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Harnessing antigenic proteins of Toxoplasma gondii for efficient diagnosis: a study of promising candidates. 利用刚地弓形虫抗原蛋白进行有效诊断:一项有前途的候选研究。
Q3 Immunology and Microbiology Pub Date : 2025-12-01 Epub Date: 2025-10-06 DOI: 10.1007/s12639-025-01863-7
Saumya Srivastava, Anil Kumar Gupta, Amit Singh, Sudip Kumar Datta, Sarman Singh

Toxoplasma gondii is a widespread protozoan parasite that poses significant health risks globally. Current serological tests for diagnosing T. gondii infections are hindered by high costs, cumbersomeness, and the necessity for skills and expertise. This study aimed to identify promising antigens for the development of an immunochromatographic rapid diagnostic test (RDT). Whole-cell antigens were isolated from the virulent RH strain of T. gondii maintained in Swiss albino male mice. After infection, peritoneal fluid was harvested, and tachyzoites were processed to obtain whole cell lysates, which were subjected to SDS-PAGE and Western blot analysis. Five novel antigenic protein bands reactive to anti-Toxoplasma IgG and IgM antibodies were identified on western blot. Subsequent LC-MS/MS analysis revealed 158 proteins. However, only 18 proteins were selected on the basis of high mascot score (> 40) and were investigated further. On BLAST search 10 of these proteins exhibited significant homology (> 90%) with closely related microorganisms hence these were excluded. Out of remaining 8, T. gondii specific glyceraldehyde-3-phosphate dehydrogenase (GAPDH1) and lactate dehydrogenase (LDH1) were found to be reactive to both IgG and IgM on western blot, indicating their potential as reliable biomarkers for T. gondii infection.

刚地弓形虫是一种广泛存在的原生动物寄生虫,在全球范围内构成重大健康风险。目前用于诊断弓形虫感染的血清学检测因成本高、繁琐以及对技能和专业知识的需要而受到阻碍。本研究旨在为开发免疫层析快速诊断试验(RDT)鉴定有前途的抗原。从瑞士白化雄性小鼠体内的弓形虫RH毒株中分离出全细胞抗原。感染后,收集腹膜液,处理速殖子获得全细胞裂解物,进行SDS-PAGE和Western blot分析。免疫印迹法鉴定出5条新的对弓形虫IgG和IgM抗体有反应的抗原蛋白条带。随后LC-MS/MS分析发现158个蛋白。然而,在高吉祥物评分(bbb40)的基础上,仅选择了18种蛋白质进行进一步研究。在BLAST搜索中,这些蛋白中有10个与密切相关的微生物具有显著的同源性(> 90%),因此将其排除在外。在剩余的8个蛋白中,经western blot检测发现,弓形虫特异性甘油醛-3-磷酸脱氢酶(GAPDH1)和乳酸脱氢酶(LDH1)对IgG和IgM均有反应,表明它们有可能作为弓形虫感染的可靠生物标志物。
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引用次数: 0
Morphological and molecular investigation of hydatid cyst isolated from small ruminants in Rasht, Iran. 伊朗拉什特地区小反刍动物包虫病的形态和分子研究。
Q3 Immunology and Microbiology Pub Date : 2025-12-01 Epub Date: 2025-04-28 DOI: 10.1007/s12639-025-01808-0
Saeed Farokhpey, Soheil Sadr, Saeed Yaghfoori, Hassan Borji

Cystic echinococcosis is an important zoonotic disease and pose a significant health threat worldwide. Echinococcus granulosus (E. granulosus) has ten strains and exhibits many characteristics. Hence, the current study aims to identify the hydatid cysts genotype isolated from sheep and goats in Rasht County through morphological and molecular analyses. During 6 months (winter 2018 to summer 2019), 50 samples, including liver and lung tissues, were collected at Rasht County slaughterhouse (30 goats and 20 sheep). Hydatid cyst fluid (HCF) was extracted, and protocoleces were collected and rostellar hooks' morphological parameters were examined. DNA was extracted, polymerase chain reaction (PCR) was performed using primers on the ITS 1 gene using EgF and EgR, and the enzyme Bsh1236 I was used for digestion. The morphological and molecular analysis identified sheep and goat hydatid cyst isolated as strain G1-G3. This study highlights the importance of carefully monitoring the prevalence of hydatid disease in Rasht, Iran, especially in small ruminants. It is especially important for future studies in strain identification and awareness-raising about methods for preventing and controlling zoonotic diseases caused by E. granulosus. This research can be considered important for epidemiological studies and examining how the parasite spreads in other regions of the country and even globally in the face of drug resistance and common diseases between humans and livestock.

