of Tg AMPKα. The amino acid sequences of this α-helix are not conserved among various AMPKα proteins, likely because it is involved in interactions with Tg AMPKβ, which only have limited sequence similarities to AMPKβ in other eukaryotes. The essential role of the less conserved C-terminus of Tg AMPKα provides opportunities for parasite specific drug designs targeting Tg AMPKα.
研究领域:
寄生虫学
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分子生物学
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医学
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产品关联
DOI
PubMed
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
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2024
·
IF 3.1
Xiaozhou Li,Qi Wang,Xintong Li,Cong Wang,Jinhui Lu,Enhui Zhang,Chaolan Liang,Wenjing Wang,Yongshui Fu,Chengyao Li,Ling Zhang,Tingting Li
Toxoplasmosis is a common zoonotic disease caused by a protozoan parasite Toxoplasma gondii (Tox), approximately infecting one-third of human populations worldwide. This study developed the carbon nanospheres (CNPs) based dual spectral-overlapped fluorescence quenching lateral flow immunoassay (CNPs-FQLFIA) for detection of Tox antibodies (ToxAbs). The CNPs have been effectively coupled with Tox antigen (ToxAg), which can completely overlap the excitation and emission spectra of europium nanospheres (EuNPs) and CdSe/ZnS quantum dots (QDs) in testing strips of CNPs-QDs-FQLFIA or CNPs-EuNPs-FQLFIA. The sensitivity of CNPs-EuNPs-FQLFIA or CNPs-QDs-FQLFIA was 4 or 8 IU/mL under natural light readout, or both 4 IU/mL ToxAbs under ultraviolet (UV) light readout by the naked eyes, respectively. The limit of detection (LOD) of two types of CNPs-FQLFIA was both 1 IU/mL ToxAbs under UV light by a dry fluorescence analyzer, but no cross-reaction was found with other antibodies. The intra-assay coefficient variation (CV) of both CNPs-EuNPs-FQLFIA and CNPs-QDs-FQLFIA was less than 8%, while the inter-assay CV was less than 14%, respectively. The correlation coefficient (R 2 ) of CNPs-EuNPs-FQLFIA or CNPs-QDs-FQLFIA to measure the different concentrations of ToxAbs spiked serum samples was 0.99712 and 0.99896, respectively. The CNPs-FQLFIA presented a characteristics of 94.3% sensitivity, 100% specificity and 98% accuracy for detection of ToxAbs in clinical serum samples. In conclusion, CNPs-FQLFIA with EuNPs or QDs fluorescence reporter was an easy, rapid, sensitive, precise and quantitative assay for detecting Tox antibodies in human blood samples.
CAS / MDL:
研究领域:
纳米技术
·
免疫学
·
医学诊断
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寄生虫学
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产品关联
DOI
PubMed
高影响因子
PARASITOLOGY RESEARCH
·
2019
·Vol. 118
·期 3
·935-944
·
IF 2.067
Ye Shu,Xia Ningbo,Zhao Pengfei,Yang Jichao,Zhou Yanqin,Shen Bang,Zhao Junlong
Toxoplasma gondii is a ubiquitous parasitic protozoan infecting humans and a wide variety of animals. Fast-replicating tachyzoites during acute infection and slowly growing bradyzoites during chronic infection are the two basic forms of T. gondii in intermediate hosts. Interconversion between the two contributes to the transmission and pathogenesis of this parasite. Secretory micronemal proteins are thought to mediate interactions with host cells and facilitate parasite invasion, therefore the majority of them are highly expressed in tachyzoites. Micronemal protein 13 (MIC13) is unique in that its expression is low in tachyzoites and is upregulated under bradyzoite-inducing conditions. Previous attempts to disrupt this gene were not successful, implying that it may play critical roles during parasite growth. However, in this study, MIC13 was successfully disrupted in type 1 strain RH and type 2 strain ME49 using CRISPR/Cas9-mediated gene disruption techniques. Consistent with its low expression in tachyzoites and increased expression under stress or bradyzoite-inducing conditions, MIC13-inactivated mutants displayed normal growth, host cell invasion, intracellular replication, and egress, as well as acute virulence at the tachyzoite stage. However, under stress conditions, such as high pH or oxygen limitation, MIC13-disrupted parasites showed significantly slower growth rates compared to the parental strains, suggesting that it is required for optimal parasite growth under bradyzoite-inducing or stress conditions. This is the first micronemal protein reported to have such expression pattern and function modes, which expands our understanding of the diverse functions of micronemal proteins.
