首页 > 最新文献

Microbial pathogenesis最新文献

英文 中文
Immunomodulatory effects of the TIRAP/MAL rs8177374 (S180L) variant: Meta-Analytic evidence from severe and Plasmodium falciparum malaria TIRAP/MAL rs8177374 (S180L)变异的免疫调节作用:重症疟疾和恶性疟原虫的meta分析证据
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-12-04 DOI: 10.1016/j.micpath.2025.108226
Noelia Ivett González-Castillo , Sandra Guadalupe Prado-Rodríguez , Omar Iñiguez-Mosqueda , Liliana Íñiguez-Gutiérrez , Jorge Manuel Silva-Jara , Mariana Díaz-Zaragoza , Omar Graciano-Machuca

Background

The rs8177374 (S180L) polymorphism in TIRAP has been implicated in altered susceptibility to various infectious diseases, including malaria, though results across studies have been inconsistent.

Objective

To systematically review and meta-analyze the association between the TIRAP/MAL rs8177374 polymorphism and malaria susceptibility, including severe malaria and Plasmodium falciparum infection.

Methods

A systematic search of PubMed, Scopus, and Web of Science was conducted up to December 31, 2024, without language or geographic restrictions. Case-control and cohort studies reporting genotype and allele frequencies of rs8177374 in malaria patients and controls were included. Studies with control groups deviating from Hardy–Weinberg equilibrium were excluded. Two reviewers independently screened records, extracted data, and assessed study quality using the Newcastle–Ottawa Scale. Pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated under six genetic models using fixed- or random-effects meta-analyses. Heterogeneity was assessed with Cochran's Q and I2 statistics. Sensitivity analyses were performed using a leave-one-out approach. Publication bias was assessed using Egger's and Begg's tests.

Results

Ten studies comprising 4103 malaria cases and 2460 controls were included. No significant association was observed between rs8177374 and overall malaria susceptibility under any genetic model. In contrast, the T allele and heterozygous genotypes (TC) were consistently associated with a lower risk of severe malaria (T vs. C: OR = 0.51, 95 % CI: 0.40–0.65, p < 0.001). Conversely, in the P. falciparum subgroup, the variant was linked to an increased risk of infection (T vs. C: OR = 1.47, 95 % CI: 1.09–1.98, p = 0.012). Sensitivity analyses confirmed the stability of these associations, and no single study significantly influenced the pooled estimates.

Limitations

Limited number of studies in subgroup analyses, high heterogeneity in several comparisons, and geographic restriction to Asian and African populations.

