Cell Membrane Permeability

细胞膜通透性
  • 文章类型: Journal Article
    多重耐药细菌的出现被认为是影响全世界人类的全球危机。由于常规抗生素的局限性,迫切需要新的抗感染策略。然而,临床需求和抗菌治疗创新之间的差距越来越大,以及膜通透性障碍,尤其是革兰氏阴性菌,可怕地限制了抗菌策略的改革。金属有机框架(MOFs)具有可调孔径的优点,高载药率,可剪裁的结构,和优越的生物相容性,使其能够在生物治疗应用中用作药物递送载体。此外,MOFs中的金属元素通常具有杀菌性。本文对最先进的设计进行了回顾,基于MOF和MOF的载药材料的潜在抗菌机制和抗菌应用。此外,并讨论了MOF和MOF基载药材料存在的问题和未来的前景。
    The emergence of multidrug-resistant bacteria has been deemed a global crisis that affects humans worldwide. Novel anti-infection strategies are desperately needed because of the limitations of conventional antibiotics. However, the increasing gap between clinical demand and antimicrobial treatment innovation, as well as the membrane permeability obstacle especially in gram-negative bacteria fearfully restrict the reformation of antibacterial strategy. Metal-organic frameworks (MOFs) have the advantages of adjustable apertures, high drug-loading rates, tailorable structures, and superior biocompatibilities, enabling their utilization as drug delivery carriers in biotherapy applications. Additionally, the metal elements in MOFs are usually bactericidal. This article provides a review of the state-of-The-art design, the underlying antibacterial mechanisms and antibacterial applications of MOF- and MOF-based drug-loading materials. In addition, the existing problems and future perspectives of MOF- and MOF-based drug-loading materials are also discussed.
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  • 文章类型: Journal Article
    肽-寡核苷酸缀合物(POCs)代表了增加细胞摄取的日益成功但昂贵的方法之一。组织输送,生物利用度,and,因此,治疗性核酸的整体效率,例如,反义寡核苷酸和小干扰RNA。这篇综述将POCs的化学合成主题置于治疗性寡核苷酸和核酸药物递送问题的更广泛背景下,细胞穿透肽结构类型,它们的细胞内运输机制,以及应用的方式,这包括与寡核苷酸(肽添加剂)或共价缀合形成非共价复合物。详细介绍了POCs合成的主要策略,在概念上分为(a)逐步固相合成方法和(b)在溶液中或固相上的合成后共轭,特别是通过各种点击化学。讨论并比较了两种策略的相对优缺点。
    Peptide-oligonucleotide conjugates (POCs) represent one of the increasingly successful albeit costly approaches to increasing the cellular uptake, tissue delivery, bioavailability, and, thus, overall efficiency of therapeutic nucleic acids, such as, antisense oligonucleotides and small interfering RNAs. This review puts the subject of chemical synthesis of POCs into the wider context of therapeutic oligonucleotides and the problem of nucleic acid drug delivery, cell-penetrating peptide structural types, the mechanisms of their intracellular transport, and the ways of application, which include the formation of non-covalent complexes with oligonucleotides (peptide additives) or covalent conjugation. The main strategies for the synthesis of POCs are viewed in detail, which are conceptually divided into (a) the stepwise solid-phase synthesis approach and (b) post-synthetic conjugation either in solution or on the solid phase, especially by means of various click chemistries. The relative advantages and disadvantages of both strategies are discussed and compared.
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  • 文章类型: Journal Article
    The number of sources of anthropogenic magnetic and electromagnetic fields generated by various underwater facilities, industrial equipment, and transferring devices in aquatic environment is increasing. These have an effect on an array of fish life processes, but especially the early developmental stages. The magnitude of these effects depends on field strength and time of exposure and is species-specific. We review studies on the effect of magnetic fields on the course of embryogenesis, with special reference to survival, the size of the embryos, embryonic motor function, changes in pigment cells, respiration hatching, and directional reactions. We also describe the effect of magnetic fields on sperm motility and egg activation. Magnetic fields can exert positive effects, as in the case of the considerable extension of sperm capability of activation, or have a negative influence in the form of a disturbance in heart rate or developmental instability in inner ear organs.
