首页 > 最新文献

Experimental parasitology最新文献

英文 中文
Chemical composition and insecticidal activity of the essential oil of Pseudobrickellia brasiliensis (Spreng) R. M. King & H. Rob (Asteraceae) on Lutzomyia longipalpis (Diptera: Psychodidae) 巴西Pseudobrickellia brasiliensis (Spreng) R. M. King和H. Rob (Asteraceae)精油对长掌Lutzomyia longipalpis的化学成分和杀虫活性(双翅目:心梗科)
IF 1.6 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-08-19 DOI: 10.1016/j.exppara.2025.109004
Sâmia F. Silva , Fernanda Batista-Santos , Thiago Santos , Débora M. Lima , Raquel MF. Sousa , Ricardo A. Barata
In Brazil, Leishmania infantum is transmitted mainly through the bite of the sand fly Lutzomyia longipalpis, the main visceral leishmaniasis (VL) vector. Although the most common vector control strategy is the application of synthetic insecticides, growing resistance to these products has sparked interest in developing new alternatives. In this context, plants emerge as a viable possibility due to the diversity of secondary metabolites with insecticidal potential. This work aimed to chemically characterize the essential oil of Pseudobrickellia brasiliensis and evaluate its toxicity on L. longipalpis. The essential oil was obtained by hydrodistillation in a Clevenger apparatus from fresh leaves of P. brasiliensis and chemically analyzed using gas chromatography coupled to mass spectrometry (GC-MS). For the bioassay, sand flies were collected in the field and then exposed to different concentrations of the essential oil (2.5, 5.0 and 10 mg mL−1), also being used in the negative and positive control group. The mortality rate was assessed at established times. GC-MS analysis of essential oil of the P. brasiliensis identified 49 compounds with the predominance of monoterpenes, sesquiterpenes, and diterpenes. α-Pinene and isobicyclogermacrenal as the main constituents of the relative peak area of the total ion chromatogram with 17.9 and 13.3 %, respectively. The bioassay showed toxicity of P. brasiliensis essential oil on L. longipalpis at all concentrations evaluated, showing it to be a promising natural insecticide to be used in vector control of VL.
在巴西,婴儿利什曼原虫主要通过沙蝇的叮咬传播,沙蝇是利什曼病的主要内脏媒介。虽然最常见的病媒控制策略是使用合成杀虫剂,但对这些产品日益增长的抗药性引发了开发新替代品的兴趣。在这种情况下,由于具有杀虫潜力的次生代谢物的多样性,植物成为一种可行的可能性。本研究旨在对巴西刺槐挥发油进行化学性质表征,并评价其对长掌松毛虫的毒性。采用Clevenger蒸馏装置从巴西青叶中提取精油,并采用气相色谱-质谱联用(GC-MS)进行化学分析。为了进行生物测定,在野外收集沙蝇,然后暴露于不同浓度的精油(2.5,5.0和10 mg mL - 1),也用于阴性和阳性对照组。在确定的时间评估死亡率。GC-MS分析鉴定出49种化合物,以单萜类、倍半萜类和二萜类为主。α-蒎烯和异双环大肾是总离子色谱相对峰面积的主要成分,分别占17.9%和13.3%。生物测定结果表明,在不同浓度下,巴西木挥发油对长掌螨均有一定的毒性,是一种很有前途的天然杀虫剂,可用于病媒防治。
{"title":"Chemical composition and insecticidal activity of the essential oil of Pseudobrickellia brasiliensis (Spreng) R. M. King & H. Rob (Asteraceae) on Lutzomyia longipalpis (Diptera: Psychodidae)","authors":"Sâmia F. Silva ,&nbsp;Fernanda Batista-Santos ,&nbsp;Thiago Santos ,&nbsp;Débora M. Lima ,&nbsp;Raquel MF. Sousa ,&nbsp;Ricardo A. Barata","doi":"10.1016/j.exppara.2025.109004","DOIUrl":"10.1016/j.exppara.2025.109004","url":null,"abstract":"<div><div>In Brazil, <em>Leishmania infantum</em> is transmitted mainly through the bite of the sand fly <em>Lutzomyia longipalpis</em>, the main visceral leishmaniasis (VL) vector. Although the most common vector control strategy is the application of synthetic insecticides, growing resistance to these products has sparked interest in developing new alternatives. In this context, plants emerge as a viable possibility due to the diversity of secondary metabolites with insecticidal potential. This work aimed to chemically characterize the essential oil of <em>Pseudobrickellia brasiliensis</em> and evaluate its toxicity on <em>L. longipalpis</em>. The essential oil was obtained by hydrodistillation in a Clevenger apparatus from fresh leaves of <em>P. brasiliensis</em> and chemically analyzed using gas chromatography coupled to mass spectrometry (GC-MS). For the bioassay, sand flies were collected in the field and then exposed to different concentrations of the essential oil (2.5, 5.0 and 10 mg mL<sup>−1</sup>), also being used in the negative and positive control group. The mortality rate was assessed at established times. GC-MS analysis of essential oil of the <em>P. brasiliensis</em> identified 49 compounds with the predominance of monoterpenes, sesquiterpenes, and diterpenes. α-Pinene and isobicyclogermacrenal as the main constituents of the relative peak area of the total ion chromatogram with 17.9 and 13.3 %, respectively. The bioassay showed toxicity of <em>P. brasiliensis</em> essential oil on <em>L. longipalpis</em> at all concentrations evaluated, showing it to be a promising natural insecticide to be used in vector control of VL.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"276 ","pages":"Article 109004"},"PeriodicalIF":1.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885514","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
Seroprevalence of latent toxoplasmosis and its association with clinical outcomes in patients with acute ischemic stroke; a case-control study in northeastern Iran 急性缺血性脑卒中患者潜伏性弓形虫病血清阳性率及其与临床预后的关系在伊朗东北部进行的病例对照研究
IF 1.6 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-08-18 DOI: 10.1016/j.exppara.2025.109003
Amirali Ghahremani , Hasan Namdar Ahmadabad , Reza shafiei
This study examined the seroprevalence of Toxoplasma gondii (T. gondii), a neurotropic protozoan associated with neuropsychiatric disorders, in patients with acute ischemic stroke (AIS) and its influence on clinical outcomes. This case-control study included 100 AIS patients at Imam Hassan Hospital, Bojnourd. Stroke severity was assessed using the NIHSS on days one and seven post-admission. Disability was evaluated three months post-discharge with the mRS. A control group of 100 age- and sex-matched healthy individuals was included. Serum samples were tested for anti-T. gondii IgG and IgM antibodies using indirect ELISA. IgG avidity was measured with modified ELISA using urea treatment. No significant difference was observed in anti-Toxoplasma gondii IgG seroprevalence between AIS patients (48 %) and controls (35 %, P = 0.084), with all subjects seronegative for IgM. However, seropositive AIS patients had significantly higher 3-month mRS scores, indicating greater disability. Anti-T. gondii IgG levels were significantly elevated in the AIS group and correlated with higher 24-h NIHSS scores, reflecting increased stroke severity. No differences in IgG avidity were found. Although our findings do not establish T. gondii infection as a direct risk factor for AIS, they suggest a potential role in disease pathogenesis and outcomes. However, further studies are needed to validate these observations.