Conclusions

The rs8177374 polymorphism is not associated with overall malaria or P. falciparum malaria, but shows a protective effect against severe malaria. These results support a modulatory role of TIRAP/MAL in malaria pathogenesis and warrant further functional and multi-ethnic studies.
背景:TIRAP中的rs8177374 (S180L)多态性与包括疟疾在内的多种传染病易感性的改变有关,尽管研究结果不一致。目的:系统回顾和荟萃分析TIRAP/MAL rs8177374多态性与疟疾易感性(包括重症疟疾和恶性疟原虫感染)的关系。方法:系统检索PubMed、Scopus和Web of Science,截止到2024年12月31日,不受语言和地理限制。纳入报告疟疾患者和对照组rs8177374基因型和等位基因频率的病例对照和队列研究。对照组偏离Hardy-Weinberg平衡的研究被排除。两位审稿人独立筛选记录,提取数据,并使用纽卡斯尔-渥太华量表评估研究质量。采用固定效应或随机效应荟萃分析,计算六种遗传模型的合并优势比(ORs)和95%置信区间(CIs)。采用Cochran's Q和I2统计来评估异质性。敏感度分析采用留一法进行。采用Egger’s和Begg’s检验评估发表偏倚。结果:纳入了10项研究,包括4103例疟疾病例和2460例对照。在任何遗传模型下均未观察到rs8177374与总体疟疾易感性之间的显著相关性。相比之下,T等位基因和杂合基因型(TC)始终与较低的严重疟疾风险相关(T对C: OR = 0.51, 95% CI: 0.40-0.65, p < 0.001)。相反,在恶性疟原虫亚组中,该变异与感染风险增加有关(T vs C: OR = 1.47, 95% CI: 1.09-1.98, p = 0.012)。敏感性分析证实了这些关联的稳定性,没有一项研究显著影响汇总估计值。局限性:亚组分析的研究数量有限,几个比较的异质性高,亚洲和非洲人群的地理限制。结论:rs8177374多态性与整体疟疾或恶性疟原虫疟疾无关,但对重度疟疾具有保护作用。这些结果支持TIRAP/MAL在疟疾发病机制中的调节作用,值得进一步的功能性和多民族研究。
{"title":"Immunomodulatory effects of the TIRAP/MAL rs8177374 (S180L) variant: Meta-Analytic evidence from severe and Plasmodium falciparum malaria","authors":"Noelia Ivett González-Castillo ,&nbsp;Sandra Guadalupe Prado-Rodríguez ,&nbsp;Omar Iñiguez-Mosqueda ,&nbsp;Liliana Íñiguez-Gutiérrez ,&nbsp;Jorge Manuel Silva-Jara ,&nbsp;Mariana Díaz-Zaragoza ,&nbsp;Omar Graciano-Machuca","doi":"10.1016/j.micpath.2025.108226","DOIUrl":"10.1016/j.micpath.2025.108226","url":null,"abstract":"<div><h3>Background</h3><div>The rs8177374 (S180L) polymorphism in <em>TIRAP</em> has been implicated in altered susceptibility to various infectious diseases, including malaria, though results across studies have been inconsistent.</div></div><div><h3>Objective</h3><div>To systematically review and meta-analyze the association between the TIRAP/MAL rs8177374 polymorphism and malaria susceptibility, including severe malaria and <em>Plasmodium falciparum</em> infection.</div></div><div><h3>Methods</h3><div>A systematic search of PubMed, Scopus, and Web of Science was conducted up to December 31, 2024, without language or geographic restrictions. Case-control and cohort studies reporting genotype and allele frequencies of rs8177374 in malaria patients and controls were included. Studies with control groups deviating from Hardy–Weinberg equilibrium were excluded. Two reviewers independently screened records, extracted data, and assessed study quality using the Newcastle–Ottawa Scale. Pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated under six genetic models using fixed- or random-effects meta-analyses. Heterogeneity was assessed with Cochran's Q and I<sup>2</sup> statistics. Sensitivity analyses were performed using a leave-one-out approach. Publication bias was assessed using Egger's and Begg's tests.</div></div><div><h3>Results</h3><div>Ten studies comprising 4103 malaria cases and 2460 controls were included. No significant association was observed between rs8177374 and overall malaria susceptibility under any genetic model. In contrast, the T allele and heterozygous genotypes (TC) were consistently associated with a lower risk of severe malaria (T vs. C: OR = 0.51, 95 % CI: 0.40–0.65, <em>p</em> &lt; 0.001). Conversely, in the P. falciparum subgroup, the variant was linked to an increased risk of infection (T vs. C: OR = 1.47, 95 % CI: 1.09–1.98, <em>p</em> = 0.012). Sensitivity analyses confirmed the stability of these associations, and no single study significantly influenced the pooled estimates.</div></div><div><h3>Limitations</h3><div>Limited number of studies in subgroup analyses, high heterogeneity in several comparisons, and geographic restriction to Asian and African populations.</div></div><div><h3>Conclusions</h3><div>The rs8177374 polymorphism is not associated with overall malaria or <em>P. falciparum</em> malaria, but shows a protective effect against severe malaria. These results support a modulatory role of TIRAP/MAL in malaria pathogenesis and warrant further functional and multi-ethnic studies.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108226"},"PeriodicalIF":3.5,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Secnidazole and metronidazole in the treatment of Trichomoniasis: Comparative study of the mechanism of action and development of innovative 3D printed intrauterine devices 塞克硝唑与甲硝唑治疗滴虫病:新型3D打印宫内节育器的发展与作用机制比较研究。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-12-04 DOI: 10.1016/j.micpath.2025.108222
Ágata Giuseppe Menezes , Fernanda Gomes Cardoso , Giulia Bongiorni Galego , Lenon Machado Alves , Marcelo Dutra Arbo , Solange Cristina Garcia , Maiara Callegaro Velho , Janine Boniatti , Ruy Carlos Ruver Beck , Tiana Tasca
Trichomonas vaginalis is the causative agent of trichomoniasis, the most prevalent non-viral sexually transmitted infection (STI) worldwide. This study aimed to evaluate the susceptibility of five T. vaginalis isolates to secnidazole and metronidazole – two of the three FDA-approved treatments. We also investigated their mechanisms of action and explored the use of 3D printing technology for delivering anti-T. vaginalis therapy. In vitro susceptibility assays were performed using secnidazole and metronidazole. To investigate their mechanisms of action, we assessed reactive oxygen and nitrogen species (ROS/RNS) production, lipid peroxidation, type of cell death, and superoxide dismutase (SOD) gene expression by qRT-PCR. DNA integrity was evaluated using the comet assay. Additionally, we designed 3D-printed intrauterine devices (IUDs) loaded with each drug to evaluate their efficacy in eradicating T. vaginalis. All isolates were more susceptible to secnidazole than to metronidazole. Neither drug increased ROS/RNS levels or lipid peroxidation. However, both downregulated SOD expression in most isolates and induced apoptosis-like cell death, evidenced by phosphatidylserine exposure. No DNA strand breaks were detected. Drug-loaded 3D-printed IUDs eradicated T. vaginalis trophozoites within 24 h, with secnidazole achieving this effect as early as 10 h post-treatment. Secnidazole and metronidazole appear to disrupt redox homeostasis through a mechanism independent of ROS/RNS, likely by downregulating SOD and increasing cellular susceptibility to oxidative stress. Both drugs induced apoptosis-like cell death without causing DNA damage. The drug-loaded devices represent a promising strategy for localized and personalized treatment. This is the first proof-of-concept for a 3D-printed IUD loaded with secnidazole and metronidazole demonstrating trichomonacidal action and highlighting a novel, localized drug delivery strategy with potential applications in personalized medicine for the treatment of trichomoniasis.
