barrier function

屏障功能
  • 文章类型: Journal Article
    OBJECTIVE: While there are a wide range of approaches for the assessment of skin hydration, it is not always clear how data from them relate to one another or to the skin itself. With the development of in vivo Confocal Raman Spectroscopy (ICRS), it has become possible to measure water concentration as a function of protein/depth within the stratum corneum (SC). This article reports a comparison between electrical skin hydration measures/visual/optical grading and water concentration profiles measured using ICRS, to better understand the relationship between these approaches.
    METHODS: SC hydration of lower-leg skin with varying degrees of dryness was assessed using visual grading (live and from digital images), Corneometer®, Visioscan and ICRS. In addition, a custom fingerprint sensor was used to image surface capacitance (as a surrogate of SC hydration), and SC barrier function was assessed using evaporimetry (to measure trans-epidermal water loss; TEWL).
    RESULTS: Significant correlations were observed between a number of different skin grading/measurement approaches and ICRS data. ICRS hydration profiles also revealed a region near the SC surface with a relatively flat water profile in dry skin subjects.
    CONCLUSIONS: The advent of quantitative in vivo analytical techniques such as ICRS, which can be used in a clinical setting, has enabled greater insight into more conventional approaches for assessing skin dryness. While traditional skin grading and biophysical methods for measuring skin hydration have varying degrees of correlation with one another, they also provide comparatively unique information about different regions within the SC. This should enable a more informed approach to product development in the future.
    OBJECTIVE: Bien qu’il existe un large éventail d’approches pour évaluer l’hydratation de la peau, la façon dont les données qui en résultent sont liées les unes aux autres ou à la peau elle‐même n’est pas toujours claire. Avec le développement de la spectroscopie Raman confocale in vivo (ICRS), il est devenu possible de mesurer la concentration en eau en fonction du rapport protéine/profondeur au sein de la couche cornée (stratum corneum, SC). Cet article rapporte une comparaison entre les mesures électriques ou la classification visuelle/optique de l’hydratation de la peau et les profils de concentration en eau mesurés à l’aide de l’ICRS, afin de mieux comprendre la relation entre ces approches. MÉTHODES: L’hydratation du SC de la peau de la partie inférieure de la jambe avec différents degrés de sécheresse a été évaluée à l’aide d’une classification visuelle (en direct et à partir d’images numériques), du Corneometer®, du Visioscan et de l’ICRS. En outre, un capteur d’empreintes digitales personnalisé a été utilisé pour visualiser la capacité de surface (en tant que substitut de l’hydratation du SC) et la fonction de barrière du SC a été évaluée par évaporimétrie (pour mesurer la perte d’eau transépidermique ; trans‐epidermal water loss, TEWL). RÉSULTATS: Des corrélations significatives ont été observées entre un certain nombre d’approches différentes de classification/mesure de la peau et les données ICRS. Les profils d’hydratation de l’ICRS ont également révélé une région près de la surface du SC ayant un profil d’eau relativement plat chez les sujets atteints de sécheresse cutanée.
    CONCLUSIONS: L’avènement de techniques d’analyse in vivo quantitatives telles que l’ICRS, qui peut être utilisée dans un contexte clinique, a permis de mieux comprendre les approches plus conventionnelles d’évaluation de la sécheresse cutanée. Bien que les méthodes traditionnelles de classification de la peau et les méthodes biophysiques de mesure de l’hydratation de la peau présentent des degrés de corrélation variables entre elles, elles fournissent également des informations comparativement uniques sur différentes régions au sein du SC. Cela devrait permettre une approche plus éclairée du développement de produits à l’avenir.