本研究检测了与神经精神疾病相关的嗜神经原生动物刚地弓形虫(弓形虫)在急性缺血性卒中(AIS)患者中的血清阳性率及其对临床结果的影响。本病例对照研究包括Bojnourd伊玛目哈桑医院的100名AIS患者。入院后第1天和第7天使用NIHSS评估卒中严重程度。出院后3个月与mrs一起评估残疾情况。对照组包括100名年龄和性别匹配的健康个体。检测血清样本的抗t抗体。采用间接ELISA法检测弓形虫IgG和IgM抗体。采用改良酶联免疫吸附法测定IgG的活性,采用尿素处理。AIS患者(48%)与对照组(35%,P = 0.084)抗刚地弓形虫IgG血清阳性率无显著差异,所有受试者血清IgM均为阴性。然而,血清阳性AIS患者的3个月mRS评分明显更高,表明更大的残疾。Anti-T。AIS组弓形虫IgG水平显著升高,并与较高的24小时NIHSS评分相关,反映了卒中严重程度的增加。IgG贪婪度无明显差异。虽然我们的研究结果并没有确定弓形虫感染是AIS的直接危险因素,但它们表明弓形虫感染在疾病发病机制和结果中具有潜在作用。然而,需要进一步的研究来验证这些观察结果。
{"title":"Seroprevalence of latent toxoplasmosis and its association with clinical outcomes in patients with acute ischemic stroke; a case-control study in northeastern Iran","authors":"Amirali Ghahremani ,&nbsp;Hasan Namdar Ahmadabad ,&nbsp;Reza shafiei","doi":"10.1016/j.exppara.2025.109003","DOIUrl":"10.1016/j.exppara.2025.109003","url":null,"abstract":"<div><div>This study examined the seroprevalence of Toxoplasma <em>gondii</em> (T. <em>gondii</em>), a neurotropic protozoan associated with neuropsychiatric disorders, in patients with acute ischemic stroke (AIS) and its influence on clinical outcomes. This case-control study included 100 AIS patients at Imam Hassan Hospital, Bojnourd. Stroke severity was assessed using the NIHSS on days one and seven post-admission. Disability was evaluated three months post-discharge with the mRS. A control group of 100 age- and sex-matched healthy individuals was included. Serum samples were tested for anti-T. <em>gondii</em> IgG and IgM antibodies using indirect ELISA. IgG avidity was measured with modified ELISA using urea treatment. No significant difference was observed in anti-Toxoplasma <em>gondii</em> IgG seroprevalence between AIS patients (48 %) and controls (35 %, <em>P</em> = 0.084), with all subjects seronegative for IgM. However, seropositive AIS patients had significantly higher 3-month mRS scores, indicating greater disability. Anti-T. <em>gondii</em> IgG levels were significantly elevated in the AIS group and correlated with higher 24-h NIHSS scores, reflecting increased stroke severity. No differences in IgG avidity were found. Although our findings do not establish T. <em>gondii</em> infection as a direct risk factor for AIS, they suggest a potential role in disease pathogenesis and outcomes. However, further studies are needed to validate these observations.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"276 ","pages":"Article 109003"},"PeriodicalIF":1.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879368","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
Preliminary evaluation of the recombinant Sj14-3-3 protein as an immunodiagnostic antigen for schistosomiasis 重组Sj14-3-3蛋白作为血吸虫病免疫诊断抗原的初步评价
IF 1.6 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-08-09 DOI: 10.1016/j.exppara.2025.109000
Kevin Austin L. Ona , Jose Ma M. Angeles , Elena A. Villacorte , Katrina Theresa M. Balboa , Atcharaphan Wanlop , Adrian Miki C. Macalanda , Pilarita T. Rivera , Shin-ichiro Kawazu
Exploring molecular targets for the diagnosis of schistosomiasis has been a key priority in Schistosoma japonicum research. In this study, the antigenicity of recombinant Sj14-3-3 protein (rSj14-3-3) was evaluated using sera from schistosome-infected subjects. rSj14-3-3 was expressed and subsequently analyzed via SDS-PAGE and Western blot. Its antigenicity was then tested with sera from schistosome-infected mice and humans through ELISA. Results showed that rSj14-3-3 had significant antigenicity when tested with infected mice sera (P < 0.05) and human sera (P < 0.05) compared to negative controls. These findings suggest that rSj14-3-3 could serve as an alternative diagnostic antigen for schistosomiasis. Nevertheless, further research is needed to fully evaluate its immunodiagnostic potential.
