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Therapeutic potential of spiramycin-nanoparticles and Aluvia in experimental congenital toxoplasmosis 螺旋霉素纳米颗粒和Aluvia治疗实验性先天性弓形虫病的潜力。
IF 1.6 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-12-01 DOI: 10.1016/j.exppara.2025.109069
Yasmen Elsayed , Amal Farahat Allam , Amel Youssef Shehab , Naglaa Fathi Abd El-Latif , Shaimaa Makled , Nermine Mogahed Fawzy Hussein Mogahed
This study aimed to evaluate the efficacy of spiramycin, spiramycin-loaded chitosan nanoparticles (CSNPs) and Aluvia for the treatment of congenital toxoplasmosis in a murine model. The study was conducted on 60 pregnant Swiss albino mice, 30 controls and 30 experimental. After performing a pilot study, mice were injected subcutaneously with the virulent Toxoplasma gondii RH strain (30 tachyzoites/mouse) on day 15 of pregnancy (3rd gestation period). The drugs were evaluated based on pregnancy outcomes (number of mice with live birth, stillbirth and abortion), number of live offspring, live pups' weight and congenital anomalies. Histopathological changes in the offspring's brain were studied. Regarding pregnancy outcomes, all mice in the non-infected control group delivered live offspring. T. gondii infection significantly decreased the live birth rate, while treatment with spiramycin, spiramycin-loaded CSNPs, and Aluvia improved pregnancy outcomes without statistical significance compared to the non-infected control. The highest number of offspring was observed in the normal non-infected control subgroup (94 pups/10 mice). Among the treated groups, spiramycin-loaded CSNPs resulted in the highest offspring count (46 pups/10 mice) and ranked first in mean pups weight, followed by Aluvia. Congenital anomalies were observed among the offspring of both infected untreated and infected treated mothers. Offspring brain tissues revealed substantial histopathological improvement in the spiramycin-loaded CSNPs and Aluvia-treated groups. In conclusion, spiramycin-loaded CSNPs and Aluvia demonstrated low parasite burden and successfully restored normal brain architecture in the offspring. However, congenital anomalies persisted and remained a significant concern.
本研究旨在评价螺旋霉素、螺旋霉素负载壳聚糖纳米颗粒(csnp)和Aluvia治疗小鼠先天性弓形虫病的疗效。研究对象为60只怀孕的瑞士白化病小鼠、30只对照小鼠和30只实验小鼠。在进行初步研究后,小鼠在妊娠第15天(第三妊娠期)皮下注射毒性强的弓形虫RH株(30个速殖子/只)。根据妊娠结局(活产鼠数、死产鼠数、流产鼠数)、活仔鼠数、活仔鼠体重和先天性异常情况对药物进行评估。研究了后代大脑的组织病理学变化。关于妊娠结局,未感染对照组的所有小鼠都产下了活的后代。弓形虫感染显著降低了活产率,而螺旋霉素、螺旋霉素负载csnp和Aluvia治疗改善了妊娠结局,但与未感染的对照组相比,无统计学意义。正常未感染对照组的子代数量最多(94只/10只)。在处理组中,携带螺旋霉素的csnp导致最高的后代数量(46只/10只小鼠),平均幼崽体重排名第一,其次是Aluvia。在感染未治疗和感染治疗的母亲的后代中都观察到先天性异常。在螺旋霉素加载csnp和aluvia处理组中,后代脑组织显示出实质性的组织病理学改善。综上所述,携带螺旋霉素的csnp和Aluvia表现出较低的寄生虫负担,并成功地恢复了后代正常的大脑结构。然而,先天性异常持续存在,仍然值得关注。
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引用次数: 0
Axenic culture of Entamoeba histolytica alters its ability to interact with pathogenic bacteria and leads to loss of virulence and pathogenicity 溶组织内阿米巴的无菌培养改变了其与致病菌相互作用的能力,并导致毒性和致病性的丧失
IF 1.6 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-12-01 DOI: 10.1016/j.exppara.2025.109072
Fabrício Marcus Silva Oliveira , Sávio Henrique de Cicco Sandes , Mario Abatemarco Junior , Elisabeth Neumann , Álvaro Cantini Nunes , Maria Aparecida Gomes , Marcelo Vidigal Caliari
