Antifungal agents

抗真菌剂
  • 文章类型: Case Reports
    背景技术隐球菌病是一种机会性真菌感染,通常发生在免疫系统受损的患者中。主要影响呼吸和中枢神经系统。然而,隐球菌骨髓炎是隐球菌感染的一种罕见表现,以非特异性临床特征为特征。这里,我们介绍一例中年妇女的椎体隐球菌性骨髓炎,并讨论诊断方法。病例报告一名56岁女性出现下背部疼痛和活动受限,不发烧,有肺结核病史.体格检查发现胸椎淋巴结肿大和压痛。计算机断层扫描引导活检证实由隐球菌引起的肉芽肿性炎症,具有丰富的10μm球形微生物孢子。两性霉素B和氟康唑治疗4周后,症状和病变改善。出院时,患者被处方口服氟康唑。随访检查显示病情稳定,血清隐球菌荚膜多糖抗原试验阴性。结论鉴于隐球菌性脊柱炎的临床特征罕见且缺乏特异性,遇到类似表现的临床医生应将结核性脊柱炎和脊柱肿瘤作为鉴别诊断。此外,应尽早对受影响的椎体进行组织活检,以确定椎体感染的类型,协助诊断,治疗,和预后。
    BACKGROUND Cryptococcosis is an opportunistic fungal infection that typically occurs in patients with compromised immune systems, primarily affecting the respiratory and central nervous systems. However, cryptococcal osteomyelitis is a rare manifestation of cryptococcal infection, characterized by nonspecific clinical features. Here, we present a case of vertebral cryptococcal osteomyelitis in a middle-aged woman and discuss diagnostic approaches. CASE REPORT A 56-year-old woman presented with lower back pain and limited mobility, without fever, and with a history of pulmonary tuberculosis. Physical examination revealed enlarged lymph nodes and tenderness in the thoracic vertebrae. A computed tomography-guided biopsy confirmed granulomatous inflammation caused by Cryptococcus, with abundant 10 μm spherical microbial spores. After 4 weeks of treatment with amphotericin B and fluconazole, symptoms and lesions improved. Upon discharge, the patient was prescribed oral fluconazole. Follow-up examinations showed a stable condition and a negative serum cryptococcal capsular polysaccharide antigen test. CONCLUSIONS Given the rarity and lack of specificity of clinical features of cryptococcal spondylitis, clinicians encountering similar presentations should consider tuberculous spondylitis and spinal tumors as differential diagnoses. Additionally, tissue biopsy of the affected vertebral bodies should be performed early to establish the type of vertebral infection, aiding in diagnosis, treatment, and prognosis.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    作为东北地区分布广泛的植物,CarexmeyerianaKunth(CMK)通常被认为具有抗菌性能;然而,这方面缺乏科学证据。因此,我们研究了CMK提取物的化学成分及其对白色念珠菌的影响。通过UPLC-Q-TOF-MS在CMK的醇提取物中鉴定出总共105种化合物。大多数是类黄酮,木犀草素是最有代表性的。其中,在白色念珠菌裂解物中发现了19种化合物。用CMK乙醇提取物处理后,从第5天开始,在阴道冲洗液中观察到白色念珠菌菌落数量显著减少(p<0.05)。此外,CMK提取物可以减少白色念珠菌孢子的数量。IL-4、IL-6、IL-10、IL-1β、通过ELISA测定,与模型组相比,阴道组织中的TNF-α和TNF-α均表现出显着降低(p<0.05)。HE染色成果显示CMK提取物能消除阴道粘膜炎症。CMK通过靶向二十六个不同的代谢物和五个特定的代谢途径来调节阴道粘膜细胞,以有效地消除炎症。同时,CMK调节针对白色念珠菌感染的二十三种代谢物和六种代谢途径。所以,CMK强烈抑制白色念珠菌的生长,并显著减少阴道炎症,使其成为治疗白色念珠菌感染的有希望的候选者。
    As a widely distributed plant in Northeast China, Carex meyeriana Kunth (CMK) is generally considered to have antibacterial properties; however, there is a lack of scientific evidence for this. Therefore, we investigated the chemical composition of CMK extract and its effect against C. albicans. A total of 105 compounds were identified in the alcohol extracts of CMK by UPLC-Q-TOF-MS. Most were flavonoids, with Luteolin being the most represented. Among them, 19 compounds are found in the C. albicans lysates. After treatment with CMK ethanol extract, a significant reduction in the number of C. albicans colonies was observed in a vaginal douche solution from day 5 (p < 0.05). Furthermore, the CMK extract can reduce the number of C. albicans spores. The levels of IL-4, IL-6, IL-10, IL-1β, and TNF-α in vaginal tissues all exhibited a significant decrease (p < 0.05) compared to those in the model group as determined by ELISA. The results of HE staining showed that CMK extract can eliminate vaginal mucosa inflammation. CMK adjusts the vaginal mucosa cells by targeting twenty-six different metabolites and five specific metabolic pathways in order to effectively eliminate inflammation. Simultaneously, the CMK regulates twenty-three types of metabolites and six metabolic pathways against C. albicans infection. So, CMK strongly inhibits the growth of C. albicans and significantly reduces vaginal inflammation, making it a promising candidate for treating C. albicans infection.