gut repair

  • 文章类型: Journal Article
    牛初乳(BC)和鸡蛋含有具有生长因子活性的蛋白质。表皮生长因子(EGF)在BC中提供了许多促修复活性。口服施用的肽生长因子的临床使用受到来自胰腺蛋白酶的消化的阻碍。
    我们使用体外和体内模型检查了添加蛋白酶抑制剂[大豆胰蛋白酶抑制剂(SBTI)或卵类粘蛋白]是否单独保护BC±卵或EGF的生物活性以抵抗胰腺消化。
    BC,鸡蛋,或单独或与胰蛋白酶抑制剂组合的EGF使用人胃腺癌(AGS)细胞测试增殖(Alamar蓝)活性,在用HCl/胃蛋白酶和胰蛋白酶/胰凝乳蛋白酶孵育之前和之后。使用2因素ANOVA分析数据。八组(n=10)成年雌性Sprague-Dawley大鼠(平均:188.3±0.8g)接受20mg/kg/d的BC蛋,100μg/d的EGF,5毫克/天的卵粘胶,或10.8毫克/天SBTI,单独或组合(在1mL3%NaHCO3中)通过管饲法9d和葡聚糖硫酸钠(DSS;饮用水中5%)进行最后7d。组织学,微观损伤评分,使用单因素方差分析评估和分析髓过氧化物酶(MPO)。
    BC的增殖活性,鸡蛋,或EGF通过HCl/胃蛋白酶暴露减少40-57%,而胰凝乳蛋白酶/胰蛋白酶进一步减少14-24%。SBTI或卵类粘蛋白的共同添加将胰凝乳蛋白酶/胰蛋白酶引起的增殖生物活性降低缩短了54-100%(P<0.01)。体内研究表明,单独口服EGF或单独给予蛋白酶抑制剂对减少DSS损伤无效,而带有EGF的SBTI或带有BC+鸡蛋的卵类粘蛋白改善了对体重增加的保护作用,疾病活动评分,结肠MPO,和组织学损伤3-4倍(P<0.01)。
    使用AGS的研究,细胞,Sprague-Dawley大鼠显示蛋白酶抑制剂卵类粘蛋白和SBTI保护BC,鸡蛋,和EGF防止由于胰腺酶而导致的生物活性丧失,当给予NaHCO3时,增强了对DSS损伤的结肠保护。
    Bovine colostrum (BC) and chicken egg contain proteins possessing growth factor activity. Epidermal growth factor (EGF) provides much of the pro-reparative activity within BC. Clinical use of orally administered peptide growth factors is hampered by digestion from pancreatic proteases.
    We examined whether adding a protease inhibitor [soybean trypsin inhibitor (SBTI) or ovomucoid] protected bioactivity of BC ± egg or EGF alone against pancreatic digestion using in vitro and in vivo models.
    BC, egg, or EGF alone or in combination with trypsin inhibitors were tested for proliferative (Alamar blue) activity using human gastric adenocarcinoma (AGS) cells, prior to and after incubation with HCl/pepsin and trypsin/chymotrypsin. Data were analyzed using 2-factor ANOVA. Eight groups (n = 10) of adult female Sprague-Dawley rats (mean: 188.3 ± 0.8 g) received 20 mg/kg/d of BC + egg, 100 μg/d of EGF, 5 mg/d ovomucoid, or 10.8 mg/d SBTI, alone or in combination (in 1 mL 3% NaHCO3) by gavage for 9 d and dextran sodium sulfate (DSS; 5% in drinking water) for the final 7 d. Histology, microscopic damage score, and myeloperoxidase (MPO) were assessed and analyzed using 1-factor ANOVA.
    Proliferative activities of BC, egg, or EGF were reduced 40-57% by HCl/pepsin exposure and further reduced 14-24% by chymotrypsin/trypsin. Co-addition of SBTI or ovomucoid truncated the decrease in proliferative bioactivity caused by chymotrypsin/trypsin by 54-100% (P < 0.01). In vivo study showed oral EGF alone or protease inhibitors given alone were ineffective in reducing DSS damage, whereas SBTI with EGF or ovomucoid with BC + egg improved protective effects on weight gain, disease activity score, colonic MPO, and histology damage by 3-4-fold (P < 0.01).
    Studies using AGS, cells, and Sprague-Dawley rats showed the protease inhibitors ovomucoid and SBTI protected BC, egg, and EGF against loss of bioactivity due to pancreatic enzymes and, when given with NaHCO3, enhanced colonic protection against DSS damage.
