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Biofilm architecture and dynamics of the oral ecosystem. 口腔生态系统的生物膜结构与动力学。
Pub Date : 2024-12-19 eCollection Date: 2024-01-01 DOI: 10.5114/bta.2024.145259
Rina Rani Ray

The oral cavity, being a nutritionally enriched environment, has been proven to be an ideal habitat for biofilm development. Various microenvironments, including dental enamel, supra- and subgingival surfaces, salivary fluid, and the dorsal surface of the tongue, harbor diverse microbes. These biofilms typically consist of four major layers. Depending on the food, age, clinical state, and lifestyle of the patient, the microbial growth dynamics in oral biofilm varies significantly. The presence of pathogenic bacteria that disrupt the normal floral composition of the oral cavity can lead to plaque biofilm formation, which is a precursor to various diseases. Noteworthy pathogenic bacteria, such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus mutans, often initiate biofilm formation. Undiagnosed and untreated oral biofilm can lead to severe diseases like periodontitis and eventual tooth loss. Therefore, studying the architecture and dynamics of oral biofilms is essential and can be achieved through image analysis and modern technologies, such as AI-enabled technologies and surface topography-adaptive robotic superstructures.

口腔作为一个营养丰富的环境,已被证明是生物膜发育的理想栖息地。不同的微环境,包括牙釉质、龈上和龈下表面、唾液液和舌背表面,孕育着不同的微生物。这些生物膜通常由四层组成。根据患者的食物、年龄、临床状态和生活方式的不同,口腔生物膜中的微生物生长动态也有很大差异。致病菌的存在破坏了口腔正常的菌群组成,可导致斑块生物膜的形成,这是各种疾病的前兆。值得注意的致病菌,如牙龈卟啉单胞菌、核梭杆菌和变形链球菌,经常引发生物膜的形成。未经诊断和治疗的口腔生物膜会导致严重的疾病,如牙周炎和最终的牙齿脱落。因此,研究口腔生物膜的结构和动力学是必不可少的,可以通过图像分析和现代技术来实现,例如人工智能技术和表面地形自适应机器人上层建筑。
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引用次数: 0
Gliclazide protects ionizing radiation-induced intestinal injury in mice by inhibiting oxidative stress and caspase-3. 格列齐特通过抑制氧化应激和caspase-3来保护电离辐射诱导的小鼠肠道损伤。
Pub Date : 2024-12-19 eCollection Date: 2024-01-01 DOI: 10.5114/bta.2024.145257
Soroush Arzani, Soghra Farzipour, Fereshteh Talebpour Amiri, Seyed Jalal Hosseinimehr

Gliclazide (GLZ), an oral antihyperglycemic medication, has additional beneficial effects, such as anti-inflammatory and antioxidant properties, besides lowering blood glucose levels. In this study, the radio-protective effect of GLZ was evaluated against ionizing radiation (IR)-induced intestinal injury in mice. Eight groups of mice were randomized as follows: control, GLZ (5, 10, and 25 mg/kg), IR (6 Gy), and IR + GLZ (at 5, 10, and 25 mg/kg). GLZ was administered to the mice for eight consecutive days, after which they were exposed to X-rays at a single dose of 6 Gy. After irradiation, biochemical parameters, immunohistochemical, and histological examinations were conducted on the ileum of the mice. IR exposure increased the levels of malondialdehyde and protein carbonyl, while glutathione levels, as oxidative stress biomarkers, decreased. Apoptosis in ileum tissues was also assessed. Furthermore, histopathological changes were observed in the irradiated mice. GLZ treatment significantly mitigated these changes. The administration of GLZ resulted in a marked decrease in caspase-3 immunoreactivity in the ileum of irradiated mice. This preclinical study exhibited that GLZ has a radioprotective effect against intestinal injury by inhibiting oxidative stress and apoptosis.