探索血吸虫病诊断的分子靶点一直是日本血吸虫研究的重点。本研究利用血吸虫感染者血清对重组Sj14-3-3蛋白(rSj14-3-3)的抗原性进行了评价。表达rSj14-3-3并进行SDS-PAGE和Western blot分析。用ELISA法检测了其抗原性。结果表明,rSj14-3-3在感染小鼠血清中具有显著的抗原性(P <;0.05)和人血清(P <;0.05)。这些结果提示rSj14-3-3可作为血吸虫病的替代诊断抗原。然而,需要进一步的研究来充分评估其免疫诊断潜力。
{"title":"Preliminary evaluation of the recombinant Sj14-3-3 protein as an immunodiagnostic antigen for schistosomiasis","authors":"Kevin Austin L. Ona ,&nbsp;Jose Ma M. Angeles ,&nbsp;Elena A. Villacorte ,&nbsp;Katrina Theresa M. Balboa ,&nbsp;Atcharaphan Wanlop ,&nbsp;Adrian Miki C. Macalanda ,&nbsp;Pilarita T. Rivera ,&nbsp;Shin-ichiro Kawazu","doi":"10.1016/j.exppara.2025.109000","DOIUrl":"10.1016/j.exppara.2025.109000","url":null,"abstract":"<div><div>Exploring molecular targets for the diagnosis of schistosomiasis has been a key priority in <em>Schistosoma japonicum</em> research. In this study, the antigenicity of recombinant Sj14-3-3 protein (rSj14-3-3) was evaluated using sera from schistosome-infected subjects. rSj14-3-3 was expressed and subsequently analyzed <em>via</em> SDS-PAGE and Western blot. Its antigenicity was then tested with sera from schistosome-infected mice and humans through ELISA. Results showed that rSj14-3-3 had significant antigenicity when tested with infected mice sera (<em>P</em> &lt; 0.05) and human sera (<em>P</em> &lt; 0.05) compared to negative controls. These findings suggest that rSj14-3-3 could serve as an alternative diagnostic antigen for schistosomiasis. Nevertheless, further research is needed to fully evaluate its immunodiagnostic potential.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"276 ","pages":"Article 109000"},"PeriodicalIF":1.6,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144810476","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
Comparison of three Schistosoma mansoni strains: Infection, morphometry and susceptibility to treatment 3株曼氏血吸虫感染、形态测定及对治疗的敏感性比较。
IF 1.6 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-08-09 DOI: 10.1016/j.exppara.2025.109001
Marilia Bergamini Valentini, Tiago Manuel Fernandes Mendes, Silmara Marques Allegretti
Different Schistosoma mansoni strains exhibit distinct phenotypes, influencing parasite distribution, control strategies, and therapeutic alternatives for schistosomiasis. This study compared three Brazilian strains: Belo Horizonte/MG (SmBH), Ilha das Flores/SE (SmSE), and São José dos Campos/SP (SmSJ). To understand differences in infection, morphometry and response to praziquantel (PZQ) treatment, BALB/c mice were infected with each strain and treated 45 days post-infection (dpi) with praziquantel (PZQ) in different dosages. Egg elimination was monitored weekly from 30 dpi and euthanasia was performed 60 dpi. Untreated groups showed SmBH with the highest infection rates, with a larger number of recovered worms and a greater number of eggs. Morphometric analysis showed that SmSE females were significantly longer, while SmBH eggs were larger. Granuloma size was similar in SmBH- and SmSJ-infected mice, but SmSE-induced granulomas were smaller. SmBH infection resulted in a greater number of granulomas, suggesting higher pathogenicity. PZQ treatment at 150 or 300 mg/kg significantly reduced parasite burden, fecal egg count, and hepatic/intestinal granulomas in SmBH- and SmSJ-infected mice. SmBH infection also showed fewer immature and mature eggs and more dead eggs after treatment. However, SmSE-infected mice exhibited no significant differences between treated and untreated groups, suggesting higher resistance/tolerance to PZQ. These findings highlight phenotypic differences among S. mansoni strains: SmBH produced and retained more eggs, aggravating pathology; SmSJ had the lowest egg production; SmSE showed the highest resistance to PZQ. Understanding strain variability is crucial for improving schistosomiasis control and advancing drug development.
不同的曼氏血吸虫株表现出不同的表型,影响寄生虫的分布、控制策略和血吸虫病的治疗方案。本研究比较了3种巴西菌株:Belo Horizonte/MG (SmBH)、Ilha das Flores/SE (SmSE)和s o jos dos Campos/SP (SmSJ)。为了解BALB/c小鼠感染、形态及对吡喹酮(PZQ)治疗的反应差异,分别感染各菌株,并在感染后45天给予不同剂量的吡喹酮(PZQ)治疗。每周从30 dpi开始监测卵子清除,60 dpi进行安乐死。未处理组显示SmBH感染率最高,恢复的蠕虫数量和卵数量较多。形态计量学分析表明,SmSE雌虫明显较长,而SmBH雌虫的卵较大。SmBH-和smsj感染小鼠的肉芽肿大小相似,但smse诱导的肉芽肿较小。SmBH感染导致肉芽肿数量较多,提示致病性较高。150或300 mg/kg的PZQ治疗显著降低了SmBH-和smsj感染小鼠的寄生虫负担、粪卵数量和肝脏/肠道肉芽肿。SmBH感染治疗后未成熟卵和成熟卵较少,死卵较多。然而,smse感染小鼠在治疗组和未治疗组之间没有显着差异,表明对PZQ有更高的抗性/耐受性。这些发现突出了曼氏链球菌菌株之间的表型差异:SmBH产生并保留了更多的卵子,加重了病理;SmSJ的产蛋量最低;SmSE对PZQ的抗性最高。了解菌株变异对改善血吸虫病控制和推进药物开发至关重要。
{"title":"Comparison of three Schistosoma mansoni strains: Infection, morphometry and susceptibility to treatment","authors":"Marilia Bergamini Valentini,&nbsp;Tiago Manuel Fernandes Mendes,&nbsp;Silmara Marques Allegretti","doi":"10.1016/j.exppara.2025.109001","DOIUrl":"10.1016/j.exppara.2025.109001","url":null,"abstract":"<div><div>Different <em>Schistosoma mansoni</em> strains exhibit distinct phenotypes, influencing parasite distribution, control strategies, and therapeutic alternatives for schistosomiasis. This study compared three Brazilian strains: Belo Horizonte/MG (SmBH), Ilha das Flores/SE (SmSE), and São José dos Campos/SP (SmSJ). To understand differences in infection, morphometry and response to praziquantel (PZQ) treatment, BALB/c mice were infected with each strain