alkaline phosphatase

碱性磷酸酶
  • 文章类型: Journal Article
    IX型分泌系统(T9SS)是细菌病原体用来促进感染的纳米机械。该系统由用作其激活开关的信令级联来调节。这个级联中的关键成员,反应调节蛋白PorX,代表了一个有希望的药物靶标,以防止毒力因子的分泌。这里,我们提供了PorX在体外和体内的全面表征。首先,我们的结构研究表明,PorX拥有一个独特的酶效应子结构域,which,令人惊讶的是,与碱性磷酸酶超家族结构相似,参与核苷酸和脂质信号通路。重要的是,到目前为止,此类途径尚未与T9SS相关。PorX效应子结构域的酶学表征揭示了锌依赖性磷酸二酯酶活性,具有适合于容纳大基底的活性位点尺寸。与典型的反应调节剂不同,它们通过磷酸化后的受体结构域二聚化,我们发现锌也可以诱导构象变化,并通过意想不到的界面促进PorX的二聚化。这些发现表明PorX可以作为细胞锌传感器,扩大我们对其监管机制的理解。尽管在利用T9SS的细菌中严格保存了PorX,我们证明,PorX是必不可少的毒力因子分泌在牙龈卟啉单胞菌和影响代谢酶分泌的非致病性黄杆菌,但不是为了分泌滑翔的粘附素。总的来说,这项研究促进了我们对PorX的结构和功能的理解,强调其作为旨在破坏T9SS和减轻致病物种毒力的干预策略的药物靶标的潜力。
    The type IX secretion system (T9SS) is a nanomachinery utilized by bacterial pathogens to facilitate infection. The system is regulated by a signaling cascade serving as its activation switch. A pivotal member in this cascade, the response regulator protein PorX, represents a promising drug target to prevent the secretion of virulence factors. Here, we provide a comprehensive characterization of PorX both in vitro and in vivo. First, our structural studies revealed PorX harbors a unique enzymatic effector domain, which, surprisingly, shares structural similarities with the alkaline phosphatase superfamily, involved in nucleotide and lipid signaling pathways. Importantly, such pathways have not been associated with the T9SS until now. Enzymatic characterization of PorX\'s effector domain revealed a zinc-dependent phosphodiesterase activity, with active site dimensions suitable to accommodate a large substrate. Unlike typical response regulators that dimerize via their receiver domain upon phosphorylation, we found that zinc can also induce conformational changes and promote PorX\'s dimerization via an unexpected interface. These findings suggest that PorX can serve as a cellular zinc sensor, broadening our understanding of its regulatory mechanisms. Despite the strict conservation of PorX in T9SS-utilizing bacteria, we demonstrate that PorX is essential for virulence factors secretion in Porphyromonas gingivalis and affects metabolic enzymes secretion in the nonpathogenic Flavobacterium johnsoniae, but not for the secretion of gliding adhesins. Overall, this study advances our structural and functional understanding of PorX, highlighting its potential as a druggable target for intervention strategies aimed at disrupting the T9SS and mitigating virulence in pathogenic species.
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  • 文章类型: Journal Article
    纳米酶是有前途的抗菌药物,因为它们产生活性氧(ROS)。然而,在区分正常菌群和致病菌时,ROS内在缺乏选择性,这剥夺了纳米酶对理想抗微生物剂的必要选择性。在这里,我们利用细菌的生理条件(高碱性磷酸酶(ALP)表达)使用一种新型的CuO纳米颗粒(NP)纳米酶系统来启动ALP激活的ROS前药系统,用于按需精确杀死细菌。前药策略涉及使用2-磷酸-L-抗坏血酸三钠盐(AAP),其催化病原菌中的ALP产生抗坏血酸(AA),由CuONPs转换,具有内在的抗坏血酸氧化酶和过氧化物酶样活性,生产ROS。值得注意的是,前药系统选择性地杀死大肠杆菌(致病菌),由于它们的ALP表达水平不同,对人葡萄球菌(非致病菌)的影响最小。与CuONP/AA系统相比,通常在储存期间耗尽ROS,CuONP/AAP表现出明显更高的稳定性,而不影响其抗菌活性。此外,使用大鼠模型来表明CuONPs/AAP纤维蛋白凝胶在体内伤口消毒中的适用性,副作用可忽略不计。这项研究揭示了这种双功能串联纳米酶平台在ALP激活条件下对致病菌的治疗精度。
    Nanozymes are promising antimicrobials, as they produce reactive oxygen species (ROS). However, the intrinsic lack of selectivity of ROS in distinguishing normal flora from pathogenic bacteria deprives nanozymes of the necessary selectivities of ideal antimicrobials. Herein, we exploit the physiological conditions of bacteria (high alkaline phosphatase (ALP) expression) using a novel CuO nanoparticle (NP) nanoenzyme system to initiate an ALP-activated ROS prodrug system for use in the on-demand precision killing of bacteria. The prodrug strategy involves using 2-phospho-L-ascorbic acid trisodium salt (AAP) that catalyzes the ALP in pathogenic bacteria to generate ascorbic acid (AA), which is converted by the CuO NPs, with intrinsic ascorbate oxidase- and peroxidase-like activities, to produce ROS. Notably, the prodrug system selectively kills Escherichia coli (pathogenic bacteria), with minimal influence on Staphylococcus hominis (non-pathogenic bacteria) due to their different levels of ALP expression. Compared to the CuO NPs/AA system, which generally depletes ROS during storage, CuO NPs/AAP exhibits a significantly higher stability without affecting its antibacterial activity. Furthermore, a rat model is used to indicate the applicability of the CuO NPs/AAP fibrin gel in wound disinfection in vivo with negligible side effects. This study reveals the therapeutic precision of this bifunctional tandem nanozyme platform against pathogenic bacteria in ALP-activated conditions.
