Antiporters

反派者
  • 文章类型: Journal Article
    阴离子交换剂3(AE3)在调节整个兴奋组织的细胞内pH中起着关键作用,然而,与其他阴离子交换剂相比,其结构复杂性和功能动力学仍未得到充分探索。这项研究揭示了人类AE3的结构见解,包括AE3跨膜结构域(TMD)的低温电子显微镜结构以及将AE3N末端结构域(NTD)与AE2TMD(hAE3NTD2TMD)结合的嵌合体。我们的分析揭示了一个底物结合位点,NTD-TMD联锁机构,以及对面向外的构象的偏好。与AE2不同,AE2具有更强大的酸负载能力,AE3的结构,包括由于缺少关键的NTD-TMD相互作用而导致的不太稳定的面向内的构象,有助于其适度的pH调节活性和增加对抑制剂DIDS的敏感性。这些结构差异强调了AE3在特定组织中的独特功能作用,并强调了阴离子交换家族中结构动力学和功能特异性之间的复杂相互作用。增强我们对阴离子交换家族的生理和病理作用的理解。
    Anion exchanger 3 (AE3) is pivotal in regulating intracellular pH across excitable tissues, yet its structural intricacies and functional dynamics remain underexplored compared to other anion exchangers. This study unveils the structural insights into human AE3, including the cryo-electron microscopy structures for AE3 transmembrane domains (TMD) and a chimera combining AE3 N-terminal domain (NTD) with AE2 TMD (hAE3NTD2TMD). Our analyzes reveal a substrate binding site, an NTD-TMD interlock mechanism, and a preference for an outward-facing conformation. Unlike AE2, which has more robust acid-loading capabilities, AE3\'s structure, including a less stable inward-facing conformation due to missing key NTD-TMD interactions, contributes to its moderated pH-modulating activity and increased sensitivity to the inhibitor DIDS. These structural differences underline AE3\'s distinct functional roles in specific tissues and underscore the complex interplay between structural dynamics and functional specificity within the anion exchanger family, enhancing our understanding of the physiological and pathological roles of the anion exchanger family.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    替加环素非易感肺炎克雷伯菌(TNSKP)正在增加,并已成为全球公共卫生问题。然而,替加环素耐药机制尚不清楚。这项研究的目的是研究外排泵系统在替加环素耐药性中的潜在作用。收集29株替加环素非敏感型肺炎克雷伯菌(TNSKP),并通过肉汤微量稀释法测定其最低抑菌浓度(MIC)。ramR,acrR,rpsJ,tet(A),和tet(X)通过聚合酶链反应(PCR)扩增。通过实时PCR分析不同外排泵基因和调节基因的mRNA表达。此外,选择KP14进行基因组测序。KP14基因没有acrB,OQXB,使用自杀质粒对TetA进行修饰,并研究了目标基因敲除的KP14替加环素的MIC。已发现,一旦与苯基-精氨酸-β-萘甲酰胺二盐酸盐(PaβN)结合,29种TNSKP菌株中的20种替加环素的MIC降低了四倍以上。大多数菌株表现出AcrAB和oqxAB外排泵的上调。带有acrB的菌株,OQXB,构建了被敲除的tetA基因,其中替加环素对KP14ΔacrB和KP14ΔtetA的MIC为2µg/mL(降低16倍),替加环素对KP14ΔacrBΔTetA的MIC为0.25µg/mL(降低128倍),但替加环素对KP14ΔoqxB的MIC保持不变,为32µg/mL。大多数TNSKP菌株显示AcrAB-TolC和oqxAB的表达增加,而某些菌株在与替加环素抗性相关的其他基因中显示出突变。在KP14中,AcrAB-TolC的过表达和tet(A)基因突变均导致替加环素耐药机制。
    Tigecycline-non-susceptible Klebsiella pneumoniae (TNSKP) is increasing and has emerged as a global public health issue. However, the mechanism of tigecycline resistance remains unclear. The objective of this study was to investigate the potential role of efflux pump system in tigecycline resistance. 29 tigecycline-non-susceptible Klebsiella pneumoniae (TNSKP) strains were collected and their minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The ramR, acrR, rpsJ, tet(A), and tet(X) were amplified by polymerase chain reaction (PCR). The mRNA expression of different efflux pump genes and regulator genes were analyzed by real-time PCR. Additionally, KP14 was selected for genome sequencing. KP14 genes without acrB, oqxB, and TetA were modified using suicide plasmids and MIC of tigecycline of KP14 with target genes knocked out was