and treated 45 days post-infection (dpi) with praziquantel (PZQ) in different dosages. Egg elimination was monitored weekly from 30 dpi and euthanasia was performed 60 dpi. Untreated groups showed SmBH with the highest infection rates, with a larger number of recovered worms and a greater number of eggs. Morphometric analysis showed that SmSE females were significantly longer, while SmBH eggs were larger. Granuloma size was similar in SmBH- and SmSJ-infected mice, but SmSE-induced granulomas were smaller. SmBH infection resulted in a greater number of granulomas, suggesting higher pathogenicity. PZQ treatment at 150 or 300 mg/kg significantly reduced parasite burden, fecal egg count, and hepatic/intestinal granulomas in SmBH- and SmSJ-infected mice. SmBH infection also showed fewer immature and mature eggs and more dead eggs after treatment. However, SmSE-infected mice exhibited no significant differences between treated and untreated groups, suggesting higher resistance/tolerance to PZQ. These findings highlight phenotypic differences among <em>S</em>. <em>mansoni</em> strains: SmBH produced and retained more eggs, aggravating pathology; SmSJ had the lowest egg production; SmSE showed the highest resistance to PZQ. Understanding strain variability is crucial for improving schistosomiasis control and advancing drug development.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"276 ","pages":"Article 109001"},"PeriodicalIF":1.6,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821002","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
Corrigendum to “Evaluation of β-caryophyllene(1–3) as a potential anti-tick molecule for controlling tick infestations on animals” [Experimental Parasitology 2025, 108969] “β-石竹烯(1-3)作为潜在的抗蜱虫分子控制动物蜱虫侵害的评价”[实验寄生虫学2025,108969]。
IF 1.6 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-08-01 DOI: 10.1016/j.exppara.2025.108989
Gajanan M. Chigure , Anil Kumar Sharma , K.G. Ajithkumar , Ashutosh Fular , Amol B. Tayade , Rajesh Kumar , Nitin D. Jadhav , Sachin Kumar , Suman Gupta , Gaurav Nagar , Reghu Ravindran , Satyanshu Kumar , Sanis Julliet , Muthu Sankar , Srikanta Ghosh
{"title":"Corrigendum to “Evaluation of β-caryophyllene(1–3) as a potential anti-tick molecule for controlling tick infestations on animals” [Experimental Parasitology 2025, 108969]","authors":"Gajanan M. Chigure ,&nbsp;Anil Kumar Sharma ,&nbsp;K.G. Ajithkumar ,&nbsp;Ashutosh Fular ,&nbsp;Amol B. Tayade ,&nbsp;Rajesh Kumar ,&nbsp;Nitin D. Jadhav ,&nbsp;Sachin Kumar ,&nbsp;Suman Gupta ,&nbsp;Gaurav Nagar ,&nbsp;Reghu Ravindran ,&nbsp;Satyanshu Kumar ,&nbsp;Sanis Julliet ,&nbsp;Muthu Sankar ,&nbsp;Srikanta Ghosh","doi":"10.1016/j.exppara.2025.108989","DOIUrl":"10.1016/j.exppara.2025.108989","url":null,"abstract":"","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"275 ","pages":"Article 108989"},"PeriodicalIF":1.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625683","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
A dual In vitro and In silico approach to evaluate 1,4-naphthoquinone-1,2,3-triazole hybrids against atovaquone-resistant malaria 体外和计算机双方法评价1,4-萘醌-1,2,3-三唑杂种抗阿托伐醌耐药疟疾的作用。
IF 1.6 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-07-31 DOI: 10.1016/j.exppara.2025.108991
Priyanka Agarwal , David D. N’Da , C. Johan van der Westhuizen , Robyn L. van Zyl
Malaria continues to pose a major global health burden affecting millions annually. Despite advancements in treatment, the emergence of drug-resistant Plasmodium strains has undermined current treatment strategies, including atovaquone. Atovaquone is a key mitochondrial inhibitor targeting the cytochrome bc1 (cyt bc1) complex, with resistance primarily driven by mutation in the cytochrome b gene. Moreover, atovaquone's reliance on a single target site and its pharmacokinetic limitations further underscore the urgent need for alternative drugs. To address these challenges, this dual in vitro and in silico study evaluated ten 1,4-naphthoquinone-1,2,3-triazole hybrids targeting atovaquone-resistant (FCR3) P. falciparum. Molecular modelling studies were performed on Saccharomyces cerevisiae (PDB ID 3CX5), involving the building of a mutant model to simulate the Y279S mutation (equivalent to Y268S mutation in P. falciparum), in order to rationalise the observed results. Additionally, pharmacokinetic properties and drug-likeness of these hybrids were predicted in silico. Hybrids D12 and D13 exhibited strong antiplasmodial activities, 61- and 52-fold, respectively, more than atovaquone. Molecular modelling studies indicated a strong correlation between in silico and in vitro activities by displaying binding interactions between the ligand and the mutant model. Structure-activity relationships (SAR) analysis identified key structural features essential for favourable binding interactions with target binding site residues. Furthermore, in silico evaluations of these hybrids suggested good oral bioavailability and high gastrointestinal absorption, with no significant risk of severe toxicity. Hybrids D12 and D13 exhibit potential as lead candidates, with their strong in vitro efficacy well-supported by in silico data, warranting further optimisation and development.