研究领域:
寄生虫学
·
分子生物学
·
传染病学
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DOI
PubMed
高影响因子
MEDICINAL CHEMISTRY RESEARCH
·
2021
·Vol. 30
·期 12
·2228-2239
·
IF 1.965
Shang Fan-Fan,Wang Mei-Yuan,Ai Jiang-Ping,Shen Qing-Kun,Guo Hong-Yan,Jin Chun-Mei,Chen Fen-Er,Quan Zhe-Shan,Jin Lili,Zhang Changhao
Nineteen mycophenolic acid (MPA) derivatives were designed and synthesized, and their anti- Toxoplasma activity evaluated for the first time. Among them, N -propylimidazole-modified compound E5 demonstrated the strongest activity, and the IC 50 against HFF-1 (Human Foreskin Fibroblasts-1) cells following infection with T. gondii is 80.9 μM (MPA-211.5 μM) and its selectivity index is 2.2 (MPA-1.2). In vivo experiments, E5 can significantly inhibit the proliferation of tachyzoites in the abdominal cavity of mice acutely infected with T. gondii (inhibition rates 46.7%), and this inhibitory effect was greater than that of spiramycin (inhibition rates 31.3%) and MPA (inhibition rates 15.9%), this indicated that E5 had significant protective effects on the host during acute Toxoplasma infection. In addition, E5 can reduce the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum of infected mice, significantly increase the level of glutathione (GSH) in the liver, and significantly reduce the level of malondialdehyde (MDA), indicating that it has a hepatoprotective effect against T. gondii infection. Similarly, E5 can relieve hepatomegaly and splenomegaly induced by acute Toxoplasma infection. Spiramycin aggravated appetite loss in infected mice, while E5 did not. In summary, the results indicated that E5 has potential as a candidate anti- T. gondii drug.
研究领域:
药理学
·
寄生虫学
·
药物化学
✓ 已验证
DOI
高影响因子
PLACENTA
·
2024
·
IF 3
Caiqun Huang
Introduction T oxoplasma gondii is an opportunistic intracellular parasite that is a major pathogenic factor in miscarriage, especially when it occurs early in pregnancy. We have previously demonstrated that the regulation of forkhead box transcription factor (Foxp3) is associated with abortion in early pregnancy caused by excretory-secretory antigen (ESA) of strain China 1. We aimed to reveal the underlying mechanism of miscarriage caused by ESA. Methods A TLR4 −/− pregnant mouse model was successfully constructed. Pregnant mice at gestational day 5 (G5) were injected with ESA. All animals were sacrificed on G13, pregnancy outcomes were observed, and abortion rates were calculated. Placental status observed by Hematoxylin-eosin staining; gene expression was measured by IHC; flow cytometry analysis was used to determine the number and function of regulatory T cells. In EL4 cells, real-time PCR and Western blot were used to evaluate gene expression and cytokines assay. Results In vivo studies revealed that ESA injection caused 83% abortion in pregnant mice but only 35% abortion in TLR4−/− pregnant mice. In addition, ESA attenuated the number and function of regulatory T cells, further suppressed Foxp3, FOXO1 levels, and upregulated CD127 expression. TLR4 −/− mice partially reversed this inhibitory effect on regulatory T cells. Furthermore, in vitro studies revealed that ESA inhibited TLR4/NF-κB signaling pathway expression and that TLR4 agonists significantly restored the ESA-induced decrease in Foxp3. Discussion These findings suggest that ESA suppresses Foxp3 expression by blocking TLR4/NF-κB signaling, resulting in miscarriage. More importantly, the results indicated that miscarriage caused by ESA is TLR4 dependent.
研究领域:
免疫学
·
寄生虫学
·
生殖生物学
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产品关联
DOI
PubMed
高影响因子
SENSORS
·
2023
·Vol. 23
·期 11
·5218
·
IF 3.9
Huiji Chen,Binbin Luo,Shengxi Wu,Shenghui Shi,Qin Dai,Zehua Peng,Mingfu Zhao
Simple SummaryA microfluidic biosensor based on a thin-core microfiber coated with molybdenum disulfide for immune detection ofToxoplasma gondiiwas illustrated. The detection range, limit of detection, detection sensitivity, specificity, and clinical properties of the proposed biosensor were explored.AbstractToxoplasma gondii(T. gondii) is a zoonotic parasite that is widely distributed and seriously endangers public health and human health. Therefore, accurate and effective detection ofT. gondiiis crucial. This study proposes a microfluidic biosensor using a thin-core microfiber (TCMF) coated with molybdenum disulfide (MoS2) for immune detection ofT. gondii. The single-mode fiber was fused with the thin-core fiber, and the TCMF was obtained by arc discharging and flame heating. In order to avoid interference and protect the sensing structure, the TCMF was encapsulated in the microfluidic chip. MoS2andT. gondiiantigen were modified on the surface of TCMF for the immune detection ofT. gondii. Experimental results showed that the detection range of the proposed biosensor forT. gondiimonoclonal antibody solutions was 1 pg/mL to 10 ng/mL with sensitivity of 3.358 nm/log(mg/mL); the detection of limit was calculated to be 87 fg/mL through the Langmuir model; the dissociation constant and the affinity constant were calculated to be about 5.79 × 10−13M and 1.727 × 1014M−1, respectively. The specificity and clinical characteristics of the biosensor was explored. The rabies virus, pseudorabies virus, andT. gondiiserum were used to confirm the excellent specificity and clinical characteristics of the biosensor, indicating that the proposed biosensor has great application potential in the biomedical field.Keywords:thin-core microfiber;microfluidic chip;molybdenum disulfide;optical fiber biosensor;toxoplasma gondii
研究领域:
生物医学工程
·
光学传感
·
寄生虫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）