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    微粒作为多室药物递送系统对于难溶性药物是有益的。在微粒技术中应用的粘膜粘附聚合物延长了药物与粘膜表面的接触,增强了药物的生物利用度并延长了药物活性。海藻酸钠(ALG)和羟丙基甲基纤维素(羟丙甲纤维素,HPMC)是天然或半合成来源的聚合物,分别。它们的特征在于粘膜粘附特性,并应用于微粒技术。喷雾干燥是一种用于微粒制备的技术,由液体在气流中的雾化组成。在这项研究中,将具有泊沙康唑的喷雾干燥的ALG/HPMC微粒的药物特性与具有相同定性和定量组成的粉末的物理混合物的特性进行了比较。泊沙康唑(POS)作为一种相对新颖的抗真菌药被用作水溶性差的模型药物,和硬明胶胶囊作为设计制剂的储库。在0.1MHCl中的释放研究显示,与粉末混合物相比,从微粒的POS释放显著延长。在模拟阴道液(SVF)中没有遵循这种关系。微粒的特征还在于更强的粘膜粘附特性,增加的溶胀率,与粉末的物理混合物相比,停留时间延长。获得的结果表明,填充有微粒的硬明胶胶囊的药物性能与具有粉末混合物的硬明胶胶囊明显不同。
    Microparticles as a multicompartment drug delivery system are beneficial for poorly soluble drugs. Mucoadhesive polymers applied in microparticle technology prolong the contact of the drug with the mucosa surface enhancing drug bioavailability and extending drug activity. Sodium alginate (ALG) and hydroxypropyl methylcellulose (hypromellose, HPMC) are polymers of a natural or semi-synthetic origin, respectively. They are characterized by mucoadhesive properties and are applied in microparticle technology. Spray drying is a technology employed in microparticle preparation, consisting of the atomization of liquid in a stream of gas. In this study, the pharmaceutical properties of spray-dried ALG/HPMC microparticles with posaconazole were compared with the properties of physical mixtures of powders with equal qualitative and quantitative compositions. Posaconazole (POS) as a relatively novel antifungal was utilized as a model poorly water-soluble drug, and hard gelatin capsules were applied as a reservoir for designed formulations. A release study in 0.1 M HCl showed significantly prolonged POS release from microparticles compared to a mixture of powders. Such a relationship was not followed in simulated vaginal fluid (SVF). Microparticles were also characterized by stronger mucoadhesive properties, an increased swelling ratio, and prolonged residence time compared to physical mixtures of powders. The obtained results indicated that the pharmaceutical properties of hard gelatin capsules filled with microparticles were significantly different from hard gelatin capsules with mixtures of powders.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    在抗菌素耐药性作为重大健康挑战的日益关注中,研究已经出现,重点阐明富含多酚的提取物的抗菌潜力,以减少对抗生素的依赖。先前的研究探索了提取物作为常规治疗策略的潜在替代品的抗真菌作用。我们旨在使用一系列革兰氏阴性和革兰氏阳性细菌以及两种酵母菌种评估标准化石榴提取物(PE)和柠檬提取物(LE)的抗菌和抗真菌作用。此外,我们评估了常见抗生素(环丙沙星,亚胺培南,庆大霉素,和头孢他啶),单独或与提取物组合,针对金黄色葡萄球菌和大肠杆菌。PE对大多数病原体表现出明显的抗菌(主要是杀菌)和抗真菌作用,而LE表现出较小的抗菌(主要是抑菌)和抗真菌特性。与抗生素相比,PE对金黄色葡萄球菌显示出比环丙沙星和头孢他啶更大的抑制区域(ZOI)(p<0.01)和与庆大霉素相当的ZOI(p=0.4)。然而,PE或LE与抗生素的组合对金黄色葡萄球菌和大肠杆菌的抗生素活性表现出中性或拮抗作用。这些发现有助于现有的关于PE和LE的抗微生物作用的证据。他们增加了研究的主体,表明多酚在抗微生物活性中既发挥拮抗作用又发挥协同作用。这突出了确定可以增强抗生素活性和降低抗生素抗性的最佳多酚浓度的重要性。进一步的体内研究,从动物试验开始,发展到人体试验,可能会导致推荐这些提取物用于治疗用途。
    Amidst the growing concern of antimicrobial resistance as a significant health challenge, research has emerged, focusing on elucidating the antimicrobial potential of polyphenol-rich extracts to reduce reliance on antibiotics. Previous studies explored the antifungal effects of extracts as potential alternatives to conventional therapeutic strategies. We aimed to assess the antibacterial and antifungal effects of standardised pomegranate extract (PE) and lemon extract (LE) using a range of Gram-negative and Gram-positive bacteria and two yeast species. Additionally, we assessed the antimicrobial activities of common