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  • 文章类型: Journal Article
    The term natural oil refers to a fixed (non-volatile) oil of animal or plant origin. These types of oils - in contrast to essential (volatile) oils, which are obtained by steam distillation methods of plant matter - are typically obtained from plant seeds and nuts by a mechanical pressing technique or solvent extraction. The natural movement in cosmetics of the 21st century has led to renewed interest in formulating skin care products with botanical ingredients. In this article, we discuss the benefits and caveats of natural oil treatments as moisturizing agents (as occlusives and emollients) as well as their utility in wound healing and treatment of skin diseases. We also address the paradoxical behaviour of natural oils in relation to barrier function and highlight the current state of our knowledge with respect to the use of natural oils in neonatal skin care. Finally, we provide a comparison of natural oils to conventional petroleum-based oils.
    Le terme huile naturelle fait référence à une huile fixe (non volatile) d\'origine animale ou végétale. Ces types d\'huiles, contrairement aux huiles essentielles (volatiles) qui sont obtenues par des méthodes de distillation à la vapeur de matières végétales, sont généralement obtenues à partir de graines et de noix de plantes par une technique de pressage mécanique ou d\'extraction par solvant. Le mouvement naturel des cosmétiques du XXI siècle a suscité un regain d\'intérêt pour la formulation de produits de soins pour la peau à base d\'ingrédients botaniques. Dans cet article, nous examinons les avantages et les mises en garde des traitements à base d\'huiles naturelles en tant qu\'agents hydratants (comme occlusifs et émollients), ainsi que leur utilité dans la cicatrisation des plaies et le traitement des maladies de la peau. Nous abordons également le comportement paradoxal des huiles naturelles par rapport à la fonction barrière et mettons en évidence l\'état actuel de nos connaissances en ce qui concerne l\'utilisation des huiles naturelles dans les soins de la peau néonatale. Enfin, nous comparons les huiles naturelles aux huiles conventionnelles à base de pétrole.
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  • 文章类型: Journal Article
    肠内分泌细胞(EEC)以其全身激素作用而闻名,尤其是在调节食欲和血糖方面。人们对EEC生产的产品如何调节肠道内的局部环境知之甚少。这里,我们专注于EECs与其他肠细胞之间的旁分泌相互作用,因为它们调节肠稳态和生理的三个基本方面:1)肠干细胞功能和增殖;2)营养吸收;和3)粘膜屏障功能。我们还讨论了EEC表达多种激素的能力,描述体外和体内模型以研究EEC,并考虑胃肠道疾病中EECs是如何改变的。
    Enteroendocrine cells (EECs) are well-known for their systemic hormonal effects, especially in the regulation of appetite and glycemia. Much less is known about how the products made by EECs regulate their local environment within the intestine. Here, we focus on paracrine interactions between EECs and other intestinal cells as they regulate three essential aspects of intestinal homeostasis and physiology: 1) intestinal stem cell function and proliferation; 2) nutrient absorption; and 3) mucosal barrier function. We also discuss the ability of EECs to express multiple hormones, describe in vitro and in vivo models to study EECs, and consider how EECs are altered in GI disease.
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  • 文章类型: Journal Article
    缺氧在膀胱出口梗阻的病理过程中起着重要作用。以前的研究主要集中在膀胱平滑肌细胞的功能障碍上,与膀胱收缩直接相关。本研究探讨了缺氧条件下尿路上皮细胞的屏障功能变化。结果表明,经过5天的培养,SV-HUC-1形成单层和/或双层细胞片,紧密连接的形成,但没有观察到不对称的单位膜。qPCR和蛋白质印迹显示了TJ相关蛋白的表达(occludin,低氧组claudin1和ZO-1)以时间依赖性方式显着降低。在尿plaakin中未观察到表达变化。与常氧组相比,免疫荧光染色显示缺氧组TJ相关蛋白的表达减少。跨上皮电阻(TEER)显示缺氧组电阻在统计学上显着降低。异硫氰酸荧光素缀合的葡聚糖测定与TEER的结果成反比。一起来看,缺氧下调TJ相关蛋白的表达并破坏紧密连接,从而损害人尿路上皮细胞的屏障功能。
    Hypoxia plays an important role in the pathological process of bladder outlet obstruction. Previous research has mostly focused on the dysfunction of bladder smooth muscle cells, which are directly related to bladder contraction. This study delves into the barrier function changes of the urothelial cells under exposure to hypoxia. Results indicated that after a 5-day culture, SV-HUC-1 formed a monolayer and/or bilayer of cell sheets, with tight junction formation, but no asymmetrical unit membrane was observed. qPCR and western blotting revealed the expression of TJ-associated proteins (occludin, claudin1 and ZO-1) was significantly decreased in the hypoxia group in a time-dependent manner. No expression changes were observed in uroplakins. When compared to normoxic groups, immunofluorescent staining revealed a reduction in the expression of TJ-associated proteins in the hypoxia group. Transepithelial electrical resistance (TEER) revealed a statistically significant decrease in resistance in the hypoxia group. Fluorescein isothiocyanate-conjugated dextran assay was inversely proportional to the results of TEER. Taken together, hypoxia down-regulates the expression of TJ-associated proteins and breaks tight junctions, thus impairing the barrier function in human urothelial cells.