Entamoeba histolytica is an anaerobic eukaryotic protozoan capable of infecting humans and causing amoebiasis, a disease responsible for approximately 50 million cases and an estimated 100,000 deaths annually worldwide. The virulence of Entamoeba histolytica trophozoites and their ability to cause amoebic colitis and hepatic abscesses in the host involve various molecules, such as a specific lectin that recognizes galactose and N-acetylgalactosamine residues, cysteine proteinases, and amoebapores. To determine whether axenization of the Entamoeba histolytica strain affects its ability to interact with and respond to the presence of other microorganisms, we cultured trophozoites of an Entamoeba histolytica EGG strain in both xenic and axenic media. We then associated them with Salmonella typhimurium and evaluated the expression of virulence factors by real-time PCR. Subsequently, we infected rats to assess whether the Enatmoeba histolytica EGG strain cultured under xenic and axenic conditions exhibited differences in pathogenicity. This study showed that the absence of bacterial microbiota in axenic culture led to a reduced capacity to produce virulence factors in vitro, even when stimulated with Salmonella typhimurium. Furthermore, in vivo analysis revealed that axenic culture altered the parasite's behavior by reducing its ability to produce intestinal lesions, even in a co-infection setting. We suggest that the expression profiles of virulence genes are influenced by continuous environmental stress and that the presence of microbiota in xenic cultures of Enatmoeba histolytica contributes to such stress and supports the maintenance of virulence gene expression.
溶组织内阿米巴原虫是一种厌氧真核原生动物,能够感染人类并引起阿米巴病,阿米巴病每年在全世界造成约5000万例病例和估计10万人死亡。溶组织内阿米巴滋养体的毒力及其在宿主中引起阿米巴结肠炎和肝脓肿的能力涉及各种分子,如识别半乳糖和n -乙酰半乳糖胺残基的特定凝集素、半胱氨酸蛋白酶和阿米巴孢子。为了确定溶组织内阿米巴菌株的无菌化是否会影响其与其他微生物相互作用和反应的能力,我们在xenic和xenic培养基中培养了溶组织内阿米巴卵细胞菌株的滋养体。然后,我们将它们与鼠伤寒沙门菌联系起来,并通过实时PCR评估毒力因子的表达。随后,我们感染了大鼠,以评估在无菌和无菌条件下培养的溶组织肠内巴卵细胞菌株是否具有不同的致病性。这项研究表明,无菌培养中细菌微生物群的缺乏导致体外产生毒力因子的能力降低,即使用鼠伤寒沙门菌刺激也是如此。此外,体内分析显示,即使在共同感染环境中,无菌培养也会通过降低其产生肠道病变的能力来改变寄生虫的行为。我们认为,毒力基因的表达谱受到持续环境胁迫的影响,而溶组织肠杆菌异种培养中微生物群的存在有助于这种胁迫,并支持毒力基因表达的维持。
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引用次数: 0
A predictive model for predicting the occurrence of liver cancer in patients with schistosomiasis cirrhosis 血吸虫病肝硬化患者肝癌发生的预测模型
IF 1.6 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-12-01 DOI: 10.1016/j.exppara.2025.109071
Yiming Wu , Jing Huang , Chenzhou Xu

Objective

Early diagnosis of liver cancer following schistosomiasis cirrhosis remains challenging. This study aims to develop a predictive model for identifying precancerous liver lesions and early-stage liver cancer in patients with schistosomiasis cirrhosis.

Methods

Patients diagnosed with schistosomiasis cirrhosis over the past 14 years and managed by the Jiaxing Schistosomiasis Management Office were included in the study. Univariate regression analysis was conducted to assess the correlation between various indices and liver cancer. The predictive diagnostic efficiency was evaluated using the AUROC's cross-sectional area, with the optimal cutoff point identified through the Youden index.

Results

Univariate regression revealed significant associations with RBC count, ALT level, and other factors (P<0.1). Multivariate regression analysis identified AST, GGT, and additional factors as significant predictors (P<0.05). From these findings, two predictive models were developed: one for early-stage liver cancer (ESLC model) and another for precancerous lesions (PL model). The AUROC confirmed the superior diagnostic performance of both models compared to AFP, particularly in predicting precancerous lesions, thus addressing some of AFP's limitations.