阴道毛滴虫是滴虫病的病原体,滴虫病是世界上最普遍的非病毒性性传播感染(STI)。本研究旨在评价5株阴道T. T. alis分离株对fda批准的三种治疗方法中的两种——塞克硝唑和甲硝唑的敏感性。我们还研究了它们的作用机制,并探索了使用3D打印技术来提供抗t。鞘突治疗。用塞克硝唑和甲硝唑进行体外药敏试验。为了研究它们的作用机制,我们通过qRT-PCR评估了活性氧和氮种(ROS/RNS)的产生、脂质过氧化、细胞死亡类型和超氧化物歧化酶(SOD)基因的表达。DNA完整性用彗星测定法评估。此外,我们设计了装载每种药物的3d打印宫内节育器(iud),以评估其根除阴道绦虫的效果。所有分离株对塞克硝唑的敏感性均高于甲硝唑。两种药物均未增加ROS/RNS水平或脂质过氧化。然而,在大多数分离株中,两者都下调SOD表达并诱导细胞凋亡样死亡,磷脂酰丝氨酸暴露证明了这一点。未检测到DNA链断裂。满载药物的3d打印宫内节育器在24小时内根除了阴道T.滋养体,塞克硝唑早在治疗后10小时就达到了这一效果。塞硝唑和甲硝唑似乎通过一种独立于ROS/RNS的机制破坏氧化还原稳态,可能是通过下调SOD和增加细胞对氧化应激的易感性。两种药物均诱导细胞凋亡样死亡,但不引起DNA损伤。装载药物的设备代表了一种有前途的本地化和个性化治疗策略。这是加载塞克硝唑和甲硝唑的3d打印宫内节育器的第一个概念验证,展示了滴虫杀灭作用,并突出了一种新的局部药物递送策略,在滴虫病治疗的个性化医疗中具有潜在的应用前景。
{"title":"Secnidazole and metronidazole in the treatment of Trichomoniasis: Comparative study of the mechanism of action and development of innovative 3D printed intrauterine devices","authors":"Ágata Giuseppe Menezes ,&nbsp;Fernanda Gomes Cardoso ,&nbsp;Giulia Bongiorni Galego ,&nbsp;Lenon Machado Alves ,&nbsp;Marcelo Dutra Arbo ,&nbsp;Solange Cristina Garcia ,&nbsp;Maiara Callegaro Velho ,&nbsp;Janine Boniatti ,&nbsp;Ruy Carlos Ruver Beck ,&nbsp;Tiana Tasca","doi":"10.1016/j.micpath.2025.108222","DOIUrl":"10.1016/j.micpath.2025.108222","url":null,"abstract":"<div><div><em>Trichomonas vaginalis</em> is the causative agent of trichomoniasis, the most prevalent non-viral sexually transmitted infection (STI) worldwide. This study aimed to evaluate the susceptibility of five <em>T. vaginalis</em> isolates to secnidazole and metronidazole – two of the three FDA-approved treatments. We also investigated their mechanisms of action and explored the use of 3D printing technology for delivering anti-<em>T. vaginalis</em> therapy. <em>In vitro</em> susceptibility assays were performed using secnidazole and metronidazole. To investigate their mechanisms of action, we assessed reactive oxygen and nitrogen species (ROS/RNS) production, lipid peroxidation, type of cell death, and superoxide dismutase (SOD) gene expression by qRT-PCR. DNA integrity was evaluated using the comet assay. Additionally, we designed 3D-printed intrauterine devices (IUDs) loaded with each drug to evaluate their efficacy in eradicating <em>T. vaginalis</em>. All isolates were more susceptible to secnidazole than to metronidazole. Neither drug increased ROS/RNS levels or lipid peroxidation. However, both downregulated SOD expression in most isolates and induced apoptosis-like cell death, evidenced by phosphatidylserine exposure. No DNA strand breaks were detected. Drug-loaded 3D-printed IUDs eradicated <em>T. vaginalis</em> trophozoites within 24 h, with secnidazole achieving this effect as early as 10 h post-treatment. Secnidazole and metronidazole appear to disrupt redox homeostasis through a mechanism independent of ROS/RNS, likely by downregulating SOD and increasing cellular susceptibility to oxidative stress. Both drugs induced apoptosis-like cell death without causing DNA damage. The drug-loaded devices represent a promising strategy for localized and personalized treatment. This is the first proof-of-concept for a 3D-printed IUD loaded with secnidazole and metronidazole demonstrating trichomonacidal action and highlighting a novel, localized drug delivery strategy with potential applications in personalized medicine for the treatment of trichomoniasis.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108222"},"PeriodicalIF":3.5,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Human metapneumovirus: Insights into immune evasion, pathogenesis and liposome-based vaccine strategies 人偏肺病毒:免疫逃避、发病机制和基于脂质体的疫苗策略
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-12-03 DOI: 10.1016/j.micpath.2025.108224
Fahad A. Alhumaydhi , Mohammad Hamza Khan , Masood Alam Khan
Human Metapneumovirus (HMPV) remains a major contributor to respiratory diseases, particularly affecting infants, the elderly, and immunocompromised individuals. HMPV, first identified in 2001, has been a prominent cause of respiratory tract infections, ranging from mild upper respiratory symptoms to severe pneumonia and bronchiolitis. Despite its impact, there are currently no licensed vaccines or specific antivirals treatments targeting HMPV. The virus evades host immunity by suppressing interferon signaling through pathways such as RIG-I/MAVS and JAK-STAT, and by impairing dendritic cell maturation, which collectively delays adaptive immunity. Vaccine development efforts focus on live-attenuated, subunit, viral vector-based, and mRNA platforms, with the F protein identified as the primary target for eliciting neutralizing antibodies. Advancements such as lipid nanoparticles and virus-like particles have enhanced vaccine delivery and immunogenicity. Understanding HMPV-host immune interactions is essential for reducing the global disease burden and advancing both novel preventive and therapeutic interventions. This review consolidates current knowledge on HMPV virology, immune evasion, and vaccine development while highlighting emerging diagnostic innovations and multivalent vaccine platforms. Global research collaboration remains crucial in combating HMPV-related respiratory diseases and improving preventive strategies. Future directions emphasize to develop multivalent vaccines against multiple respiratory viruses, the optimization of adjuvants, and the deployment of modular vaccine platforms to address antigenic variability.
人偏肺病毒(HMPV)仍然是呼吸道疾病的主要致病因素,尤其影响婴儿、老年人和免疫功能低下的个体。2001年首次发现的人乳头状病毒是呼吸道感染的主要原因,从轻微的上呼吸道症状到严重的肺炎和细支气管炎。尽管它有影响,但目前还没有针对HMPV的许可疫苗或特定抗病毒治疗方法。该病毒通过rig - 1 /MAVS和JAK-STAT等途径抑制干扰素信号,并通过损害树突状细胞成熟,从而共同延缓适应性免疫,从而逃避宿主免疫。疫苗开发工作主要集中在减毒活疫苗、亚基疫苗、基于病毒载体的疫苗和mRNA平台上,其中F蛋白被确定为引发中和抗体的主要靶点。脂质纳米颗粒和病毒样颗粒等技术进步增强了疫苗的递送和免疫原性。了解hmpv -宿主免疫相互作用对于减少全球疾病负担和推进新的预防和治疗干预措施至关重要。这篇综述整合了目前关于HMPV病毒学、免疫逃避和疫苗开发的知识,同时强调了新兴的诊断创新和多价疫苗平台。全球研究合作在防治与人乳头状病毒有关的呼吸道疾病和改进预防战略方面仍然至关重要。未来的方向强调开发针对多种呼吸道病毒的多价疫苗,优化佐剂,部署模块化疫苗平台以解决抗原变异性。
{"title":"Human metapneumovirus: Insights into immune evasion, pathogenesis and liposome-based vaccine strategies","authors":"Fahad A. Alhumaydhi ,&nbsp;Mohammad Hamza Khan ,&nbsp;Masood Alam Khan","doi":"10.1016/j.micpath.2025.108224","DOIUrl":"10.1016/j.micpath.2025.108224","url":null,"abstract":"<div><div>Human Metapneumovirus (HMPV) remains a major contributor to respiratory diseases, particularly affecting infants, the elderly, and immunocompromised individuals. HMPV, first identified in 2001, has been a prominent cause of respiratory tract infections, ranging from mild upper respiratory symptoms to severe pneumonia and bronchiolitis. Despite its impact, there are currently no licensed vaccines or specific antivirals treatments targeting HMPV. The virus evades host immunity by suppressing interferon signaling through pathways such as RIG-I/MAVS and JAK-STAT, and by impairing dendritic cell maturation, which collectively delays adaptive immunity. Vaccine development efforts focus on live-attenuated, subunit, viral vector-based, and mRNA platforms, with the F protein identified as the primary target for eliciting neutralizing antibodies. Advancements such as lipid nanoparticles and virus-like particles have enhanced vaccine delivery and immunogenicity. Understanding HMPV-host immune interactions is essential for reducing the global disease burden and advancing both novel preventive and therapeutic interventions. This review consolidates current knowledge on HMPV virology, immune evasion, and vaccine development while highlighting emerging diagnostic innovations and multivalent vaccine platforms. Global research collaboration remains crucial in combating HMPV-related respiratory diseases and improving preventive strategies. Future directions emphasize to develop multivalent vaccines against multiple respiratory viruses, the optimization of adjuvants, and the deployment of modular vaccine platforms to address antigenic variability.