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  • 文章类型: Journal Article
    胆管癌(CCA),或者胆管癌,是第二常见的肝脏恶性肿瘤,随着西方国家发病率的增加。缺乏与缺乏早期症状相关的有效治疗方法凸显了寻找新的CCA治疗靶标的必要性。硫化物(STs),一种磺基鞘糖脂,在胆道里被发现,CCA和其他类型癌症的水平升高。作为质膜脂筏的一部分,STs参与蛋白质运输和细胞粘附。我们旨在通过GAL3ST1的遗传靶向研究STs在CCA中的作用,GAL3ST1是一种参与ST合成的酶。我们使用CRISPR-Cas9系统来产生GAL3ST1缺陷型TFK1细胞。与TFK1细胞相比,GAL3ST1KO细胞显示出较低的增殖和克隆活性以及降低的糖酵解活性。与TFK1wt细胞相比,极化的TFK1GAL3ST1KO细胞显示出增加的跨上皮阻力和降低的通透性。GAL3ST1的丢失对DepMap数据库中34个胆道癌细胞系中的30个的生长显示出负面影响。GAL3ST1缺乏部分恢复了上皮身份和屏障功能,并降低了CCA细胞的增殖活性。硫肽合成可以为CCA提供新的治疗靶标。
    Cholangiocarcinoma (CCA), or bile duct cancer, is the second most common liver malignancy, with an increasing incidence in Western countries. The lack of effective treatments associated with the absence of early symptoms highlights the need to search for new therapeutic targets for CCA. Sulfatides (STs), a type of sulfoglycosphingolipids, have been found in the biliary tract, with increased levels in CCA and other types of cancer. STs are involved in protein trafficking and cell adhesion as part of the lipid rafts of the plasma membrane. We aimed to study the role of STs in CCA by the genetic targeting of GAL3ST1, an enzyme involved in ST synthesis. We used the CRISPR-Cas9 system to generate GAL3ST1-deficient TFK1 cells. GAL3ST1 KO cells showed lower proliferation and clonogenic activity and reduced glycolytic activity compared to TFK1 cells. Polarized TFK1 GAL3ST1 KO cells displayed increased transepithelial resistance and reduced permeability compared to TFK1 wt cells. The loss of GAL3ST1 showed a negative effect on growth in 30 out of 34 biliary tract cancer cell lines from the DepMap database. GAL3ST1 deficiency partially restored epithelial identity and barrier function and reduced proliferative activity in CCA cells. Sulfatide synthesis may provide a novel therapeutic target for CCA.
