Sulfinic Acids

亚硫酸
  • 文章类型: Journal Article
    仔猪低出生体重是影响养猪企业的重要因素。胎盘,作为母亲和胎儿之间物质交换的关键器官,直接影响胎儿的生长发育。大蒜素表现出各种生物活性,包括抗炎和抗氧化特性。它还可能在增强母猪繁殖性能和胎盘血管生成中起关键作用。在这项研究中,我们使用了70头泌乳长白猪×约克郡二元杂合母猪,以探讨大蒜素对母猪繁殖性能和胎盘发育的影响。母猪被随机分配到大蒜素组(大蒜素),用含有0.25%大蒜素的饮食喂养,阴性对照组,用基础饲料喂养。从交配之日到分娩结束,实验期为114d。结果表明,在妊娠日粮中添加大蒜素增加了出生仔猪的总数,活着出生的小猪,和高出生体重的仔猪,减少围产期氧化应激,减轻母猪糖脂代谢失调,并增加胎盘中抗氧化标记物的水平。通过非靶向代谢组学对母体血浆和胎盘样品中代谢物的差异分析显示大蒜素改善了胆固醇代谢,类固醇生物合成,母猪血浆孕酮水平升高。大蒜素促进硫代谢,胎盘样品中的半胱氨酸和蛋氨酸代谢,并增加胎盘中的硫化氢(H2S)含量。此外,实时定量PCR,Westernblot和免疫荧光结果显示大蒜素上调血管生成相关基因的表达,VEGF-A,FLK1和Ang1,在胎盘中,暗示它促进胎盘血管生成。这些结果表明,在妊娠母猪的饮食中补充大蒜素可以减少氧化应激,缓解围产期糖脂代谢失调,并通过增加血浆孕酮水平和胎盘H2S含量来促进胎盘血管生成和胎儿发育。
    The low-birth-weight of piglets is an important factor affecting pig enterprises. The placenta, as a key organ for material exchange between mother and foetus, directly influences the growth and development of the foetus. Allicin exhibits various biological activities, including anti-inflammatory and antioxidant properties. It may also play a crucial role in enhancing sow reproductive performance and placental angiogenesis. In this study, we used 70 lactating Landrace × Yorkshire binary heterozygous sows to explore the effect of allicin on the reproductive performance of sows and placental development. The sows were randomly assigned into the Allicin group (Allicin), which was fed with a diet containing 0.25% allicin, and the negative control group, which was fed with basal feed. The experimental period lasted for 114 d from the date of mating to the end of farrowing. The results showed that the addition of allicin to the gestation diets increased the number of total born piglets, born alive piglets, and high-birth-weight piglets, reduced peripartum oxidative stress, alleviated dysregulation of glucose-lipid metabolism in sows, and increased the levels of antioxidant markers in the placenta. Differential analysis of metabolites in maternal plasma and placenta samples by non-targeted metabolomics revealed that allicin improved cholesterol metabolism, steroid biosynthesis, and increased plasma progesterone levels in sows. Allicin promoted sulphur metabolism, cysteine and methionine metabolism in placental samples and increased the hydrogen sulphide (H2S) content in the placenta. In addition, Quantitative Real-time PCR, Western blot and immunofluorescence results showed that allicin upregulated the expression of angiogenesis-related genes, VEGF-A, FLK 1 and Ang 1, in the placenta, implying that it promoted placental angiogenesis. These results indicate that supplementing the diet of pregnant sows with allicin reduces oxidative stress, alleviates dysregulation of glucose-lipid metabolism during the periparturient period, and promotes placental angiogenesis and foetal development by increasing plasma progesterone level and placental H2S content.