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108224"},"PeriodicalIF":3.5,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145665492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 hyphenated approach of chemical profiling, anti-bacterial assays, and molecular docking to validate the traditionally claimed anti-bacterial (Krimiroga) potential of Cyperus rotundus L. 采用化学分析、抗菌测定和分子对接相结合的方法,验证了传统上声称的圆草抗菌(Krimiroga)潜力。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-12-03 DOI: 10.1016/j.micpath.2025.108220
Raman Singh , Shamli Chandel , Shourabh Rav , Anmol , Gaurav Aggarwal , Dharam Singh , Upendra Sharma
Cyperus rotundus L. is an invasive weed plant traditionally known for its anti-bacterial potential, as documented in the Ayurvedic pharmacopoeia of India (API). The present work focuses on systematic validation of anti-bacterial potential (krimiroga) of this plant by evaluating its extract, fractions, and essential oil [extracted using hydrodistillation and deep eutectic solvent (DES)] against Gram-positive (Bacillus subtilis, Staphylococcus aureus), and Gram-negative (Escherichia coli, Salmonella typhimurium) bacterial type strains. The percentage inhibition of each sample, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) were evaluated. Anti-bacterial assay revealed potent activity of n-butanol fraction (81.67–100 %) and EOs (81.20–100 %) against targeted bacterial type strains. UHPLC-QTOF-MS/MS and GC-MS-based chemical profiling led to the identification of fifty major metabolites. Further, these identified compounds were screened in silico, targeting the proteins of selected bacteria. Molecular docking study revealed potent docking scores (kcal/mol) against different bacterial proteins (higher than positive control), such as rotunduside H (−11.32), scirpusin B (−11.62) against E. coli; scirpusin B (−10.35) and scirpusin A (−9.80) against S. aureus; aristolochic acid (−6.88) against S. typhimurium; and epicatechin gallate (−12.28) and methoxycyperotundol (−11.24) against B. subtilis. Hence, the present work highlights a systematic approach for identifying anti-bacterial leads to scientifically validate traditionally documented knowledge. EOs exhibited higher in vitro activity than the extract/fractions (with the n-butanol fraction showing the highest efficacy), and can be utilized for preparing anti-bacterial formulations with potential applications in food coatings, packaging materials, surface disinfectants, and wound dressings, following proper safety evaluations and regulatory compliance studies.
圆草是一种入侵杂草植物,传统上以其抗菌潜力而闻名,如印度阿育吠陀药典(API)所记载的那样。目前的工作重点是通过评价该植物的提取物、馏分和精油[用加氢蒸馏和深共溶溶剂(DES)提取]对革兰氏阳性[枯草芽孢杆菌(B. subtilis),金黄色葡萄球菌(S. aureus)和革兰氏阴性(大肠杆菌(E. coli),鼠伤寒沙门氏菌(S. typhimurium)]菌株的抗菌潜力(krimiroga)进行系统验证。测定各样品的抑菌率、最小抑菌浓度(MIC)和最小杀菌浓度(MBC)。结果表明,正丁醇组分(81.67 ~ 100%)和EOs组分(81.20 ~ 100%)对目标菌株具有较强的抑菌活性。UHPLC-QTOF-MS/MS和GC-MS-based化学分析鉴定了50种主要代谢物。此外,这些鉴定的化合物在硅筛选,针对选定的细菌的蛋白质。分子对接研究显示,对不同细菌蛋白的对接分数(kcal/mol)均高于阳性对照,如对大肠杆菌的对接分数为-11.32,对大肠杆菌的对接分数为-11.62;scirpusin B(-10.35)和scirpusin A(-9.80)抑制金黄色葡萄球菌;马兜铃酸对鼠伤寒沙门氏菌的抑制作用为-6.88;表儿茶素没食子酸酯(-12.28)和甲氧cyperotundol(-11.24)对枯草芽孢杆菌有抑制作用。因此,目前的工作强调了一种系统的方法来识别抗菌导联,以科学地验证传统记录的知识。EOs在体外表现出比提取物/组分更高的活性(其中正丁醇部分表现出最高的功效),并且可以用于制备抗菌配方,在食品涂料,包装材料,表面消毒剂和伤口敷料中具有潜在的应用,经过适当的安全性评估和法规遵从性研究。
{"title":"A hyphenated approach of chemical profiling, anti-bacterial assays, and molecular docking to validate the traditionally claimed anti-bacterial (Krimiroga) potential of Cyperus rotundus L.","authors":"Raman Singh ,&nbsp;Shamli Chandel ,&nbsp;Shourabh Rav ,&nbsp;Anmol ,&nbsp;Gaurav Aggarwal ,&nbsp;Dharam Singh ,&nbsp;Upendra Sharma","doi":"10.1016/j.micpath.2025.108220","DOIUrl":"10.1016/j.micpath.2025.108220","url":null,"abstract":"<div><div><em>Cyperus rotundus</em> L. is an invasive weed plant traditionally known for its anti-bacterial potential, as documented in the Ayurvedic pharmacopoeia of India (API). The present work focuses on systematic validation of anti-bacterial potential (<em>krimiroga</em>) of this plant by evaluating its extract, fractions, and essential oil [extracted using hydrodistillation and deep eutectic solvent (DES)] against Gram-positive (<em>Bacillus subtilis</em>, <em>Staphylococcus aureus</em>), and Gram-negative (<em>Escherichia coli, Salmonella typhimurium</em>) bacterial type strains. The percentage inhibition of each sample, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) were evaluated. Anti-bacterial assay revealed potent activity of <em>n</em>-butanol fraction (81.67–100 %) and EOs (81.20–100 %) against targeted bacterial type strains. UHPLC-QTOF-MS/MS and GC-MS-based chemical profiling led to the identification of fifty major metabolites. Further, these identified compounds were screened <em>in silico</em>, targeting the proteins of selected bacteria. Molecular docking study revealed potent docking scores (kcal/mol) against different bacterial proteins (higher than positive control), such as rotunduside H (−11.32), scirpusin B (−11.62) against <em>E. coli</em>; scirpusin B (−10.35) and scirpusin A (−9.80) against <em>S. aureus</em>; aristolochic acid (−6.88) against <em>S. typhimurium;</em> and epicatechin gallate (−12.28) and methoxycyperotundol (−11.24) against <em>B. subtilis.</em> Hence, the present work highlights a systematic approach for identifying anti-bacterial leads to scientifically validate traditionally documented knowledge. EOs exhibited higher <em>in vitro</em> activity than the extract/fractions (with the <em>n</em>-butanol fraction showing the highest efficacy), and can be utilized for preparing anti-bacterial formulations with potential applications in food coatings, packaging materials, surface disinfectants, and wound dressings, following proper safety evaluations and regulatory compliance studies.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108220"},"PeriodicalIF":3.5,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Plasmatic biochemical changes in COVID-19: Relevant markers that reflect patient genotypic predisposal COVID-19血浆生化变化:反映患者基因型易感的相关标志物
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-12-03 DOI: 10.1016/j.micpath.2025.108225
Jeferson S. Ursulino , Eloiza L.L. Tanabe , Aldilane L.X. Marques , Elaine C.O. da Silva , Juliana G.C. Leal , Larissa S. Pinto , Edmilson R.R. Júnior , Luana K.C. Santos , Carolinne Sales-Marques , Jorg A.P.M. Coelho , Marcos V.S. Sales , Eduardo J.S. Fonseca , Thiago S. Fragoso , Emiliano O. Barreto , Alexandre U. Borbely , Ana C.R. Leite , Thiago M. Aquino