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  • 文章类型: Journal Article
    由于升高的温度变化增强,被确定为组成型合成的分子伴侣,这种热休克蛋白HSP70已被证明与许多蛋白质生物发生密切相关,在细胞生长过程中促进蛋白质的合成和折叠以及新生肽的运输。HSP70在蛋白质组装中也起着至关重要的作用,与多种蛋白质的调节和相互作用。应激诱导的细胞死亡受凋亡调节剂Bcl-2家族的控制,并表现出促凋亡或抗凋亡活性。受到热冲击等应力条件的影响,据报道,细胞表达HSP70的表达升高。此外,这种分子伴侣已显示出在多个水平上通过修复抑制一些Bcl-2成员的应激诱导的凋亡信号,重新合成受损的蛋白质,和稳定未折叠的蛋白质。因此,HSP70合成可以作为致死条件下细胞存活和适应的必需恢复模式。
    Identified as a molecular chaperone constitutively being synthesized due to enhanced elevated temperature change, this heat shock protein HSP70 has shown to be intimately involved in many protein biogenesis, facilitating the synthesis and folding of proteins and trafficking of nascent peptides during cell growth. HSP70 also plays a vital role in protein assembly, regulation and interaction with a wide variety of proteins. Stress-induced cell death is under the control of the Bcl-2 family of apoptotic regulators and display either pro-apoptotic or anti-apoptotic activities. Subjected to stress conditions such as heat shock, cells have been reported to express elevated expressions of HSP70. Moreover, this molecular chaperon has shown to act at multiple levels to suppress stressed-induced apoptotic signals of some Bcl-2 members by repairing, re-synthesizing damaged proteins, and stabilizing unfolded proteins. Therefore, HSP70 synthesis can act as an essential recovery mode for cellular survival and adaptation during lethal conditions.
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  • 文章类型: Journal Article
    Many studies have revealed that transmembrane mucins, large glycoproteins with heavily glycosylated glycans, are essential for maintaining ocular surface epithelium lubrication and wettability. Recent reports indicate that transmembrane mucins and galectin-3, a chimera type of galectin that binds β-galactoside in the glycan, play a crucial role in maintaining the epithelial glycocalyx barrier. This review summarizes current evidence regarding the role of galectin-3, the role of the three major transmembrane mucins (i.e., MUC1, MUC4, and MUC16), in the maintenance of ocular surface wettability and transcellular barrier. Pathological mechanisms of glycocalyx barrier disruption and epithelial surface wettability decreases in dry eye disease are also summarized. Lastly, new ophthalmic drugs that target transmembrane mucin are described.
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  • 文章类型: Journal Article
    电穿孔是众所周知的现象,当细胞暴露于高强度电脉冲时,会发生在细胞膜上。根据电脉冲幅度和脉冲数,应用的电穿孔可以是可逆的,膜通透性恢复或不可逆。可逆电穿孔用于将药物或遗传物质引入细胞而不影响细胞活力。电化学疗法是指联合治疗:电穿孔和药物注射以增强博来霉素的细胞毒性作用高达1000倍。几年来,电化学疗法作为微创肿瘤治疗越来越受欢迎。在介入肿瘤学中采用电化学疗法提出了几个未解决的问题,由于合适的肿瘤组织学和大小以及治疗效果仍需加深。电化学疗法通常用于姑息性治疗,用于治疗不可切除的肿瘤患者,以减轻疼痛并改善生活质量。在大多数情况下,当无法进行根治性手术治疗时,它可用于治疗晚期肿瘤(例如,由于病变位置,尺寸,和/或数字)。Further,电化学疗法允许在血管和神经等重要结构附近治疗肿瘤结节,因为治疗不涉及组织加热。总的来说,电化学疗法的安全性是有利的。大多数观察到的不良事件是局部和短暂的,中度局部疼痛,红斑,水肿,和电穿孔时的肌肉收缩。本文的目的是回顾最近发表的在深层肿瘤中使用电化学疗法的临床经验,尤其是肝脏病例。简要介绍了电化学疗法的原理以及在皮肤转移中的应用。对骨转移治疗的简短见解,无法切除的胰腺癌,并给予软组织肉瘤。讨论了电化疗对肝脏病变的治疗效果以及所采用方法的安全性的临床前和临床研究。