antibiotics (Ciprofloxacin, Imipenem, Gentamicin, and Ceftazidime), either alone or in combination with extracts, against Staphylococcus aureus and Escherichia coli. PE displayed substantial antibacterial (primarily bactericidal) and antifungal effects against most pathogens, while LE exhibited antibacterial (mostly bacteriostatic) and antifungal properties to a lesser extent. When compared with antibiotics, PE showed a greater zone of inhibition (ZOI) than Ciprofloxacin and Ceftazidime (p < 0.01) and comparable ZOI to Gentamicin (p = 0.4) against Staphylococcus aureus. However, combinations of either PE or LE with antibiotics exhibited either neutral or antagonistic effects on antibiotic activity against Staphylococcus aureus and Escherichia coli. These findings contribute to the existing evidence regarding the antimicrobial effects of PE and LE. They add to the body of research suggesting that polyphenols exert both antagonistic and synergistic effects in antimicrobial activity. This highlights the importance of identifying optimal polyphenol concentrations that can enhance antibiotic activity and reduce antibiotic resistance. Further in vivo studies, starting with animal trials and progressing to human trials, may potentially lead to recommendation of these extracts for therapeutic use.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    植物病原性真菌是商业上重要作物中的疾病的原因,并在全球食物链中引起主要的供应问题。在人类在保护植物方面发挥积极作用之前,植物能够保护自己免受疾病的侵害。已知它们合成多种次级代谢产物(SMs),比如萜烯,生物碱,和酚类化合物,可以使用常规和非常规技术提取以配制生物杀真菌剂;植物提取物具有抗真菌活性和针对这些生物的各种作用机制。此外,它们被认为是无植物毒性的,可能对疾病控制有效。它们是用于农业的可持续和经济上可行的替代品,这就是为什么生物杀菌剂越来越被认为是解决合成杀菌剂引起的问题的有吸引力的选择。目前,有机农业继续发展,强调开发环境友好型作物生产替代品的重要性。这篇综述提供了关于生物合成的文献汇编,次级代谢产物对植物病原菌的作用机制,生物杀菌剂的提取技术和配方,植物提取物对植物病原真菌的生物活性,regulation,优势,并概述了生物杀菌剂在农业中的使用现状。
    Phytopathogenic fungi are responsible for diseases in commercially important crops and cause major supply problems in the global food chain. Plants were able to protect themselves from disease before humans played an active role in protecting plants. They are known to synthesize a variety of secondary metabolites (SMs), such as terpenes, alkaloids, and phenolic compounds, which can be extracted using conventional and unconventional techniques to formulate biofungicides; plant extracts have antifungal activity and various mechanisms of action against these organisms. In addition, they are considered non-phytotoxic and potentially effective in disease control. They are a sustainable and economically viable alternative for use in agriculture, which is why biofungicides are increasingly recognized as an attractive option to solve the problems caused by synthetic fungicides. Currently, organic farming continues to grow, highlighting the importance of developing environmentally friendly alternatives for crop production. This review provides a compilation of the literature on biosynthesis, mechanisms of action of secondary metabolites against phytopathogens, extraction techniques and formulation of biofungicides, biological activity of plant extracts on phytopathogenic fungi, regulation, advantages, disadvantages and an overview of the current use of biofungicides in agriculture.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    本文描述了异烟酸酯衍生的内消旋芳基卟啉的合成,已通过光谱方法(包括荧光光谱法)充分表征,以及元素分析和HR-MS。正己烷单溶剂化物的结构已通过单晶X射线衍射分析确定。已测量了这种新卟啉对2,2-二苯基-1-吡啶酰肼(DPPH)自由基的自由基清除活性。其对三种酵母菌株的抗真菌活性(C.白色念珠菌ATCC90028,光滑念珠菌ATCC64677和热带念珠菌ATCC64677)已使用圆盘扩散和微量稀释方法进行了测试。而测得的抗氧化活性较低,卟啉显示出中等但令人鼓舞的抗真菌活性。最后,对其对扁豆种子萌发的影响的研究揭示了有趣的化感特性。