疟疾继续造成重大的全球健康负担,每年影响数百万人。尽管在治疗方面取得了进展,但耐药疟原虫菌株的出现破坏了目前的治疗策略,包括阿托伐醌。Atovaquone是一种针对细胞色素bc1 (cyt bc1)复合物的关键线粒体抑制剂,其耐药性主要由细胞色素b基因突变驱动。此外,阿托伐酮对单一靶点的依赖及其药代动力学的局限性进一步强调了替代药物的迫切需要。为了应对这些挑战,这项体外和计算机双试验评估了10个针对阿托伐醌耐药(FCR3)恶性疟原虫的1,4-萘醌-1,2,3-三唑杂交体。我们对酿酒酵母(PDB ID 3CX5)进行了分子模型研究,包括建立一个突变模型来模拟Y279S突变(相当于恶性疟原虫中的Y268S突变),以使观察到的结果合理化。此外,用计算机预测了这些杂交种的药代动力学性质和药物相似性。D12和D13表现出较强的抗疟原虫活性,分别是阿托伐醌的61倍和52倍。分子模型研究表明,通过显示配体和突变模型之间的结合相互作用,在硅和体外活性之间存在很强的相关性。结构-活性关系(SAR)分析确定了与目标结合位点残基有利的结合相互作用所必需的关键结构特征。此外,这些混合物的计算机评价表明,良好的口服生物利用度和高胃肠道吸收,没有严重毒性的显著风险。杂种D12和D13表现出作为主要候选物的潜力,其强大的体外功效得到了硅数据的支持,值得进一步优化和开发。
{"title":"A dual In vitro and In silico approach to evaluate 1,4-naphthoquinone-1,2,3-triazole hybrids against atovaquone-resistant malaria","authors":"Priyanka Agarwal ,&nbsp;David D. N’Da ,&nbsp;C. Johan van der Westhuizen ,&nbsp;Robyn L. van Zyl","doi":"10.1016/j.exppara.2025.108991","DOIUrl":"10.1016/j.exppara.2025.108991","url":null,"abstract":"<div><div>Malaria continues to pose a major global health burden affecting millions annually. Despite advancements in treatment, the emergence of drug-resistant <em>Plasmodium</em> strains has undermined current treatment strategies, including atovaquone. Atovaquone is a key mitochondrial inhibitor targeting the cytochrome <em>bc</em><sub>1</sub> (cyt <em>bc</em><sub>1</sub>) complex, with resistance primarily driven by mutation in the cytochrome <em>b</em> gene. Moreover, atovaquone's reliance on a single target site and its pharmacokinetic limitations further underscore the urgent need for alternative drugs. To address these challenges, this dual <em>in vitro</em> and <em>in silico</em> study evaluated ten 1,4-naphthoquinone-1,2,3-triazole hybrids targeting atovaquone-resistant (FCR3) <em>P. falciparum</em>. Molecular modelling studies were performed on <em>Saccharomyces cerevisiae</em> (PDB ID <span><span>3CX5</span><svg><path></path></svg></span>), involving the building of a mutant model to simulate the Y279S mutation (equivalent to Y268S mutation in <em>P. falciparum</em>), in order to rationalise the observed results. Additionally, pharmacokinetic properties and drug-likeness of these hybrids were predicted <em>in silico</em>. Hybrids <strong>D12</strong> and <strong>D13</strong> exhibited strong antiplasmodial activities, 61- and 52-fold, respectively, more than atovaquone. Molecular modelling studies indicated a strong correlation between <em>in silico</em> and <em>in vitro</em> activities by displaying binding interactions between the ligand and the mutant model. Structure-activity relationships (SAR) analysis identified key structural features essential for favourable binding interactions with target binding site residues. Furthermore, <em>in silico</em> evaluations of these hybrids suggested good oral bioavailability and high gastrointestinal absorption, with no significant risk of severe toxicity. Hybrids <strong>D12</strong> and <strong>D13</strong> exhibit potential as lead candidates, with their strong <em>in vitro</em> efficacy well-supported by <em>in silico</em> data, warranting further optimisation and development.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"276 ","pages":"Article 108991"},"PeriodicalIF":1.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768560","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
A novel colourimetric loop-mediated isothermal amplification (LAMP) assay for rapid field-level detection of Theileria orientalis 一种新型环介导等温扩增(LAMP)比色法快速检测东方蓟马。
IF 1.6 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-07-30 DOI: 10.1016/j.exppara.2025.108983
Sunkara Prathyusha , R. Radhika , Bindu Lakshmanan , K. Syamala , Marykutty Thomas , K. Justin Davis , K. Devada
Theileria orientalis, the causative agent of oriental theileriosis is a globally distributed protozoan parasite affecting livestock. Rapid and accurate parasite detection is crucial for effective disease management and evaluating therapeutic interventions. The high prevalence of T. orientalis in Kerala, a south Indian state demanded the development of a sensitive field tool for specific detection. Loop-mediated isothermal amplification (LAMP) is a rapid and highly sensitive nucleic acid amplification technique conducted under isothermal conditions. In this study, a LAMP assay was developed targeting the major piroplasm surface protein (MPSP) gene of T. orientalis using colourimetric dyes (both hydroxy naphthol blue (HNB) and phenol red) for improved visual detection of amplification. This assay utilised a set of six specifically designed primers, recognizing eight distinct regions on the target gene. Both wet LAMP assays demonstrated the ability to amplify DNA at levels as low as 10−4 ng (0.1 pg), corresponding to a parasitaemia level of 0.0012 % and exhibited higher detection abilities than PCR. The assay also demonstrated high specificity, with no amplification observed for DNA template from other haemoprotozoans. Positive LAMP products were identified by a distinct colour change from violet to blue and pink to yellow for HNB and phenol red dyes, respectively. Results were confirmed using agarose gel electrophoresis, showing characteristic ladder patterns. The LAMP assays detected T. orientalis in 62.8 % of samples, outperforming PCR (60 %) and microscopy (52.8 %). With a sensitivity of 100 %, specificity of 93 %, positive predictive value of 95.54 % and negative predictive value of 100 %, the wet LAMP assay demonstrated diagnostic efficacy for T. orientalis.