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  • 文章类型: Journal Article
    大蒜素是大蒜衍生的有机硫化物之一,具有多种药理作用。有研究报道AL对肝癌有显著的抑制作用,胃癌,乳腺癌,和其他癌症。然而,关于其在人鼻咽癌中的作用尚无相关报道。铁凋亡是非凋亡调节的细胞死亡的铁依赖性形式。越来越多的证据表明,铁凋亡的诱导可以抑制增殖,迁移,入侵,和各种癌细胞的存活,在癌症中充当肿瘤抑制因子。在这项研究中,我们证实AL可以抑制细胞增殖,迁移,入侵,和人鼻咽癌细胞的存活。我们的发现表明,AL可以通过降低GSH和GPX4的水平并促进毒性LPO和ROS的诱导来诱导铁凋亡轴。人鼻咽癌细胞中AL介导的细胞毒性依赖于铁凋亡。因此,AL具有良好的抗癌特性,有望成为治疗鼻咽癌的潜在药物。
    Allicin (AL) is one of garlic-derived organosulfides and has a variety of pharmacological effects. Studies have reported that AL has notable inhibitory effects on liver cancer, gastric cancer, breast cancer, and other cancers. However, there are no relevant reports about its role in human nasopharyngeal carcinoma. Ferroptosis is an iron-dependent form of non-apoptotic regulated cell death. Increasing evidence indicates that induction of ferroptosis can inhibit the proliferation, migration, invasion, and survival of various cancer cells, which act as a tumor suppressor in cancer. In this study, we confirmed that AL can inhibit cell proliferation, migration, invasion, and survival in human nasopharyngeal carcinoma cells. Our finding shows that AL can induce the ferroptosis axis by decreasing the level of GSH and GPX4 and promoting the induction of toxic LPO and ROS. AL-mediated cytotoxicity in human nasopharyngeal carcinoma cells is dependent on ferroptosis. Therefore, AL has good anti-cancer properties and is expected to be a potential drug for the treatment of nasopharyngeal carcinoma.
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  • 文章类型: Journal Article
    大蒜(AlliumsativumL.)是一种广泛丰富的香料,以其香气和辛辣的味道而闻名。它含有几种生物活性化合物,为人类提供广泛的健康益处,包括那些与营养有关的,生理学,和医学。因此,大蒜被认为是最有效的疾病预防饮食之一。许多体外和体内研究报道了含硫化合物,大蒜素和ajoene,因为它们有效的抗癌,抗糖尿病,抗炎,抗氧化剂,抗菌,免疫增强,和心脏保护特性。作为生物活性化合物的丰富天然来源,包括多糖,皂苷,单宁,芳樟醇,香叶醇,phellandrene,β-phellandrene,ajoene,Alliin,S-烯丙基-巯基半胱氨酸,和β-phellandrene,大蒜具有许多治疗性应用,可能在针对各种人类疾病的药物开发中发挥作用。在当前的审查中,讨论了大蒜及其主要生物活性成分及其生物学功能和作用机制,以及它们在疾病预防和治疗中的作用。
    Garlic (Allium sativum L.) is a widely abundant spice, known for its aroma and pungent flavor. It contains several bioactive compounds and offers a wide range of health benefits to humans, including those pertaining to nutrition, physiology, and medicine. Therefore, garlic is considered as one of the most effective disease-preventive diets. Many in vitro and in vivo studies have reported the sulfur-containing compounds, allicin and ajoene, for their effective anticancer, anti-diabetic, anti-inflammatory, antioxidant, antimicrobial, immune-boosting, and cardioprotective properties. As a rich natural source of bioactive compounds, including polysaccharides, saponins, tannins, linalool, geraniol, phellandrene, β-phellandrene, ajoene, alliin, S-allyl-mercapto cysteine, and β-phellandrene, garlic has many therapeutic applications and may play a role in drug development against various human diseases. In the current review, garlic and its major bioactive components along with their biological function and mechanisms of action for their role in disease prevention and therapy are discussed.
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  • 文章类型: Journal Article
    已知黄曲霉毒素B1(AFB1)抑制生长,并通过干扰蛋白质合成造成肝损伤。大蒜素,已被认为是一种有效的抗氧化剂,能够保护肝脏免受氧化伤害。本研究旨在研究AFB1对牛肝细胞的损伤以及大蒜素对AFB1诱导的细胞毒性的保护作用。在这项研究中,在添加AFB1进行共培养之前,用大蒜素预处理细胞。我们的发现表明AFB1损害了细胞完整性,抑制核因子红系2相关因子2(Nrf2)的表达。此外,大蒜素通过促进Nrf2通路的表达和减少细胞凋亡来减轻AFB1对牛肝细胞的氧化损伤。总之,这项研究的结果将有助于推进临床研究和应用,为肝脏疾病的预防和治疗提供了新的选择和方向。
    Aflatoxin B1 (AFB1) is known to inhibit growth, and inflict hepatic damage by interfering with protein synthesis. Allicin, has been acknowledged as an efficacious antioxidant capable of shielding the liver from oxidative harm. This study aimed to examine the damage caused by AFB1 on bovine hepatic cells and the protective role of allicin against AFB1-induced cytotoxicity. In this study, cells were pretreated with allicin before the addition of AFB1 for co-cultivation. Our findings indicate that AFB1 compromises cellular integrity, suppresses the expression of nuclear factor erythroid 2-related factor 2 (Nrf2). In addition, allicin attenuates oxidative damage to bovine hepatic cells caused by AFB1 by promoting the expression of the Nrf2 pathway and reducing cell apoptosis. In conclusion, the results of this study will help advance clinical research and applications, providing new options and directions for the prevention and treatment of liver diseases.