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  • 文章类型: Journal Article
    尽管肠道炎症和生态失调与2019年冠状病毒病严重病例(COVID-19)的病理生理学有关,肠道抗炎酶的作用,如碱性磷酸酶,仍未充分开发。因此,本研究的目的是比较轻中度和重度COVID-19患者的肠道碱性磷酸酶(iALP)活性及其促炎底物-细菌脂多糖(LPS)浓度.
    从53名轻度至中度和57名重度成人COVID-19患者收集的粪便样本,以前参加过国家多中心横断面研究(NCT04355741),分析iALP活性和LPS浓度。
    在调整临床和肠道微生物参数后,与轻度至中度COVID-19患者相比,重度患者的iALP活性降低了40%(中位数[四分位距]120.6[25.2-593.1]nmolpNP/min/g蛋白质,而202.8[102.1-676.1]nmolpNP/min/g蛋白质;P=.04)。关于粪便LPS,在重症患者中发现其浓度降低(平均值±标准误差为18,118±1225EU/g粪便vs22,508±1203EU/g粪便;P=0.01),尽管该参数与血浆C反应蛋白水平无关(P=.08),全身性炎症的敏感生物标志物。相比之下,粪便ALP活性/LPS浓度比,iALP效率的指标,与轻中度COVID-19患者相比,重度患者增加(P=0.04)。
    在严重COVID-19患者中发现的iALP动力学参数的变化可能代表了抵消与COVID-19严重程度相关的肠道稳态改变(例如炎症和菌群失调)的潜在机制。
    UNASSIGNED: Although gut inflammation and dysbiosis have been implicated in the pathophysiology of severe cases of coronavirus disease 2019 (COVID-19), the role of intestinal anti-inflammatory enzymes, such as alkaline phosphatase, is still underexplored. Therefore, the aim of this study was to compare intestinal alkaline phosphatase (iALP) activity and its proinflammatory substrate - bacterial lipopolysaccharide (LPS) - concentration between mild-to-moderate and severe COVID-19 patients.
    UNASSIGNED: Stool samples collected from 53 mild-to-moderate and 57 severe adult COVID-19 patients, previously enrolled in a national multicentre cross-sectional study (NCT04355741), were analysed for iALP activity and LPS concentration.
    UNASSIGNED: iALP activity decreased by 40% in severe compared to mild-to-moderate COVID-19 patients (median [interquartile range] of 120.6 [25.2-593.1] nmol pNP/min/g of protein vs 202.8 [102.1-676.1] nmol pNP/min/g of protein; P = .04) after adjustment for clinical and gut microbiota parameters. Regarding fecal LPS, its concentration was found to be decreased in severe patients (mean ± standard error of mean of 18,118 ± 1225 EU/g of feces vs 22,508 ± 1203 EU/g of feces; P = .01), although this parameter did not correlate with plasma levels of C-reactive protein (P = .08), a sensitive biomarker of systemic inflammation. In contrast, fecal ALP activity / LPS concentration ratio, an indicator of iALP efficiency, was found to be increased in severe compared to mild-to-moderate COVID-19 patients (P = .04).