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  • 文章类型: Journal Article
    初乳是出生后最初几天产生的牛奶,含有高水平的免疫球蛋白,抗菌肽,和增长因素。初乳对支持生长很重要,发展,和新生儿的免疫防御。初乳以组合的方式天然包装,其有助于防止其破坏并保持生物活性,直到其到达更远的肠道区域,并且使得存在于其中的保护剂和修复剂之间能够产生协同反应。牛初乳作为传统或补充疗法用于多种疾病和兽医实践已有数百年的历史。部分由于担心标准西药的副作用,人们对使用天然产品感兴趣,其中初乳是一个很好的例子。许多临床前和临床研究已经证明了牛初乳对各种适应症的治疗益处,包括维护福祉,医疗条件的治疗和畜牧业。本特刊《营养素》中的文章涵盖了牛初乳的作用和使用,我们描述了主要成分,质量控制和牛初乳在健康和疾病中的应用概述。
    Colostrum is the milk produced during the first few days after birth and contains high levels of immunoglobulins, antimicrobial peptides, and growth factors. Colostrum is important for supporting the growth, development, and immunologic defence of neonates. Colostrum is naturally packaged in a combination that helps prevent its destruction and maintain bioactivity until it reaches more distal gut regions and enables synergistic responses between protective and reparative agents present within it. Bovine colostrum been used for hundreds of years as a traditional or complementary therapy for a wide variety of ailments and in veterinary practice. Partly due to concerns about the side effects of standard Western medicines, there is interest in the use of natural-based products of which colostrum is a prime example. Numerous preclinical and clinical studies have demonstrated therapeutic benefits of bovine colostrum for a wide range of indications, including maintenance of wellbeing, treatment of medical conditions and for animal husbandry. Articles within this Special Issue of Nutrients cover the effects and use bovine colostrum and in this introductory article, we describe the main constituents, quality control and an overview of the use of bovine colostrum in health and disease.
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  • 文章类型: Journal Article
    鸡蛋和牛初乳含有具有抗菌作用的蛋白质,免疫调节,和生长因子活性。卵子影响肠道防御和修复的能力在很大程度上尚未被探索。
    我们使用细胞培养和动物模型检查了巴氏灭菌的喷雾干燥的鸡蛋对胃肠道损伤的影响,并试图确定添加初乳是否提供额外的益处。
    仅鸡蛋,只有初乳,和40:60卵:初乳组合在1mg下测试增殖(Alamar蓝)和迁移(受伤的单层)活性。mL-1使用人结肠腺癌(Caco-2),人胃癌(AGS),和大鼠肠上皮样1(RIE1)细胞。四组成年雄性C57BL/6小鼠接收20mg。kg-1.d-1测试产品在饮用水中7d和吲哚美辛(85mg。kg-1,皮下给药)在第7天。评估绒毛高度和形态。三组成年雄性SpragueDawley大鼠接受20mg。kg-1.d-1测试产品,灌胃9d和葡聚糖硫酸钠(DSS,在饮用水中4%)的最后7天。组织学,微观损伤评分,和髓过氧化物酶进行评估。
    仅鸡蛋或初乳可导致细胞增殖和迁移增加3倍(与基线相比P<0.05)。加热鸡蛋会降低其生物活性。添加中和抗体或伤寒蛋白显示卵类粘蛋白,卵白蛋白,表皮生长因子受体介导卵的作用(均与卵相比P<0.05)。卵使吲哚美辛引起的小鼠绒毛缩短减少了34%,使DSS引起的大鼠结肠损伤减少了44-61%(与DSS相比P<0.05)。单独使用初乳观察到类似的结果。在每次检测中,与相同剂量的鸡蛋或初乳相比,40:60组合的结果有所改善(P<0.05)。
    使用AGS的研究,RIE1和Caco-2细胞,C57BL/6小鼠,和SpragueDawley大鼠表现出卵对肠道损伤的保护作用。如果将初乳和卵共同施用,则观察到增强的结果。含或不含初乳的蛋粉可能对预防和治疗肠道损伤具有治疗价值。
    Chicken eggs and bovine colostrum contain proteins possessing antimicrobial, immunoregulatory, and growth factor activity. The ability of eggs to influence gut defense and repair is largely unexplored.
    We examined the effect of pasteurized spray-dried egg on gastrointestinal injury using cell culture and animal models and sought to determine whether adding colostrum provided extra benefit.