囊性棘球蚴病是一种重要的人畜共患疾病,在世界范围内构成重大的健康威胁。细粒棘球绦虫(E. granulosus)有10个菌株,表现出许多特征。因此,本研究旨在通过形态学和分子分析鉴定从拉什特县绵羊和山羊分离的包虫病基因型。在6个月内(2018年冬季至2019年夏季),在Rasht县屠宰场收集了50份样本,包括肝脏和肺组织(30只山羊和20只绵羊)。提取包虫囊液(HCF),收集标本,检测其形态参数。提取DNA,用EgF和EgR对ITS 1基因进行聚合酶链反应(PCR),用bsh1236i酶切。形态学和分子分析鉴定分离的绵羊和山羊包虫病为G1-G3。这项研究强调了在伊朗拉什特仔细监测包虫病流行的重要性,特别是在小反刍动物中。这对今后的菌株鉴定和提高人们对预防和控制由细粒棘球绦虫引起的人畜共患疾病的认识具有重要意义。这项研究对于流行病学研究以及在面临耐药性和人类与牲畜之间常见疾病的情况下,检查寄生虫如何在该国其他地区甚至全球传播具有重要意义。
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引用次数: 0
The role of blood nested B1-gene in differentiation of acute toxoplasmosis from chronic infection during pregnancy. 血巢b1基因在妊娠期急性弓形虫病与慢性感染分化中的作用。
Q3 Immunology and Microbiology Pub Date : 2025-12-01 Epub Date: 2025-07-16 DOI: 10.1007/s12639-025-01834-y
Tayebe Roostaei, Seyed Ali Hosseini, Faeze Foroughi-Parvar, Mousa Motavalli Haghi, Mehrdad Hajilooi, Mohammad Matini

Toxoplasma gondii causes common parasitic infection, and congenital toxoplasmosis is considered a serious public health concern. This study aimed to evaluate the utility of maternal blood PCR in distinguishing acute from chronic toxoplasmosis during pregnancy. From January to June 2023, 291 pregnant women in Malayer, western Iran, were screened for T. gondii IgG antibodies via ELISA. Seropositive samples underwent further testing for IgG avidity and IgM antibodies. Peripheral blood samples from IgG-positive women were then analyzed for T. gondii DNA by targeting the B1 gene through nested PCR. Among the 291 pregnant women, 77 (26.46%; 95% CI: 21.39-31.53) tested positive for anti-Toxoplasma IgG. Seropositivity rates were significantly higher in women aged 39 years or older. Anti-Toxoplasma IgM was detected in two of the IgG-positive samples. IgG avidity results showed low levels in four asymptomatic women, borderline levels in four women, and high levels in 69 women. The Toxoplasma B1 gene was detected in four out of the 77 seropositive samples. Based on the combination of serological and PCR results, primary infection was diagnosed in three PCR-positive women with low and borderline IgG avidity. Finally, acute toxoplasmosis was diagnosed in three pregnant women (1%), indicating that the risk of congenital toxoplasmosis remains a serious issue. Furthermore, these findings suggest that serology results should be interpreted in conjunction with additional confirmatory tests.

刚地弓形虫引起常见的寄生虫感染,先天性弓形虫病被认为是一个严重的公共卫生问题。本研究旨在评估母体血液PCR在妊娠期区分急性和慢性弓形虫病中的应用价值。2023年1 - 6月,对伊朗西部Malayer地区291名孕妇进行了弓形虫IgG抗体ELISA筛查。血清阳性样本进一步检测IgG贪婪度和IgM抗体。然后通过巢式PCR针对B1基因分析igg阳性妇女外周血样本中的弓形虫DNA。291例孕妇中,77例(26.46%,95% CI: 21.39 ~ 31.53)检测弓形虫IgG阳性。血清阳性率在39岁及以上的女性中明显更高。在两个igg阳性样本中检测到抗弓形虫IgM。IgG贪婪度结果显示,4名无症状妇女低水平,4名妇女处于边缘水平,69名妇女高水平。77份血清阳性样本中有4份检测到弓形虫B1基因。结合血清学和PCR结果,诊断为原发性感染的3名PCR阳性妇女低和交界性IgG贪婪。最后,三名孕妇(1%)被诊断出急性弓形虫病,表明先天性弓形虫病的风险仍然是一个严重的问题。此外,这些发现表明血清学结果应与其他确认性测试一起解释。
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引用次数: 0
A review on molecular markers of Plasmodium falciparum. 恶性疟原虫分子标记研究进展。
Q3 Immunology and Microbiology Pub Date : 2025-12-01 Epub Date: 2025-08-04 DOI: 10.1007/s12639-025-01840-0
Wagaw Abebe, Dagmawi Woldesenbet

