Cellular

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  • 文章类型: Journal Article
    最近,磁场(MF)由于其潜在的治疗应用和生物学效应而受到了广泛的关注。这篇综述全面分析了MFs的细胞和分子影响,专注于体外和体内研究。我们研究了MFs影响细胞行为的机制,包括基因表达的修饰,蛋白质合成,和细胞信号通路。MFs与细胞成分如离子通道的相互作用,膜,分析细胞骨架,以及它们对细胞增殖等过程的影响,分化,和凋亡。分子洞察提供了MFs如何调节氧化应激和炎症反应,在各种病理条件下至关重要。此外,我们探索了MF在再生医学中的治疗潜力,癌症治疗,和神经退行性疾病。通过综合目前的发现,本文旨在阐明MFs的复杂生物效应,从而促进其在医学和生物技术领域的优化应用。
    Recently, magnetic fields (MFs) have received major attention due to their potential therapeutic applications and biological effects. This review provides a comprehensive analysis of the cellular and molecular impacts of MFs, with a focus on both in vitro and in vivo studies. We investigate the mechanisms by which MFs influence cell behavior, including modifications in gene expression, protein synthesis, and cellular signaling pathways. The interaction of MFs with cellular components such as ion channels, membranes, and the cytoskeleton is analyzed, along with their effects on cellular processes like proliferation, differentiation, and apoptosis. Molecular insights are offered into how MFs modulate oxidative stress and inflammatory responses, which are pivotal in various pathological conditions. Furthermore, we explore the therapeutic potential of MFs in regenerative medicine, cancer treatment, and neurodegenerative diseases. By synthesizing current findings, this article aims to elucidate the complex bioeffects of MFs, thereby facilitating their optimized application in medical and biotechnological fields.
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  • 文章类型: Journal Article
    布鲁氏菌病疫苗旨在诱导细胞免疫。有效的布鲁氏菌病疫苗可以诱导细胞和体液免疫。血清杀菌试验(SBA)是确定疫苗体液免疫的重要方法。本研究首次通过SBA观察布鲁氏菌病的体液免疫。
    提取的流产布鲁氏菌(B.abortus)将脂多糖(LPS)和外膜蛋白(OMPs)注射到兔体内。第1组注射25μgLPS,第2组注射50μgOMPs,第3组注射1毫升联合疫苗,每2周3次。两组在第二次注射中接受B.abortus544攻击。在最后一次注射后2周分离血清。进行了SBA,并将每个孔条纹培养到布鲁氏菌琼脂平板中。对每个板进行菌落计数。
    结果显示,联合疫苗的第三次注射的最高滴度为164,疫苗的有效率为87.71%。
    作为结论,这项研究的结果表明,来自B.abortus的LPS和OMP可以提供可接受的免疫力。
    UNASSIGNED: Brucellosis vaccines are designed to induce cellular immunity. An effective brucellosis vaccine could induce both cellular and humoral immunity. Serum Bactericidal Assay (SBA) is an important method for determining vaccine humoral immunity. This study is the first to observe humoral immunity in brucellosis by SBA.
    UNASSIGNED: Extracted Brucella abortus (B. abortus) Lipopolysaccharide (LPS) and Outer Membrane Proteins (OMPs) were injected into rabbits. Group 1 was injected with 25 μg of LPS, Group 2 was injected with 50 μg of OMPs, and Group 3 was injected with 1 ml of combined vaccine, 3 times every 2 weeks. The groups were challenged with B. abortus 544 in the second injection. Sera were separated 2 weeks after the last injection. SBA was performed, and each well was streak-cultured into a plate of Brucella agar. A colony count was done for each plate.
    UNASSIGNED: Results have shown, the third injection of the combined vaccine had the highest titer of 1 64 , and the efficacy of the vaccine was 87.71%.
    UNASSIGNED: As a conclusion, the results of this study showed that LPS and OMP\'s from B. abortus can provide acceptable immunity.