格列齐特(GLZ)是一种口服降糖药物,除了降低血糖水平外,还具有其他有益作用,如抗炎和抗氧化特性。本研究评价了GLZ对电离辐射(IR)致小鼠肠道损伤的辐射保护作用。8组小鼠随机分为:对照组、GLZ(5、10、25 mg/kg)、IR (6 Gy)和IR + GLZ(5、10、25 mg/kg)。小鼠连续8天服用GLZ,之后接受单次剂量为6 Gy的x射线照射。辐照后对小鼠回肠进行生化指标、免疫组化和组织学检查。红外暴露增加了丙二醛和蛋白质羰基的水平,而作为氧化应激生物标志物的谷胱甘肽水平下降。回肠组织的细胞凋亡也被评估。此外,观察到辐照小鼠的组织病理学变化。GLZ治疗显著减轻了这些变化。给药GLZ导致辐照小鼠回肠caspase-3免疫反应性明显降低。本临床前研究表明,GLZ通过抑制氧化应激和细胞凋亡对肠道损伤具有辐射保护作用。
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引用次数: 0
Quercetin nanoparticles as a therapeutic approach: pharmacological actions and potential applications in therapy. 槲皮素纳米颗粒作为一种治疗方法:药理作用和潜在的治疗应用。
Pub Date : 2024-12-19 eCollection Date: 2024-01-01 DOI: 10.5114/bta.2024.145258
Reham Farouk El-Sayed Baiomy

The utilization of quercetin nanoparticles as a novel therapeutic strategy has garnered significant attention in recent years. These nanoparticles offer a unique approach to enhancing delivery and effectiveness while overcoming the drawbacks of quercetin. By exploiting the advantages of nanotechnology, such as increased stability and improved bioavailability, quercetin nanoparticles hold significant potential for developing innovative treatments across various medical fields. Quercetin nanoparticles have emerged as an indispensable component in numerous pharmaceutical and medicinal formulations. They are recognized for their anticancer, antitumor, anti-inflammatory, and antidiabetic properties, making them valuable in addressing allergic reactions, metabolic disorders, inflammatory disorders, cardiovascular diseases, and arthritis. From a pharmacological perspective, quercetin nanoparticles have demonstrated beneficial effects against Alzheimer's disease, primarily through their inhibitory impact on acetylcholinesterase. Furthermore, these nanoparticles have been scientifically documented to possess antioxidant, anticarcinogenic, hepatoprotective, and cytotoxic activities. This comprehensive review aims to explore the pharmacokinetics and biological activities associated with quercetin nanoparticles. It also highlights their potential as therapeutic agents in treating a wide range of diseases, including Alzheimer's disease, cancer, and neurodegenerative disorders.

近年来,槲皮素纳米颗粒作为一种新的治疗策略得到了广泛的关注。这些纳米颗粒提供了一种独特的方法来增强递送和有效性,同时克服了槲皮素的缺点。槲皮素纳米粒子利用纳米技术的优势,如增加稳定性和提高生物利用度,在开发各种医学领域的创新疗法方面具有巨大潜力。槲皮素纳米颗粒已成为许多药物和药物配方中不可或缺的成分。它们被认为具有抗癌、抗肿瘤、抗炎和抗糖尿病的特性,这使得它们在治疗过敏反应、代谢紊乱、炎症紊乱、心血管疾病和关节炎方面很有价值。从药理学角度来看,槲皮素纳米颗粒主要通过对乙酰胆碱酯酶的抑制作用,证明了对阿尔茨海默病的有益作用。此外,这些纳米颗粒已被科学证明具有抗氧化、抗癌、保护肝脏和细胞毒性活性。本文旨在探讨槲皮素纳米颗粒的药代动力学和生物活性。它还强调了它们作为治疗多种疾病的治疗药物的潜力,包括阿尔茨海默病、癌症和神经退行性疾病。
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引用次数: 0
Investigation of antioxidant, antimicrobial, and enzymatic properties of thermophilic cyanobacteria extracts. 嗜热蓝藻提取物的抗氧化、抗菌和酶促特性研究。
Pub Date : 2024-12-19 eCollection Date: 2024-01-01 DOI: 10.5114/bta.2024.145253
Aytan Fataliyeva, Meral Yilmaz Cankilic, Nalan Yilmaz Sariozlu

Background: The present study investigated the antioxidant, antimicrobial, and partial enzymatic properties of 52 thermophilic cyanobacteria isolates in vitro.

Materials and methods: The DPPH scavenging method was applied to test the antioxidant potential of isolates' methanol extracts. Agar block diffusion and agar well diffusion methods were used to evaluate the antimicrobial activity and measured in milimeters. The measurement of enzyme activity was carried out by a modification of the agar block method by the growth of the cyanobacteria.