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  • 文章类型: Journal Article
    有限的蒜氨酸酶资源导致硫代亚磺酸酯的生物合成困难(例如,大蒜素),限制了它们在农业和食品工业中的应用。为了有效地生物合成硫代亚磺酸酯,本研究旨在挖掘细菌蒜氨酸酶资源,阐明其催化特性。从大蒜根际分离株中鉴定出两种对L-(-)-alliin具有高alliinase活性(>60Umg-1)的细菌cystathionineβ-裂解酶(MetCs)。宏基因组学研究表明,蜡样芽孢杆菌(BcPatB)对L-(±)-蒜氨酸和L-()-蒜氨酸(208.6和225.1Umg-1)均具有较高的活性,分别。尽管这些酶都优选l-半胱氨酸S-缀合亚砜作为底物,BcPatB与Alliumalliinase具有更紧密的系统发育关系,并且与A.sativumalliinase具有相似的特征。有趣的是,Trp30Ile31Ala32Asp33Met34基序在BcPatB的尖点环中,尤其是主题顶部的31和32,被建模为位于L-()-alliin的亚砜附近,对于底物立体特异性很重要。此外,突变体I31V和A32G对L-()-alliin的立体选择性和活性高于突变体I31L/D33E对L-(-)-alliin的立体选择性和活性。使用细菌蒜氨酸酶和化学合成的底物,我们获得了具有高抗微生物和抗线虫活性的硫代亚磺酸盐,可以为作物和食物的保护提供见解。
    Limited alliinase resources cause difficulties in the biosynthesis of thiosulfinates (e.g., allicin), restricting their applications in the agricultural and food industries. To effectively biosynthesize thiosulfinates, this study aimed to excavate bacterial alliinase resources and elucidate their catalytic properties. Two bacterial cystathionine β-lyases (MetCs) possessing high alliinase activity (>60 U mg -1) toward L-(-)-alliin were identified from Allium sativum rhizosphere isolates. Metagenomic exploration revealed that cystathionine β-lyase from Bacillus cereus (BcPatB) possessed high activity toward both L-(±)-alliin and L-(+)-alliin (208.6 and 225.1 U mg -1), respectively. Although these enzymes all preferred l-cysteine S-conjugate sulfoxides as substrates, BcPatB had a closer phylogenetic relationship with Allium alliinases and shared several similar features with A. sativum alliinase. Interestingly, the Trp30Ile31Ala32Asp33 Met34 motif in a cuspate loop of BcPatB, especially sites 31 and 32 at the top of the motif, was modeled to locate near the sulfoxide of L-(+)-alliin and is important for substrate stereospecificity. Moreover, the stereoselectivity and activity of mutants I31V and A32G were higher toward L-(+)-alliin than those of mutant I31L/D33E toward L-(-)-alliin. Using bacterial alliinases and chemically synthesized substrates, we obtained thiosulfinates with high antimicrobial and antinematode activities that could provide insights into the protection of crops and food.
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  • 文章类型: Journal Article
    目的:已经观察到HER2阳性转移性乳腺癌患者的预后使用HER2靶向药物显着改善。然而,对于接受过HER2阳性转移性乳腺癌辅助和/或新辅助曲妥珠单抗治疗的患者,仍缺乏关于一线抗HER2治疗方案的证据.此外,没有可靠的标志物可以预测抗HER2治疗在这些患者中的疗效.
    方法:纳入接受过HER2阳性转移性乳腺癌辅助和/或新辅助曲妥珠单抗治疗的患者。使用吡罗替尼加白蛋白结合的紫杉醇作为一线治疗。主要终点是客观缓解率(ORR)。还评估了安全性。为了探索使用Olink技术的预测性生物标志物,血液样本是动态收集的。
    结果:从2019年12月到2023年8月,研究的第一阶段涉及27名符合条件的患者。尽管中位随访时间为17.8个月,但尚未达到中位PFS。疗效评价显示ORR为92.6%,DCR为100%。3级或更高的不良事件包括腹泻(29.6%),白细胞减少症(11.1%),中性粒细胞减少症(25.9%),口腔黏膜炎(3.7%),和手足综合症(3.7%)。Toll样受体3(TLR3)和原癌基因酪氨酸蛋白激酶受体(RET)是与这些患者PFS显着相关的蛋白质。
    结论:这项研究表明,对于接受过HER2阳性转移性乳腺癌辅助和/或新辅助曲妥珠单抗治疗的患者,吡托替尼联合白蛋白结合型紫杉醇作为一线治疗方案显示出良好的疗效和可控制的安全性。此外,TLR3和RET的表达水平与患者PFS之间存在显著关联.