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  • 文章类型: Journal Article
    局部产品的体外渗透测试(IVPT)是在人体尸体皮肤上进行的,它被冷冻保存很长时间。冷冻保存技术是不经济的并且是麻烦的过程。此外,已知在冷冻状态下长时间保存皮肤和频繁的冻融会影响皮肤屏障的完整性。因此,研究了冻干作为保护皮肤组织免受微生物污染和变性的替代方法。值得注意的是,该项目的目的是研究冷冻干燥过程对皮肤屏障性能的影响。测量冻干皮肤的形态计量学。组织学研究未发现由于冷冻干燥过程,层的组织和完整性发生了任何显着变化。皮肤的生物物理属性,如经表皮水分蒸发速率和经表皮电阻率(TEER),在对照皮肤(未进行冷冻干燥过程)和冷冻干燥皮肤(FDS)之间没有显着差异。咖啡因的渗透性,亲水模型渗透物,还有尼古丁,亲脂性模型渗透物,在对照和FDS之间是一致的。从研究中可以明显看出,冻干过程没有显著影响皮肤的屏障性质和渗透性。
    The in vitro permeation testing (IVPT) of topical products is performed across the human cadaver skin, which is stored frozen for a prolonged duration. The cryo-preservation technique is not economical and is a cumbersome process. Moreover, prolonged skin preservation in a frozen state and frequent freeze-thawing are known to affect the integrity of the skin barrier. Therefore, lyophilization was explored as an alternative to protect the skin tissue from microbial contamination and degeneration. Notably, the project\'s objective was to investigate the impact of the freeze-drying process on the skin\'s barrier properties. The morphometrics of the lyophilized skin were measured. Histological studies did not reveal any notable changes in the organization and intactness of the layers due to the freeze-drying process. The biophysical attributes of the skin, such as transepidermal water evaporation rate and transepidermal electrical resistivity (TEER), were not significantly different between the control skin (not subjected to the freeze-drying process) and the freeze-dried skin (FDS). The permeability of caffeine, a hydrophilic model permeant, and nicotine, a lipophilic model permeant, were consistent across the control and the FDS. It is evident from the studies that the lyophilization process did not significantly impact the barrier properties and permeability of the skin.
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  • 文章类型: Journal Article
    干燥综合征(SS)是一种以外分泌腺功能障碍为特征的自身免疫性疾病。主要受影响的是唾液腺,表现出最常见的病理变化。发病机制涉及易感基因,非遗传因素,如感染,免疫细胞包括T细胞和B细胞,巨噬细胞,树突状细胞,和唾液腺上皮细胞。炎症介质,如自身抗体,细胞因子,趋化因子也起着关键作用。激活的关键信号通路包括IFN,TLR,BAFF/BAFF-R,PI3K/Akt/mTOR,在其他人中。全面了解这些机制对于制定有针对性的治疗干预措施至关重要。因此,这项研究探讨了SS相关唾液腺损伤的细胞和分子机制,旨在提出新的靶向治疗方法。
    Sjögren\'s Syndrome (SS) is an autoimmune disorder characterized by dysfunction of exocrine glands. Primarily affected are the salivary glands, which exhibit the most frequent pathological changes. The pathogenesis involves susceptibility genes, non-genetic factors such as infections, immune cells-including T and B cells, macrophage, dendritic cells, and salivary gland epithelial cells. Inflammatory mediators such as autoantibodies, cytokines, and chemokines also play a critical role. Key signaling pathways activated include IFN, TLR, BAFF/BAFF-R, PI3K/Akt/mTOR, among others. Comprehensive understanding of these mechanisms is crucial for developing targeted therapeutic interventions. Thus, this study explores the cellular and molecular mechanisms underlying SS-related salivary gland damage, aiming to propose novel targeted therapeutic approaches.
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  • 文章类型: Case Reports
    背景:本案例研究的目的是提出双(DA)和三(TA)牙基牙种植体的新设计的合理性和科学证据,其特定的生物动力学优化的种植体周围组织(BOPiT)的新概念。
    方法:这些具有抛物面几何形状的基台的创新设计基于BOPiT,同时涉及机械生物学原理,生物多样性,和机械转换。因此,本病例研究包括使用创新的DA(n=28)和TA(n=15)对43种植入物进行单种植牙修复的37例连续个体/43例。DA和TA在单个植入物上支持2或3个牙冠,分别。在T1(4个月后加载)和T2进行临床和影像学检查[最终检查,平均随访时间为7.2年(>3至12年)]。
    结果:在T2时,菌斑指数的平均得分,植入体周围探查出血,种植体周围探测深度低,描绘健康的种植体周围条件。与T1相比,所有放射学图像均显示出微不足道的年度边缘骨丢失(0.022±0.05mm),反映出骨稳定性。
    结论:DA和TA,基于BOPiT的概念,代表一个有利的,简单的和非侵入性的机制的长寿和健康调节的植入物周围组织。
    BACKGROUND: The aim of this case study is to present the rationality and scientific evidence of a new design for a double (DA) and triple (TA) dental abutment-implant with their specific new concept of biodynamic optimized peri-implant tissue (BOPiT).