Conclusion

The proposed predictive model serves as a valuable tool for early detection of precancerous liver lesions. It outperforms AFP in this regard, with AST, GGT, TB, BA, PT, PCIII, and AFP identified as independent predictors of liver cancer.
目的血吸虫病肝硬化后肝癌的早期诊断仍然具有挑战性。本研究旨在建立血吸虫病肝硬化患者癌前病变和早期肝癌的预测模型。方法选取嘉兴市血吸虫病管理办公室管理的14年内确诊为肝硬化的患者为研究对象。采用单因素回归分析评价各指标与肝癌的相关性。使用AUROC的横截面积评估预测诊断效率,并通过约登指数确定最佳截止点。结果单因素回归显示与RBC计数、ALT水平及其他因素有显著相关性(P<0.1)。多因素回归分析发现AST、GGT和其他因素是显著的预测因子(P<0.05)。根据这些发现,开发了两种预测模型:一种用于早期肝癌(ESLC模型),另一种用于癌前病变(PL模型)。AUROC证实,与AFP相比,这两种模型的诊断性能更好,特别是在预测癌前病变方面,从而解决了AFP的一些局限性。结论该预测模型可作为早期发现肝癌前病变的有效工具。在这方面,它优于AFP, AST、GGT、TB、BA、PT、PCIII和AFP被确定为肝癌的独立预测因子。
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引用次数: 0
Infection dynamics of Metarhizium anisopliae in Rhipicephalus microplus and the role of tick traits in susceptibility 金龟子绿僵菌在微小鼻头虫中的感染动态及蜱虫性状对其易感性的影响。
IF 1.6 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-11-21 DOI: 10.1016/j.exppara.2025.109070
Nurul Fatin Amirah Mohd Azmi , Samsuddin Ahmad Syazwan , Ruhil Hayati Hamdan , Tan Li Peng
Tick-borne diseases (TBDs) pose a major threat to global livestock production, particularly in tropical and subtropical regions, and their burden is projected to increase worldwide in the coming decades as a result of climate change. In Brazil, tick infestations are responsible for economic losses estimated at about USD 3.24 billion annually. Growing resistance to chemical acaricides necessitates alternative control strategies such as biological agents. This study assessed the pathogenicity of a local strain of Metarhizium anisopliae (PR1) against adult Rhipicephalus microplus ticks using the Adult Immersion Test at conidial concentrations of 107, 108, and 109 conidia/mL, each tested in triplicate alongside positive and negative controls. All concentrations caused complete tick mortality within 14 days, with higher concentrations accelerating tick death and completely inhibiting oviposition and larval hatchability. The estimated LT50 and LT90 values for the 109 conidia/mL treatment were 2.46 [2.09–2.75] days and 3.63 [3.25–4.29] days, respectively. In contrast, untreated ticks exhibited only 6.7 % mortality and laid an average of 1567 ± 314 eggs, of which 84 % hatched. A significant positive correlation was observed between tick weight and the time to death at the highest concentration, suggesting heavier ticks resisted infection longer, potentially due to higher energy reserves or thicker cuticular. These results underline the potent in vitro pathogenic and reproductive-suppressing effects of M. anisopliae strain PR1 under laboratory conditions, while emphasizing the need for further field validation before considering its application in broader vector management programs.