    OBJECTIVE: It has been observed that the prognosis of patients with HER2-positive metastatic breast cancer has improved significantly with HER2-targeted agents. However, there is still a lack of evidence regarding first-line anti-HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti-HER2 treatment in these patients.
    METHODS: Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer were enrolled. Pyrotinib plus albumin-bound paclitaxel were used as first-line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically.
    RESULTS: From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow-up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand-foot syndrome (3.7%). Toll-like receptor 3 (TLR3) and Proto-oncogene tyrosine-protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients.
    CONCLUSIONS: This study demonstrates that pyrotinib plus albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients.
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  • 文章类型: Journal Article
    背景:大蒜素调节巨噬细胞自噬和衰老,抑制肝癌细胞生长.本研究探讨了大蒜素抑制肝癌细胞生长的机制。
    方法:将Hepa1-6小鼠肝癌细胞皮下注射到C57BL/6J小鼠体内,构建肿瘤移植模型。用肝癌细胞的上清液培养巨噬细胞以构建细胞模型。通过RTqPCR检测mRNA和蛋白水平以及Sestrin2泛素化水平,免疫荧光和蛋白质印迹。试剂盒测定自噬相关因子水平和衰老相关β-半乳糖苷酶活性,通过环己酰亚胺(CHX)示踪检测蛋白质稳定性。
    结果:临床样本数据分析显示RBX1在肿瘤组织中高表达,而Sestrin2在肿瘤组织中低水平表达。大蒜素可促进肿瘤巨噬细胞自噬相关蛋白LC3和Beclin-1的表达,抑制衰老相关蛋白p16和p21的表达,从而促进巨噬细胞自噬,抑制细胞衰老。此外,大蒜素可以抑制RBX1的表达,从而减少Sestrin2的泛素化,增强Sestrin2的稳定性,激活肿瘤巨噬细胞的自噬,抑制衰老。此外,大蒜素处理抑制了与巨噬细胞共培养的肝癌细胞的增殖和迁移,并显着改善了小鼠肝癌的发展。
    结论:大蒜素通过调节Sestrin2的泛素化作用,影响巨噬细胞自噬,抑制肝癌细胞的生长。
    BACKGROUND: Allicin regulates macrophage autophagy and senescence, and inhibits hepatoma cell growth. This study investigated the mechanism by which allicin inhibits the growth of hepatoma cells.
    METHODS: Hepa1-6 mouse hepatoma cells were subcutaneously injected into C57BL/6 J mice to construct a tumor transplantation model. Macrophages were cultured with the supernatant of hepatoma cells to construct a cell model. The levels of mRNA and proteins and the level of Sestrin2 ubiquitination were measured by RTqPCR, immunofluorescence and Western blotting. The levels of autophagy-related factors and the activity of senescence-associated β-galactosidase were determined by kits, and protein stability was detected by cycloheximide (CHX) tracking.
    RESULTS: Data analysis of clinical samples revealed that RBX1 was highly expressed in tumor tissues, while Sestrin2 was expressed at low levels in tumor tissues. Allicin can promote the expression of the autophagy-related proteins LC3 and Beclin-1 in tumor macrophages and inhibit the expression of the aging-related proteins p16 and p21, thus promoting autophagy in macrophages and inhibiting cell senescence. Moreover, allicin can inhibit the expression of RBX1, thereby reducing the ubiquitination of Sestrin2, enhancing the stability of Sestrin2, activating autophagy in tumor macrophages and inhibiting senescence. In addition, allicin treatment inhibited the proliferation and migration of hepatoma carcinoma cells cocultured with macrophages and significantly improved the development of liver cancer in mice.
    CONCLUSIONS: Allicin can affect the autophagy of macrophages and restrain the growth of hepatoma cells by regulating the ubiquitination of Sestrin2.