    The present article describes the synthesis of an isonicotinate-derived meso-arylporphyrin, that has been fully characterized by spectroscopic methods (including fluorescence spectroscopy), as well as elemental analysis and HR-MS. The structure of an n-hexane monosolvate has been determined by single-crystal X-ray diffraction analysis. The radical scavenging activity of this new porphyrin against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical has been measured. Its antifungal activity against three yeast strains (C. albicans ATCC 90028, C. glabrata ATCC 64677, and C. tropicalis ATCC 64677) has been tested using the disk diffusion and microdilution methods. Whereas the measured antioxidant activity was low, the porphyrin showed moderate but encouraging antifungal activity. Finally, a study of its effect on the germination of lentil seeds revealed interesting allelopathic properties.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    病原真菌引起的植物病害严重影响作物的产量和品质,造成巨大的经济损失,并对全球粮食安全构成相当大的威胁。基于生物碱白麦酸设计并合成了苯基吡咯类似物。所有目标化合物通过1HNMR表征,13CNMR,和HRMS。评价了它们对7种植物病原真菌的抗真菌活性。结果表明,大多数化合物在50μg/mL时具有广谱抗菌活性;14个化合物对谷物根瘤菌和核盘菌具有60%以上的杀菌活性,特别是,化合物8g和8h对小麦根瘤菌的杀菌活性均在90%以上,可进一步开发为水溶性杀菌剂的先导剂。分子对接结果表明,化合物8g和8h可以通过氢键与14α-脱甲基酶(RcCYP51)相互作用,具有很强的亲和力。
    Plant diseases caused by pathogenic fungi seriously affect the yield and quality of crops, cause huge economic losses, and pose a considerable threat to global food security. Phenylpyrrole analogues were designed and synthesized based on alkaloid lycogalic acid. All target compounds were characterized by 1H NMR, 13C NMR, and HRMS. Their antifungal activities against seven kinds of phytopathogenic fungi were evaluated. The results revealed that most compounds had broad-spectrum fungicidal activities at 50 μg/mL; 14 compounds displayed more than 60% fungicidal activities against Rhizoctonia cerealis and Sclerotinia sclerotiorum, and in particular, the fungicidal activities of compounds 8g and 8h against Rhizoctonia cerealis were more than 90%, which could be further developed as lead agents for water-soluble fungicides. The molecular docking results indicate that compounds 8g and 8h can interact with 14α-demethylase (RcCYP51) through hydrogen bonding with strong affinity.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    杂环化合物,特别是那些含有唑环的,已经显示出广泛的生物活性,包括抗癌,抗菌,和抗真菌特性。其中,咪唑环因其多样化的治疗潜力而脱颖而出。在提出的研究中,我们设计并合成了一系列咪唑衍生物,以鉴定具有高生物潜力的化合物。我们专注于两组:氨基硫脲衍生物和腙衍生物。我们使用常规方法合成了这些化合物,并通过核磁共振波谱(NMR)证实了它们的结构,MS,和元素分析,然后使用肉汤微量稀释法对革兰氏阳性和革兰氏阴性细菌进行体外抗菌和抗真菌活性的评估,以及念珠菌属。菌株。我们的结果表明,氨基硫脲衍生物对革兰氏阳性细菌表现出不同的活性,MIC值范围为31.25至1000µg/mL。腙衍生物,然而,没有显示出显著的抗菌活性。这些发现表明,结构修饰可以显着影响咪唑衍生物的抗菌功效,强调氨基硫脲衍生物作为抗菌疗法进一步发展的有希望的候选药物的潜力。此外,评估了对四种癌细胞系的细胞毒活性。酰肼-腙的两种衍生物显示出中等的抗癌活性。
    Heterocyclic compounds, particularly those containing azole rings, have shown extensive biological activity, including anticancer, antibacterial, and antifungal properties. Among these, the imidazole ring stands out due to its diverse therapeutic potential. In the presented study, we designed and synthesized a series of imidazole derivatives to identify compounds with high biological potential. We focused on two groups: thiosemicarbazide derivatives and hydrazone derivatives. We synthesized these compounds using conventional methods and confirmed their structures via nuclear magnetic resonance spectroscopy (NMR), MS, and elemental analysis, and then assessed their antibacterial and antifungal activities in vitro using the broth microdilution method against Gram-positive and Gram-negative bacteria, as well as Candida spp. strains. Our results showed that thiosemicarbazide derivatives exhibited varied activity against Gram-positive bacteria, with MIC values ranging from 31.25 to 1000 µg/mL. The hydrazone derivatives, however, did not display significant antibacterial activity. These findings suggest that structural modifications can significantly influence the antimicrobial efficacy of imidazole derivatives, highlighting the potential of thiosemicarbazide derivatives as promising candidates for further development in antibacterial therapies. Additionally, the cytotoxic activity against four cancer cell lines was evaluated. Two derivatives of hydrazide-hydrazone showed moderate anticancer activity.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Case Reports