    Electroporation is a well-known phenomenon that occurs at the cell membrane when cells are exposed to high-intensity electric pulses. Depending on electric pulse amplitude and number of pulses, applied electroporation can be reversible with membrane permeability recovery or irreversible. Reversible electroporation is used to introduce drugs or genetic material into the cell without affecting cell viability. Electrochemotherapy refers to a combined treatment: electroporation and drug injection to enhance its cytotoxic effect up to 1000-fold for bleomycin. Since several years, electrochemotherapy is gaining popularity as minimally invasive oncologic treatment. The adoption of electrochemotherapy procedure in interventional oncology poses several unsolved questions, since suitable tumor histology and size as well as therapeutic efficacy still needs to be deepen. Electrochemotherapy is usually applied in palliative settings for the treatment of patients with unresectable tumors to relieve pain and ameliorate quality of life. In most cases, it is used in the treatment of advanced stages of neoplasia when radical surgical treatment is not possible (eg, due to lesion location, size, and/or number). Further, electrochemotherapy allows treating tumor nodules in the proximity of important structures like vessels and nerves as the treatment does not involve tissue heating. Overall, the safety profile of electrochemotherapy is favorable. Most of the observed adverse events are local and transient, moderate local pain, erythema, edema, and muscle contractions during electroporation. The aim of this article is to review the recent published clinical experiences of electrochemotherapy use in deep-seated tumors with particular focus on liver cases. The principle of electrochemotherapy as well as the application to cutaneous metastases is briefly described. A short insight in the treatment of bone metastases, unresectable pancreas cancer, and soft tissue sarcoma will be given. Preclinical and clinical studies on treatment efficacy with electrochemotherapy of hepatic lesions and safety of the procedure adopted are discussed.
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  • 文章类型: Journal Article
    The discovery of highly active antiretroviral therapy (HAART) in 1996 has significantly reduced the global mortality and morbidity caused by the acquired immunodeficiency syndrome (AIDS). However, the therapeutic strategy of HAART that targets multiple viral proteins may render off-target toxicity and more importantly results in drug-resistant escape mutants. These have been the main challenges for HAART and refinement of this therapeutic strategy is urgently needed. Antibody-mediated treatments are emerging therapeutic modalities for various diseases. Most therapeutic antibodies have been approved by Food and Drug Administration (FDA) mainly for targeting cancers. Previous studies have also demonstrated the promising effect of therapeutic antibodies against HIV-1, but there are several limitations in this therapy, particularly when the viral targets are intracellular proteins. The conventional antibodies do not cross the cell membrane, hence, the pathogenic intracellular proteins cannot be targeted with this classical therapeutic approach. Over the years, the advancement of antibody engineering has permitted the therapeutic antibodies to comprehensively target both extra- and intra-cellular proteins in various infections and diseases. This review aims to update on the current progress in the development of antibody-based treatment against intracellular targets in HIV-1 infection. We also attempt to highlight the challenges and limitations in the development of antibody-based therapeutic modalities against HIV-1.