Malaria is an infectious disease caused by parasitic protozoans of the genus Plasmodium. Malaria control efforts on a global scale are in danger due to the emergence and spread of drug-resistant malaria. Despite stakeholders' dedication to the prevention and treatment of malaria, the current state of global health does not offer an effective answer to the issue of drug resistance. Furthermore, there is an information gap about the molecular mechanisms of Plasmodium falciparum's drug resistance, which makes it difficult to develop monitoring systems. Most countries lack adequate and comprehensive information on antimalarial drug efficacy. Plasmodium falciparum has developed resistance to almost all anti-malarial drugs, which poses a significant danger to malaria control worldwide. The fundamental mechanism of artemisinin resistance is due to point mutations in the beta-propeller domain of the gene encoding Kelch protein 13. Atovaquone resistance can be caused by a variety of mutations in the cytochrome b gene, with the majority of mutations affecting the protein's ubiquinol binding site. Similarly, mutations in the Plasmodium falciparum chloroquine resistance transporter, Plasmodium falciparum multi-drug resistance 1, and an increase in Plasmodium falciparum Plasmepsin II and III copy numbers all lead to 4-aminoquinoline drug resistance. Also, the number of amino acid substitutions in dihydrofolate reductase and dihydropteroate synthase is correlated with the degree of antifolate drug resistance. Moreover, amino alcohol drug resistance is caused by Plasmodium falciparum multidrug resistance protein 1 and Plasmodium falciparum Na+/H + exchanger 1 mutations. In general, Plasmodium falciparum chloroquine resistance transporter, Plasmodium falciparum multidrug resistance protein 1, Plasmodium falciparum Na+/H + exchanger 1, plasmepsin II & III, cytochrome b gene, dihydrofolate reductase, Plasmodium falciparum ATPases 6, Plasmodium falciparum Kelch protein 13, and dihydropteroate synthase were just the molecular markers of drug resistance of Plasmodium falciparum. Future research on the molecular mechanisms of drug resistance in P. falciparum should focus on significant area including using transcriptomic and genomic technologies to identify genetic variations associated with resistance. Finding the protein interactions that underlie these resistance mechanisms requires proteomic research. Additionally, the possibility of resistance development may be decreased by investigating combination therapies that target several phases of the P. falciparum lifecycle. In order to successfully address drug resistance in malaria, it will be essential to strengthen worldwide monitoring systems and promote interdisciplinary collaboration among researchers and healthcare professionals. Furthermore, regular monitoring, identification, and limiting of dr

疟疾是一种由疟原虫属寄生原生动物引起的传染病。由于耐药疟疾的出现和传播,全球范围内的疟疾控制工作处于危险之中。尽管利益攸关方致力于预防和治疗疟疾,但目前的全球健康状况并没有为耐药性问题提供有效的答案。此外,关于恶性疟原虫耐药的分子机制还存在信息缺口,这给开发监测系统带来了困难。大多数国家缺乏关于抗疟药物功效的充分和全面的信息。恶性疟原虫已对几乎所有抗疟疾药物产生耐药性,这对全世界的疟疾控制构成重大威胁。青蒿素耐药性的基本机制是由于编码Kelch蛋白13的基因β -螺旋桨结构域的点突变。阿托伐酮耐药可由细胞色素b基因的多种突变引起,其中大多数突变影响蛋白质的泛醇结合位点。同样,恶性疟原虫氯喹耐药转运体突变、恶性疟原虫多重耐药1、恶性疟原虫Plasmepsin II和III拷贝数增加都导致4-氨基喹啉耐药。二氢叶酸还原酶和二氢叶酸合酶中氨基酸取代数与抗叶酸药耐药程度相关。此外,氨基醇耐药是由恶性疟原虫多药耐药蛋白1和恶性疟原虫Na+/H +交换器1突变引起的。一般来说,恶性疟原虫氯喹耐药转运蛋白、恶性疟原虫多重耐药蛋白1、恶性疟原虫Na+/H +交换物1、plasmepsin II和III、细胞色素b基因、二氢叶酸还原酶、恶性疟原虫ATPases 6、恶性疟原虫Kelch蛋白13、二氢蝶呤合成酶只是恶性疟原虫耐药的分子标记。未来对恶性疟原虫耐药分子机制的研究应集中在包括利用转录组学和基因组学技术鉴定与耐药相关的遗传变异等重要领域。发现这些抗性机制背后的蛋白质相互作用需要蛋白质组学研究。此外,通过研究针对恶性疟原虫生命周期的几个阶段的联合治疗,可能会降低耐药性发展的可能性。为了成功地解决疟疾耐药性问题,必须加强全球监测系统并促进研究人员和卫生保健专业人员之间的跨学科合作。此外,必须继续通过体内疗效试验、体外试验、联合治疗、分子技术和适当政策,定期监测、识别和限制耐药恶性疟原虫菌株,以确保疟疾治疗的有效性。
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引用次数: 0
Evaluation of the therapeutic efficacy of albendazole and nitazoxanide loaded chitosan nanoparticles against experimental echinococcosis. 阿苯达唑和硝唑尼特负载壳聚糖纳米颗粒治疗实验性棘球蚴病的疗效评价。
Q3 Immunology and Microbiology Pub Date : 2025-12-01 Epub Date: 2025-07-14 DOI: 10.1007/s12639-025-01832-0
Naglaa Fathi Abd El-Latif, Mona Hassan Elsayad, Dekam Eisay Abdulsalam, Wessam El-Hadidy, Gehan A M Khodear, Amani Kazem, Heba El-Hadad