Background

The emergence of COVID-19 as a global health threat, particularly exacerbated in pre-existing chronic conditions, underscores the imperative for continuous exploration of biomarkers to enhance clinical management.

Methods

This study employs multidimensional techniques, analyzing COVID-19 and control blood samples through plasma NMR, Raman spectroscopy, and leukocyte SNP genotyping.

Results

NMR metabolomics identifies heightened levels of L-lactic acid, D-glucose, VLDL/LDL, L-glutamic acid, and 1-methyl-histidine in COVID-19, alongside reduced levels of L-alanine and L-histidine. ROC curves exhibit robust discriminatory power, affirming the model's efficacy in distinguishing COVID-19 from control samples. Raman spectroscopy unveils bands associated with molecular vibrations of amino acids, lipids, and carotenoids in COVID-19. SNP genotyping reveals the rs2070788-TMPRSS2 association with elevated COVID-19 risk and rs8259-CD147 association with protective effects.

Conclusions

Our findings provides a comprehensive investigation of acute COVID-19, highlighting novel biomarkers, particularly the correlation between 1-methyl-histidine levels and the TMPRSS2 GG + AG genotype.
背景:COVID-19作为全球健康威胁的出现,特别是在已有慢性疾病中加剧,强调了不断探索生物标志物以加强临床管理的必要性。方法:本研究采用多维技术,通过血浆核磁共振、拉曼光谱、白细胞SNP基因分型对COVID-19和对照血样进行分析。结果:核磁共振代谢组学发现,在COVID-19中,l-乳酸、d -葡萄糖、VLDL/LDL、l-谷氨酸和1-甲基组氨酸水平升高,l-丙氨酸和l-组氨酸水平降低。ROC曲线表现出稳健的区分能力,证实了该模型在区分COVID-19和对照样本方面的有效性。拉曼光谱揭示了与COVID-19中氨基酸、脂质和类胡萝卜素的分子振动相关的波段。SNP基因分型显示rs2070788-TMPRSS2与COVID-19风险升高相关,rs8259-CD147与保护作用相关。结论:我们的研究结果提供了对急性COVID-19的全面调查,突出了新的生物标志物,特别是1-甲基组氨酸水平与TMPRSS2 GG+AG基因型之间的相关性。
{"title":"Plasmatic biochemical changes in COVID-19: Relevant markers that reflect patient genotypic predisposal","authors":"Jeferson S. Ursulino ,&nbsp;Eloiza L.L. Tanabe ,&nbsp;Aldilane L.X. Marques ,&nbsp;Elaine C.O. da Silva ,&nbsp;Juliana G.C. Leal ,&nbsp;Larissa S. Pinto ,&nbsp;Edmilson R.R. Júnior ,&nbsp;Luana K.C. Santos ,&nbsp;Carolinne Sales-Marques ,&nbsp;Jorg A.P.M. Coelho ,&nbsp;Marcos V.S. Sales ,&nbsp;Eduardo J.S. Fonseca ,&nbsp;Thiago S. Fragoso ,&nbsp;Emiliano O. Barreto ,&nbsp;Alexandre U. Borbely ,&nbsp;Ana C.R. Leite ,&nbsp;Thiago M. Aquino","doi":"10.1016/j.micpath.2025.108225","DOIUrl":"10.1016/j.micpath.2025.108225","url":null,"abstract":"<div><h3>Background</h3><div>The emergence of COVID-19 as a global health threat, particularly exacerbated in pre-existing chronic conditions, underscores the imperative for continuous exploration of biomarkers to enhance clinical management.</div></div><div><h3>Methods</h3><div>This study employs multidimensional techniques, analyzing COVID-19 and control blood samples through plasma NMR, Raman spectroscopy, and leukocyte SNP genotyping.</div></div><div><h3>Results</h3><div>NMR metabolomics identifies heightened levels of L-lactic acid, D-glucose, VLDL/LDL, L-glutamic acid, and 1-methyl-histidine in COVID-19, alongside reduced levels of L-alanine and L-histidine. ROC curves exhibit robust discriminatory power, affirming the model's efficacy in distinguishing COVID-19 from control samples. Raman spectroscopy unveils bands associated with molecular vibrations of amino acids, lipids, and carotenoids in COVID-19. SNP genotyping reveals the rs2070788-TMPRSS2 association with elevated COVID-19 risk and rs8259-CD147 association with protective effects.</div></div><div><h3>Conclusions</h3><div>Our findings provides a comprehensive investigation of acute COVID-19, highlighting novel biomarkers, particularly the correlation between 1-methyl-histidine levels and the TMPRSS2 GG + AG genotype.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108225"},"PeriodicalIF":3.5,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Zinc oxide-polyvinyl alcohol nanocomposite: A promising antiviral agent against acyclovir-sensitive and resistant herpes simplex virus type 1 氧化锌-聚乙烯醇纳米复合材料:一种有前途的抗病毒药物,可用于治疗对阿昔洛韦敏感和耐药的1型单纯疱疹病毒。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-12-03 DOI: 10.1016/j.micpath.2025.108223
Zahra Salavatiha , Ahmad Tavakoli , Seyed Jalal Kiani , Farah Bokharaei-Salim , Alijan Tabarraei , Ahmad Dehdast , Vahid Pirhajati Mahabadi , Roya Mokari Nejad , Seyed Hamidreza Monavari

Background

Acyclovir-resistant herpes simplex virus type 1 (HSV-1) strains have emerged as a health concern in both immunocompromised and healthy individuals, necessitating the development of effective treatments. Recent advances in nanotechnology have offered innovative approaches for treating viral infections. In this study, the antiviral effect of zinc oxide nanoparticles (ZnONPs) conjugated with polyvinyl alcohol (PVA)—a ZnO-PVA nanocomposite—was investigated against both acyclovir-sensitive and acyclovir-resistant HSV-1 strains.

Materials and methods

The ZnO-PVA nanocomposite was synthesized and characterized using electron microscopy, dynamic light scattering, thermogravimetric analysis, and X-ray diffraction. Its cytotoxicity was evaluated with an MTT assay, and its antiviral activity was assessed via quantitative real-time PCR. Furthermore, the inhibitory effect of the nanocomposite on viral antigen expression was confirmed by an immunofluorescence assay.

Results

At the highest non-toxic concentration (800 μg/mL), the nanocomposite reduced the viral loads of acyclovir-sensitive and acyclovir-resistant HSV-1 strains by 99.5 % and 98.3 %, respectively (p-values <0.001). Furthermore, treatment of HSV-1-infected cells with the ZnO-PVA nanocomposite significantly decreased the expression of viral antigens compared to the control group.

Conclusion

The ZnO-PVA nanocomposite exhibited significant antiviral effects against both acyclovir-sensitive and acyclovir-resistant HSV-1, suggesting its potential as an effective therapeutic agent.
背景:无环韦耐药性1型单纯疱疹病毒(HSV-1)毒株已成为免疫功能低下和健康个体的健康问题,需要开发有效的治疗方法。纳米技术的最新进展为治疗病毒感染提供了创新的方法。在这项研究中,研究了氧化锌纳米颗粒(ZnONPs)与聚乙烯醇(PVA)- ZnO-PVA纳米复合材料-结合对无环鸟苷敏感和耐药的HSV-1菌株的抗病毒作用。材料与方法:合成了ZnO-PVA纳米复合材料,并利用电子显微镜、动态光散射、热重分析和x射线衍射对其进行了表征。MTT法测定其细胞毒性,实时荧光定量PCR法测定其抗病毒活性。此外,通过免疫荧光实验证实了纳米复合材料对病毒抗原表达的抑制作用。结果:在最高无毒浓度(800 μg/mL)下,ZnO-PVA纳米复合材料对无环病毒敏感株和无环病毒耐药株的病毒载量分别降低99.5%和98.3% (p值)。结论:ZnO-PVA纳米复合材料对无环病毒敏感株和无环病毒耐药株均有显著的抗病毒作用,提示其可能是一种有效的治疗药物。
{"title":"Zinc oxide-polyvinyl alcohol nanocomposite: A promising antiviral agent against acyclovir-sensitive and resistant herpes simplex virus type 1","authors":"Zahra Salavatiha ,&nbsp;Ahmad Tavakoli ,&nbsp;Seyed Jalal Kiani ,&nbsp;Farah Bokharaei-Salim ,&nbsp;Alijan Tabarraei ,&nbsp;Ahmad Dehdast ,&nbsp;Vahid Pirhajati Mahabadi ,&nbsp;Roya Mokari Nejad ,&nbsp;Seyed Hamidreza Monavari","doi":"10.1016/j.micpath.2025.108223","DOIUrl":"10.1016/j.micpath.2025.108223","url":null,"abstract":"<div><h3>Background</h3><div>Acyclovir-resistant herpes simplex virus type 1 (HSV-1) strains have emerged as a health concern in both immunocompromised and healthy individuals, necessitating the development of effective treatments. Recent advances in nanotechnology have offered innovative approaches for treating viral infections. In this study, the antiviral effect of zinc oxide nanoparticles (ZnONPs) conjugated with polyvinyl alcohol (PVA)—a ZnO-PVA nanocomposite—was investigated against both acyclovir-sensitive and acyclovir-resistant HSV-1 strains.</div></div><div><h3>Materials and methods</h3><div>The ZnO-PVA nanocomposite was synthesized and characterized using electron microscopy, dynamic light scattering, thermogravimetric analysis, and X-ray diffraction. Its cytotoxicity was evaluated with an MTT assay, and its antiviral activity was assessed via quantitative real-time PCR. Furthermore, the inhibitory effect of the nanocomposite on viral antigen expression was confirmed by an immunofluorescence assay.</div></div><div><h3>Results</h3><div>At the highest non-toxic concentration (800 μg/mL), the nanocomposite reduced the viral loads of acyclovir-sensitive and acyclovir-resistant HSV-1 strains by 99.5 % and 98.3 %, respectively (p-values &lt;0.001). Furthermore, treatment of HSV-1-infected cells with the ZnO-PVA nanocomposite significantly decreased the expression of viral antigens compared to the control group.</div></div><div><h3>Conclusion</h3><div>The ZnO-PVA nanocomposite exhibited significant antiviral effects against both acyclovir-sensitive and acyclovir-resistant HSV-1, suggesting its potential as an effective therapeutic agent.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108223"},"PeriodicalIF":3.5,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Synergistic interaction between tuberculosis and depression: Changes in miRNA expression 结核病和抑郁症的协同作用:miRNA表达的变化。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-12-02 DOI: 10.1016/j.micpath.2025.108211
Kevser Elçi , Necmiye Canacankatan , Cem Yalaza , Mukadder Çalıkoğlu , Semra Erdoğan , Gönül Aslan

Aim

Depression in TB patients results in non-adherence to anti-TB treatment, prolonged infectiousness, drug resistance and constitutes a significant obstacle to the elimination of TB. Understanding and addressing the social and biological complexities of TB is critical to controlling TB. In this study, the expression levels of miR-128–3p, miR-34a-5p, miR-223–3p, miR-221–3p, miR-24–3p, miR-107, miR-134–5p, miR-135a and miR-1202 which are associated with Depression (DP) pathology, were investigated in active Tuberculosis (TB), patients in order to evaluate the synergy between TB and DP.