investigated. It was found that MIC of tigecycline of 20 out of the 29 TNSKP strains decreased by over four folds once combined with phenyl-arginine-β-naphthylamide dihydrochloride (PaβN). Most strains exhibited upregulation of AcrAB and oqxAB efflux pumps. The strains with acrB, oqxB, and tetA genes knocked out were constructed, wherein the MIC of tigecycline of KP14∆acrB and KP14∆tetA was observed to be 2 µg/mL (decreased by 16 folds), the MIC of tigecycline of KP14ΔacrBΔTetA was 0.25 µg/mL (decreased by 128 folds), but the MIC of tigecycline of KP14∆oqxB remained unchanged at 32 µg/mL. The majority of TNSKP strains demonstrated increased expression of AcrAB-TolC and oqxAB, while certain strains showed mutations in other genes associated with tigecycline resistance. In KP14, both overexpression of AcrAB-TolC and tet(A) gene mutation contributed to the mechanism of tigecycline resistance.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    硼(B)对植物生长和发育至关重要。B缺乏会损害许多生理和代谢过程,特别是在根发育和花粉萌发中,严重阻碍作物生长和产量。然而,硼信号感知和信号转导的分子机制相当有限。在这项研究中,我们发现CPK10是CPK家族中的一种钙依赖性蛋白激酶,与硼转运蛋白BOR1的相互作用最强。CPK10的突变导致B缺乏条件下的生长和根系发育缺陷,而组成型活性的CPK10增强了植物对B缺乏症的耐受性。此外,我们发现CPK10在Ser689残基与BOR1相互作用并磷酸化。通过各种生化分析和补充酵母和植物中的B转运,我们发现BOR1的Ser689对其运输活性很重要。总之,这些发现强调了CPK10-BOR1信号通路在维持植物B稳态中的重要性,并为作物对B缺乏胁迫的耐受性的遗传改良提供了目标。
    Boron (B) is crucial for plant growth and development. B deficiency can impair numerous physiological and metabolic processes, particularly in root development and pollen germination, seriously impeding crop growth and yield. However, the molecular mechanism underlying boron signal perception and signal transduction is rather limited. In this study, we discovered that CPK10, a calcium-dependent protein kinase in the CPK family, has the strongest interaction with the boron transporter BOR1. Mutations in CPK10 led to growth and root development defects under B-deficiency conditions, while constitutively active CPK10 enhanced plant tolerance to B deficiency. Furthermore, we found that CPK10 interacted with and phosphorylated BOR1 at the Ser689 residue. Through various biochemical analyses and complementation of B transport in yeast and plants, we revealed that Ser689 of BOR1 is important for its transport activity. In summary, these findings highlight the significance of the CPK10-BOR1 signaling pathway in maintaining B homeostasis in plants and provide targets for the genetic improvement of crop tolerance to B-deficiency stress.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    糖原贮积病Ib型(GSD-Ib)是由SLC37A4突变引起的一种罕见的先天性糖原代谢错误。患有GSD-Ib的患者具有发生炎症性肠病(IBD)的高风险。我们评估了依帕列净的疗效,肾钠葡萄糖协同转运蛋白2(SGLT2)抑制剂,GSD相关性IBD患者结肠黏膜愈合的研究.一个潜在的,单臂,开放标签临床试验纳入了2022年7月1日至2023年12月31日中国广东省人民医院8例GSD相关IBD患者.招募了8名患者,平均年龄为10.34±2.61岁。四男四女。内镜特征包括深圆形和大圆形溃疡,炎性增生,阻塞和狭窄。与依帕列净之前相比,在第48周SES-CD评分显着降低。6例患者完成了48周的依帕列净治疗和内窥镜检查显示粘膜溃疡的显著改善或愈合,炎性增生,狭窄,和阻塞。一名患者出汗严重,需要补液,并出现尿路感染。无严重或危及生命的不良事件。本研究提示依帕列净可能促进结肠黏膜愈合,减少增生。狭窄,与GSD相关的IBD患儿的梗阻。
    Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism caused by mutations in SLC37A4. Patients with GSD-Ib are at high risk of developing inflammatory bowel disease (IBD). We evaluated the efficacy of empagliflozin, a renal sodium‒glucose cotransporter protein 2 (SGLT2) inhibitor, on colonic mucosal healing in patients with GSD-associated IBD. A prospective, single-arm, open-label clinical trial enrolled eight patients with GSD-associated IBD from Guangdong Provincial People\'s Hospital in China from July 1, 2022 through December 31, 2023. Eight patients were enrolled with a mean age of 10.34 ± 2.61 years. Four male and four female. The endoscopic features included deep and large circular ulcers, inflammatory hyperplasia, obstruction and stenosis. The SES-CD score significantly decreased at week 48 compared with before empagliflozin. Six patients completed 48 weeks of empagliflozin therapy and endoscopy showed significant improvement or healing of mucosal ulcers, inflammatory hyperplasia, stenosis, and obstruction. One patient had severe sweating that required rehydration and developed a urinary tract infection. No serious or life-threatening adverse events. This study suggested that empagliflozin may promote colonic mucosal healing and reduce hyperplasia, stenosis, and obstruction in children with GSD-associated IBD.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    产气荚膜梭菌是一类广泛存在于人和动物肠道组织中的厌氧革兰氏阳性菌。产气荚膜梭菌的主要毒力因子是其外毒素。产气荚膜梭菌C型是家畜疾病的主要毒株,其外毒素可引起坏死性肠炎和肠毒血症,导致饲料转化率降低,严重影响育种生产性能。我们的研究发现,用外毒素治疗会降低人单核细胞白血病细胞(THP-1)细胞的细胞活力并触发细胞内活性氧(ROS)。通过转录组测序分析,我们发现,用外毒素治疗后,血红素加氧酶1(HO-1)和铁凋亡信号通路等相关蛋白的水平显著升高.为了研究巨噬细胞外毒素处理后是否发生铁凋亡,我们证实了抗氧化因子谷胱甘肽过氧化物酶4/铁凋亡抑制蛋白1/胱氨酸/谷氨酸反转运溶质载体家族7成员11(GPX4/FSP1/xCT)的蛋白表达水平,铁凋亡相关蛋白核受体共激活因子4/转铁蛋白/转铁蛋白受体(NCOA4/TF/TFR)/铁蛋白和脂质过氧化水平均有显著改变。基于以上结果,我们的研究表明,产气荚膜梭菌C型外毒素可通过氧化应激和铁凋亡诱导巨噬细胞损伤。
    Clostridium perfringens is a kind of anaerobic Gram-positive bacterium that widely exists in the intestinal tissue of humans and animals. And the main virulence factor in Clostridium perfringens is its exotoxins. Clostridium perfringens type C is the main strain of livestock disease, its exotoxins can induce necrotizing enteritis and enterotoxemia, which lead to the reduction in feed conversion, and a serious impact on breeding production performance. Our study found that treatment with exotoxins reduced cell viability and triggered intracellular reactive oxygen species (ROS) in human mononuclear leukemia cells (THP-1) cells. Through transcriptome sequencing analysis, we found that the levels of related proteins such as heme oxygenase 1 (HO-1) and ferroptosis signaling pathway increased significantly after treatment with exotoxins. To investigate whether ferroptosis occurred after exotoxin treatment in macrophages, we confirmed that the protein expression levels of antioxidant factors glutathione peroxidase 4/ferroptosis-suppressor-protein 1/the cystine/glutamate antiporter solute carrier family 7 member 11 (GPX4/FSP1/xCT), ferroptosis-related protein nuclear receptor coactivator 4/transferrin/transferrin receptor (NCOA4/TF/TFR)/ferritin and the level of lipid peroxidation were significantly changed. Based on the above results, our study suggested that Clostridium perfringens type C exotoxins can induce macrophage injury through oxidative stress and ferroptosis.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    背景:糖原贮积病Ib型(GSDIb)是一种罕见的疾病,其特征是由SLC37A4基因突变引起的葡萄糖稳态受损。它是一种与低血糖相关的严重遗传性代谢疾病,高脂血症,乳酸性酸中毒,肝肿大,和中性粒细胞减少症.传统治疗包括饲喂生玉米淀粉,这可以帮助调节能量代谢,但对中性粒细胞减少症没有积极作用,这对这些患者来说是致命的。最近,已经发现GSDIb中性粒细胞功能障碍和中性粒细胞减少的病理生理机制,SGLT2抑制剂empaglifozin的治疗现在已经确立。2020年,SGLT2抑制剂empagliflozin开始在全球GSDIb患者的中性粒细胞中用作有前途的1,5AG6P的有效去除剂。然而,有必要考虑一种新型治疗方法的长期效用和安全性。