Cystic echinococcosis is a neglected helminthic zoonosis caused by Echinococcus spp., mostly E. granulosus. Current chemotherapeutic treatment options are based on benzimidazoles; mainly albendazole (ABZ) which are of limited effectiveness. Therefore, new anti-echinococcosis treatment agents are needed. Nitazoxanide (NTZ) is a broad-spectrum drug against a wide variety of intestinal parasites. The current work aimed to evaluate the efficacy of ABZ, ABZ chitosan nanoparticles (ABZ/Cs NPs), NTZ and NTZ/Cs NPs in mice experimentally infected with E. granulosus. Swiss albino mice were inoculated intra-peritoneally with ~ 1000 protoscoleces harvested from hydatid cysts from slaughtered camels. Drugs were administered orally daily to mice subgroups as follows: ABZ (50 mg/kg/4 weeks), blank Cs NPs (30 mg/Kg/4 weeks), ABZ/Cs NPs (50 mg/kg/4 weeks), NTZ (200 mg /kg/ 14 days) NTZ/Cs NPs (200 mg/ kg /14 days) 16 weeks after infection. Drug efficacy was assessed by parasitological, morphological and histopathological studies on hydatid cysts collected from the studied groups. Results revealed that the studied treatments had variable efficacy. ABZ/Cs NPs showed higher anti-cystic activity relative to ABZ, NTZ, NTZ/ CSNPs. Survival time increased in subgroups treated with ABZ/Cs NPs and Cs NPs followed by NTZ/Cs NPs. Mice received ABZ and ABZ/Cs NPs showed the highest reduction of hydatid cysts in different organs. SEM revealed severe morphological changes mainly in subgroups receiving ABZ and ABZ/Cs NPs. It was concluded that chitosan nanoparticles could enhance the therapeutic efficacy of ABZ and NTZ in the treatment of cystic echinococcosis.

囊性棘球绦虫病是一种被忽视的由棘球绦虫引起的寄生虫病,主要由细粒棘球绦虫引起。目前的化疗方案是基于苯并咪唑;主要是阿苯达唑(ABZ),但疗效有限。因此,需要新的抗棘球蚴病治疗剂。硝唑胺(Nitazoxanide, NTZ)是一种抗多种肠道寄生虫的广谱药物。本研究旨在评价ABZ、ABZ壳聚糖纳米颗粒(ABZ/Cs NPs)、NTZ和NTZ/Cs NPs对实验性颗粒棘球蚴感染小鼠的作用。用从屠宰骆驼的包虫病囊中提取的约1000个原头节给瑞士白化小鼠腹腔接种。感染16周后,小鼠每日口服ABZ (50 mg/kg/4周)、空白Cs NPs (30 mg/kg/4周)、ABZ/Cs NPs (50 mg/kg/4周)、NTZ (200 mg/kg/ 14天)、NTZ/Cs NPs (200 mg/kg/ 14天)。通过对实验组包虫病的寄生虫学、形态学和组织病理学研究来评估药物的疗效。结果显示,所研究的治疗方法疗效不一。与ABZ、NTZ、NTZ/ csnp相比,ABZ/Cs NPs具有较高的抗囊性活性。以ABZ/Cs NPs和Cs NPs治疗后再以NTZ/Cs NPs治疗的亚组的生存时间增加。注射ABZ和ABZ/Cs NPs后,小鼠各脏器中包虫囊的减少幅度最大。扫描电镜显示,主要在接受ABZ和ABZ/Cs NPs的亚组中出现了严重的形态学改变。由此可见,壳聚糖纳米颗粒可增强ABZ和NTZ治疗囊性包虫病的疗效。
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引用次数: 0
Overcoming the challenges of Plasmodium falciparum histidine-rich protein 2 and 3 deletions in malaria diagnosis and control. 克服恶性疟原虫富组氨酸蛋白2和3缺失在疟疾诊断和控制中的挑战。
Q3 Immunology and Microbiology Pub Date : 2025-12-01 Epub Date: 2025-06-30 DOI: 10.1007/s12639-025-01826-y
Emmanuel Okoro Enyi, Joy Chimuanya Nnanna