Results: Among the cyanobacterial extracts, strain 37 (0.78 ± 0.055 mg/ml) showed an IC50 value close to ascorbic acid (0.22 ± 0.04 mg/ml), indicating that it has a specific antioxidant source. Isolate G13 was shown to have the strongest antimicrobial activity against Micrococcus luteus NRRL B-4375 in the agar well diffusion method. In addition, the ability to produce enzymes was determined in isolate G1 (25 ± 5.66 mm), which had the highest cellulase activity at pH 8, and isolate K42 (22 ± 0.71 mm), which had the highest lipase activity at pH 7.

Conclusion: When percent inhibition and IC50 values were examined, it was found that cyanobacterial methanol extracts had moderate and low scavenging activity in comparison to the standard antioxidant ascorbic acid. In a study using the agar well diffusion method, the activity of cyanobacterial extracts against test bacteria was observed. In light of the results obtained, it is believed that the isolates exhibited lipase and cellulase (pH 7 and 8) enzyme activity at both pH levels and have potential for industrial use.

背景:本研究对52株嗜热蓝藻的体外抗氧化、抗菌和部分酶特性进行了研究。材料与方法:采用DPPH清除法检测分离物甲醇提取物的抗氧化能力。采用琼脂块扩散法和琼脂孔扩散法对其抗菌活性进行了评价,并以毫米为单位进行了测定。酶活性的测定是通过蓝藻的生长对琼脂块法的改进进行的。结果:在蓝藻提取物中,菌株37(0.78±0.055 mg/ml)的IC50值与抗坏血酸(0.22±0.04 mg/ml)接近,表明其具有特定的抗氧化来源。在琼脂孔扩散法中,分离物G13对黄体微球菌NRRL B-4375的抑菌活性最强。此外,分离物G1(25±5.66 mm)在pH 8时纤维素酶活性最高,分离物K42(22±0.71 mm)在pH 7时脂肪酶活性最高。结论:蓝藻甲醇提取物与标准抗坏血酸相比,具有中等和较低的清除活性。在琼脂孔扩散法的研究中,观察了蓝藻提取物对试验细菌的活性。根据所获得的结果,认为分离物在两个pH水平下均表现出脂肪酶和纤维素酶(pH 7和8)酶活性,具有工业应用潜力。
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引用次数: 0
First identification report for amino acid composition of red algae Gracilaria spp. obtained from Central Java, Indonesia. 印度尼西亚中爪哇红藻紫菜属(Gracilaria spp.)氨基酸组成首次鉴定报告。
Pub Date : 2024-12-19 eCollection Date: 2024-01-01 DOI: 10.5114/bta.2024.145254
Klara Kharisma Bunga Chandra, Tri Rini Nuringtyas, Tri Joko Raharjo

Gracilaria is a genus of red algae found mainly in Asia. Various species of Gracilaria are distributed throughout Indonesia's marine waters, especially in coastal areas, and are cultivated for research and economic purposes. Gracilaria mainly consists of polysaccharides and pigments, which have hindered protein identification. The unique protein expressions have never been analyzed using a proteomic approach, and no reports are available on Gracilaria spp. amino acid sequences in Central Java. Based on this background, we aimed to explore Gracilaria protein characterization using unique peptide sequence analysis via LC-HRMS. The usage of liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) has been growing in biomedical and environmental sciences, offering high accuracy in protein detection. We followed the LC-HRMS standard protocol with an optimized precipitation procedure. TCA/acetone precipitation was used for protein purification, after which the precipitate was subjected to protein digestion to obtain small peptide fractions. Protein analysis results are presented as protein concentrations, molecular models, and peptide sequences. This experiment identified four sequences derived from the Rhodophyta database: TKKILDK (845.5455 Da), TVKSLLTK (889.5717 Da), ILVKTLK (814.5761 Da), and TGcGRSKR (921.4683 Da). This study reveals peptide sequences for Gracilaria spp., showing similarities with other red algae species, along with the functions of the peptide sequences. Furthermore, amino acid models of secondary structures were provided to support our findings.