    结果:在这项研究中,我们回顾性地检查了临床表现,生化检查结果,基因型,自2009年以来在我们部门就诊的35名GSDIb儿童的长期结局和随访。自2020年以来,其中14名患者接受了empagliflozin治疗。这项研究是中国最大的儿童GSDIb患者队列,也是迄今为止在单个中心接受依帕列净治疗的最大的儿童GSDIb患者队列。该研究还讨论了小儿GSDIb患者的长期管理经验。
    结论:Empagliflozin治疗小儿GSDIb患者是有效和安全的。尿糖的增加是药效的信号,然而,建议注意尿路感染和低血糖。
    BACKGROUND: Glycogen storage disease type Ib (GSD Ib) is a rare disorder characterized by impaired glucose homeostasis caused by mutations in the SLC37A4 gene. It is a severe inherited metabolic disease associated with hypoglycemia, hyperlipidemia, lactic acidosis, hepatomegaly, and neutropenia. Traditional treatment consists of feeding raw cornstarch which can help to adjust energy metabolism but has no positive effect on neutropenia, which is fatal for these patients. Recently, the pathophysiologic mechanism of the neutrophil dysfunction and neutropenia in GSD Ib has been found, and the treatment with the SGLT2 inhibitor empaglifozin is now well established. In 2020, SGLT2 inhibitor empagliflozin started to be used as a promising efficient remover of 1,5AG6P in neutrophil of GSD Ib patients worldwide. However, it is necessary to consider long-term utility and safety of a novel treatment.
    RESULTS: In this study, we retrospectively examined the clinical manifestations, biochemical examination results, genotypes, long-term outcomes and follow-up of thirty-five GSD Ib children who visited our department since 2009. Fourteen patients among them underwent empagliflozin treatment since 2020. This study is the largest cohort of pediatric GSD Ib patients in China as well as the largest cohort of pediatric GSD Ib patients treated with empagliflozin in a single center to date. The study also discussed the experience of long-term management on pediatric GSD Ib patients.
    CONCLUSIONS: Empagliflozin treatment for pediatric GSD Ib patients is efficient and safe. Increase of urine glucose is a signal for pharmaceutical effect, however attention to urinary infection and hypoglycemia is suggested.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    目的:阐明由tet(A)变异基因介导的大肠埃希菌对替加环素的耐药机制。
    方法:E.大肠杆菌573菌株携带质粒携带的tet(A)变异基因,暂时指定为TET(A)TIG,这导致替加环素敏感性降低(MIC0.5mg/L)。当暴露于浓度增加的替加环素(0.25-8mg/L)时,获得了以2、4和8mg/L生长的突变体并进行了测序。通过WGS和定量PCR(qPCR)测定突变体中质粒和tet(A)TIG相对于染色体DNA的拷贝。通过RT-qPCR评估突变体中tet(A)TIG的表达。通过S1-PFGE和Southern印迹杂交观察携带tet(A)TIG的质粒。PCR用于检测携带tet(A)TIG的非常规可环化结构(UCS)。
    结果:在替加环素存在下选择的大肠杆菌突变体中观察到最大MIC为16mg/L的替加环素抗性。与亲本菌株相比,在2、4和8mg/L替加环素存在下,突变体中tet(A)TIG的相对拷贝数和转录水平显着增加,分别。随着替加环素选择压力的增加,突变体中携带tet(A)TIG的质粒大小增加,与带有tet(A)TIG的ΔTnAs1侧翼UCS的串联扩增数相关。这些串联扩增在不存在替加环素的情况下是不稳定的。
    结论:替加环素抗性是由于大肠杆菌中ΔTnAs1侧翼的tet(A)TIG携带质粒片段的串联扩增。在存在/不存在替加环素的情况下串联扩增物的获得/损失代表了细菌在替加环素存在下存活的经济方式。
    To elucidate the mechanism of tigecycline resistance in Escherichia coli that is mediated by the tet(A) variant gene.