蜱传疾病(tbd)对全球畜牧业生产构成重大威胁,特别是在热带和亚热带地区,预计未来几十年,由于气候变化,其负担将在全球范围内增加。在巴西,蜱虫侵扰每年造成的经济损失估计约为32.4亿美元。对化学杀螨剂的抗药性日益增强,需要采用生物制剂等替代控制策略。本研究采用成虫浸没试验,在分生孢子浓度分别为107、108和109分生孢子/mL的情况下,对当地一株金银绿僵菌(PR1)对微头蜱成虫的致病性进行了评估。各浓度均能使蜱在14 d内完全死亡,浓度越高,则加速了蜱的死亡,并完全抑制了其产卵和幼虫的孵化能力。109个分生孢子/mL处理的LT50和LT90分别为2.46[2.09-2.75]天和3.63[3.25-4.29]天。相比之下,未经处理的蜱死亡率仅为6.7%,平均产卵1567±314枚,其中84%孵化。在最高浓度下,蜱的体重与死亡时间呈显著正相关,表明较重的蜱对感染的抵抗力较长,可能是由于能量储备较高或表皮较厚。这些结果强调了绿僵菌PR1在实验室条件下具有强大的体外致病和生殖抑制作用,同时强调了在考虑将其应用于更广泛的媒介管理计划之前需要进一步的现场验证。
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引用次数: 0
Evaluation of the efficacy of four fasciolicides in naturally infected cattle in Beni-Suef governorate, Egypt: First report of therapeutic failure of triclabendazole 埃及贝尼-苏韦夫省四种杀片虫剂对自然感染牛的疗效评价:首次报道三氯咪唑治疗失败。
IF 1.6 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-11-21 DOI: 10.1016/j.exppara.2025.109067
Mohamed G. Abdelrahman , Shawky M. Aboelhadid , Sherin R. Rouby , Ahmed Zaitoun , Ahmed M. El-Sherif
The emergence of anthelmintic resistance presents a major threat to the health and productivity of grazing livestock. This study aimed to evaluate the efficacy of commonly used fasciolicides against Fasciola spp. in naturally infected cattle from Beni-Suef, Egypt—an area where fasciolosis is endemic. Twenty adult female cattle, confirmed by microscopic examination to be infected with Fasciola spp., were selected and divided into three experimental trials to evaluate the efficacy of four commercial fasciolicides: triclabendazole (TCBZ), rafoxanide (RAF), nitroxynil (NIT), and oxyclozanide (OCZ). Experiment I evaluated possible resistance to TCBZ, RAF, and NIT by administering two consecutive doses of each drug. Experiment II investigated potential multidrug resistance by treating animals resistant to RAF and NIT with a single dose of TCBZ. Experiment III examined the efficacy of OCZ as an alternative treatment. The fecal egg count reduction test (FECRT) was used as the primary assessment method in all trials. In Experiment I, cattle treated with RAF or NIT showed no reduction in egg counts, even after the second dose. TCBZ treatment resulted in a marked decrease in egg counts at day 7 post-treatment, but counts gradually increased from day 14 onwards, returning to pre-treatment levels by day 56. In Experiment II, animals treated with TCBZ again showed a significant drop in egg counts at day 7, followed by a steady rise to baseline values by day 28. In Experiment III, OCZ achieved complete elimination of eggs by day 7, with 100 % efficacy. This study provides the first documented evidence of triclabendazole (TCBZ) treatment failure in animals in Egypt, highlighting the urgent need for large-scale investigations across the country. In contrast, oxyclozanide (OCZ) showed high efficacy in eliminating Fasciola infections in cattle, emphasizing its potential as a valuable alternative for improving fasciolosis control and management strategies in Egypt.
抗虫性的出现对放牧牲畜的健康和生产力构成了重大威胁。本研究旨在评估常用的杀片形虫剂对埃及贝尼-苏韦夫自然感染的牛片形虫的疗效。贝尼-苏韦夫是片形虫病流行的地区。选取镜检证实感染片吸虫病的成年母牛20头,分为3个试验,分别评价三氯苄达唑(TCBZ)、拉福昔尼(RAF)、硝基尼(NIT)和羟氯胺酮(OCZ) 4种市售片吸虫药的杀灭效果。实验1通过连续给药两剂来评估对TCBZ、RAF和NIT的可能耐药性。实验二通过单剂量TCBZ治疗对RAF和NIT耐药的动物,研究潜在的多药耐药。实验三考察了OCZ作为一种替代疗法的疗效。所有试验均采用粪卵计数减少试验(FECRT)作为主要评估方法。在实验1中,用RAF或NIT处理的牛,即使在第二次剂量后,卵子数量也没有减少。TCBZ处理导致鸡蛋数量在处理后第7天显著下降,但从第14天开始逐渐增加,到第56天恢复到处理前水平。在实验二中,经TCBZ处理的动物在第7天再次显示卵子数量显著下降,随后在第28天稳定上升到基线值。在实验三中,OCZ在第7天完全消除了卵子,有效率为100%。本研究首次提供了埃及动物使用三氯咪唑(TCBZ)治疗失败的文献证据,强调了在全国范围内开展大规模调查的迫切需要。相比之下,羟氯胺(oxyclozanide, OCZ)在消除牛片形虫感染方面表现出高效率,强调了其作为改善埃及片形虫病控制和管理战略的一种有价值的替代方案的潜力。
{"title":"Evaluation of the efficacy of four fasciolicides in naturally infected cattle in Beni-Suef governorate, Egypt: First report of therapeutic failure of triclabendazole","authors":"Mohamed G. Abdelrahman ,&nbsp;Shawky M. Aboelhadid ,&nbsp;Sherin R. Rouby ,&nbsp;Ahmed Zaitoun ,&nbsp;Ahmed M. El-Sherif","doi":"10.1016/j.exppara.2025.109067","DOIUrl":"10.1016/j.exppara.2025.109067","url":null,"abstract":"<div><div>The emergence of anthelmintic resistance presents a major threat to the health and productivity of grazing livestock. This study aimed to evaluate the efficacy of commonly used fasciolicides against <em>Fasciola</em> spp. in naturally infected cattle from Beni-Suef, Egypt—an area where fasciolosis is endemic. Twenty adult