    UNASSIGNED: Changes in iALP kinetic parameters found in severe COVID-19 patients may represent a potential mechanism to counterbalance alterations in gut homeostasis (eg inflammation and dysbiosis) associated with COVID-19 severity.
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  • 文章类型: Journal Article
    脂多糖(LPS)是最有效的炎症介质之一。在养猪业中,断奶与LPS诱导的肠道炎症有关,由于发炎的肠道吸收不良,导致生长速度下降。治疗LPS介导的疾病的潜在策略是施用肠碱性磷酸酶(IAP)。后者可以解毒脂质A,LPS的毒性成分,通过去除磷酸基团。目前,已经描述了183种来自大肠杆菌的LPSO-血清型,然而,阐明LPS血清型之间功能差异的比较实验很少。此外,这些功能差异可能会影响LPS解毒酶的功效。这里,我们评估了来自大肠杆菌的四种LPS血清型(O26:B6,O55:B5,O111:B4和O127:B8)触发猪PBMC分泌促炎细胞因子的能力。我们还测试了三种市售IAP对这些LPS血清型进行解毒的能力。结果表明,LPS血清型在其触发免疫细胞分泌细胞因子的能力不同,特别是在较低的浓度。此外,IAP显示测试血清型的不同解毒效率。一起,本研究揭示了LPS结构对IAP解毒的影响。然而,需要进一步的研究来阐明LPS血清型特异性作用及其对开发新型治疗方案以减轻断奶仔猪中LPS诱导的肠道炎症的影响。
    Lipopolysaccharide (LPS) is one of the most potent mediators of inflammation. In swine husbandry, weaning is associated with LPS-induced intestinal inflammation, resulting in decreased growth rates due to malabsorption of nutrients by the inflamed gut. A potential strategy to treat LPS-mediated disease is administering intestinal alkaline phosphatase (IAP). The latter can detoxify lipid A, the toxic component of LPS, by removal of phosphate groups. Currently, 183 LPS O-serotypes from E. coli have been described, however, comparative experiments to elucidate functional differences between LPS serotypes are scarce. In addition, these functional differences might affect the efficacy of LPS detoxifying enzymes. Here, we evaluated the ability of four LPS serotypes (O26:B6, O55:B5, O111:B4 and O127:B8) derived from Escherichia coli to trigger the secretion of pro-inflammatory cytokines by porcine PBMCs. We also tested the ability of three commercially available IAPs to detoxify these LPS serotypes. The results show that LPS serotypes differ in their ability to trigger cytokine secretion by immune cells, especially at lower concentrations. Moreover, IAPs displayed a different detoxification efficiency of the tested serotypes. Together, this study sheds light on the impact of LPS structure on the detoxification by IAPs. Further research is however needed to elucidate the LPS serotype-specific effects and their implications for the development of novel treatment options to alleviate LPS-induced gut inflammation in weaned piglets.
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  • 文章类型: Journal Article
    目的:评估血清碱性磷酸酶(ALP)的预测价值,肿瘤特异性生长因子(TSGF),和巨噬细胞移动抑制因子(MIF)联合免疫抑制和靶向治疗骨肉瘤(OS)的疗效。
    方法:回顾性分析2020年10月至2022年10月西安红会医院161例OS患者的临床资料。患者接受干扰素-α(IFN-α)和贝伐单抗治疗12周。血清ALP水平,TSGF,治疗前后测量MIF。根据治疗效果,患者分为有效组和无效组.单变量和逻辑回归分析均用于评估这些生物标志物对治疗结果的影响。
    结果:血清ALP显著降低,TSGF,发现治疗后的MIF水平(均P<0.001)。这些生物标志物的治疗前水平较高与疗效较差相关(P<0.001)。
    结论:治疗前ALP水平,TSGF,和MIF是OS患者对免疫靶向治疗反应的重要独立预测因子,表明它们在指导治疗策略方面的潜在作用。
    OBJECTIVE: To assess the predictive value of serum alkaline phosphatase (ALP), tumor-specific growth factor (TSGF), and macrophage migration inhibitory factor (MIF) for the efficacy of combined immunosuppressive and targeted therapy in osteosarcoma (OS).
    METHODS: We retrospectively analyzed clinical data from 161 OS patients treated at Xi\'an Honghui Hospital from October 2020 to October 2022. Patients received 12 weeks of therapy with interferon-α (IFN-α) and bevacizumab. Serum levels of ALP, TSGF, and MIF were measured before and after treatment. Based on treatment efficacy, patients were categorized into effective and ineffective groups. Both univariate and logistic regression analyses were utilized to evaluate the influence of these biomarkers on therapy outcomes.