    E. coli strain 573 carried a plasmid-borne tet(A) variant gene, tentatively designated tet(A)TIG, that conferred decreased tigecycline susceptibility (MIC 0.5 mg/L). When exposed to increasing concentrations of tigecycline (0.25-8 mg/L), mutants growing at 2, 4 and 8 mg/L were obtained and sequenced. Copies of plasmid and tet(A)TIG relative to the chromosomal DNA in the mutants were determined by WGS and quantitative PCR (qPCR). Expression of tet(A)TIG in the mutants was evaluated by RT-qPCR. The tet(A)TIG-carrying plasmids were visualized by S1-PFGE and Southern blot hybridization. PCR served for the detection of a tet(A)TIG-carrying unconventional circularizable structure (UCS).
    Tigecycline resistance with maximum MICs of 16 mg/L was seen in E. coli mutants selected in the presence of tigecycline. Compared with the parental strain, the relative copy number and transcription level of tet(A)TIG in the mutants increased significantly in the presence of 2, 4 and 8 mg/L tigecycline, respectively. With increasing tigecycline selection pressure, the tet(A)TIG-carrying plasmids in the mutants increased in size, correlating with the number of tandem amplificates of a ΔTnAs1-flanked UCS harbouring tet(A)TIG. These tandem amplificates were not stable in the absence of tigecycline.
    Tigecycline resistance is due to the tandem amplification of a ΔTnAs1-flanked tet(A)TIG-carrying plasmid-borne segment in E. coli. The gain/loss of the tandem amplificates in the presence/absence of tigecycline represents an economic way for the bacteria to survive in the presence of tigecycline.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    筛选和研究水稻中具有耐盐活性的内生细菌对于相关微生物制剂的开发具有重要的现实意义。从24份耐盐水稻种子样品中分离出179株内生菌,这些细菌中几乎95%表现出对2%(0.34mol/L)的盐含量的耐受性。在筛选过程之后,鉴定出一种名为G9H01的细菌,表现出高达15%(2.57mol/L)的耐盐性和对稻瘟病的抗性,稻瘟病的病原体。系统发育分析证实G9H01为副衣芽孢杆菌菌株。对G9H01的完整基因组进行测序和组装,揭示了相当多的基因编码与耐盐性相关的蛋白质。进一步分析表明,G9H01可能通过多种机制缓解高盐环境中的盐胁迫。这些机制包括利用蛋白质,如K+转运蛋白,反搬运工,和Na+/H+反搬运工,参与K+吸收和Na+排泄。G9H01还证明了吸收和积累甜菜碱的能力,以及分泌细胞外多糖。总的来说,这些发现表明,副衣芽孢杆菌G9H01具有作为生物防治剂的潜力,能够在耐盐碱条件下促进水稻生长。
    It holds significant practical importance to screen and investigate endophytic bacteria with salt-tolerant activity in rice for the development of relevant microbial agents. A total of 179 strains of endophytic bacteria were isolated from 24 samples of salt-tolerant rice seeds, with almost 95 % of these bacteria exhibiting tolerance to a salt content of 2 % (0.34 mol/L). Following the screening process, a bacterium named G9H01 was identified, which demonstrated a salt tolerance of up to 15 % (2.57 mol/L) and resistance to Magnaporthe oryzae, the causal agent of rice blast disease. Phylogenetic analysis confirmed G9H01 as a strain of Bacillus paralicheniformis. The complete genome of G9H01 was sequenced and assembled, revealing a considerable number of genes encoding proteins associated with salt tolerance. Further analysis indicated that G9H01 may alleviate salt stress in a high-salt environment through