紫菜属是一种红藻属,主要分布在亚洲。各种各样的江蓠分布在印度尼西亚的海水中,特别是在沿海地区,并为研究和经济目的而种植。江蓠主要由多糖和色素组成,这阻碍了蛋白质的鉴定。这些独特的蛋白表达从未用蛋白质组学方法分析过,也没有关于中爪哇江蓠属氨基酸序列的报道。在此背景下,我们旨在利用LC-HRMS进行独特的肽序列分析,探索江蓠蛋白的特征。液相色谱联用高分辨率质谱法(LC-HRMS)在生物医学和环境科学领域的应用越来越广泛,为蛋白质检测提供了高精度的方法。我们遵循LC-HRMS标准方案,优化沉淀程序。用TCA/丙酮沉淀法纯化蛋白质,沉淀后进行蛋白质消化,得到小片段肽。蛋白质分析结果呈现为蛋白质浓度,分子模型和肽序列。本实验从Rhodophyta数据库中鉴定出4条序列:TKKILDK (845.5455 Da)、TVKSLLTK (889.5717 Da)、ILVKTLK (814.5761 Da)和TGcGRSKR (921.4683 Da)。本研究揭示了江蓠属的肽序列与其他红藻的相似之处,以及肽序列的功能。此外,二级结构的氨基酸模型也支持了我们的发现。
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引用次数: 0
Newly developed genomic SSR markers revealed the population structure and genetic characteristics of abaca (Musa textilis Nee). 新开发的基因组SSR标记揭示了abaca (Musa textilis Nee)的群体结构和遗传特征。
Pub Date : 2024-12-19 eCollection Date: 2024-01-01 DOI: 10.5114/bta.2024.145255
Mariecris Rizalyn R Mendoza, Antonio C Laurena, Maria Genaleen Q Diaz, Eureka Teresa M Ocampo, Tonette P Laude, Antonio G Lalusin

Abaca (Musa textilis Nee) is the primary source of manila hemp fiber, a vital industrial product for the country. Previous studies have relied on molecular markers designed for other Musa species or distant genera like rice, limiting accurate genetic characterization and germplasm conservation. To address this, we developed 50 genome-specific molecular markers based on the recently released whole genome sequence assembly of Abaca var. Abuab by Galvez et al. (2021). Among these markers, 28 showed high polymorphism, with an average PIC value of 0.78. Population analysis revealed a heterozygosity of 0.428, indicating moderate genetic diversity, supported by an alpha value of 0.0735 and an F stp value of 0.0815, which suggests moderate genetic differentiation among abaca accessions. Cluster analyses, generated by DARwin and STRUCTURE software with 91% similarity, identified four clusters. The new markers were also able to distinguish six Musa accessions exhibiting morphological traits of both abaca and banana. Discrepancies in sample identification due to identical or inverted names were resolved using population structure analysis. Molecular variance analysis showed a 12% variance among the four abaca subpopulations and 88% within populations, suggesting recent divergence. Our study highlights the diversity, identity, and genetic variation within the abaca collection using accurate, robust, cost-effective, and computationally simple genome-specific markers. These markers are pivotal for genetic studies of abaca, including traitmarker mapping and the differentiation of accessions even in the juvenile stage, when phenotypic differences may be subtle.

Abaca (Musa texilis Nee)是马尼拉麻纤维的主要来源,是该国重要的工业产品。以前的研究依赖于为其他Musa物种或遥远的属(如水稻)设计的分子标记,限制了准确的遗传表征和种质资源保护。为了解决这个问题,我们基于Galvez等人(2021)最近发布的Abaca var. Abuab全基因组序列组装开发了50个基因组特异性分子标记。多态性较高的标记有28个,平均PIC值为0.78。群体分析显示,杂合度为0.428,遗传多样性中等;α值为0.0735,F - stp值为0.0815,遗传分化中等。由DARwin和STRUCTURE软件生成的聚类分析具有91%的相似性,确定了四个聚类。新标记还能区分出6个同时具有abaca和banana形态特征的Musa材料。使用人口结构分析解决了由于相同或倒置的名称而导致的样本识别差异。分子变异分析表明,4个亚种间的变异率为12%,亚种内的变异率为88%,表明亚种间存在近期分化。我们的研究使用准确、稳健、经济、计算简单的基因组特异性标记,强调了abaca收集中的多样性、身份和遗传变异。这些标记是abaca遗传研究的关键,包括性状标记作图和即使在表型差异可能很微妙的幼年期也能进行分化。
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引用次数: 0
Investigation of CNS depressant and muscle relaxant effects of the ethnomedicinal plant Macropanax dispermus on Swiss Albino mice and its effect against oxidative stress. 民族药用植物大戟对瑞士白化小鼠中枢神经系统抑制和肌肉松弛作用的研究及其对氧化应激的影响
Pub Date : 2024-09-30 eCollection Date: 2024-01-01 DOI: 10.5114/bta.2024.141804
Syeda Rubaiya Afrin, Mohammad Rashedul Islam, Md Ashraful Alam, Ummah Tasnim Nisat, Bakul Akter, Mohammed Kamrul Hossain