Method

The study was carried out with 2 groups: TB Patient Group and Control Group. Expression levels of miRNAs were detected by Real-Time PCR method.

Results

It was determined that miR-128–3p, miR-34a-5p, miR-223–3p, miR-221–3p, miR-24–3p, miR-107, miR-134–5p and miR-135a expression levels in the TB Patient Group showed a statistically significant increase compared to the Control Group (p < 0.05). There was no difference between the groups in miR-1202 levels (p = 0.169).

Conclusion

The fact that miR-128–3p, miR-34a-5p, miR-223–3p, miR-221–3p and miR-24–3p, whose expressions were detected to increase in DP patients in previous studies, were also found to be increased in TB patients in this study, suggests that the miRNAs mentioned may be effective in the synergy between TB and DP. In addition, miR-24–3p, miR-107, miR-134–5p and miR-135a, whose expression was increased in TB patients in this study, can be considered as new biomarker candidates for TB.
目的:结核病患者的抑郁症导致抗结核治疗不坚持、传染性延长、耐药,并构成消除结核病的重大障碍。了解和处理结核病的社会和生物学复杂性对控制结核病至关重要。本研究通过对活动性结核(TB)患者中与抑郁(DP)病理相关的miR-128-3p、miR-34a-5p、miR-223-3p、miR-221-3p、miR-24-3p、miR-107、miR-134-5p、miR-135a和miR-1202的表达水平进行研究,以评价结核与DP的协同作用。方法:研究分为两组:结核患者组和对照组。采用Real-Time PCR法检测mirna的表达水平。结果:测定结核患者组miR-128-3p、miR-34a-5p、miR-223-3p、miR-221-3p、miR-24-3p、miR-107、miR-134-5p、miR-135a的表达水平较对照组有统计学意义升高(p)。miR-128-3p、miR-34a-5p、miR-223-3p、miR-221-3p和miR-24-3p在以往的研究中在DP患者中表达增加,在本研究中也发现在TB患者中表达增加,提示上述mirna可能在TB与DP的协同作用中有效。此外,miR-24-3p、miR-107、miR-134-5p和miR-135a在本研究中结核患者中表达升高,可以考虑作为新的结核生物标志物候选物。
{"title":"Synergistic interaction between tuberculosis and depression: Changes in miRNA expression","authors":"Kevser Elçi ,&nbsp;Necmiye Canacankatan ,&nbsp;Cem Yalaza ,&nbsp;Mukadder Çalıkoğlu ,&nbsp;Semra Erdoğan ,&nbsp;Gönül Aslan","doi":"10.1016/j.micpath.2025.108211","DOIUrl":"10.1016/j.micpath.2025.108211","url":null,"abstract":"<div><h3>Aim</h3><div>Depression in TB patients results in non-adherence to anti-TB treatment, prolonged infectiousness, drug resistance and constitutes a significant obstacle to the elimination of TB. Understanding and addressing the social and biological complexities of TB is critical to controlling TB. In this study, the expression levels of miR-128–3p, miR-34a-5p, miR-223–3p, miR-221–3p, miR-24–3p, miR-107, miR-134–5p, miR-135a and miR-1202 which are associated with Depression (DP) pathology, were investigated in active Tuberculosis (TB), patients in order to evaluate the synergy between TB and DP.</div></div><div><h3>Method</h3><div>The study was carried out with 2 groups: TB Patient Group and Control Group. Expression levels of miRNAs were detected by Real-Time PCR method.</div></div><div><h3>Results</h3><div>It was determined that miR-128–3p, miR-34a-5p, miR-223–3p, miR-221–3p, miR-24–3p, miR-107, miR-134–5p and miR-135a expression levels in the TB Patient Group showed a statistically significant increase compared to the Control Group (p &lt; 0.05). There was no difference between the groups in miR-1202 levels (p = 0.169).</div></div><div><h3>Conclusion</h3><div>The fact that miR-128–3p, miR-34a-5p, miR-223–3p, miR-221–3p and miR-24–3p, whose expressions were detected to increase in DP patients in previous studies, were also found to be increased in TB patients in this study, suggests that the miRNAs mentioned may be effective in the synergy between TB and DP. In addition, miR-24–3p, miR-107, miR-134–5p and miR-135a, whose expression was increased in TB patients in this study, can be considered as new biomarker candidates for TB.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108211"},"PeriodicalIF":3.5,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Antimicrobial and therapeutic effect of gold Nanoparticle–Aptamer conjugated antimicrobial peptide RW-BP100 in Brucella canis infected mice and RAW 264.7 cells 金纳米颗粒-适体偶联抗菌肽RW-BP100对犬布鲁氏菌感染小鼠和RAW 264.7细胞的抗菌和治疗作用
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-12-01 DOI: 10.1016/j.micpath.2025.108217
Seong Eun Cho , Tran Xuan Ngoc Huy , Trang Thi Nguyen , Ched Nicole Turbela Aguilar , Said Abdi Salad , Il-Hwa Hong , Won-Gi Min , Hu-Jang Lee , Ji-Hyun Yeom , Suk Kim
Canine brucellosis is a common zoonosis worldwide, but treatment is challenging due to the stealthy and chronic infection caused by the bacterium Brucella (B.) canis. Antimicrobial peptides (AMPs) are promising candidates for combating drug-resistant microbes, and gold nanoparticle aptamer (AuNP-Apt) aids the delivery of peptides to mammalian cells. This study evaluated the therapeutic efficacy of AuNP-AptHis conjugated antimicrobial peptide RW-BP100His (AuNP-AptHis-RW-BP100His) against B. canis in murine macrophage RAW 264.7 cells and BALB/c mice. In vitro, a high concentration of RW-BP100His alone had a bactericidal effect. AuNP-AptHis-RW-BP100His inhibited intracellular bacterial replication and decreased nitric oxide (NO) production in RAW 264.7 cells infected with B. canis. The production of proinflammatory cytokines in RAW 264.7 cells was elevated after AuNP-AptHis-RW-BP100His treatment. In vivo, AuNP-AptHis-RW-BP100His treatment reduced bacterial burden and microgranulomas in the liver and spleen. CD4+, CD8+ T cells, and Th1 cytokines IFN-γ and TNF were elevated in the treated mice. The results indicate that the therapeutic mechanism of AuNP-AptHis-RW-BP100His is immunomodulation of the infected host to upregulate cell-mediated immunity for B. canis clearance. Therefore, it is a promising candidate to treat canine brucellosis as an alternative to conventional antibiotics.
犬布鲁氏菌病是世界范围内常见的人畜共患病,但由于布鲁氏菌(b)犬引起的隐性和慢性感染,治疗具有挑战性。抗菌肽(AMPs)是对抗耐药微生物的有希望的候选者,而金纳米粒子适体(AuNP-Apt)有助于将肽递送到哺乳动物细胞。本研究评价了AuNP-AptHis结合抗菌肽RW-BP100His (AuNP-AptHis-RW-BP100His)在小鼠巨噬细胞RAW 264.7细胞和BALB/c小鼠中对犬双歧杆菌的治疗效果。在体外,高浓度RW-BP100His单独具有杀菌作用。AuNP-AptHis-RW-BP100His抑制细胞内细菌复制,并降低犬b感染的RAW 264.7细胞中一氧化氮(NO)的产生。AuNP-AptHis-RW-BP100His处理后,RAW 264.7细胞中促炎细胞因子的产生升高。在体内,AuNP-AptHis-RW-BP100His治疗减少了肝脏和脾脏的细菌负荷和微肉芽肿。治疗小鼠的CD4+、CD8+ T细胞和Th1细胞因子IFN-γ和TNF升高。结果表明,AuNP-AptHis-RW-BP100His的治疗机制是通过免疫调节感染宿主上调细胞介导的免疫清除犬B.。因此,它是一种有前途的候选治疗犬布鲁氏菌病作为替代常规抗生素。