female cattle, confirmed by microscopic examination to be infected with <em>Fasciola</em> spp., were selected and divided into three experimental trials to evaluate the efficacy of four commercial fasciolicides: triclabendazole (TCBZ), rafoxanide (RAF), nitroxynil (NIT), and oxyclozanide (OCZ). Experiment I evaluated possible resistance to TCBZ, RAF, and NIT by administering two consecutive doses of each drug. Experiment II investigated potential multidrug resistance by treating animals resistant to RAF and NIT with a single dose of TCBZ. Experiment III examined the efficacy of OCZ as an alternative treatment. The fecal egg count reduction test (FECRT) was used as the primary assessment method in all trials. In Experiment I, cattle treated with RAF or NIT showed no reduction in egg counts, even after the second dose. TCBZ treatment resulted in a marked decrease in egg counts at day 7 post-treatment, but counts gradually increased from day 14 onwards, returning to pre-treatment levels by day 56. In Experiment II, animals treated with TCBZ again showed a significant drop in egg counts at day 7, followed by a steady rise to baseline values by day 28. In Experiment III, OCZ achieved complete elimination of eggs by day 7, with 100 % efficacy. This study provides the first documented evidence of triclabendazole (TCBZ) treatment failure in animals in Egypt, highlighting the urgent need for large-scale investigations across the country. In contrast, oxyclozanide (OCZ) showed high efficacy in eliminating <em>Fasciola</em> infections in cattle, emphasizing its potential as a valuable alternative for improving fasciolosis control and management strategies in Egypt.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"280 ","pages":"Article 109067"},"PeriodicalIF":1.6,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145586036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genome-wide screening, identification and analysis of BAR domain-containing proteins in Toxoplasma gondii 刚地弓形虫BAR结构域蛋白的全基因组筛选、鉴定和分析。
IF 1.6 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-11-19 DOI: 10.1016/j.exppara.2025.109068
Weiwei Sun, An Yan, Lifang Wang, Bohan Wang, Baoliang Pan
Toxoplasma gondii is an important zoonotic pathogen that infects nucleated cells in all warm-blooded animals, and affects about one-third of the world's population. The treatment for T. gondii relies on drugs, but there is no specific cure. The discovery, identification and understanding of key protein families of T. gondii are of great significance for candidate antigen screening, vaccine development, and novel prevention and control program. The Bin, amphiphysin and Rvs (BAR) superfamily is a category of proteins with the BAR domain, which plays an important role in membrane tubulation and constriction during vesicle formation in mammalian cells, and is essential for material transport. However, the information of BAR proteins in T. gondii is not comprehensive. In present study, we screened and identified four BAR domain-containing proteins (Bcps), including TGGT1_259720, TGGT1_320760, TGGT1_232180 and TGGT1_224070 in the T. gondii genome using HMM search and local blast. All above-mentioned Bcps contained the BAR domain, and the 3D structures present the typical crescent shaped helical dimer of BAR. The classification of BAR domains was analyzed by evolutionary tree clustering, and it was found that TGGT1_259720 belonged to F-BAR and the other three belonged to N-BAR. The phylogenetic analysis of four protozoa showed that the Bcps of T. gondii were the closest relative to those of N. caninum, which was consistent with the result of collinearity analysis among species. Moreover, conserved motif and gene composition analysis further confirmed that these closely related proteins are more similar in these structures. The prediction of interacting proteins also showed that Bcps had strong interaction with the key proteins of vesicle transport. The quantification of BAR genes by qPCR showed that these BAR genes were expressed during the growth and proliferation of T. gondii, and the expression patterns were different under different nutritional conditions with the increase of FBS concentration gradient, indicating that these genes played different roles.