    RESULTS: A significant reduction in serum ALP, TSGF, and MIF levels post-treatment was found (all P<0.001). Higher pre-treatment levels of these biomarkers were associated with less effective outcomes (P<0.001).
    CONCLUSIONS: Pre-treatment levels of ALP, TSGF, and MIF are significant independent predictors of response to immunotargeted therapy in OS patients, suggesting their potential role in guiding treatment strategies.
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  • 文章类型: Journal Article
    背景:血清碱性磷酸酶(ALP)水平升高是血液透析患者全因死亡的危险因素。传统上在日本,ALP测量使用JSCC方法进行,比IFCC方法产生更高的ALP测量值,主要是由于其对肠道ALP的敏感性增加。
    方法:比较了521例血液透析患者不同血型之间从JSCC转换为IFCC前后的血清总ALP水平(研究1)。分析了通过JSCC方法测量的ALP水平与7年死亡率之间的关系,包括血型和肝功能参数作为协变量,510例血液透析患者(研究2)。
    结果:通过JSCC方法测得的ALP水平比通过IFCC方法测得的ALP水平高约三倍,与A型和AB型血相比,B型和O型血的患者显着升高。同样,通过IFCC方法测量的ALP水平在血型B和O的患者中明显高于血型A和AB的患者(研究1)。最高的三元组ALP水平显示全因死亡率的风险显着增加,即使在调整患者背景之后。然而,当血清肝功能相关标志物或炎症标志物作为协变量纳入时,这一显著性消失(研究2).
    结论:通过JSCC方法测量的ALP水平与生活预后相关,但是,由于B型和O型血患者以及肝功能障碍或炎症患者的升高,应谨慎行事。
    BACKGROUND: Elevated serum alkaline phosphatase (ALP) levels are a risk factor for all-cause mortality in hemodialysis patients. Traditionally in Japan, ALP measurements were conducted using the JSCC method, which yields higher ALP measurement values than the IFCC method, mainly due to its increased sensitivity to intestinal ALP.
    METHODS: Serum total ALP levels before and after switching the assay method from JSCC to IFCC were compared among different blood types in 521 hemodialysis patients (Study 1). The association between ALP levels measured by the JSCC method and 7-year mortality was analyzed, including blood types and liver function parameters as covariates, in 510 hemodialysis patients (Study 2).
    RESULTS: ALP levels measured by the JSCC method were approximately three times higher than those measured by the IFCC method, with significant elevation in patients with blood types B and O compared to those with blood types A and AB. Similarly, ALP levels measured by the IFCC method were significantly higher in patients with blood types B and O compared to those with blood types A and AB (Study 1). The highest tertile of ALP levels showed a significantly increased risk of all-cause mortality, even after adjusting for patient background. However, this significance disappeared when serum liver function-related or inflammatory markers were included as covariates (Study 2).
    CONCLUSIONS: ALP levels measured by the JSCC method are associated with life prognosis, but caution should be exercised due to their elevation in patients with blood types B and O and in those with hepatic dysfunction or inflammation.
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  • 文章类型: Journal Article
    目的:使用全血体外常温机器灌注(NMP),我们评估了再灌注下的猪边缘肾脏。目的是将可测量的机器和临床血液参数与当前使用的视觉评估联系起来。这可以作为标准化评估评分的基线,以确定将来可能可移植的肾脏。
    方法:从屠宰场猪(n=33)获得肾脏和自体全血,并使用NMP灌注4小时。血流动力学参数动脉压(AP),测量肾血流量(RBF)和肾内阻力(IRR)。天冬氨酸转氨酶(AST)活性,γ-谷氨酰转移酶(GGT),碱性磷酸酶(ALP),在0/1/2/4h时评估血液中的乳酸脱氢酶(LDH)和乳酸。由经验丰富的医生根据NMP后肾脏的整体宏观外观,将肾脏分为“潜在可移植”(PT)或“不可移植”(NT)。
    结果:PT肾(n=20)的IRR和RBF明显低于NT肾(n=13)。GGT,ALP和LDH没有显著差异,但是在4小时,与NT肾脏相比,PT肾脏中的AST明显更高。NMP期间,NT肾脏的乳酸水平持续上升,并且在1/2/4小时时明显高于PT肾脏。
    结论:立即评估的检查肾脏的宏观方面与血液动力学参数相关,在这项研究中,乳酸增加,AST降低。在未来,通过允许在移植前评估边缘肾脏的未知特征,具有全血的NMP可能是扩大供体库的有用工具。
    OBJECTIVE: Using ex vivo normothermic machine perfusion (NMP) with whole blood we assessed marginal porcine kidneys under reperfusion. The aim was to link measureable machine and clinical blood parameters with the currently used visual assessment. This could serve as a baseline for a standardized evaluation score to identify potentially transplantable kidneys in the future.