Malaria is a major public health concern responsible for significant mortality and morbidity, especially in sub-Saharan Africa. Accurate diagnosis is crucial for effective malaria control and elimination strategies. Recent studies have confirmed the existence of Plasmodium falciparum histidine-rich protein 2 and 3 (Pfhrp2/3) deficient malaria parasites, which pose significant challenges to malaria diagnosis and control. This review provides a comprehensive overview of the existing literature on Pfhrp2/3 deletions and their implications on malaria diagnosis and control. A literature search was conducted using a combination of keywords (Pfhrp2/3 deletions, malaria diagnosis, malaria control, rapid diagnostic tests) and medical subject headings (MeSH) terms (Malaria/diagnosis, Malaria/parasitology, Plasmodium falciparum/genetics) in ScienceDirect, Springer, Google Scholar, and PubMed. Studies published in English between 2018 and 2024 were included, and a total of 83 studies were selected for inclusion in the review based on predefined inclusion and exclusion criteria. This review highlights the significant challenges posed by Pfhrp2/3 deletions to malaria diagnosis and control and identifies potential solutions, including alternative diagnostic approaches and novel RDTs targeting multiple antigens.

疟疾是造成大量死亡率和发病率的主要公共卫生问题,特别是在撒哈拉以南非洲。准确诊断对于有效控制和消除疟疾战略至关重要。最近的研究证实了恶性疟原虫富组氨酸蛋白2和3 (Pfhrp2/3)缺陷疟疾寄生虫的存在,这对疟疾的诊断和控制构成了重大挑战。本文综述了Pfhrp2/3缺失及其在疟疾诊断和控制中的意义。利用关键词(Pfhrp2/3缺失、疟疾诊断、疟疾控制、快速诊断试验)和医学主题词(MeSH)术语(疟疾/诊断、疟疾/寄生虫学、恶性疟原虫/遗传学)在ScienceDirect、施普林格、谷歌Scholar和PubMed中进行文献检索。纳入了2018年至2024年间发表的英文研究,根据预定义的纳入和排除标准,共选择了83项研究纳入本综述。这篇综述强调了Pfhrp2/3缺失对疟疾诊断和控制带来的重大挑战,并确定了潜在的解决方案,包括替代诊断方法和针对多种抗原的新型rdt。
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引用次数: 0
Therapeutic outcome of bone marrow stem cells and ginger in chronic murine toxoplasmosis. 骨髓干细胞和生姜对慢性小鼠弓形虫病的治疗效果。
Q3 Immunology and Microbiology Pub Date : 2025-12-01 Epub Date: 2025-05-17 DOI: 10.1007/s12639-025-01817-z
Zeinab R Hassan, Yasmeen M Shaaban, Eman M Mahmoud, Amany Mesbah Mohammed Ali, Fatma Al-Zahraa Nabil Al-Shahed, Doaa E A Salama, Amira Nasr Ismail Elsokary, Ranya M Abdelgalil, Marwa A Alanany, Mona T Koullah, Nora Seliem, Doaa Refaat Amin, Shimaa A Mohamed, Mai Ali Mohammad Etewa, Sara Nagdy Mahmoud Mousa, Mona M Amin, Maryam Mohammed Mohammed Hamouda, Shimaa Attia Atta, Reham Abdelmonem Gadallah, Sami Mohamed Nasr

Toxoplasmosis is a common protozoal disease that can cause serious complications. Hence the available drug therapies possess limited activity against chronic forms of the disease; thus, it is urgent to find more effective agents. The current study highlighted the therapeutic activity of bone marrow mesenchymal stem cells (BMSCs) and ginger combined with spiramycin against chronic experimental toxoplasmosis. A total of 48 male Swiss albino mice were distributed into 8 groups: non-infected non-treated, infected non-treated, infected treated by spiramycin, infected treated by BMSCs, infected treated by ginger, infected treated by combined BMSCs and spiramycin, infected treated by combined BMSCs and ginger, and infected treated by combined BMSCs, ginger, and spiramycin. The evaluation was performed through parasitological counting of brain cyst burden, histopathological examination, immunohistochemical cyclooxygenase-2 (COX-2) staining assessment, serum IL-10 measurement, and apoptotic gene markers assay. The results revealed that combined BMSCs, ginger, and spiramycin displayed significantly reduced parasitic cyst burden, restored histopathological changes, decreased COX2 expression, and downregulated caspases gene expression. It can be concluded that adding BMSCs and ginger to spiramycin provides a potent therapeutic agent against chronic toxoplasmosis.