刚地弓形虫是一种重要的人畜共患病原体,感染所有温血动物的有核细胞,影响世界上约三分之一的人口。弓形虫的治疗依赖于药物,但没有特效药。弓形虫关键蛋白家族的发现、鉴定和认识,对候选抗原筛选、疫苗研制和新型防控规划具有重要意义。Bin, amphiphysin and Rvs (BAR)超家族是一类具有BAR结构域的蛋白质,在哺乳动物细胞囊泡形成过程中,在膜管和收缩中起重要作用,对物质运输至关重要。然而,关于弓形虫中BAR蛋白的信息并不全面。本研究利用隐马尔可夫搜索和局部blast技术,从弓形虫基因组中筛选出4个BAR结构域蛋白(bps),分别为TGGT1_259720、TGGT1_320760、TGGT1_232180和TGGT1_224070。上述Bcps均含有BAR结构域,三维结构呈现典型的BAR新月形螺旋二聚体。采用进化树聚类方法对BAR结构域进行分类,发现TGGT1_259720属于F-BAR,其余3个属于N-BAR。4种原生动物的系统发育分析表明,弓形虫的Bcps与犬奈虫的Bcps最接近,这与种间共线性分析结果一致。此外,保守基序和基因组成分析进一步证实了这些密切相关的蛋白在这些结构上更加相似。相互作用蛋白的预测也表明,Bcps与囊泡运输的关键蛋白具有较强的相互作用。通过qPCR对BAR基因的定量分析发现,这些BAR基因在弓形虫生长和增殖过程中均有表达,且随着FBS浓度梯度的增加,不同营养条件下BAR基因的表达模式不同,说明这些基因发挥了不同的作用。
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引用次数: 0
Novel anticoagulant proteins identified in the salivary glands of Rhipicephalus sanguineus and their interaction with coagulation factor X 在血鼻猪唾液腺中鉴定的新型抗凝蛋白及其与凝血因子X的相互作用
IF 1.6 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-11-13 DOI: 10.1016/j.exppara.2025.109063
YaJun Lu , YaE Zhao , XingZhi Feng
In the salivary glands of the hematophagous arthropod R. sanguineus, a total of 122 protein coding sequences interacting with coagulation factor X (FX) were identified using the yeast two-hybrid (Y2H) technology, including 100 characterized proteins, and 22 uncharacterized. Three proteins, ferritin-like, tyrosine-protein phosphatase Lar-like, and elongation factor 1 alpha, were selected for cloning, demonstrated significant impacts on four key coagulation parameters: prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB) levels. They significantly prolonged PT, APTT, and TT, and reduced FIB levels, indicating interactions with both extrinsic and endogenous coagulation pathways and potential interference with fibrinogen synthesis, metabolism, or functional activity. Docking simulations between the proteins and FX provided evidence of stable, specific protein-protein complexes, mediated by hydrophobic forces. The high confidence scores and diverse interaction modes suggested evolutionary refinement for tight, specific binding to FX. The study introduced promising anticoagulant molecules from hematophagous arthropods, rigorously validated their activity, and highlighted their potential for research and therapeutic applications. These findings have implications for the development of new anticoagulant and antithrombotic therapeutics, underscoring the importance of exploring natural sources for new drugs to expand the drug pipeline in cardiovascular medicine.