    METHODS: The innovative design of these abutments with a paraboloid geometry was based on BOPiT, simultaneously involving the principles of mechanobiology, biotensegrity, and mechanotransduction. Thus, 37 consecutive individuals/43 cases rehabilitated with single dental implant using the innovative DA (n = 28) and TA (n = 15) on 43 implants were included in this case study. The DA and TA support 2 or 3 dental crowns on a single implant, respectively. Clinic and radiographic examinations were presented at T1 (loading after 4 months) and T2 [final examination with an average follow-up time of 7.2 years (>3 to 12 years)].
    RESULTS: At T2, mean scores for plaque index, peri-implant bleeding on probing, and peri-implant probing depth were low, depicting healthy peri-implant conditions. All radiographic images showed insignificant annual marginal bone loss (0.022 ± 0.05 mm) when compared to T1, reflecting great bone stability.
    CONCLUSIONS: DA and TA, based on the BOPiT concept, represent an advantageous, simple and non-invasive mechanism for the longevity and healthy regulation of the peri-implant tissues.
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  • 文章类型: Interview
    JohannesGräff(JG):史蒂夫,为这次谈话做准备,我从书架上拿出埃里克·坎德尔写的《寻找记忆》。显然,一个大问题是,鉴于这本书是20多年前写的:我们到了吗?我们找到记忆了吗?
    Johannes Gräff (JG): Steve, in preparation for this conversation, I pulled out the book \"In search of memory\" by Eric Kandel from my bookshelf. Obviously one big question is, given that this book was written more than 20 years ago: Are we there yet? Have we found memory?
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  • 文章类型: Journal Article
    在这项新的大规模多重免疫荧光研究中,我们全面表征和比较了成年恒河猴的广泛发散的背外侧前额叶皮层(A46)和初级视觉皮层(A17)的感兴趣区域内的层特异性蛋白质组特征。在连续染色的轮次中对28个标记进行了成像,它们的空间分布在灰质层和浅层白质中精确量化。细胞被分类为神经元,星形胶质细胞,少突胶质细胞,小胶质细胞,或内皮细胞。通过对感兴趣区域的染色强度进行定量来评估纤维和血管的分布。该方法揭示了层和区域之间的多变量相似性和差异。神经元中的蛋白质表达是层状和区域差异的最强决定因素,而神经胶质中的蛋白质表达对于区域内层状差异更为重要。在具体结果中,我们观察到A17的神经胶质细胞与神经元的比率低于A46,而泛神经元标记HuD和NeuN在两个大脑区域中的差异分布,与A46和其他A17层相比,A17的第4层和第5层的NeuN强度较低。星形胶质细胞和少突胶质细胞表现出不同的标记特异性层状分布,这些层状分布在区域之间不同;值得注意的是,在A17的第4层中,表达ALDH1L1的星形胶质细胞和少突胶质细胞标志物的比例很高。这里观察到的层和区域之间蛋白质表达的许多细微差别突出了直接评估蛋白质的必要性。除了RNA表达,并为未来在正常和病理条件下对这些和其他大脑区域进行以蛋白质为重点的研究奠定了基础。
    In this novel large-scale multiplexed immunofluorescence study we comprehensively characterized and compared layer-specific proteomic features within regions of interest of the widely divergent dorsolateral prefrontal cortex (A46) and primary visual cortex (A17) of adult rhesus monkeys. Twenty-eight markers were imaged in rounds of sequential staining, and their spatial distribution precisely quantified within gray matter layers and superficial white matter. Cells were classified as neurons, astrocytes, oligodendrocytes, microglia, or endothelial cells. The distribution of fibers and blood vessels were assessed by quantification of staining intensity across regions of interest. This method revealed multivariate similarities and differences between layers and areas. Protein expression in neurons was the strongest determinant of both laminar and regional differences, whereas protein expression in glia was more important for intra-areal laminar distinctions. Among specific results, we observed a lower glia-to-neuron ratio in A17 than in A46 and the pan-neuronal markers HuD and NeuN were differentially distributed in both brain areas with a lower intensity of NeuN in layers 4 and 5 of A17 compared to A46 and other A17 layers. Astrocytes and oligodendrocytes exhibited distinct marker-specific laminar distributions that differed between regions; notably, there was a high proportion of ALDH1L1-expressing astrocytes and of oligodendrocyte markers in layer 4 of A17. The many nuanced differences in protein expression between layers and regions observed here highlight the need for direct assessment of proteins, in addition to RNA expression, and set the stage for future protein-focused studies of these and other brain regions in normal and pathological conditions.