东方盲肠菌是一种全球分布的家畜寄生原虫,是东方盲肠菌病的病原体。快速和准确的寄生虫检测对于有效的疾病管理和评估治疗干预措施至关重要。在印度南部喀拉拉邦,东方弓形虫的高流行率要求开发一种敏感的现场检测工具。环介导等温扩增(LAMP)是一种在等温条件下进行的快速、高灵敏度的核酸扩增技术。本研究采用羟基萘酚蓝(HNB)和酚红两种比色染料,建立了一种针对东洋田螺主要螺质表面蛋白(MPSP)基因的LAMP检测方法,以提高检测效果。该试验利用了一组6个专门设计的引物,识别目标基因上的8个不同区域。两种湿式LAMP检测方法都显示出在低至10-4 ng (0.1 pg)的水平下扩增DNA的能力,相当于寄生虫血症水平为0.0012%,并且表现出比PCR更高的检测能力。该检测还显示出高特异性,对其他血原动物的DNA模板没有扩增。在HNB和酚红染料中,LAMP阳性产物的颜色分别由紫色变为蓝色和粉红色变为黄色。琼脂糖凝胶电泳证实了结果,显示出特有的阶梯结构。LAMP法在62.8%的样品中检出东方弓形虫,优于PCR法(60%)和显微镜法(52.8%)。湿法LAMP检测方法的灵敏度为100%,特异度为93%,阳性预测值为95.54%,阴性预测值为100%,具有较好的诊断效果。
{"title":"A novel colourimetric loop-mediated isothermal amplification (LAMP) assay for rapid field-level detection of Theileria orientalis","authors":"Sunkara Prathyusha ,&nbsp;R. Radhika ,&nbsp;Bindu Lakshmanan ,&nbsp;K. Syamala ,&nbsp;Marykutty Thomas ,&nbsp;K. Justin Davis ,&nbsp;K. Devada","doi":"10.1016/j.exppara.2025.108983","DOIUrl":"10.1016/j.exppara.2025.108983","url":null,"abstract":"<div><div><em>Theileria orientalis</em>, the causative agent of oriental theileriosis is a globally distributed protozoan parasite affecting livestock. Rapid and accurate parasite detection is crucial for effective disease management and evaluating therapeutic interventions. The high prevalence of <em>T. orientalis</em> in Kerala, a south Indian state demanded the development of a sensitive field tool for specific detection. Loop-mediated isothermal amplification (LAMP) is a rapid and highly sensitive nucleic acid amplification technique conducted under isothermal conditions. In this study, a LAMP assay was developed targeting the major piroplasm surface protein <em>(MPSP)</em> gene of <em>T. orientalis</em> using colourimetric dyes (both hydroxy naphthol blue (HNB) and phenol red) for improved visual detection of amplification. This assay utilised a set of six specifically designed primers, recognizing eight distinct regions on the target gene. Both wet LAMP assays demonstrated the ability to amplify DNA at levels as low as 10<sup>−4</sup> ng (0.1 pg), corresponding to a parasitaemia level of 0.0012 % and exhibited higher detection abilities than PCR. The assay also demonstrated high specificity, with no amplification observed for DNA template from other haemoprotozoans. Positive LAMP products were identified by a distinct colour change from violet to blue and pink to yellow for HNB and phenol red dyes, respectively. Results were confirmed using agarose gel electrophoresis, showing characteristic ladder patterns. The LAMP assays detected <em>T. orientalis</em> in 62.8 % of samples, outperforming PCR (60 %) and microscopy (52.8 %). With a sensitivity of 100 %, specificity of 93 %, positive predictive value of 95.54 % and negative predictive value of 100 %, the wet LAMP assay demonstrated diagnostic efficacy for <em>T. orientalis</em>.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"276 ","pages":"Article 108983"},"PeriodicalIF":1.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764726","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
Exposure to Bisphenol-A increases susceptibility to Trypanosoma cruzi infection 暴露于双酚a会增加对克氏锥虫感染的易感性
IF 1.4 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-07-24 DOI: 10.1016/j.exppara.2025.108990
Aracely López-Monteon , Anahí Sosa-Arróniz , Mariana Colorado-Zuñiga , Enrique Méndez-Bolaina , Jesús Torres-Montero , Angel Ramos-Ligonio
Bisphenol-A (BPA), an endocrine disruptor, disrupts hormonal and chemical signaling within the body, negatively impacting health. One target of this disruption is the immune system. While BPA has been implicated in increased susceptibility to some pathogen infections, its effects on protozoan parasite infections remain understudied. This work evaluated the effect of BPA exposure on experimental Trypanosoma cruzi parasitemia in BALB/c mice.
Parasitemia was evaluated in BALB/c mice by counting parasites in a Neubauer chamber. Additionally, ELISA assays were used to identify the presence of antibodies, cytokine gene expression was analyzed by RT-PCR, and liver marker levels were quantified using enzymatic kinetic methods. Both pre- and post-exposure to BPA increased parasitemia during T. cruzi infection and decreased levels of IgG1, IgG2a, and IgG2b isotypes. Furthermore, BPA modulated the expression of pro-inflammatory cytokines in response to infection. In addition, all mice exposed to BPA showed alterations in liver enzymes compared to the control group. These results demonstrate that the immune system during critical periods of T. cruzi infection is highly sensitive to BPA exposure, increasing susceptibility to the parasite.