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  • 文章类型: Journal Article
    目的:睾丸扭转-扭转引起的睾丸缺血再灌注增加活性氧水平,导致睾丸损伤.大蒜素,大蒜中最有活性的成分之一,是一种显著的外源抗氧化剂。在研究中,评估了大蒜素治疗睾丸缺血再灌注损伤的疗效.
    方法:本研究纳入60只雄性SD大鼠。建立3组,每组20只大鼠,分别为:对照组,睾丸缺血/再灌注诱导组,睾丸缺血再灌注+大蒜素组治疗。对照组行左睾丸假手术,无其他干预。在睾丸缺血/再灌注诱导组中,大鼠左睾丸接受720°扭转两小时,然后扭曲。在大蒜素治疗组中,除了睾丸缺血再灌注,腹腔注射大蒜素50mg/kg,在扭曲之后立即开始。取睾丸组织标本测定黄嘌呤氧化酶的蛋白表达,这是活性氧形成的主要来源,丙二醛水平(活性氧的可靠标志),和睾丸生精功能。
    结果:睾丸缺血再灌注显著增加同侧睾丸黄嘌呤氧化酶和丙二醛的表达水平,同时降低睾丸生精功能。在同侧睾丸中黄嘌呤氧化酶和丙二醛的表达水平显著降低,而大蒜素治疗组的睾丸生精功能明显高于睾丸缺血再灌注组。
    结论:我们的研究结果表明,大蒜素通过抑制黄嘌呤氧化酶的表达来限制活性氧的产生,从而改善缺血/再灌注诱导的睾丸损伤。
    OBJECTIVE: Testicular ischemia-reperfusion induced by testicular torsion-detorsion increases the level of reactive oxygen species, leading to testicular damage. Allicin, one of the most active ingredients in garlic, is a significant exogenous antioxidant. In the research, the efficacy of allicin in treating testicular ischemia-reperfusion injury was assessed.
    METHODS: The study included sixty Sprague-Dawley male rats. Three groups with 20 rats per group were created as follows: control group, testicular ischemia/reperfusion-induced group, and testicular ischemia-reperfusion plus treatment with allicin group. The control group underwent a sham operation of the left testis without other interventions. In the testicular ischemia/reperfusion-induced group, rat left testis was subjected to 720° torsion for two hours and then detorsion. In the allicin-treated group, in addition to testicular ischemia-reperfusion, 50 mg/kg of allicin was injected intraperitoneally, starting immediately following detorsion. Testicular tissue samples were obtained to measure the protein expression of xanthine oxidase, which is a major source of reactive oxygen species formation, malondialdehyde level (a reliable marker of reactive oxygen species), and testicular spermatogenic function.
    RESULTS: Testicular ischemia-reperfusion significantly increased the expression of xanthine oxidase and malondialdehyde levels in ipsilateral testes while reducing testicular spermatogenic function. The expression of xanthine oxidase and malondialdehyde levels were significantly lower in ipsilateral testes, whereas testicular spermatogenic function in the allicin-treated group was significantly higher compared with those in the testicular ischemia-reperfusion group.
    CONCLUSIONS: Our findings indicate that allicin administration improves ischemia/reperfusion-induced testicular damage by limiting reactive oxygen species generation via inhibition of xanthine oxidase expression.