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  • 文章类型: Journal Article
    小(30-150nm)细胞外囊泡(sEV),也被称为外泌体,在细胞间信号转导中起关键作用。它们是由所有细胞产生的,自由循环并存在于所有体液中。证据表明细胞因子存在于sEV的表面和/或内腔中。囊内细胞因子对血浆中细胞因子水平的贡献是未知的。
    sEV通过超滤/尺寸排阻色谱法从头颈部鳞状细胞癌(HNSCC)患者和健康供体(HD)获得的预清除血浆中分离出来。多重免疫测定用于测量配对的未处理和去污剂处理的(0.5%TritonX-100)血浆和血浆衍生的去污剂处理的sEV中的细胞因子水平。非参数检验用于评估细胞因子水平的差异。
    通过免疫印迹和珠上流式细胞术确认从患者血浆中分离的sEV中存在细胞因子。sEV相关的细胞因子在各种体外测定中是有功能的。sEV中的细胞因子水平在HNSCC患者中有所不同,并且通常显着高于在HDs的sEV中观察到的水平。与未经处理的血浆相比,在去污剂处理的血浆中,大多数(40/51)被评估蛋白的水平显著较高(P<0.0001-0.03).此外,sEV中24/51蛋白质的水平,包括IL6,TNFRII,IL-17a,IFNa和IFNg,与去污剂处理的血浆和未处理的血浆中检测到的水平之间的差异显着正相关。
    数据表明sEV相关的细胞因子解释了在洗涤剂处理的血浆与未处理的血浆中测量的细胞因子水平的差异。使用未处理的血浆的基于Ab的测定仅检测sEV内腔中携带的可溶性细胞因子和缺失细胞因子。用温和的去污剂渗透sEV允许基于Ab检测血浆中的sEV相关和可溶性细胞因子。未能检测sEV管腔中携带的细胞因子导致体液中细胞因子水平的不准确估计。
    UNASSIGNED: Small (30-150nm) extracellular vesicles (sEV), also known as exosomes, play a key role in cell-to-cell signaling. They are produced by all cells, circulate freely and are present in all body fluids. Evidence indicates that cytokines are present on the surface and/or in the lumen of sEV. The contribution of intravesicular cytokines to cytokine levels in plasma are unknown.
    UNASSIGNED: sEV were isolated by ultrafiltration/size exclusion chromatography from pre-cleared plasma obtained from patients with head and neck squamous cell carcinoma (HNSCC) and healthy donors (HDs). Multiplex immunoassays were used to measure cytokine levels in paired untreated and detergent-treated (0.5% Triton X-100) plasma and plasma-derived detergent-treated sEV. Non-parametric tests were used to assess differences in cytokine levels.
    UNASSIGNED: The presence of cytokines in sEV isolated from patients\' and HDs\' plasma was confirmed by immunoblots and on-bead flow cytometry. sEV-associated cytokines were functional in various in vitro assays. Levels of cytokines in sEV varied among the HNSCC patients and were generally significantly higher than the levels observed in sEV from HDs. Compared to untreated plasma, levels for the majority (40/51) of the evaluated proteins were significantly higher in detergent-treated plasma (P<0.0001-0.03). In addition, levels of 24/51 proteins in sEV, including IL6, TNFRII, IL-17a, IFNa and IFNg, were significantly positively correlated with the difference between levels detected in detergent-treated plasma and untreated plasma.
    UNASSIGNED: The data indicate that sEV-associated cytokines account for the differences in cytokine levels measured in detergent-treated versus untreated plasma. Ab-based assays using untreated plasma detect only soluble cytokines and miss cytokines carried in the lumen of sEV. Permeabilization of sEV with a mild detergent allows for Ab-based detection of sEV-associated and soluble cytokines in plasma. The failure to detect cytokines carried in the sEV lumen leads to inaccurate estimates of cytokine levels in body fluids.