双酚a (BPA)是一种内分泌干扰物,会干扰体内的荷尔蒙和化学信号,对健康产生负面影响。这种破坏的一个目标是免疫系统。虽然BPA与某些病原体感染的易感性增加有关,但其对原生动物寄生虫感染的影响仍未得到充分研究。本研究评估了BPA暴露对BALB/c小鼠实验性克氏锥虫寄生虫病的影响。BALB/c小鼠的寄生虫血症通过Neubauer室中的寄生虫计数来评估。此外,采用ELISA法鉴定抗体的存在,采用RT-PCR分析细胞因子基因表达,并采用酶动力学方法定量肝脏标志物水平。暴露于BPA前和暴露于BPA后均增加了克氏锥虫感染期间的寄生虫血症,并降低了IgG1、IgG2a和IgG2b同型的水平。此外,BPA在感染反应中调节促炎细胞因子的表达。此外,与对照组相比,所有暴露于BPA的小鼠的肝酶都发生了变化。这些结果表明,在感染T. cruzi的关键时期,免疫系统对BPA暴露高度敏感,增加了对寄生虫的易感性。
{"title":"Exposure to Bisphenol-A increases susceptibility to Trypanosoma cruzi infection","authors":"Aracely López-Monteon ,&nbsp;Anahí Sosa-Arróniz ,&nbsp;Mariana Colorado-Zuñiga ,&nbsp;Enrique Méndez-Bolaina ,&nbsp;Jesús Torres-Montero ,&nbsp;Angel Ramos-Ligonio","doi":"10.1016/j.exppara.2025.108990","DOIUrl":"10.1016/j.exppara.2025.108990","url":null,"abstract":"<div><div>Bisphenol-A (BPA), an endocrine disruptor, disrupts hormonal and chemical signaling within the body, negatively impacting health. One target of this disruption is the immune system. While BPA has been implicated in increased susceptibility to some pathogen infections, its effects on protozoan parasite infections remain understudied. This work evaluated the effect of BPA exposure on experimental <em>Trypanosoma cruzi</em> parasitemia in BALB/c mice.</div><div>Parasitemia was evaluated in BALB/c mice by counting parasites in a Neubauer chamber. Additionally, ELISA assays were used to identify the presence of antibodies, cytokine gene expression was analyzed by RT-PCR, and liver marker levels were quantified using enzymatic kinetic methods. Both pre- and post-exposure to BPA increased parasitemia during <em>T. cruzi</em> infection and decreased levels of IgG1, IgG2a, and IgG2b isotypes. Furthermore, BPA modulated the expression of pro-inflammatory cytokines in response to infection. In addition, all mice exposed to BPA showed alterations in liver enzymes compared to the control group. These results demonstrate that the immune system during critical periods of <em>T. cruzi</em> infection is highly sensitive to BPA exposure, increasing susceptibility to the parasite.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"275 ","pages":"Article 108990"},"PeriodicalIF":1.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711395","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
Computational design of inhibitory peptides and an mRNA-Based multi-epitope vaccine targeting the MIC3 protein of Eimeria tenella 针对柔嫩艾美耳球虫MIC3蛋白的抑制肽和基于mrna的多表位疫苗的计算设计。
IF 1.4 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-07-11 DOI: 10.1016/j.exppara.2025.108986
Roohollah Fattahi , Ali Shivaee , Maryam Bahraminia , Nazanin Omidi , Behrooz Sadeghi Kalani
This study addresses coccidiosis, a prevalent disease causing significant economic losses, and focuses on the EtMIC3 protein due to its critical role in Eimeria tenella pathogenesis. Our goal is to develop innovative therapeutic and preventive strategies leveraging the potential of the EtMIC3 protein.
In this investigation, we evaluate the interaction of the EtMIC3 protein with its receptors, develop inhibitory peptides, and select epitopes from EtMIC3 using immunoinformatic tools. We assess the presentation of these epitopes to immune cells, model a multi-epitope protein, predict the mRNA structure, and evaluate the immune response to the newly designed vaccine.
Docking studies indicated that the predicted peptides exhibited a strong affinity for binding to the EtMIC3 protein, with identified epitopes residing within the antigen-binding groove of their respective MHC alleles. The developed vaccine demonstrated stability, non-toxicity, and non-allergenicity, effectively eliciting responses from both the innate and adaptive immune systems.
These findings suggest that the EtMIC3 protein is a promising target for both the inhibition of E. tenella and vaccine development. However, further validation through experimental and clinical studies is essential to corroborate these computational predictions.
本研究针对球虫病这一造成重大经济损失的流行疾病,并将重点放在EtMIC3蛋白上,因为它在柔嫩艾美耳球虫发病机制中起着关键作用。我们的目标是利用EtMIC3蛋白的潜力开发创新的治疗和预防策略。在这项研究中,我们评估了EtMIC3蛋白与其受体的相互作用,开发了抑制肽,并使用免疫信息学工具从EtMIC3中选择了表位。我们评估了这些表位在免疫细胞中的呈现,建立了多表位蛋白模型,预测了mRNA结构,并评估了对新设计疫苗的免疫反应。对接研究表明,预测的肽与EtMIC3蛋白结合具有很强的亲和力,鉴定的表位位于各自MHC等位基因的抗原结合槽内。所开发的疫苗具有稳定性、无毒性和非过敏原性,可有效地引起先天和适应性免疫系统的反应。这些发现表明,EtMIC3蛋白是一个有希望的靶点,既可以抑制tenella,也可以开发疫苗。然而,通过实验和临床研究进一步验证是必不可少的,以证实这些计算预测。
{"title":"Computational design of inhibitory peptides and an mRNA-Based multi-epitope vaccine targeting the MIC3 protein of Eimeria tenella","authors":"Roohollah Fattahi ,&nbsp;Ali Shivaee ,&nbsp;Maryam Bahraminia ,&nbsp;Nazanin Omidi ,&nbsp;Behrooz Sadeghi Kalani","doi":"10.1016/j.exppara.2025.108986","DOIUrl":"10.1016/j.exppara.2025.108986","url":null,"abstract":"<div><div>This study addresses coccidiosis, a prevalent disease causing significant economic losses, and focuses on the EtMIC3 protein due to its critical role in Eimeria <em>tenella</em> pathogenesis. Our goal is to develop innovative therapeutic and preventive strategies leveraging the potential of the EtMIC3 protein.</div><div>In this investigation, we evaluate the interaction of the EtMIC3 protein with its receptors, develop inhibitory peptides, and select epitopes from EtMIC3 using immunoinformatic tools. We assess the presentation of these epitopes to immune cells, model a multi-epitope protein, predict the mRNA structure, and evaluate the immune response to the newly designed vaccine.</div><div>Docking studies indicated that the predicted peptides exhibited a strong affinity for binding to the EtMIC3 protein, with identified epitopes residing within the antigen-binding groove of their respective MHC alleles. The developed vaccine demonstrated stability, non-toxicity, and non-allergenicity, effectively eliciting responses from both the innate and adaptive immune systems.</div><div>These findings suggest that the EtMIC3 protein is a promising target for both the inhibition of <em>E. tenella</em> and vaccine development. However, further validation through experimental and clinical studies is essential to corroborate these computational predictions.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"275 ","pages":"Article 108986"},"PeriodicalIF":1.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625682","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