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  • 文章类型: Journal Article
    目的:感染后肠易激综合征(PI-IBS)在流行病学上是众所周知的;然而,它的生理和分子特征没有得到很好的研究。我们的目的是确定生理表型,结肠转录组,粪便微生物组,和PI-IBS中的代谢组。
    方法:纳入51例罗马III弯曲杆菌PI-IBS患者和39例健康志愿者(HV)。参与者填写了问卷,体内肠道通透性,胃肠运输,和直肠感觉.收集粪便样本用于鸟枪宏基因组学,非靶向代谢组学,和大量RNAseq的乙状结肠活检。差异基因表达,确定了微生物群组成和代谢物丰度的差异。通过加权基因相关网络分析并确定与临床和生理参数的相关性来鉴定基因和代谢物簇。
    结果:PI-IBS(59%F,46±2年。)和HV(64%F,42±2年。)人口统计数据具有可比性。平均IBS症状严重程度评分为227分;94%为非便秘。PI-IBS中2-24h乳果糖排泄增加,提示结肠通透性增加(4.4±0.5mgvs.2.6±0.3mg,p=0.01)。两组之间的结肠运输和感觉阈值相似。总的来说,2036个粘膜基因和223个粪便代谢物的表达不同,女性的变化更加突出。粪便N-乙酰腐胺在PI-IBS中增加,并与结肠通透性相关,更严重的腹泻,并与Collinsellaaerofaciens的丰度呈负相关。组胺和N-乙酰组胺与2-24小时乳果糖排泄呈正相关。八个加权基因共表达模块与表型显著相关(性别,大便频率,结肠通透性,transit).
    结论:弯曲杆菌PI-IBS患者表现出较高的结肠通透性,这与多胺和组胺代谢物的变化有关。女性患者表现出更大的分子变化。
    OBJECTIVE: Postinfection irritable bowel syndrome (PI-IBS) is well-known epidemiologically; however, its physiological and molecular characteristics are not well studied. We aimed to determine the physiological phenotypes, colonic transcriptome, fecal microbiome, and metabolome in PI-IBS.
    METHODS: Fifty-one Rome III Campylobacter PI-IBS patients and 39 healthy volunteers (HV) were enrolled. Participants completed questionnaires, in vivo intestinal permeability, gastrointestinal transit, and rectal sensation. Fecal samples were collected for shotgun metagenomics, untargeted metabolomics, and sigmoid colonic biopsies for bulk RNAseq. Differential gene expression, differences in microbiota composition, and metabolite abundance were determined. Gene and metabolite clusters were identified via weighted gene correlation network analysis and correlations with clinical and physiological parameters determined.
    RESULTS: PI-IBS (59% female; 46 ± 2 years) and HV (64% female; 42 ± 2 years) demographics were comparable. Mean IBS-symptom severity score was 227; 94% were nonconstipation. Two- to 24-hour lactulose excretion was increased in PI-IBS, suggesting increased colonic permeability (4.4 ± 0.5 mg vs 2.6 ± 0.3 mg; P = .01). Colonic transit and sensory thresholds were similar between the 2 groups. Overall, expression of 2036 mucosal genes and 223 fecal metabolites were different, with changes more prominent in females. Fecal N-acetylputrescine was increased in PI-IBS and associated with colonic permeability, worse diarrhea, and negatively correlated with abundance of Collinsella aerofaciens. Histamine and N-acetylhistamine positively associated with 2- to 24-hour lactulose excretion. Eight weighted gene coexpression modules significantly correlated with phenotypes (sex, stool frequency, colonic permeability, transit).
    CONCLUSIONS: Campylobacter PI-IBS patients demonstrate higher colonic permeability, which associated with changes in polyamine and histamine metabolites. Female patients demonstrated greater molecular changes.