    METHODS: Kidneys and autologous whole blood were procured from slaughterhouse pigs (n = 33) and were perfused for 4 h using NMP. The hemodynamic parameters arterial pressure (AP), renal blood flow (RBF) and intrarenal resistance (IRR) were measured. Activity of aspartate transaminase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and lactate were assessed in blood at 0/1/2/4 h. Kidneys were grouped into \"potentially transplantable\" (PT) or \"not transplantable\" (NT) based on their overall macroscopic appearance after NMP by an experienced physician.
    RESULTS: PT-kidneys (n = 20) had a significantly lower IRR and higher RBF than NT-kidneys (n = 13). GGT, ALP and LDH did not differ significantly, but at 4 h, AST was significantly higher in PT-kidneys compared to NT-kidneys. Lactate levels kept increasing during NMP in NT-kidneys and were significantly higher at 1/2/4 h than in PT-kidneys.
    CONCLUSIONS: The immediately assessed macroscopic aspects of examined kidneys correlated with hemodynamic parameters, increased lactate and lower AST in this study. In the future, NMP with whole blood could be a useful tool to extend the donor pool by allowing the assessment of otherwise unknown characteristics of marginal kidneys before transplantation.
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  • 文章类型: Journal Article
    铜离子(Cu2+),焦磷酸盐(PPi),和碱性磷酸酶(ALP)参与各种生化过程,如DNA复制,细胞代谢在人体生长发育中起着重要作用。因此,建立一种灵敏的Cu2+检测方法具有重要意义,PPi和ALP。在这项工作中,以硫酸肼为还原剂,通过一锅法成功合成了聚乙烯亚胺封端的银纳米簇(PEI-AgNCs),在约339nm的近紫外区域表现出独特的强荧光发射。由于PEI-AgNCs的荧光可以通过内部过滤效应(IFE)被Cu2+猝灭,然后通过焦磷酸盐和Cu2+的竞争性结合回收,后来又被碱性磷酸酶的催化水解削弱,建立了基于荧光“ON”或“OFF”变化的灵敏和选择性策略来检测Cu2+,PPi和ALP。这三种分析物的LOD为36nM,0.2μM,和0.14UL-1,S/N比为3。一系列用于感测铜离子的逻辑门电路,焦磷酸盐,并成功构建了碱性磷酸酶。建立的方法具有生物传感和环境分析的潜力,PEI-AgNCs的特定UV-A荧光特性可能在光子和光学领域有所帮助。
    Cupric ions (Cu2+), pyrophosphate (PPi), and alkaline phosphatase (ALP) are involved in a variety of biochemical processes such as DNA replication, cellular metabolism and play an important role in human growth and development. It is of great significance to establish a method for the sensitive detection of Cu2+, PPi and ALP. In this work, polyethyleneimine-capped silver nanoclusters (PEI-AgNCs) were successfully synthesized by a one-pot method using hydrazine sulfate as reductant, exhibiting a unique strong fluorescence emission in the near-ultraviolet region at ∼339 nm. Since the fluorescence of PEI-AgNCs can be quenched by Cu2+ through inner filtering effect (IFE), then recovered by competitive binding of pyrophosphate and Cu2+, and later weakened again by catalytic hydrolysis of alkaline phosphatase, a sensitive and selective strategy based on the changes of fluorescence \"ON\" or \"OFF\" was established to detect Cu2+, PPi and ALP. The LODs of these three analytes were 36 nM, 0.2 μM, and 0.14 U L-1 at a S/N ratio of 3, respectively. A series of logic gate circuits for sensing cupric ions, pyrophosphate, and alkaline phosphatase were successfully constructed. The established methods have the potential for biosensing and environmental analysis and the specific UV-A fluorescence property of PEI-AgNCs may be helpful in photonic and optical areas.