Background and objective: Since plant-based natural drugs are widely accepted in modern times and possess numerous pharmacological effects with an extensive therapeutic range, an ethnomedicinal plant native to Bangladesh was selected to investigate for investigation of its various pharmacological effects. Macropanax dispermus has been traditionally used and has demonstrated numerous pharmacological effects in preclinical investigations. Therefore, this research aimed to assess the central nervous system (CNS) depressant and antioxidant activities of the crude methanol extracts of the stem barks (MDMS), leaves (MDML), and their different fractions.

Methods: The CNS depressant activity was assessed using the hole cross, rota-rod, and elevated plus maze tests on Swiss Albino mice, while the antioxidant activity was evaluated using the 2,2-diphenyl-1-picrylhydrazyl free radical, hydrogen peroxide (H2O2) nonradical scavenging, and ferric reducing power assays.

Results: The conducted assays successfully demonstrated that the chloroform fraction of MDML is a significantly (P < 0.001) effective CNS depressant, muscle relaxant, and anxiolytic agent with excellent antioxidative effects compared to standard and control. The aqueous fraction of MDML also acted as a significantly (P < 0.001) active CNS depressant and muscle relaxant, and it was a highly active ferric-reducing agent. All effects were dose and concentration-dependent.

Conclusion: The presence of various phytochemicals might contribute to these activities. However, further research is suggested to isolate their active compounds and evaluate their mechanisms of action.

背景和目的:由于以植物为基础的天然药物在现代已被广泛接受,并且具有多种药理作用和广泛的治疗范围,因此我们选择了一种原产于孟加拉国的民族药用植物来研究其各种药理作用。Macropanax dispermus 是一种传统的药用植物,在临床前研究中已证明其具有多种药理作用。因此,本研究旨在评估茎皮(MDMS)、叶片(MDML)及其不同馏分的粗甲醇提取物的中枢神经系统(CNS)抑制和抗氧化活性:中枢神经系统抑制活性通过对瑞士白化小鼠进行的孔十字试验、rota-rod试验和高架加迷宫试验进行评估,而抗氧化活性则通过2,2-二苯基-1-苦基肼自由基、过氧化氢(H2O2)非自由基清除和铁还原力试验进行评估:实验结果表明,与标准品和对照品相比,MDML 的氯仿馏分是一种有效的中枢神经系统抑制剂、肌肉松弛剂和抗焦虑剂,具有极佳的抗氧化效果(P < 0.001)。MDML 的水馏分也具有明显(P < 0.001)的中枢神经系统抑制和肌肉松弛活性,并且是一种高活性的铁还原剂。所有作用都与剂量和浓度有关:结论:各种植物化学物质的存在可能是产生这些活性的原因。结论:各种植物化学物质的存在可能是产生这些活性的原因之一,但还需要进一步研究,以分离其活性化合物并评估其作用机制。
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引用次数: 0
Investigation of the new substitution glycine to alanine within the Kringle-2 domain of reteplase: a molecular dynamics study. 研究网状血小板酶 Kringle-2 结构域中甘氨酸到丙氨酸的新取代:分子动力学研究。
Pub Date : 2024-09-30 eCollection Date: 2024-01-01 DOI: 10.5114/bta.2024.141801
Kaveh Haji-Allahverdipoor, Habib Eslami, Koosha Rokhzadi, Mokhtar Jalali Javaran, Sajad Rashidi Monfared, Mohamad Bagher Khademerfan

Background: Recombinant plasminogen activator (r-PA) consists of the Kringle-2 and protease domains of human tissue-type plasminogen. It is used clinically to treat coronary artery thrombosis and acute myocardial infarction. However, the expression and production of reteplase (r-PA) are limited due to its susceptibility to proteolysis during manufacturing processes. Therefore, efforts have been made to address this limitation.