弓形虫病是一种常见的原虫病,可引起严重并发症。因此,现有的药物疗法对慢性形式的疾病具有有限的活性;因此,迫切需要寻找更有效的药物。本研究强调了骨髓间充质干细胞(BMSCs)和生姜联合螺旋霉素对慢性实验性弓形虫病的治疗作用。将48只雄性瑞士白化小鼠分为8组:未感染未治疗组、感染未治疗组、螺旋霉素感染组、骨髓间充质干细胞感染组、生姜感染组、骨髓间充质干细胞与螺旋霉素联合感染组、骨髓间充质干细胞与生姜联合感染组、骨髓间充质干细胞与生姜联合感染组。通过脑囊负荷寄生虫学计数、组织病理学检查、免疫组织化学环氧化酶-2 (COX-2)染色评估、血清IL-10测定、凋亡基因标记测定等方法进行评价。结果显示,BMSCs、生姜和螺旋霉素联合使用可显著降低寄生虫囊肿负荷,恢复组织病理改变,降低COX2表达,下调caspases基因表达。由此可见,在螺旋霉素中加入骨髓间充质干细胞和生姜是一种有效的治疗慢性弓形虫病的药物。
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引用次数: 0
Molecular docking, design, synthesis and in vitro analysis identify [1,2,4]triazolo[4,3-b]pyridazine derivatives as inhibitors of Leishmania donovani sterol methyltransferase. 分子对接、设计、合成及体外分析鉴定了[1,2,4]三唑[4,3-b]吡嗪衍生物作为多诺瓦利什曼原虫甾醇甲基转移酶抑制剂。
Q3 Immunology and Microbiology Pub Date : 2025-12-01 Epub Date: 2025-08-30 DOI: 10.1007/s12639-025-01849-5
Patrick O Sakyi, Samuel K Kwofie, Theresa Manful Gwira, Christine Moore, Cynthia Amisigo, Emmanuel Broni, Whelton A Miller, Michael D Wilson, Richard K Amewu

The current therapeutic agents for the treatments of visceral leishmaniasis are ineffective, and cytotoxic. Therefore, there is the urgent need for new chemotypes for the treatment of the disease with novel mechanisms of action. In our previous investigation, we identified the triazolopyridazine, STOCK6S-84928 as a potential inhibitor of Leishmania donovani sterol methyltransferase (LdSMT) with IC50 value of 118.3 µM. To improve the biological activity of the initial hit compound, we hereby describe the results of structural-activity relationship studies on STOCK6S-84928 via chemical modifications on the scaffold and virtually screening of 250 compounds obtained against the Modeller generated LdSMT structure. A total of 21 compounds were found to have binding energies ranging from - 7.0 to - 9.2 kcal/mol lower or comparable to the 22,26-azasterol (- 7.6 kcal/mol), the known inhibitor of the target. Molecular docking and molecular dynamics simulations revealed Ile272 and Tyr275 to be pivotal for ligand binding. The compounds were predicted to possess leishmanicidal activities with good drug-like properties. Significantly, the compounds 8, 9, 21, and 23 were predicted to possess antineoplastic, anti-inflammatory, analgesics, protein and MAP kinase inhibitory activities with probability of activity (Pa) > 0.2 and probability of inactivity (Pi) < 0.16. Through the applications of cyclization, amination, Williamson's ether synthesis, and Suzuki cross-coupling reactions, the selected analogues of STOCK6S-84928 were synthesised in moderate to high yields and characterized by FTIR, LC-MS, and NMR spectroscopy methods. In vitro antileishmanial evaluation of the synthesized compounds identified 23 as the most potent, exhibiting L. donovani promastigotes inhibitory activities with IC50 value of (1.9 ± 0.1) µM. The ortho-difluoropheneyl group as well as the triazolopyridine moieties were suspected to be responsible for the observed activity. Similarly, the compounds 10 and 16 required (0.8 ± 0.1) µM and (0.6 ± 0.0) µM, respectively to eliminate 50% of Trypanosoma brucei.