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  • 文章类型: Journal Article
    特应性皮炎的特征是慢性炎症和干燥伴有严重瘙痒。保湿剂和局部抗炎药的联合使用对于缓解特应性皮炎至关重要。我们已经开发了一种含有类固醇的局部抗炎药和含有类肝素的保湿剂,两者都在含有合成假神经酰胺的基于层状结构的制剂中。这里,评估了该组合治疗特应性皮炎的疗效。
    我们纳入了22名轻度至中度特应性皮炎患者,并对他们进行了为期7周的测试制剂治疗,随后是四周的治疗期。
    治疗一周后,患者的临床发现和生活质量显著改善。此外,在第1周和第3周时,皮肤水合作用和经表皮水分流失显着改善,分别。Cer[NP]/[NS]比率,表皮周转的指标,在治疗期间大幅增加,此后仍保持升高。角质层功能的改善在屏障功能较低的参与者中是独特的。
    这些研究结果表明,抗炎药和保湿剂的联合使用,都是基于层状结构的配方,对屏障功能脆弱的特应性皮炎患者有效。
    UNASSIGNED: Atopic dermatitis is characterized by chronic inflammation and dryness accompanied by severe itching. The combined use of moisturizers and topical anti-inflammatory drugs is essential for alleviating atopic dermatitis. We have developed a topical anti-inflammatory drug with a steroid and a moisturizer with heparinoid, both in lamellar structure-based formulations containing synthetic pseudo-ceramides. Here, assessed the efficacy of this combination in the treatment of atopic dermatitis.
    UNASSIGNED: We included 22 patients with mild to moderate atopic dermatitis and subjected them to a seven-week treatment with the test formulations, followed by a four-week post-treatment period.
    UNASSIGNED: Clinical findings and the quality of life of participants remarkably improved after one week of treatment. Furthermore, skin hydration and transepidermal water loss considerably improved at weeks one and three, respectively. The Cer [NP]/[NS] ratio, an indicator of epidermal turnover, substantially increased during the treatment period and remained elevated even thereafter. The improvement in stratum corneum function was distinctive in participants with lower barrier function.
    UNASSIGNED: These findings indicated that the combined use of the anti-inflammatory drug and moisturizer, both in lamellar structure-based formulations, is effective in treating atopic dermatitis in patients with fragile barrier function.
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  • 文章类型: Journal Article
    机械力通过影响内皮细胞的行为和功能在调节血管稳态方面具有重要意义。粘附连接是内皮细胞中机械转导的关键位点。β-连环蛋白,粘附连接的一个组成部分和典型的Wnt信号通路,在机械激活中起作用。有证据表明,β-catenin参与流量传感并响应张力,影响接头动力学。β-连环蛋白信号的机械调节是上下文相关的,受机械载荷的类型和持续时间的影响。在内皮细胞中,β-连环蛋白的核易位和信号传导受剪切应力和应变的影响,影响内皮通透性。这项研究调查了剪切应力,应变,和表面形貌影响粘附体连接动力学,调节β-连环蛋白定位,并影响内皮屏障特性。观察箱机械负荷通过未完全阐明的机制是内皮功能的有效调节剂。表面形貌,壁剪切应力和循环壁变形有助于重叠的机械刺激,内皮单层响应以适应和维持屏障功能。定制开发的流动室和生物反应器的使用允许量化成熟的人内皮对明确定义的壁剪切应力和应变梯度的响应。这里,底物形貌对β-连环蛋白的机械调节,墙体剪应力,分析和循环拉伸,并将其与内皮通透性的单层控制联系起来。
    Mechanical forces are of major importance in regulating vascular homeostasis by influencing endothelial cell behavior and functions. Adherens junctions are critical sites for mechanotransduction in endothelial cells. β-catenin, a component of adherens junctions and the canonical Wnt signaling pathway, plays a role in mechanoactivation. Evidence suggests that β-catenin is involved in flow sensing and responds to tensional forces, impacting junction dynamics. The mechanoregulation of β-catenin signaling is context-dependent, influenced by the type and duration of mechanical loads. In endothelial cells, β-catenin\'s nuclear translocation and signaling are influenced by shear stress and strain, affecting endothelial permeability. The study investigates how shear stress, strain, and surface topography impact adherens junction dynamics, regulate β-catenin localization, and influence endothelial barrier properties. Insight box Mechanical loads are potent regulators of endothelial functions through not completely elucidated mechanisms. Surface topography, wall shear stress and cyclic wall deformation contribute overlapping mechanical stimuli to which endothelial monolayer respond to adapt and maintain barrier functions. The use of custom developed flow chamber and bioreactor allows quantifying the response of mature human endothelial to well-defined wall shear stress and gradients of strain. Here, the mechanoregulation of β-catenin by substrate topography, wall shear stress, and cyclic stretch is analyzed and linked to the monolayer control of endothelial permeability.