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  • 文章类型: Journal Article
    中耳炎(OM)是指中耳(ME)的炎症性疾病,不论病因或病理机制。在评估OM病理学的分子生物学研究中,有研究水通道蛋白(AQP)在ME和咽鼓管(ET)中的表达。迄今为止,15项研究评估了AQPs在ME和ET中的表达。尽管各个AQPs的表达因物种和模型而异,11种AQP,发现AQP1至AQP11在哺乳动物ME和ET中表达。综述显示:(1)不同类型的AQPs在ME和ET中表达;(2)AQP的表达可能因物种而异;(3)AQPs的分布和表达水平可能取决于炎症的存在与否。即使在同一物种和同一组织中也存在差异。ME和ET中的液体积聚是所有类型OM的共同病理机制,引起组织水肿和炎症,因此可能涉及各种AQP。几种AQP的表达模式,特别是AQP1,4和5,被发现在响应炎症刺激时发生改变,包括脂多糖(LPS),表明AQPs在OM中可能具有免疫功能。
    Otitis media (OM) refers to inflammatory diseases of the middle ear (ME), regardless of cause or pathological mechanism. Among the molecular biological studies assessing the pathology of OM are investigations of the expression of aquaporins (AQPs) in the ME and Eustachian tube (ET). To date, fifteen studies have evaluated AQPs expression in the ME and ET. Although the expression of individual AQPs varies by species and model, eleven types of AQP, AQP1 to AQP11, were found to be expressed in mammalian ME and ET. The review showed that: (1) various types of AQPs are expressed in the ME and ET; (2) AQP expression may vary by species; and (3) the distribution and levels of expression of AQPs may depend on the presence or absence of inflammation, with variations even in the same species and same tissue. Fluid accumulation in the ME and ET is a common pathological mechanism for all types of OM, causing edema in the tissue and inducing inflammation, thereby possibly involving various AQPs. The expression patterns of several AQPs, especially AQP1, 4 and 5, were found to be altered in response to inflammatory stimuli, including lipopolysaccharide (LPS), suggesting that AQPs may have immunological functions in OM.
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  • 文章类型: Journal Article
    Biosurfactant rhmnolipids have been applied in many fields, especially in environmental bioremediation. According to previous researches, many research groups have studied the influence of rhamnolipids on microorganism characteristics and/or its application in composting. In this review, the effects of rhamnolipids on the cell surface properties of microorganisms was discussed firstly, such as cell surface hydrophobicity (CSH), electrical, surface compounds, etc. Moreover, the deeper mechanisms were also discussed, such as the effects of rhamnolipids on the structural characteristics and functional characteristics of the cell membrane, and the effects of rhamnolipids on the related enzymes and genes. Additionally, the application of rhamnolipids in composting was discussed, which is an important way for pollutant biodegradation and resource reutilization. It is believed that rhamnolipids will play more and more important role in composting.
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  • 文章类型: Journal Article
    搜索了五个医学数据库,以进行评估ERβ在女性心血管系统中的作用以及年龄和绝经对ERβ功能的影响的研究。在9472个参考文献中,88项研究符合我们的纳入标准(71项动物模型实验研究,15项人体模型实验研究和2项基于人群的研究)。通过调节一氧化氮的活性,显示ERβ信号具有血管扩张剂和抗血管生成特性,改变血管平滑肌细胞的膜离子通透性,抑制血管平滑肌细胞迁移和增殖,并通过调节动脉的肾上腺素能控制。此外,27项研究提示ERβ信号传导通过基因组和非基因组途径对左心室肥厚和缺血/再灌注损伤的可能保护作用.此外,5项研究报道,ERβ的血管效应可能是血管特异性的,并且可能因年龄和绝经状态而异。ERβ似乎在女性心血管系统中具有多种功能。需要进一步的研究来评估同工型选择性ERβ配体是否可能有助于心血管疾病的预防。
    Five medical databases were searched for studies that assessed the role of ERβ in the female cardiovascular system and the influence of age and menopause on ERβ functioning. Of 9472 references, 88 studies met our inclusion criteria (71 animal model experimental studies, 15 human model experimental studies and 2 population based studies). ERβ signaling was shown to possess vasodilator and antiangiogenic properties by regulating the activity of nitric oxide, altering membrane ionic permeability in vascular smooth muscle cells, inhibiting vascular smooth muscle cell migration and proliferation and by regulating adrenergic control of the arteries. Also, a possible protective effect of ERβ signaling against left ventricular hypertrophy and ischemia/reperfusion injury via genomic and non-genomic pathways was suggested in 27 studies. Moreover, 5 studies reported that the vascular effects of ERβ may be vessel specific and may differ by age and menopause status. ERβ seems to possess multiple functions in the female cardiovascular system. Further studies are needed to evaluate whether isoform-selective ERβ-ligands might contribute to cardiovascular disease prevention.
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