Graphical abstract:

Supplementary information: The online version contains supplementary material available at 10.1007/s12639-025-01849-5.

目前用于治疗内脏利什曼病的药物是无效的,并且具有细胞毒性。因此,迫切需要新的化学型来治疗具有新的作用机制的疾病。在我们之前的研究中,我们发现三唑吡嗪STOCK6S-84928是利什曼原虫甾醇甲基转移酶(LdSMT)的潜在抑制剂,IC50值为118.3µM。为了提高初始命中化合物的生物活性,我们在此描述通过对支架进行化学修饰和对modeleller生成的LdSMT结构进行虚拟筛选获得的250种化合物对STOCK6S-84928进行结构-活性关系研究的结果。共有21个化合物的结合能范围在- 7.0至- 9.2 kcal/mol之间,低于或与已知靶标抑制剂22,26-阿扎甾醇(- 7.6 kcal/mol)相当。分子对接和分子动力学模拟显示Ile272和Tyr275在配体结合中起关键作用。预测该化合物具有利什曼尼杀灭活性,具有良好的药物性质。化合物8、9、21和23具有抗肿瘤、抗炎、镇痛、蛋白和MAP激酶抑制活性,其中活性概率(Pa) > .2,无活性概率(Pi) 23最强,其抑制L. donovani promastigotes的IC50值为(1.9±0.1)µM。邻二氟苯基以及三唑吡啶部分被怀疑是所观察到的活性的原因。同样,化合物10和16分别需要(0.8±0.1)µM和(0.6±0.0)µM才能杀灭50%的布氏锥虫。图片摘要:补充资料:在线版本包含补充资料,可在10.1007/s12639-025-01849-5获得。
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引用次数: 0
Comparative efficacy of trypanocide brands against experimental Trypanosoma brucei brucei infections in mice. 几种杀锥虫剂对小鼠实验性布氏锥虫感染的比较疗效。
Q3 Immunology and Microbiology Pub Date : 2025-12-01 Epub Date: 2025-10-24 DOI: 10.1007/s12639-025-01874-4
M I Okpala, C F Obi, G E Aneru, O O Uzondu, C N Iheagwam, C T Oyiga, I O Ezeh, R C Ezeokonkwo, D N Onah

African animal trypanosomosis is a major constraint to livestock production in sub-Saharan Africa. Chemotherapy remains the primary control strategy, but the efficacy of various trypanocide brands in circulation in Africa, especially in Nigeria, remains uncertain. This study aimed to evaluate and compare the efficacy of selected, commonly used commercial brands of diminazene aceturate and isometamidium chloride against experimental Trypanosoma brucei brucei infection in mice. A total of 35 adult male mice were randomly assigned to seven groups of five mice each. Group 1 served as the uninfected control, while groups 2-7 were intraperitoneally (i.p.) infected with 10⁶ trypanosomes. Group 2 was left untreated, while groups 3-5 were treated with diminazene aceturate brands (TrypanocideDA 1-3) respectively at a dose of 7.0 mg/kg on day 13 post-infection (p.i). Groups 6 and 7 received isometamidium chloride brands (TrypanocideISM 1 and 2) respectively at a dose of 0.5 mg/kg on day 13 p.i. Efficacy was assessed through clinical signs, parasitaemia, haematological parameters (PCV, Hb concentration, erythrocyte count, leucocyte counts), parasite clearance time, body weight, rectal temperature, and survival. Parasite clearance was fastest in group 3 (2.4 days post-treatment) compared to other treated groups (3 days post-treatment). Diminazene aceturate-treated groups exhibited shorter relapse times than isometamidium chloride-treated groups. Treatment reversed the reduction in haematological indices across all groups. The study concluded that isometamidium chloride brands demonstrated superior efficacy compared to diminazene aceturate brands in treating T. brucei brucei infections.