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  • 文章类型: Journal Article
    本研究旨在探讨组蛋白甲基转移酶SET和含MYND结构域3(SMYD3)在氟暴露成骨细胞骨代谢中的作用。尿氟化物的水平,BALP,在知情同意的情况下,测定氟骨症患者和未接触氟的人的OC和SMYD3的mRNA表达。SMYD3蛋白的表达,OC内容,在氟化钠(NaF)处理48h的人成骨细胞样MG63细胞和大鼠原代成骨细胞中检测BALP活性。通过透射电子显微镜观察自噬体。然后,我们将SMYD3敲低,以确认其是否参与骨形成的调节,并与自噬和Wnt/β-catenin通路有关。我们观察到骨性氟中毒患者的OC和BALP水平显著升高,而SMYD3的mRNA表达在氟骨症组显著降低。体外,OC内容,BALP活动,SMYD3的表达显著增加,在NaF处理的成骨细胞中观察到许多自噬体。SMYD3下调显著抑制OC含量,BALP活动,和自噬相关蛋白的表达,但Wnt/β-catenin通路无明显变化。我们的结果表明,燃煤污染的氟化物暴露会导致骨科损伤以及OC和BALP水平异常,并阻碍了正常的骨代谢。沉默SMYD3基因可通过抑制氟诱导的自噬增加而显著降低OC和BALP水平。
    This study aimed to explore the role of histone methyltransferase SET and MYND domain containing 3 (SMYD3) in bone metabolism of osteoblasts exposed to fluoride. The levels of urine fluoride, BALP, and OC and the mRNA expression of SMYD3 were determined in patients with skeletal fluorosis and non-fluoride-exposed people on informed consent. The expression of SMYD3 protein, OC contents, and BALP activities were detected in human osteoblast-like MG63 cells and rat primary osteoblasts treated with sodium fluoride (NaF) for 48 h. The autophagosomes were observed by transmission electron microscopy. Then, we knocked down SMYD3 to confirm whether it was involved in the regulation of bone formation and related to autophagy and Wnt/β-catenin pathway. We observed that OC and BALP levels in patients with skeletal fluorosis significantly increased, while the mRNA expression of SMYD3 significantly decreased in the skeletal fluorosis groups. In vitro, the OC contents, BALP activities, and expression of SMYD3 significantly increased, and many autophagosomes were observed in NaF treated osteoblasts. The downregulation of SMYD3 significantly inhibited OC contents, BALP activities, and expression of autophagy-related proteins, but with no significant changes in the Wnt/β-catenin pathway. Our results demonstrated that fluoride exposure with coal-burning pollution caused orthopedic injuries and abnormalities in the levels of OC and BALP and hindered normal bone metabolism. Silencing the SMYD3 gene could significantly reduce OC and BALP levels via inhibiting the increase in autophagy induced by fluoride.
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  • 文章类型: Journal Article
    脓毒症,广泛地描述为全身性感染,是世界范围内死亡和长期残疾的主要原因之一。可用于改善存活和/或改善存活者的生活质量的治疗选择有限。伊洛福酶阿尔法,也称为重组碱性磷酸酶(recAP),在一部分脓毒症相关急性肾损伤患者中,与死亡率降低相关.然而,recAP是否在肾脏以外的其他器官系统中显示任何治疗益处尚不清楚.这项研究的目的是评估recAP对生存的影响,行为,和脓毒症小鼠模型的肠道炎症,盲肠结扎和穿孔(CLP)。在CLP之后,通过每日腹膜内注射施用recAP或盐水载体,以确定其从早期到晚期脓毒症的治疗功效.我们发现,recAP的给药抑制了肠道和肝脏的炎症指数,但不能改善生存率或行为结果。这些结果表明,recAP在肠道和肝脏中的治疗效果可能为改善脓毒症幸存者的长期预后提供有价值的治疗方法。
    Sepsis, broadly described as a systemic infection, is one of the leading causes of death and long-term disability worldwide. There are limited therapeutic options available that either improve survival and/or improve the quality of life in survivors. Ilofotase alfa, also known as recombinant alkaline phosphatase (recAP), has been associated with reduced mortality in a subset of patients with sepsis-associated acute kidney injury. However, whether recAP exhibits any therapeutic benefits in other organ systems beyond the kidney is less clear. The objective of this study was to evaluate the effects of recAP on survival, behavior, and intestinal inflammation in a mouse model of sepsis, cecal ligation and puncture (CLP). Following CLP, either recAP or saline vehicle was administered via daily intraperitoneal injections to determine its treatment efficacy from early through late sepsis. We found that administration of recAP suppressed indices of inflammation in the gut and liver but did not improve survival or behavioral outcomes. These results demonstrate that recAP\'s therapeutic efficacy in the gut and liver may provide a valuable treatment to improve long-term outcomes in sepsis survivors.
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