Furan derivative affects the cell division and mitochondrial integrity of tachyzoites of Toxoplasma gondii 呋喃衍生物影响刚地弓形虫速殖子细胞分裂和线粒体完整性
IF 1.4 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-07-08 DOI: 10.1016/j.exppara.2025.108988
Juliana de Araujo Portes , Anushree Achari , Jayaraman Vinayagam , Pinaki Bhattacharjee , Sourav Chatterjee , Parasuraman Jaisankar , Wanderley de Souza
Toxoplasma gondii is an obligate intracellular protozoan, the causative agent of toxoplasmosis. The current treatment against toxoplasmosis is based on the combination of sulfadiazine and pyrimethamine, which are toxic and unable to clear the infection. Due to the need for new active drugs against T. gondii, we have described here the effects of Furan derivatives on T. gondii in vitro. They were previously used with relevant activity against Leishmania amazonensis and Trypanosoma cruzi. The anti-Toxoplasma effects of the furan derivatives were evaluated using tachyzoites of T. gondii from RH strain and as host cells the human foreskin fibroblast (HFF) and the epithelial lineage from Macaca mulatta LLC-MK2. High-content screening and other microscopy techniques were employed to analyze the infected cells after incubation in the presence of the compounds tested. The most effective derivative was 3g, presenting a 50 % inhibitory concentration (IC50) of 4.3 μM after 48 h of incubation. The 50 % cytotoxic concentration (CC50) in the host cells was 50 μM after a 72-h treatment. The ultrastructural analysis showed that after treatment the parasites presented cytoplasmic emptying, mitochondrial swelling, and interference with cell division. It was revealed by TUNEL assay that the parasites dyed in part due to an apoptosis-like cell death. These findings suggest that the furan derivative 3g is a potential candidate for further studies in vivo to find alternative drugs to treat T. gondii infections.
刚地弓形虫是一种专性细胞内原生动物,是弓形虫病的病原体。目前对弓形虫病的治疗是基于磺胺嘧啶和乙胺嘧啶的组合,这是有毒的,不能清除感染。由于需要新的抗弓形虫活性药物,我们在这里描述了呋喃衍生物对弓形虫的体外作用。它们以前用于对亚马逊利什曼原虫和克氏锥虫具有相关活性。以RH株刚地弓形虫速殖子为宿主细胞,人包皮成纤维细胞(HFF)和猕猴LLC-MK2上皮细胞系为宿主细胞,对呋喃衍生物的抗弓形虫作用进行了评价。高含量筛选和其他显微镜技术被用来分析感染细胞在被测试化合物的存在下孵育后。最有效的衍生物是3g,孵育48 h后,IC50为4.3 μM,达到50%的抑制浓度。作用72 h后,宿主细胞50%细胞毒浓度(CC50)为50 μM。超微结构分析显示,处理后的寄生虫细胞质出现排空、线粒体肿胀、细胞分裂受到干扰。TUNEL实验显示,寄生虫染色的部分原因是细胞凋亡样死亡。这些发现表明呋喃衍生物3g是一个潜在的候选者,可以在体内进一步研究寻找治疗弓形虫感染的替代药物。
{"title":"Furan derivative affects the cell division and mitochondrial integrity of tachyzoites of Toxoplasma gondii","authors":"Juliana de Araujo Portes ,&nbsp;Anushree Achari ,&nbsp;Jayaraman Vinayagam ,&nbsp;Pinaki Bhattacharjee ,&nbsp;Sourav Chatterjee ,&nbsp;Parasuraman Jaisankar ,&nbsp;Wanderley de Souza","doi":"10.1016/j.exppara.2025.108988","DOIUrl":"10.1016/j.exppara.2025.108988","url":null,"abstract":"<div><div><em>Toxoplasma gondii</em> is an obligate intracellular protozoan, the causative agent of toxoplasmosis. The current treatment against toxoplasmosis is based on the combination of sulfadiazine and pyrimethamine, which are toxic and unable to clear the infection. Due to the need for new active drugs against <em>T. gondii</em>, we have described here the effects of Furan derivatives on <em>T. gondii in vitro</em>. They were previously used with relevant activity against <em>Leishmania amazonensis</em> and <em>Trypanosoma cruzi.</em> The <em>anti-Toxoplasma</em> effects of the furan derivatives were evaluated using tachyzoites of <em>T. gondii</em> from RH strain and as host cells the human foreskin fibroblast (HFF) and the epithelial lineage from Macaca mulatta LLC-MK2. High-content screening and other microscopy techniques were employed to analyze the infected cells after incubation in the presence of the compounds tested. The most effective derivative was <strong>3g</strong>, presenting a 50 % inhibitory concentration (IC50) of 4.3 μM after 48 h of incubation. The 50 % cytotoxic concentration (CC50) in the host cells was 50 μM after a 72-h treatment. The ultrastructural analysis showed that after treatment the parasites presented cytoplasmic emptying, mitochondrial swelling, and interference with cell division<strong>.</strong> It was revealed by TUNEL assay that the parasites dyed in part due to an apoptosis-like cell death. These findings suggest that the furan derivative <strong>3g</strong> is a potential candidate for further studies <em>in vivo</em> to find alternative drugs to treat <em>T. gondii</em> infections.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"275 ","pages":"Article 108988"},"PeriodicalIF":1.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604918","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
期刊
Experimental parasitology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1