Materials and methods: To enhance the conformational stability of r-PA and increase its resistance to proteolysis, we used Gly 6 Ala substitutions in the Kringle-2 domain through in silico . We created an in silico mutant collection with eight structures, incorporating four designated mutations (R103S, G39A, G53A, and G55A). Using MODELLER software and homology modeling, we developed three-dimensional structures for two Kringle-2 and tissue plasminogen activator protease domains, including the wild noncleavable form (R103S) and mutants with all four designated mutations. We assessed protein stability using a dynamic cross-correlation matrix by extracting global properties such as Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF) from trajectory files.

Results: The findings revealed that a single glycine-alanine substitution (G39A) enhanced the conformational stability of r-PA, as evidenced by improvements in RMSD, RMSF, radius of gyration, surface accessibility, hydrogen bond formation, eigenvector projection, and density analysis.

Conclusion: The conformational stability of r-PA conferred by glycine replacement with alanine may decrease the propensity for proteolysis in protease - rich environments across various recombinant systems and potentially enhance its production and expression levels.

背景:重组纤溶酶原激活剂(r-PA)由人类组织型纤溶酶原的 Kringle-2 和蛋白酶结构域组成。它在临床上用于治疗冠状动脉血栓和急性心肌梗死。然而,由于其在生产过程中易被蛋白水解,再普酶(r-PA)的表达和生产受到限制。因此,人们一直在努力解决这一局限性:为了增强 r-PA 的构象稳定性并提高其抗蛋白酶解的能力,我们在 Kringle-2 结构域中使用了 Gly 6 Ala 的硅代。我们创建了一个具有八个结构的硅突变体集合,其中包含四个指定的突变(R103S、G39A、G53A 和 G55A)。利用 MODELLER 软件和同源建模,我们开发出了两个 Kringle-2 和组织纤溶酶原激活物蛋白酶结构域的三维结构,包括野生的不可裂解形式(R103S)和所有四个指定突变的突变体。通过从轨迹文件中提取均方根偏差(RMSD)和均方根波动(RMSF)等全局属性,我们利用动态交叉相关矩阵评估了蛋白质的稳定性:研究结果表明,单个甘氨酸-丙氨酸取代(G39A)增强了r-PA的构象稳定性,这体现在RMSD、RMSF、回旋半径、表面可及性、氢键形成、特征向量投影和密度分析等方面:用丙氨酸取代甘氨酸可赋予 r-PA 构象稳定性,这可能会降低各种重组系统在蛋白酶丰富的环境中的蛋白水解倾向,并有可能提高其生产和表达水平。
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引用次数: 0
Nanotechnology in cancer therapeutics, diagnosis, and management. 癌症治疗、诊断和管理中的纳米技术。
Pub Date : 2024-09-30 eCollection Date: 2024-01-01 DOI: 10.5114/bta.2024.141807
Disha Hazarika, Sumit Sarma, Priyanka Shankarishan

Nanotechnology presents an exciting opportunity in cancer research by offering significant advancements in therapies, diagnosis, and management. It possesses unparalleled potential to enhance the accuracy and effectiveness of cancer therapy while simultaneously reducing adverse effects, owing to its distinctive capability to manipulate matter at a molecular level. Using nanoparticle carriers has facilitated the precise administration of therapeutic agents to afflicted areas within the human body through customized drug delivery systems, resulting in improved treatment accuracy and efficacy while reducing adverse effects. These techniques improve drug solubility and stability, leading to elevated levels of biochemical availability and improved efficacy outcomes for patients with minimal negative effects during treatment cycles. Another use case for nanoparticles includes tumor imaging; functionalized with targeting ligands containing diagnostic agents, they foster early detection, making quicker remedial action plans possible. Overall, the incorporation of nanotechnology ensures a promising future, although it stresses the need to address regulatory hurdles and safety concerns before widespread clinical implementation. Despite the complexity of cancer research and patient care, nanotechnology shows promise in transforming both fields.