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  • 文章类型: Journal Article
    免疫抑制个体,如艾滋病毒携带者(PLWH),仍然容易受到严重COVID-19的影响。我们分析了特异性SARS-CoV-2体液和细胞免疫反应的持续性,PLWH抗逆转录病毒治疗的横断面研究。在104名参与者中,70.2%有抗SIgG抗体,在替代病毒中和测试中,55.8%对Omicron变体具有显着的中和活性。只有38.5%的人接种了疫苗(前8.76±4.1个月),所有显示抗SIgG,75%与中和抗体和抗SIgA。总的来说,29.8%的PLWH没有SARS-CoV-2血清学标志物;它们显示出显着降低的CD4计数和更高的HIV病毒载量。严重的免疫抑制(出现在12.5%的参与者中)与较低水平的可检测的抗SIgG有关(p=0.0003),抗SIgA(p<0.0001)和缺乏针对Omicron变体的中和活性(p<0.0001)。86.7%的测试参与者存在T细胞反应,即使是那些缺乏血清学标记的人。在没有严重免疫抑制的PLWH中,中和抗体和T细胞应答在感染或接种疫苗后持续长达9个月.晚期免疫抑制导致体液免疫反应减弱,但保留了特异性细胞免疫。
    Immunosuppressed individuals, such as people living with HIV (PLWH), remain vulnerable to severe COVID-19. We analyzed the persistence of specific SARS-CoV-2 humoral and cellular immune responses in a retrospective, cross-sectional study in PLWH on antiretroviral therapy. Among 104 participants, 70.2% had anti-S IgG antibodies, and 55.8% had significant neutralizing activity against the Omicron variant in a surrogate virus neutralization test. Only 38.5% were vaccinated (8.76 ± 4.1 months prior), all displaying anti-S IgG, 75% with neutralizing antibodies and anti-S IgA. Overall, 29.8% of PLWH had no SARS-CoV-2 serologic markers; they displayed significantly lower CD4 counts and higher HIV viral load. Severe immunosuppression (present in 12.5% of participants) was linked to lower levels of detectable anti-S IgG (p = 0.0003), anti-S IgA (p < 0.0001) and lack of neutralizing activity against the Omicron variant (p < 0.0001). T-cell responses were present in 86.7% of tested participants, even in those lacking serological markers. In PLWH without severe immunosuppression, neutralizing antibodies and T-cell responses persisted for up to 9 months post-infection or vaccination. Advanced immunosuppression led to diminished humoral immune responses but retained specific cellular immunity.
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  • 文章类型: Journal Article
    这项研究涉及壳聚糖纳米颗粒的合成和表征负载有诺比林(CNpN),并评估其毒性和细胞内化在真核细胞模型(酿酒酵母和白色念珠菌)。通过纳米沉淀法制备纳米颗粒,并进行物理化学表征,以使用动态光散射(DLS)确定其流体动力学直径,通过ζ电位测量它们的表面电荷,通过傅里叶变换红外光谱(FTIR)及其化学结构。发现壳聚糖纳米颗粒(CNp)和CNpN的流体动力学直径和ζ电位为288.74±2.37nm和596.60±35.49nm,34.51±0.66mV和37.73±0.19mV,分别。扫描电子显微镜(SEM)图像显示约346±69nm的粒径,CNpN具有显著的球形度。FTIR分析提供了壳聚糖与川陈皮素之间潜在的亚胺键合的证据。在用碘化丙锭染色的酿酒酵母和白色念珠菌酵母中均可观察到膜完整性损伤,证明由CNp和CNpN引起的膜完整性损伤,高浓度处理抑制了酵母细胞的发育。这些发现表明CNpN的选择性治疗潜力,这对于开发抗真菌和抗癌疗法可能是有希望的。这项研究有助于理解纳米粒子与真核细胞之间的相互作用,为未来的生物医学应用提供见解。
    This study involved the synthesis and characterization of chitosan nanoparticles loaded with nobiletin (CNpN) and assessed their toxicity and cellular internalization in eukaryotic cell models (Saccharomyces cerevisiae and Candida albicans). Nanoparticles were prepared via the nanoprecipitation method and physicochemically characterized to determine their hydrodynamic diameter using dynamic light scattering (DLS), their surface charge through ζ-potential measurements, and their chemical structure via Fourier-transform infrared spectroscopy (FTIR). The hydrodynamic diameter and ζ-potential of chitosan nanoparticles (CNp) and CNpN were found to be 288.74 ± 2.37 nm and 596.60 ± 35.49 nm, and 34.51 ± 0.66 mV and 37.73 ± 0.19 mV, respectively. The scanning electron microscopy (SEM) images displayed a particle size of approximately 346 ± 69 nm, with notable sphericity for CNpN. FTIR analysis provided evidence of potential imine bonding between chitosan and nobiletin. Membrane integrity damage could be observed in both S. cerevisiae and C. albicans yeast stained with propidium iodide, demonstrating membrane integrity damage caused by CNp and CNpN, where higher concentration treatments inhibited the development of yeast cells. These findings suggest a selective therapeutic potential of CNpN, which could be promising for the development of antifungal and anticancer therapies. This study contributes to understanding the interaction between nanoparticles and eukaryotic cells, offering insights for future biomedical applications.
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