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  • 文章类型: Journal Article
    伯克霍尔德利亚剑兰pv。alliicola,B.洋葱,B.orbicola是洋葱常见的细菌病原体。洋葱在细胞分解后产生有机硫硫代亚磺酸酯防御化合物。使用全基因组测序和计算机模拟分析,我们在多个与洋葱相关的伯克霍尔德菌物种中鉴定了推定的硫代亚磺酸耐性基因(TTG)簇,其特征与其他与葱属相关的内生菌和病原体相似.序列分析显示存在三种伯克霍尔德氏菌TTG簇类型,A型和B型广泛分布在剑兰芽孢杆菌中,B.洋葱,和B.orbicola在染色体和质粒中。基于分离的自然变异和等基因菌株的产生,我们确定了剑兰芽孢杆菌中TTG簇的体外和体内贡献,B.洋葱,B.orbicola.伯克霍尔德氏菌TTG簇有助于增强大蒜素耐受性,并改善所有三种物种过滤洋葱提取物的生长。TTG簇也对剑兰芽孢杆菌叶面坏死症状和细菌种群做出了明确的贡献。令人惊讶的是,TTG簇对这三个物种的洋葱鳞片中的细菌种群没有贡献。根据我们的发现,我们假设与洋葱相关的伯克霍尔德菌可能逃避或抑制洋葱鳞茎组织中硫代亚磺酸盐的产生。
    Burkholderia gladioli pv. alliicola, B. cepacia, and B. orbicola are common bacterial pathogens of onion. Onions produce organosulfur thiosulfinate defensive compounds after cellular decompartmentalization. Using whole-genome sequencing and in silico analysis, we identified putative thiosulfinate tolerance gene (TTG) clusters in multiple onion-associated Burkholderia species similar to those characterized in other Allium-associated bacterial endophytes and pathogens. Sequence analysis revealed the presence of three Burkholderia TTG cluster types, with both Type A and Type B being broadly distributed in B. gladioli, B. cepacia, and B. orbicola in both the chromosome and plasmids. Based on isolate natural variation and generation of isogenic strains, we determined the in vitro and in vivo contribution of TTG clusters in B. gladioli, B. cepacia, and B. orbicola. The Burkholderia TTG clusters contributed to enhanced allicin tolerance and improved growth in filtered onion extracts by all three species. TTG clusters also made clear contributions to B. gladioli foliar necrosis symptoms and bacterial populations. Surprisingly, the TTG cluster did not contribute to bacterial populations in onion bulb scales by these three species. Based on our findings, we hypothesize onion-associated Burkholderia may evade or inhibit the production of thiosulfinates in onion bulb tissues. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
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  • 文章类型: Journal Article
    目的:该研究试图探索大蒜素如何通过促进SHP2表达以抑制I/R小鼠中的p-PERK来降低氧化应激水平。
    方法:使用GEO数据库和RNA测序来预测下游基因。用TTC染色观察心肌梗死面积。Masson染色用于评估纤维化水平。IF用于检测SHP2,CTGF的表达,ROS。RT-PCR分析用于定量SHP2mRNA的表达。Westernblot检测SHP2、p-PERK、MFN1、NLRP3、NOX2和NOX3。
    结果:GEO和转录组数据显示SHP2在I/R小鼠心脏组织中的低表达。在I/R鼠标模型中,TTC染色结果显示大蒜素可以减少心肌梗死面积;Masson染色结果显示大蒜素可以减少纤维化;巨噬细胞转录组测序发现SHP2是大蒜素的靶基因;免疫荧光显示大蒜素可以增加SHP2;qPCR结果显示大蒜素可以提高SHP2的mRNA水平;免疫荧光显示大蒜素可以抑制心肌梗死组织中的ROS。但是特定的SHP2-KD消除了ROS的变化。Westernblot分析表明,大蒜素能增加SHP2蛋白的表达,降低p-PERK的表达,MFN1、NLRP3、NOX2和NOX3;SHP2-KD消除了p-PERK的表达差异,MFN1、NLRP3、NOX2和NOX3。
    结论:大蒜素可以通过增强SHP2的表达来调节p-PERK的激活,从而抑制小鼠心肌缺血再灌注诱导的氧化应激。
    The study attempted to explore how allicin reduces oxidative stress levels by promoting SHP2 expression to inhibit p-PERK in I/R mice.
    The GEO database and RNA sequencing were used to predict downstream gene. TTC staining was used to visualize the myocardial infarction area. Masson staining was used to assess the level of fibrosis. IF was used to examine the expression of SHP2, CTGF, ROS. RT-PCR analysis was used to quantify the expression of SHP2 mRNA. Western blot was used to detect the protein expression levels of SHP2, p-PERK, MFN1, NLRP3, NOX2, and NOX3.
    GEO and transcriptomic data revealed low expression of SHP2 in the heart tissues I/R mice. In the I/R mouse model, TTC staining result showed that allicin can reduce the area of myocardial infarction; Masson staining results indicated that allicin can reduce fibrosis; Macrophage transcriptome sequencing found SHP2 is a target gene of allicin; Immunofluorescence showed allicin can increase SHP2; qPCR results showed allicin can raise SHP2 mRNA level; Immunofluorescence indicated that allicin can inhibit ROS in myocardial infarction tissue, but the specific SHP2-KD eliminates changes in ROS. Western blot analysis demonstrated allicin can increase SHP2 protein and reduce the expression of p-PERK, MFN1, NLRP3, NOX2, and NOX3; SHP2-KD eliminates the expression differences in p-PERK, MFN1, NLRP3, NOX2, and NOX3.
    Allicin can modulate p-PERK activation by enhancing the expression of SHP2, thereby inhibiting myocardial ischemia-reperfusion-induced oxidative stress in mice.
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