纳米技术在治疗、诊断和管理方面取得了重大进展,为癌症研究带来了令人振奋的机遇。由于纳米技术具有在分子水平操纵物质的独特能力,它在提高癌症治疗的准确性和有效性,同时减少不良反应方面具有无与伦比的潜力。使用纳米粒子载体有助于通过定制的给药系统将治疗药物精确地输送到人体内的患病部位,从而提高治疗的准确性和有效性,同时减少不良反应。这些技术提高了药物的溶解度和稳定性,从而提高了生化可用性水平,改善了患者的疗效,并将治疗周期中的负面影响降至最低。纳米粒子的另一个用途包括肿瘤成像;纳米粒子与含有诊断剂的靶向配体功能化,可促进早期检测,使更快的补救行动计划成为可能。总之,纳米技术的应用前景广阔,但在广泛临床应用之前,还需要解决监管障碍和安全问题。尽管癌症研究和病人护理工作十分复杂,但纳米技术有望改变这两个领域。
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引用次数: 0
Induction of an immune response by a nonreplicating adenoviruses-based formulation versus a commercial pseudo-SARS-CoV-2 vaccine. 以非复制腺病毒为基础的制剂与商用伪 SARS-CoV-2 疫苗相比可诱导免疫反应。
Pub Date : 2024-09-30 eCollection Date: 2024-01-01 DOI: 10.5114/bta.2024.141805
Joanna Baran, Łukasz Kuryk, Mariangela Garofalo, Katarzyna Pancer, Magdalena Wieczorek, Michalina Kazek, Monika Staniszewska

Screening for effective vaccines requires broad studies on their immunogenicity in vitro and ex vivo . We used a PBMC-based system to assess changes in CD4+ T cells, CD8+ T cells, and CD19+ B cells upon stimulation with different combinations of antigens and adjuvants. We studied the activation mechanism using flow cytometry and two different adenoviral adjuvants characterized by the presence or absence of costimulatory ligands for the ICOS and CD40 receptors. Our studies identified the cellular targets and molecular mechanisms driving ongoing switched-antibody diversification. Class-switched memory B cells were the main precursor cells (95.03% ± 0.38 vs. mock 82.33% ± 0.45, P < 0.05) after treatment with the immunogenic formula: adenovirus armed (MIX1) or not (MIX2) with the ICOS and CD40 ligand, the recombinant receptor binding domain (rRBD), and Lentifect™ SARS-CoV-2 spike-pseudotyped lentivirus (GeneCopoeia, USA). Bcell class-switching towards the IgG+IgM+- positive phenotypes was noted (~50-fold increase vs. mock, P < 0.05). A significant increase was observed in the CD8+TEM population of the MIX1 (~2-fold, P < 0.05) and MIX2 (~4.7-fold, P < 0.05) treated samples. CD8+TEMRA increased when PBMCs were treated with MIX2 (9.63% ± 0.90, P < 0.05) vs. mock (2.63% ± 1.96). Class-switched memory B cells were the dominant antigen-specific cells in primary reactions. We indicated a correlation between the protection offered by vaccine regimens and their ability to induce high frequencies of multifunctional T cells.

筛选有效的疫苗需要对其体外和体内免疫原性进行广泛的研究。我们使用基于 PBMC 的系统来评估 CD4+ T 细胞、CD8+ T 细胞和 CD19+ B 细胞在不同抗原和佐剂组合刺激下的变化。我们使用流式细胞术和两种不同的腺病毒佐剂研究了活化机制,这两种佐剂的特点是存在或不存在 ICOS 和 CD40 受体的成本刺激配体。我们的研究确定了细胞靶点和分子机制,这些靶点和机制驱动着正在进行的切换-抗体多样化。经免疫原性配方处理后,类调换记忆B细胞是主要的前体细胞(95.03% ± 0.38 vs. 模拟 82.33% ± 0.45,P < 0.05),免疫原性配方包括:带有或不带有ICOS和CD40配体的腺病毒(MIX1)、重组受体结合域(rRBD)和Lentifect™ SARS-CoV-2尖峰伪型慢病毒(GeneCopoeia,美国)。结果发现,B细胞向IgG+IgM+-阳性表型转变(与模拟相比增加了约50倍,P < 0.05)。经 MIX1(~2 倍,P < 0.05)和 MIX2(~4.7 倍,P < 0.05)处理的样本中 CD8+TEM 群体明显增加。用 MIX2(9.63% ± 0.90,P < 0.05)与模拟(2.63% ± 1.96)处理 PBMCs 时,CD8+TEMRA 增加。类调换记忆 B 细胞是原发反应中最主要的抗原特异性细胞。我们发现疫苗方案提供的保护与它们诱导高频率多功能 T 细胞的能力之间存在相关性。
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Biotechnologia
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