利用酵母双杂交(Y2H)技术,在嗜血节肢动物R. sanguineus唾液腺中共鉴定出122个与凝血因子X (FX)相互作用的蛋白编码序列,其中已鉴定蛋白100个,未鉴定蛋白22个。选择铁蛋白样、酪氨酸蛋白磷酸酶样和延伸因子1 α 3种蛋白进行克隆,发现它们对凝血酶原时间(PT)、活化的部分凝血活酶时间(APTT)、凝血酶时间(TT)和纤维蛋白原(FIB)水平等4个关键凝血参数有显著影响。它们显著延长了PT、APTT和TT,并降低了FIB水平,表明它们与外源性和内源性凝血途径相互作用,并可能干扰纤维蛋白原合成、代谢或功能活性。蛋白质和FX之间的对接模拟提供了由疏水力介导的稳定、特异性蛋白质复合物的证据。高置信度分数和多样化的相互作用模式表明,进化改进了与FX的紧密、特异性结合。本研究从食血节肢动物中引入了有前途的抗凝血分子,严格验证了它们的活性,并强调了它们在研究和治疗应用方面的潜力。这些发现对开发新的抗凝血和抗血栓治疗药物具有重要意义,强调了探索新药天然来源以扩大心血管医学药物管道的重要性。
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引用次数: 0
Isolation of Bacillus altitudinis A7 from Eimeria-immunized chickens and its inhibitory effect on Eimeria tenella 艾美耳球虫免疫鸡中高原芽孢杆菌A7的分离及其对艾美耳球虫的抑制作用。
IF 1.6 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-11-12 DOI: 10.1016/j.exppara.2025.109048
Zhongchuang Wang , Peiyao Shang , Man Lei , Wenjie Zhang , Ruiting Zhang , Qiping Zhao , Shunhai Zhu , Hongyu Han , Hui Dong , Lili Hao , Xingju Song
Eimeria spp. are responsible for chicken coccidiosis, the most important enteric protozoan disease in poultry, resulting in significant economic losses for the poultry industry. With the prohibition of antibiotic use in animal husbandry, researchers must find alternative preventive agents. The objective of this study was to isolate Bacillus strains and evaluate the anti-Eimeria tenella effects of B. altitudinis A7. In total, four Bacillus strains (A1, A5, A6, and A7) were isolated from the fresh feces of E. tenella-immunized chickens, and three Bacillus species, B. pumilus T246 (A1), B. altitudinis 41KF2b (A5 and A7), and B. cereus NS26 (A6), were identified with morphological and molecular methods. The consumption of B. altitudinis A7 by chickens significantly reduced oocyst production and the cecal lesion score after infection with E. tenella and significantly increased the expression of tight-junction proteins, interleukin-8 (IL-8), interleukin-10 (IL-10), and superoxide dismutase 1 (SOD1) relative to those in the E. tenella-infected, non-B. altitudinis A7-fed group (CON). B. altitudinis A7 also significantly increased the relative abundances of Pediococcus, Fournierella, Clostridium sensu stricto 1, CAG:352, and Tuzzerella compared with those in both the CON group and the normal control (N) group. These findings indicate that B. altitudinis A7 isolated from the feces of E. tenella-immunized chickens promoted host resistance to E. tenella.
鸡球虫病是禽类中最重要的肠道原生动物疾病,艾美耳球虫引起鸡球虫病,给家禽业造成重大经济损失。由于禁止在畜牧业中使用抗生素,研究人员必须找到替代的预防剂。本研究的目的是分离芽孢杆菌菌株,并评价高原芽孢杆菌A7抗柔嫩艾美耳球虫的作用。从鸡鲜粪中分离到4株芽孢杆菌(A1、A5、A6、A7),并通过形态学和分子方法鉴定出细小芽孢杆菌T246 (A1)、高原芽孢杆菌41KF2b (A5、A7)和蜡样芽孢杆菌NS26 (A6)。食用高原白僵菌A7后,鸡的卵囊产量显著降低,盲肠病变评分显著降低,紧密连接蛋白、白细胞介素-8 (IL-8)、白细胞介素-10 (IL-10)和超氧化物歧化酶1 (SOD1)的表达显著高于未感染高原白僵菌的鸡。高原a7饲喂组(CON)。与CON组和正常对照(N)组相比,B. altitudinis A7也显著提高了Pediococcus、Fournierella、Clostridium sensu stricto 1、CAG:352和Tuzzerella的相对丰度。上述结果表明,从免疫的鸡粪便中分离出的高原芽胞杆菌A7可促进宿主对腱戎杆菌的抗性。
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引用次数: 0
WITHDRAWN: Advances in Drug Delivery Systems for Treatment of Leishmaniases: A review. 利什曼病药物输送系统研究进展综述。
IF 1.6 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-11-10 DOI: 10.1016/j.exppara.2025.109061
Antara Banerjee

This article has been withdrawn: please see Elsevier policy on article withdrawal (https://www.elsevier.com/about/policies-and-standards/article-withdrawal). This article has been withdrawn at the request of the editor and publisher. The publisher regrets that an error occurred which led to the publication of this paper. This error bears no reflection on the article or its authors. The publisher apologizes to the authors and the readers for this unfortunate error.