    Egg alone, colostrum alone, and a 40:60 egg: colostrum combination were tested for proliferative (Alamar blue) and migratory (wounded monolayer) activity at 1 mg.mL-1 using human colon adenocarcinoma (Caco-2), human gastric cancer (AGS), and rat intestinal epithelioid-1 (RIE1) cells. Four groups of adult male C57BL/6 mice received 20 mg.kg-1.d-1 test products in drinking water for 7 d and indomethacin (85 mg.kg-1, administered subcutaneously) on day 7. Villus height and morphology were assessed. Three groups of adult male Sprague Dawley rats received 20 mg.kg-1.d-1 test product by gavage for 9 d and dextran sodium sulfate (DSS, 4% in drinking water) for the final 7 d. Histology, microscopic damage scoring, and myeloperoxidase were assessed.
    Egg or colostrum alone caused 3-fold increases in cell proliferation and migration (P < 0.05 compared with baseline). Heating the egg removed its bioactivity. Addition of neutralizing antibodies or tyrphostin showed that ovomucoid, ovalbumin, and the epidermal growth factor receptor mediated the effects of egg (all P < 0.05 compared with egg). Egg reduced shortening of villi caused by indomethacin in mice by 34% and reduced DSS-induced colonic damage in rats by 44-61% (P < 0.05 compared with DSS). Similar results were seen using colostrum alone. In each assay, the 40:60 combination gave improved results compared with the same dose of egg or colostrum alone (P < 0.05).
    Studies using AGS, RIE1, and Caco-2 cells, C57BL/6 mice, and Sprague Dawley rats showed protective effects of egg against gut injury. Enhanced results were seen if colostrum and egg were coadministered. Egg powder with or without colostrum may have therapeutic value for prevention and treatment of gut injuries.
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  • 文章类型: Journal Article
    The gastrointestinal (GI) tract has a diverse set of physiological functions, including peristalsis, immune defense, and nutrient absorptions. These functions are mediated by various intestinal cells such as epithelial cells, interstitial cells, smooth muscle cells, and neurocytes. The loss or dysfunction of specific cells directly results in GI disease, while supplementation of normal cells promotes gut healing. Gut bioengineering has been developing for this purpose to reconstruct the damaged tissues. Moreover, GI tract provides an accessible route for drug delivery, but the collateral damages induced by side effects cannot be ignored. Bioengineered intestinal tissues provide three-dimensional platforms that mimic the in vivo environment to study drug functions. Given the importance of gut bioengineering in current research, in this review, we summarize the advances in the technologies of gut bioengineering and their applications. We were able to identify several ground-breaking discoveries in our review, while more work is needed to promote the clinical translation of gut bioengineering.
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  • 文章类型: Journal Article
    From flies to humans, many components of the innate immune system have been conserved during metazoan evolution. This foundational observation has allowed us to develop Drosophila melanogaster, the fruit fly, into a powerful model to study innate immunity in animals. Thanks to an ever-growing arsenal of genetic tools, an easily manipulated genome, and its winning disposition, Drosophila is now employed to study not only basic molecular mechanisms of pathogen recognition and immune signaling, but also the nature of physiological responses activated in the host by microbial challenge and how dysregulation of these processes contributes to disease. Here, we present a collection of methods and protocols to challenge the fly with an assortment of microbes, both systemically and orally, and assess its humoral, cellular, and epithelial response to infection. Our review covers techniques for measuring the reaction to microbial infection both qualitatively and quantitatively. Specifically, we describe survival, bacterial load, BLUD (a measure of disease tolerance), phagocytosis, melanization, clotting, and ROS production assays, as well as efficient protocols to collect hemolymph and measure immune gene expression. We also offer an updated catalog of online resources and a collection of popular reporter lines and mutants to facilitate research efforts. This article is categorized under: Technologies > Analysis of Cell, Tissue, and Animal Phenotypes.
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  • 文章类型: Case Reports
    Secondary aortoenteric fistula (SAEF) is a rare, life-threatening complication of aortic reconstructive surgery. Graft excision associated with gut repair and extra-anatomic bypass or in situ aortic reconstruction is the best option. However, it is associated with high mortality rates, especially when undertaken in unstable patients with severe comorbidities. We present a case of SAEF successfully treated by endovascular repair and gut restoration. After laparotomy, a dense inflammatory \"frozen\" mass was found around the involved part of the duodenum and the aortic sac. Because of his comorbidities, the difficulty in dissection of the aortic sac and the risk of damage in adjacent organs, the initial plan for aortic reconstruction was abandoned. A surgical isolation of the third portion of the duodenum and a duodenum-jejunal anastomosis were performed. An Endurant endograft 32-16-16 mm (Medtronic, Inc., Minneapolis, MN) was implanted to achieve aortic continuity. Twenty months postdischarge, the patient remains in good general condition, afebrile, and with normal laboratory tests and inflammation markers. In high-risk patients, endovascular intervention combined with gut repair without further aortic reconstruction can be a permanent solution requiring, however, close surveillance.
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