various mechanisms. These mechanisms include the utilization of proteins such as K+ transporters, antiporters, and Na+/H+ antiporters, which are involved in K+ absorption and Na+ excretion. G9H01 also demonstrated the ability to uptake and accumulate betaine, as well as secrete extracellular polysaccharides. Collectively, these findings suggest that Bacillus paralicheniformis G9H01 has potential as a biocontrol agent, capable of promoting rice growth under saline-alkali-tolerant conditions.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    质膜Na/H反转运蛋白盐过度敏感1(SOS1)负责Na从细胞质中流出,植物耐盐性的重要决定因素。在这项研究中,SOS1的直系同源物,称为NsSOS1,是从锡比利亚白刺中克隆的,生长在沙漠和盐碱地的典型盐生植物,并评价了其在林木耐盐性调节中的表达和功能。NsSOS1在N.sibirica叶片中的表达水平高于根和茎中的表达水平,在盐胁迫下其表达上调。组织化学染色显示,由NsSOS1启动子驱动的β-葡萄糖醛酸苷酶(GUS)被非生物胁迫和包括盐在内的植物激素强烈诱导,干旱,低温,赤霉素,还有茉莉酸甲酯,表明NsSOS1参与多种信号通路的调节。过表达NsSOS1的转基因84K杨树(Populusalba×P.glandulosa)显示存活率提高,根系生物量,植物高度,相对水位,叶绿素和脯氨酸水平,和抗氧化酶活性与非转基因杨树(NT)在盐胁迫下。转基因杨树在根中积累了较少的Na+和较多的K+,茎,和叶子,在盐胁迫下,与NT相比,Na/K比率较低。这些结果表明,NsSOS1介导的Na外排赋予转基因杨树耐盐性,显示出更有效的光合作用,更好地清除活性氧,改善盐胁迫下的渗透调节。转基因杨树的转录组分析证实,NsSOS1不仅介导Na外排,而且还参与多种代谢途径的调节。研究结果揭示了NsSOS1的调控机制,并表明它可用于提高林木的耐盐性。
    The plasmalemma Na+/H+ antiporter Salt Overly Sensitive 1 (SOS1) is responsible for the efflux of Na+ from the cytoplasm, an important determinant of salt resistance in plants. In this study, an ortholog of SOS1, referred to as NsSOS1, was cloned from Nitraria sibirica, a typical halophyte that grows in deserts and saline-alkaline land, and its expression and function in regulating the salt tolerance of forest trees were evaluated. The expression level of NsSOS1 was higher in leaves than in roots and stems of N. sibirica, and its expression was upregulated under salt stress. Histochemical staining showed that β-glucuronidase (GUS) driven by the NsSOS1 promoter was strongly induced by abiotic stresses and phytohormones including salt, drought, low temperature, gibberellin, and methyl jasmonate, suggesting that NsSOS1 is involved in the regulation of multiple signaling pathways. Transgenic 84 K poplar (Populus alba × P. glandulosa) overexpressing NsSOS1 showed improvements in survival rate, root biomass, plant height, relative water levels, chlorophyll and proline levels, and antioxidant enzyme activities versus non-transgenic poplar (NT) under salt stress. Transgenic poplars accumulated less Na+ and more K+ in roots, stems, and leaves, which had a lower Na+/K+ ratio compared to NT under salt stress. These results indicate that NsSOS1-mediated Na+ efflux confers salt tolerance to transgenic poplars, which show more efficient photosynthesis, better scavenging of reactive oxygen species, and improved osmotic adjustment under salt stress. Transcriptome analysis of transgenic poplars confirmed that NsSOS1 not only mediates Na+ efflux but is also involved in the regulation of multiple metabolic pathways. The results provide insight into the regulatory mechanisms of NsSOS1 and suggest that it could be used to improve the salt tolerance of forest trees.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    背景:马齿轮轴和葛根对(PGP)是治疗结肠炎的传统中草药,在临床上证明对缓解腹泻和大便异常有相对有利的效果。然而,潜在的机制仍然不确定。