利什曼病是一种被忽视的热带病,由不同的临床形式和表现组成,取决于利什曼原虫的许多不同致病物种,是世界各地普遍存在的主要公共卫生问题之一。从广义上讲,疾病可分为皮肤(CL)和内脏(VL)形式,取决于组织侵犯,发病机制和表现。所有传统的治疗性抗利什曼原虫药物,如锑化合物、两性霉素B、米特福辛、喷他脒、帕罗霉素等,都有其自身的局限性。利什曼原虫寄生虫在网状内皮系统深处的巨噬细胞内以细胞内无梭菌的形式窝藏和增殖,对药物进入感染组织的递送效率、可用性和保留提出了重大挑战。近年来,新型药物输送系统(NDDS)的进展,结合了各种常规药物的纳米配方和新的候选药物,在这方面显示出更好的解决方案。有效靶向药物也减少了有效剂量,从而减少了副作用,减少了出现耐药性的机会。本文结合NDDS在CL和VL中的应用,综述了NDDS的各种方法和研究进展。虽然很少有制剂已被批准用于人类,而且AmBisome已被推荐为印度治疗VL的一线药物,但大多数其他制剂仍在不同实验模型的体外和/或体内研究中。简要介绍了未来的前景、障碍和监管问题。
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引用次数: 0
Relationship between toxoplasmosis and addiction: A systematic review and meta-analysis 弓形虫病与成瘾的关系:一项系统综述和荟萃分析。
IF 1.6 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-11-10 DOI: 10.1016/j.exppara.2025.109062
Tooran Nayeri , Mosayeb Rostamian , Mahmood Moosazadeh , Fatemeh Ghaffarifar , Abdolhossein Dalimi Asl
Chronic toxoplasmosis has been associated with behavioral alterations in both humans and animal models. Given that substance addiction involves behavioral and neurochemical changes, this study aimed to investigate the potential association between Toxoplasma gondii (T. gondii) infection and substance use disorders by synthesizing available evidence through a meta-analysis. A systematic search of five databases was conducted using relevant keywords to identify English-language articles published up to January 19, 2025. Studies were screened according to predefined inclusion and exclusion criteria. A random-effects model was applied to calculate the pooled odds ratio (OR) and corresponding p-value. A total of 18 studies were included in the systematic review, of which 9 met the criteria for inclusion in the meta-analysis, encompassing 2499 participants (1018 individuals with substance use disorders and 1481 controls). The random-effects model estimated an OR of 1.86 (95 % CI: 1.25–2.76) for anti-T. gondii IgG antibodies among individuals with substance use disorders compared with controls. Egger's test indicated no publication bias. Sensitivity analysis confirmed the robustness and stability of the observed association between anti-T. gondii IgG seropositivity and addiction. These findings demonstrate a statistically significant association between T. gondii infection and substance use disorders. However, the limited number of available studies highlights the need for further epidemiological investigations, particularly longitudinal studies, to clarify the nature and direction of this relationship.
在人类和动物模型中,慢性弓形虫病与行为改变有关。鉴于物质成瘾涉及行为和神经化学变化,本研究旨在通过荟萃分析综合现有证据,探讨弓形虫感染与物质使用障碍之间的潜在关联。利用相关关键词对5个数据库进行系统检索,确定2025年1月19日前发表的英文文章。根据预先确定的纳入和排除标准筛选研究。采用随机效应模型计算合并优势比(OR)及相应的p值。系统评价共纳入18项研究,其中9项符合纳入荟萃分析的标准,共纳入2499名参与者(1018名物质使用障碍患者和1481名对照)。随机效应模型估计抗t的OR为1.86 (95% CI: 1.25-2.76)。药物使用障碍患者的弓形虫IgG抗体与对照组比较。Egger的检验显示没有发表偏倚。敏感性分析证实了观察到的抗t。弓形虫IgG血清阳性与成瘾性。这些发现表明,弓形虫感染与药物使用障碍之间存在统计学上显著的关联。然而,现有研究数量有限,需要进一步进行流行病学调查,特别是纵向研究,以澄清这种关系的性质和方向。
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引用次数: 0
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Experimental parasitology
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