非洲动物锥虫病是撒哈拉以南非洲畜牧业生产的主要制约因素。化疗仍然是主要的控制策略,但在非洲,特别是在尼日利亚,流通的各种锥虫杀虫剂品牌的疗效仍不确定。本研究旨在评价和比较精选的常用商业品牌醋酸迪纳苯和氯异异胺对实验性小鼠布氏锥虫感染的疗效。35只成年雄性小鼠被随机分为7组,每组5只。第1组为未感染的对照组,第2 ~ 7组腹腔内感染10⁶锥虫。2组不处理,3-5组在感染后第13天(p.i)分别给予乙酰氨基苯醌(锥虫胺1-3),剂量为7.0 mg/kg。第6组和第7组分别给予盐酸异异胺(锥虫病)1和2,剂量为0.5 mg/kg,第13天p.i。通过临床症状、寄生虫血症、血液学参数(PCV、Hb浓度、红细胞计数、白细胞计数)、寄生虫清除时间、体重、直肠温度和生存率来评估疗效。与其他治疗组(治疗后3天)相比,第3组(治疗后2.4天)的寄生虫清除速度最快。醋酸迪咪那烯治疗组的复发时间比氯异异胺治疗组短。治疗逆转了所有组血液学指标的下降。该研究得出结论,氯异甲酰胺品牌在治疗布氏体感染方面表现出优于醋酸氨基苯乙酯品牌的疗效。
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引用次数: 0
Promising therapeutic effects of Portulaca Oleracea loaded iron oxide nanoparticles in Toxoplasma gondii infection in mice. 马齿苋氧化铁纳米颗粒对刚地弓形虫感染小鼠的治疗效果令人鼓舞。
Q3 Immunology and Microbiology Pub Date : 2025-12-01 Epub Date: 2025-08-19 DOI: 10.1007/s12639-025-01846-8
Eman S El-Wakil, Mohamed Farid, Walaa A El Kholy

There are few treatment options available to treat toxoplasmosis. So, investigating possible antiparasitic agents from plants and nanoparticles that are widely available and reasonably priced might be a good substitute. This study aimed to examine the effect of Portulaca oleracea (P. oleracea) aqueous and methanolic extracts as a sole agent or loaded on iron oxide nanoparticles (FeONPs) compared to spiramycin on a murine model of Toxoplasma gondii (T. gondii) ME49 strain. Forty-eight Swiss albino mice were put into eight groups: GI: uninfected negative control; GII: infected, untreated positive control; GIII, GIV, GV, GVI, GVII, and GVIII: infected, treated with spiramycin (200 mg/kg), FeONPs (2.5 mg/kg), P. oleracea aqueous extract (2.5 mg/kg), P. oleracea methanolic extractt (2.5 mg/kg), P. oleracea aqueous extract loaded on FeONPs (2.5 mg/kg) and P. oleracea methanolic extract loaded on FeONPs (2.5 mg/kg) respectively. To evaluate the treatment effectiveness, parasitological counting for T. gondii cysts and histopathological assessment for brain sections using H&E were used. Also, the immunohistochemical expression of the ionized calcium-binding adapter molecule 1 (Iba-1) was investigated. T. gondii cysts number in the infected treated mice brains was significantly reduced, with GVIII having the best therapeutic efficacy with an efficiency percentage of 84% (P > 0.000). Also, this group had a remarkable improvement in the pathological changes induced by T. gondii and the highest reduction of Iba-1 expression (P > 0.000). According to this study, P. oleracea loaded on FeONPs could be a potential therapeutic candidate for treating toxoplasmosis, and administering the medications as nanoparticles enhances their therapeutic effect.

治疗弓形虫病的治疗方法很少。因此,研究从植物和纳米颗粒中提取的可能的抗寄生虫剂可能是一个很好的替代品,这些抗寄生虫剂广泛可用且价格合理。本研究旨在研究马蹄苋(P. oleracea)水溶液和甲醇提取物单独或负载氧化铁纳米颗粒(FeONPs)对刚地弓形虫(T. gondii) ME49菌株小鼠模型的影响,并与螺旋霉素进行比较。48只瑞士白化小鼠分为8组:GI组:未感染阴性对照;GII:未治疗的感染阳性对照;GIII、GIV、GV、GVI、GVII和GVIII:分别用螺旋霉素(200 mg/kg)、FeONPs (2.5 mg/kg)、甘蓝水提物(2.5 mg/kg)、甘蓝甲醇提物(2.5 mg/kg)、甘蓝水提物负载FeONPs (2.5 mg/kg)和甘蓝甲醇提物负载FeONPs (2.5 mg/kg)处理。为了评价治疗效果,采用弓形虫囊的寄生虫学计数和H&E脑切片的组织病理学评估。此外,我们还研究了离子钙结合适配器分子1 (Iba-1)的免疫组织化学表达。感染后小鼠脑内弓形虫囊数明显减少,GVIII的治疗效果最好,有效率为84% (P > .000)。此外,该组对弓形虫引起的病理改变有显著改善,Iba-1表达降低幅度最大(P < 0.05)。根据本研究,载FeONPs的马齿苋可能是治疗弓形虫病的潜在候选药物,并且作为纳米颗粒给药可以增强其治疗效果。
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引用次数: 0
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Journal of Parasitic Diseases
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