    目的:本研究旨在评价PGP治疗小鼠结肠炎的疗效及其机制。
    方法:通过监测体重来确定PGP对结肠炎的保护作用,结肠长度,结肠重量,和小鼠的存活率。通过血清细胞因子水平评估结肠炎症,结肠H&E染色,局部中性粒细胞浸润。随后用Western印迹和组织学染色分析PGP对肠上皮屏障损伤的逆转。此外,进行RNA-seq分析和分子对接以鉴定PGP募集的潜在途径。根据转录组结果的提示,通过Westernblot验证了PGP通过IL-6/STAT3/SOCS3途径在DSS诱导的结肠炎小鼠中的作用。
    结果:PGP治疗可显著抑制DSS诱导的小鼠结肠炎。PGP治疗可显着减轻DSS诱导的小鼠结肠炎,体重的改善证明了这一点,DAI严重性,存活率,血清和结肠中的炎性细胞因子水平。此外,PGP处理上调了Slc26a3的水平,从而增加了结肠中紧密连接/粘附性连接蛋白ZO-1,闭塞蛋白和E-钙黏着蛋白的表达。RNA-seq分析显示PGP在转录水平上抑制IL-6/STAT3/SOCS3途径。分子对接表明PGP的主要成分可以与IL-6和SOCS3蛋白紧密结合。同时,Westernblot结果显示,PGP给药后,IL-6/STAT3/SOCS3途径在蛋白水平上受到抑制。
    结论:PGP能减轻DSS诱导的结肠炎小鼠结肠炎症,逆转肠上皮屏障的损伤。潜在的机制涉及IL-6/STAT3/SOCS3途径的抑制。
    BACKGROUND: Portulacae Herba and Granati Pericarpium pair (PGP) is a traditional Chinese herbal medicine treatment for colitis, clinically demonstrating a relatively favorable effect on relieving diarrhea and abnormal stools. However, the underlying mechanism remain uncertain.
    OBJECTIVE: The present study intends to evaluate the efficacy of PGP in treating colitis in mice and investigate its underlying mechanism.
    METHODS: The protective effect of PGP against colitis was determined by monitoring body weight, colon length, colon weight, and survival rate in mice. Colonic inflammation was assessed by serum cytokine levels, colonic H&E staining, and local neutrophil infiltration. The reversal of intestinal epithelial barrier damage by PGP was subsequently analyzed with Western blot and histological staining. Furthermore, RNA-seq analysis and molecular docking were performed to identify potential pathways recruited by PGP. Following the hints of the transcriptomic results, the role of PGP through the IL-6/STAT3/SOCS3 pathway in DSS-induced colitis mice was verified by Western blot.
    RESULTS: DSS-induced colitis in mice was significantly curbed by PGP treatment. PGP treatment significantly mitigated DSS-induced colitis in mice, as evidenced by improvements in body weight, DAI severity, survival rate, and inflammatory cytokines levels in serum and colon. Moreover, PGP treatment up-regulated the level of Slc26a3, thereby increasing the expressions of the tight junction/adherens junction proteins ZO-1, occludin and E-cadherin in the colon. RNA-seq analysis revealed that PGP inhibits the IL-6/STAT3/SOCS3 pathway at the transcriptional level. Molecular docking indicated that the major components of PGP could bind tightly to the proteins of IL-6 and SOCS3. Meanwhile, the result of Western blot revealed that the IL-6/STAT3/SOCS3 pathway was inhibited at the protein level after PGP administration.
    CONCLUSIONS: PGP could alleviate colonic inflammation and reverse damage to the intestinal epithelial barrier in DSS-induced colitis mice. The underlying mechanism involves the inhibition of the IL-6/STAT3/SOCS3 pathway.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

公众号