    肺毛霉菌病在肾移植受者中很少见,死亡率很高。我们报告了一例移植后1年和1个月表现为圆形肺炎的肺毛霉菌病。通过经皮肺活检证实了诊断。完全切除肺肿块,然后静脉注射脂质体两性霉素B治疗,挽救了病人的生命。总之,早期和及时诊断,然后完全切除肺毛霉菌病的病灶可以挽救生命。
    Pulmonary mucormycosis is rare in kidney transplant recipients and has a high mortality rate. We report a case of pulmonary mucormycosis presenting as round pneumonia 1 year and 1 month after the transplant. The diagnosis was confirmed by a percutaneous lung biopsy. A complete resection of the lung mass, followed by intravenous liposomal amphotericin B therapy, saved the life of the patient. In conclusion, early and prompt diagnosis followed by complete resection of the lesion in pulmonary mucormycosis is lifesaving.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    耳念珠菌,一种迅速传播的多重耐药真菌,在全球某些条件下导致致命的感染。黄芩苷(BE),从黄芩干根中提取的活性成分,具有抗真菌活性。然而,研究表明,中药在对抗真菌感染方面具有独特的优势,而BE的效果,从黄芩干根中提取的活性成分,关于C.auris,仍然未知。因此,本研究旨在评估BE作为抗真菌药物对抗新出现的多药耐药金黄色葡萄球菌的潜力。各种化验和模型,包括微量肉汤稀释,时间增长曲线分析,斑点测定,附着力试验,絮凝试验,细胞表面疏水性测定,水解酶活性测定,XTT测定,紫水晶试验,扫描电子显微镜(SEM),共聚焦激光扫描显微镜(CLSM),流式细胞术,活/死荧光染色,活性氧(ROS),细胞壁测定,聚集测定,猪皮肤模型,海绵状幼虫(G.Mellonella幼虫)感染模型,和逆转录定量聚合酶链反应(RT-PCR)用于研究黄芩素如何通过可能的多方面机制抑制C.auris。结果表明,BE强烈抑制了C.auris的生长,附着力,和生物膜的形成。它还通过破坏细胞膜和细胞壁,同时减少宿主的定植和侵袭,有效地减少了耐药性和聚集。转录组分析显示与BE处理后的不同毒力因子相关的基因表达的显着调节。总之,BE对C.auris表现出显著的有效性,由于其多方面的抑制机制,表明其作为可行的治疗选择的潜力。
    Candida auris, a rapidly spreading multi-drug-resistant fungus, is causing lethal infections under certain conditions globally. Baicalin (BE), an active ingredient extracted from the dried root of Scutellaria baicalensis Georgi, exhibits antifungal activity. However, studies have shown the distinctive advantages of Traditional Chinese medicine in combating fungal infections, while the effect of BE, an active ingredient extracted from the dried roots of Scutellaria baicalensis Georgi, on C. auris, remains unknown. Therefore, this study aims to evaluate the potential of BE as an antifungal agent against the emerging multidrug-resistant C. auris. Various assays and models, including microbroth dilution, time growth curve analysis, spot assays, adhesion tests, flocculation test, cell surface hydrophobicity assay, hydrolase activity assays, XTT assay, violet crystal assay, scanning electron microscope (SEM), confocal laser scanning microscope (CLSM), flow cytometry, Live/dead fluorescent staining, reactive oxygen species (ROS), cell wall assay, aggregation assay, porcine skin model, Galleria mellonella larvae (G. mellonella larvae) infection model, and reverse transcription-quantitative polymerase chain reaction (RT-PCR) were utilized to investigate how baicalein suppresses C. auris through possible multifaceted mechanisms. The findings indicate that BE strongly inhibited C. auris growth, adhesion, and biofilm formation. It also effectively reduced drug resistance and aggregation by disrupting the cell membrane and cell wall while reducing colonization and invasion of the host. Transcriptome analysis showed significant modulation in gene expression related to different virulence factors post-BE treatment. In conclusion, BE exhibits significant effectiveness against C. auris, suggesting its potential as a viable treatment option due to its multifaceted suppression mechanisms.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

公众号