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  • 文章类型: Journal Article
    背景:全球面膜市场以每年8.5%的速度稳步增长。然而,长期使用可能导致皮肤炎症。
    目的:研究不同类型的面罩和佩戴时间如何影响健康受试者的皮肤生理学和水通道蛋白3(AQP3)表达。
    方法:我们使用随机对照设计来研究三种类型的面膜(纯净水,透明质酸,和双裂发酵裂解物)和四种不同的持续时间(5、15、25和40分钟)对志愿者的各种皮肤参数,评估水分含量,经皮水分流失(TEWL),皮脂,角质细胞大小,和AQP3表达之前和之后的掩模应用,在评估不良反应的同时,不适,和不遵守。
    结果:首先水化和TEWL增加,然后减少。所有类型的口罩都会增加皮脂,特别是在40分钟后。血管舒张和AQP3表达与掩蔽持续时间相关。角膜细胞大小保持恒定。主要不良反应为红肿(10.71%,n=28)和干燥度(57.14%,n=28),尤其是使用超过25分钟的纯净水口罩。
    结论:短期使用面膜(<25分钟)可改善皮肤的水合作用,减少发红,和AQP3激活,而长时间使用会导致干燥和发红增加。
    BACKGROUND: The global facial mask market grows steadily at 8.5 % annually. However, prolonged use may lead to skin inflammation.
    OBJECTIVE: To investigate how various mask types and wearing durations impact skin physiology and aquaporins3 (AQP3) expression in healthy subjects.
    METHODS: We used a randomized controlled design to investigate the effects of three types of facial masks (pure water, hyaluronan, and bifida ferment lysate) and four different duration(5, 15, 25, and 40 min) on various skin parameters in volunteers, assessing moisture content, transepidermal water loss (TEWL), sebum, corneocyte size, and AQP3 expression before and after mask application, while also evaluating adverse reactions, discomfort, and noncompliance.
    RESULTS: Hydration and TEWL increased at first, then decreased. Sebum increased with all types of masks, particularly after 40 min. Vasodilation and AQP3 expression were linked to mask duration. Corneocyte sizes remained constant. The main adverse reactions were redness (10.71 %, n = 28) and dryness (57.14 %, n = 28), especially with pure water masks lasting over 25 min.
    CONCLUSIONS: Short-term use of facial sheet masks (<25 min) benefits skin with improved hydration, reduced redness, and AQP3 activation, while prolonged use can lead to increased dryness and redness.
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  • 文章类型: Journal Article
    急性呼吸窘迫综合征(ARDS)是败血症的致命临床表现,COVID,和其他肺部疾病,其中血管液体渗漏是一个严重的问题。Shadab等人在JBC中的最新发现表明,在免疫功能方面,Syk,还调节血管渗漏以应对脓毒症。现有的FDA批准的Syk抑制剂,福司替尼,防止血管渗漏,提高小鼠败血症模型的存活率,为临床ARDS治疗提供了希望。
    Acute respiratory distress syndrome (ARDS) is a deadly clinical presentation in sepsis, COVID, and other lung disorders where vascular fluid leakage is a severe problem. Recent findings by Shadab et al. in the JBC show that a well-known player in immune function, Syk, also regulates vascular leakage in response to sepsis. An existing FDA-approved inhibitor of Syk, fostamatinib, prevents the vascular leakage and improves survival in a mouse sepsis model, providing promise for ARDS treatment in the clinic.
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