{"title":"Antimicrobial and therapeutic effect of gold Nanoparticle–Aptamer conjugated antimicrobial peptide RW-BP100 in Brucella canis infected mice and RAW 264.7 cells","authors":"Seong Eun Cho ,&nbsp;Tran Xuan Ngoc Huy ,&nbsp;Trang Thi Nguyen ,&nbsp;Ched Nicole Turbela Aguilar ,&nbsp;Said Abdi Salad ,&nbsp;Il-Hwa Hong ,&nbsp;Won-Gi Min ,&nbsp;Hu-Jang Lee ,&nbsp;Ji-Hyun Yeom ,&nbsp;Suk Kim","doi":"10.1016/j.micpath.2025.108217","DOIUrl":"10.1016/j.micpath.2025.108217","url":null,"abstract":"<div><div>Canine brucellosis is a common zoonosis worldwide, but treatment is challenging due to the stealthy and chronic infection caused by the bacterium <em>Brucella</em> (<em>B.</em>) <em>canis</em>. Antimicrobial peptides (AMPs) are promising candidates for combating drug-resistant microbes, and gold nanoparticle aptamer (AuNP-Apt) aids the delivery of peptides to mammalian cells. This study evaluated the therapeutic efficacy of AuNP-Apt<sup>His</sup> conjugated antimicrobial peptide RW-BP100<sup>His</sup> (AuNP-Apt<sup>His</sup>-RW-BP100<sup>His</sup>) against <em>B. canis</em> in murine macrophage RAW 264.7 cells and BALB/c mice. <em>In vitro</em>, a high concentration of RW-BP100<sup>His</sup> alone had a bactericidal effect. AuNP-Apt<sup>His</sup>-RW-BP100<sup>His</sup> inhibited intracellular bacterial replication and decreased nitric oxide (NO) production in RAW 264.7 cells infected with <em>B. canis</em>. The production of proinflammatory cytokines in RAW 264.7 cells was elevated after AuNP-Apt<sup>His</sup>-RW-BP100<sup>His</sup> treatment. <em>In vivo</em>, AuNP-Apt<sup>His</sup>-RW-BP100<sup>His</sup> treatment reduced bacterial burden and microgranulomas in the liver and spleen. CD4<sup>+</sup>, CD8<sup>+</sup> T cells, and Th1 cytokines IFN-γ and TNF were elevated in the treated mice. The results indicate that the therapeutic mechanism of AuNP-Apt<sup>His</sup>-RW-BP100<sup>His</sup> is immunomodulation of the infected host to upregulate cell-mediated immunity for <em>B. canis</em> clearance. Therefore, it is a promising candidate to treat canine brucellosis as an alternative to conventional antibiotics.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108217"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Bactericidal activity of mastic resin against Staphylococcus pseudintermedius and Staphylococcus aureus and its therapeutic efficacy in experimental pyoderma/impetigo 乳脂树脂对假中葡萄球菌和金黄色葡萄球菌的抑菌活性及其对实验性脓皮病/脓疱疮的治疗效果。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-12-01 DOI: 10.1016/j.micpath.2025.108216
Nana Komai , Yuta Kaga , Mao Kaneki , Chiharu Ohira , Naoki Iwahsita , Jumpei Uchiyama , Tomoki Fukuyama
In recent years, inappropriate usage of antibiotics has led to a rapid increase in antimicrobial-resistant bacteria. Mastic is a natural resin obtained from the stems and leaves of Pistacia lentiscus trees. We previously demonstrated its anti-inflammatory potential for alleviating atopic dermatitis symptoms, however, its direct effects on Staphylococci are unclear. This study was performed to verify the bactericidal effects of mastic at different concentrations against staphylococcal species in vitro and to evaluate the preventive and therapeutic potential of mastic in a mouse model of pyoderma/impetigo. Mastic showed bactericidal effects against methicillin-resistant Staphylococcus pseudintermedius and Staphylococcus aureus based on counting of the bacterial colonies and measurement of the ATP content. The effects of mastic on cytotoxicity and inflammatory cytokine release induced by staphylococcal strains were monitored using a human keratinocyte cell line. A murine model of pyoderma/impetigo was developed through intracutaneous administration of staphylococci in BALB/c mice. Lesion size analysis, histological examination, bacterial count, and gene expression analyses were performed. Mastic exhibited significant bactericidal effects against both strains of staphylococci. Cellular cytotoxicity and cytokine production induced by both strains of staphylococci were significantly inhibited by mastic pre-treatment. Mastic pre-treatment of mice also significantly inhibited the development of pyoderma/impetigo induced by both strains of staphylococci. Pyoderma induced by S. pseudintermedius was also significantly alleviated by therapeutic treatment with 1 % mastic; however, this effect was less pronounced for S. aureus-induced symptoms. These findings indicate the potential of mastic administration as a preventive and therapeutic approach for managing Staphylococcus-associated skin diseases.
近年来,抗生素使用不当导致耐药细菌迅速增加。乳胶是从黄连木的茎和叶中提取的天然树脂。我们之前证明了其抗炎潜力,减轻特应性皮炎症状,然而,其对葡萄球菌的直接作用尚不清楚。本研究旨在验证乳胶在不同浓度下对葡萄球菌的体外杀菌作用,并在脓皮病/脓疱疮小鼠模型中评估乳胶的预防和治疗潜力。乳胶对耐甲氧西林葡萄球菌和金黄色葡萄球菌有一定的杀菌作用,对细菌菌落计数和ATP含量测定结果表明乳胶对耐甲氧西林葡萄球菌和金黄色葡萄球菌有一定的杀菌作用。利用人角质形成细胞系监测乳脂对葡萄球菌菌株诱导的细胞毒性和炎性细胞因子释放的影响。通过给BALB/c小鼠皮内注射葡萄球菌,建立了脓皮病/脓疱疮小鼠模型。进行病变大小分析、组织学检查、细菌计数和基因表达分析。乳胶对两种葡萄球菌均有明显的杀菌作用。乳脂预处理显著抑制了两种葡萄球菌的细胞毒性和细胞因子的产生。乳脂预处理也能显著抑制两种葡萄球菌诱导的脓皮病/脓疱病的发展。1%乳脂治疗也能显著缓解假中间葡萄球菌引起的脓皮病;然而,对于金黄色葡萄球菌引起的症状,这种效果不太明显。这些发现表明乳糜给药作为预防和治疗葡萄球菌相关皮肤病的潜在方法。
{"title":"Bactericidal activity of mastic resin against Staphylococcus pseudintermedius and Staphylococcus aureus and its therapeutic efficacy in experimental pyoderma/impetigo","authors":"Nana Komai ,&nbsp;Yuta Kaga ,&nbsp;Mao Kaneki ,&nbsp;Chiharu Ohira ,&nbsp;Naoki Iwahsita ,&nbsp;Jumpei Uchiyama ,&nbsp;Tomoki Fukuyama","doi":"10.1016/j.micpath.2025.108216","DOIUrl":"10.1016/j.micpath.2025.108216","url":null,"abstract":"<div><div>In recent years, inappropriate usage of antibiotics has led to a rapid increase in antimicrobial-resistant bacteria. Mastic is a natural resin obtained from the stems and leaves of <em>Pistacia lentiscus</em> trees. We previously demonstrated its anti-inflammatory potential for alleviating atopic dermatitis symptoms, however, its direct effects on Staphylococci are unclear. This study was performed to verify the bactericidal effects of mastic at different concentrations against staphylococcal species <em>in vitro</em> and to evaluate the preventive and therapeutic potential of mastic in a mouse model of pyoderma/impetigo. Mastic showed bactericidal effects against methicillin-resistant <em>Staphylococcus pseudintermedius</em> and <em>Staphylococcus aureus</em> based on counting of the bacterial colonies and measurement of the ATP content. The effects of mastic on cytotoxicity and inflammatory cytokine release induced by staphylococcal strains were monitored using a human keratinocyte cell line. A murine model of pyoderma/impetigo was developed through intracutaneous administration of staphylococci in BALB/c mice. Lesion size analysis, histological examination, bacterial count, and gene expression analyses were performed. Mastic exhibited significant bactericidal effects against both strains of staphylococci. Cellular cytotoxicity and cytokine production induced by both strains of staphylococci were significantly inhibited by mastic pre-treatment. Mastic pre-treatment of mice also significantly inhibited the development of pyoderma/impetigo induced by both strains of staphylococci. Pyoderma induced by <em>S. pseudintermedius</em> was also significantly alleviated by therapeutic treatment with 1 % mastic; however, this effect was less pronounced for <em>S. aureus</em>-induced symptoms. These findings indicate the potential of mastic administration as a preventive and therapeutic approach for managing <em>Staphylococcus</em>-associated skin diseases.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108216"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Advancements in photodynamic therapy for tuberculosis treatment 光动力治疗肺结核的研究进展。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-11-30 DOI: 10.1016/j.micpath.2025.108207
Siqi Lin , Qianqian Zhang , Juan Liu , Bojie Lin , Daina Zhao , Jiayi Yang , Jia Fang , Jun-Fa Xu , Jiang Pi , Fen Yang
The emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb), coupled with lengthy treatment cycles and adverse side effects of traditional therapies, poses a significant global challenge in the form of tuberculosis (TB). Photodynamic therapy (PDT) generates reactive oxygen species that target specific tissues or cells via light irradiation at specific wavelengths. It directly disrupts critical structures and components of Mtb to exert its anti-TB effects. Unlike traditional antibiotics that rely on specific targets for efficacy, PDT prevents the occurrence of drug resistance at the mechanism level. Moreover, research indicates that multiple photosensitizers (such as methylene blue and porphyrin derivatives) demonstrate significant bactericidal effects against both drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro. It can also serve as an adjunct to conventional anti-TB drugs to improve therapeutic efficacy. However, tuberculosis infections predominantly occur in the deep tissues of the lungs. Achieving precise targeted delivery of photosensitizers to the lungs and ensuring their effective activation at deep infection sites, while overcoming the technical limitations of light sources—namely their limited excitation capacity and difficulty in effectively reaching deep pulmonary tuberculosis lesions—has become the core bottleneck for the clinical translation and application of this therapy. In this review, we discuss the principles and mechanisms of PDT, explore the structural characteristics and anti-infective capabilities of various photosensitizers. Finally, we discuss its current clinical applications in tuberculosis patients and future potential, offering novel perspectives for tuberculosis treatment.
耐药结核分枝杆菌(Mtb)菌株的出现,加上漫长的治疗周期和传统疗法的不良副作用,构成了结核病形式的重大全球挑战。光动力疗法(PDT)通过特定波长的光照射产生针对特定组织或细胞的活性氧。它直接破坏结核分枝杆菌的关键结构和成分以发挥其抗结核作用。与依赖特定靶点的传统抗生素不同,PDT在机制水平上防止耐药的发生。此外,研究表明,多种光敏剂(如亚甲基蓝和卟啉衍生物)在体外对药敏和耐药结核分枝杆菌均有显著的杀菌作用。它还可以作为常规抗结核药物的辅助药物,以提高治疗效果。然而,结核感染主要发生在肺的深层组织。如何将光敏剂精准靶向递送至肺部,并确保其在深部感染部位有效激活,同时克服光源激发能力有限、难以有效到达深部肺结核病灶的技术限制,成为该疗法临床转化和应用的核心瓶颈。本文综述了PDT的原理和作用机制,探讨了各种光敏剂的结构特点和抗感染能力。最后,我们讨论了其在结核病患者中的临床应用现状和未来的潜力,为结核病的治疗提供了新的视角。
{"title":"Advancements in photodynamic therapy for tuberculosis treatment","authors":"Siqi Lin ,&nbsp;Qianqian Zhang ,&nbsp;Juan Liu ,&nbsp;Bojie Lin ,&nbsp;Daina Zhao ,&nbsp;Jiayi Yang ,&nbsp;Jia Fang ,&nbsp;Jun-Fa Xu ,&nbsp;Jiang Pi ,&nbsp;Fen Yang","doi":"10.1016/j.micpath.2025.108207","DOIUrl":"10.1016/j.micpath.2025.108207","url":null,"abstract":"<div><div>The emergence of drug-resistant strains of <em>Mycobacterium tuberculosis</em> (Mtb), coupled with lengthy treatment cycles and adverse side effects of traditional therapies, poses a significant global challenge in the form of tuberculosis (TB). Photodynamic therapy (PDT) generates reactive oxygen species that target specific tissues or cells via light irradiation at specific wavelengths. It directly disrupts critical structures and components of Mtb to exert its anti-TB effects. Unlike traditional antibiotics that rely on specific targets for efficacy, PDT prevents the occurrence of drug resistance at the mechanism level. Moreover, research indicates that multiple photosensitizers (such as methylene blue and porphyrin derivatives) demonstrate significant bactericidal effects against both drug-sensitive and drug-resistant <em>Mycobacterium tuberculosis</em> in vitro. It can also serve as an adjunct to conventional anti-TB drugs to improve therapeutic efficacy. However, tuberculosis infections predominantly occur in the deep tissues of the lungs. Achieving precise targeted delivery of photosensitizers to the lungs and ensuring their effective activation at deep infection sites, while overcoming the technical limitations of light sources—namely their limited excitation capacity and difficulty in effectively reaching deep pulmonary tuberculosis lesions—has become the core bottleneck for the clinical translation and application of this therapy. In this review, we discuss the principles and mechanisms of PDT, explore the structural characteristics and anti-infective capabilities of various photosensitizers. Finally, we discuss its current clinical applications in tuberculosis patients and future potential, offering novel perspectives for tuberculosis treatment.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108207"},"PeriodicalIF":3.5,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Microbial pathogenesis
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