ethanol

乙醇
  • 文章类型: Journal Article
    工业生物技术严重依赖于源自富含糖或淀粉的作物的碳水化合物底物的微生物转化。面对不断增加的人口和粮食短缺,这种依赖带来了重大挑战。因此,探索可再生,可持续生物加工的非竞争性碳源变得越来越重要。乙醇,一种关键的C2原料,提出了一个有希望的替代方案,特别是用于生产乙酰辅酶A衍生物。在这次审查中,我们对乙醇作为替代碳源的潜力进行了深入分析,总结其被微生物利用时的独特特征,微生物乙醇代谢途径,以及微生物对乙醇胁迫的反应和耐受机制。我们提供了乙醇生物制造和乙醇生物合成的最新进展,讨论当前的挑战,并概述潜在的研究方向,以指导该领域的未来发展。这里提出的见解可以为寻求利用乙醇生产高价值产品的潜力的研究人员和行业专业人士提供有价值的理论支持。
    Industrial biotechnology heavily relies on the microbial conversion of carbohydrate substrates derived from sugar- or starch-rich crops. This dependency poses significant challenges in the face of a rising population and food scarcity. Consequently, exploring renewable, non-competing carbon sources for sustainable bioprocessing becomes increasingly important. Ethanol, a key C2 feedstock, presents a promising alternative, especially for producing acetyl-CoA derivatives. In this review, we offer an in-depth analysis of ethanol\'s potential as an alternative carbon source, summarizing its distinctive characteristics when utilized by microbes, microbial ethanol metabolism pathway, and microbial responses and tolerance mechanisms to ethanol stress. We provide an update on recent progress in ethanol-based biomanufacturing and ethanol biosynthesis, discuss current challenges, and outline potential research directions to guide future advancements in this field. The insights presented here could serve as valuable theoretical support for researchers and industry professionals seeking to harness ethanol\'s potential for the production of high-value products.
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  • 文章类型: Journal Article
    花椒(ZR)传统上用于治疗各种疾病,包括糖尿病.氧化应激可能加速糖尿病病情。现有的抗糖尿病和抗氧化药物有许多缺点,包括耐药性,效率低下,更高的剂量,副作用和成本。当前研究的目的是通过体外评估花椒根皮(ZRRB)的乙醇提取物的抗氧化能力和抗糖尿病活性,在体内,和硅方法。使用DPPH自由基测定和总抗氧化活性测试测量ZRRB提取物的抗氧化能力。口服葡萄糖耐量试验(OGTT)和四氧嘧啶诱导的糖尿病小鼠模型也用于检查体内抗糖尿病功效。通过GCMS分析进行植物化学品鉴定。此外,计算方法,如分子对接,ADMET分析,和分子动力学(MD)建模,以确定上述药理作用。提取物表现出显著的DPPH清除活性(IC50=42.65μg/mL)。在OGTT试验和四氧嘧啶诱导的糖尿病小鼠模型中,该提取物可有效降低血糖水平。此外,胰腺α-淀粉酶的体外抑制研究表明,ZRRB提取物是一种良好的抗糖尿病原料药(IC50=81.45μg/mL)。GCMS调查证实,粗提物含有16种主要植物成分,与人过氧化物酶5,α-淀粉酶对接,和磺酰脲受体1。对接和药代动力学研究表明,在16种植物成分中,6H-吲哚并[3,2,1-de][1,5]萘啶-6-酮(CID:97176)对目标酶的结合亲和力最高,模仿Lipinski的5条规则.此外,MD模拟数据证实上述化合物对α-淀粉酶和磺酰脲受体1受体的结合位点非常稳定。来自体外的发现,体内和计算机研究表明,ZRRB提取物含有一种先导化合物,该化合物可能是抗糖尿病药物候选物的有效来源。
    Zanthoxylum rhetsa (ZR) is used traditionally to manage a variety of ailments, including diabetes. Oxidative stress may accelerate the diabetic condition. The available antidiabetic and antioxidant drugs have many shortcomings including resistance, inefficiency, higher dose, side effects and costs. The goal of the current investigation was to assess the antioxidant capacity and antidiabetic activity of an ethanolic extract of Zanthoxylum rhetsa root bark (ZRRB) through in vitro, in vivo, and in silico methods. The antioxidant capacity of the ZRRB extract was measured using both the DPPH radical assay and the total antioxidant activity test. The oral glucose tolerance test (OGTT) and alloxan-induced diabetic mice model were also used to examine in vivo antidiabetic efficacy. Phytochemicals identification was done by GCMS analysis. Additionally, computational methods such as molecular docking, ADMET analysis, and molecular dynamics (MD) modeling were performed to determine the above pharmacological effects. The extract demonstrated significant DPPH scavenging activity (IC50 = 42.65 μg/mL). In the OGTT test and alloxan-induced diabetes mice model, the extract effectively lowered blood glucose levels. Furthermore, in vitro inhibition of pancreatic α-amylase studies demonstrated the ZRRB extract as a good antidiabetic crude drug (IC50 = 81.45 μg/mL). GCMS investigation confirmed that the crude extract contains 16 major phytoconstituents, which were docked with human peroxiredoxin-5, α-amylase, and sulfonylurea receptor 1. Docking and pharmacokinetic studies demonstrated that among 16 phytoconstituents, 6H-indolo[3,2,1-de] [1,5]naphthyridin-6-one (CID: 97176) showed the highest binding affinity to targeted enzymes, and imitated Lipinski\'s rule of five. Furthermore, MD simulation data confirmed that the aforementioned compound is very steady to the binding site of α-amylase and sulfonylurea receptor 1 receptors. Findings from in vitro, in vivo and in silico investigation suggest that ZRRB extract contains a lead compound that could be a potent source of antidiabetic drug candidate.
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  • 文章类型: Journal Article
    肝硬化患者容易发生急性肾损伤(AKI),这导致了糟糕的结果。我们进行了一项研究,以评估肝硬化患者的AKI谱。
    这项研究是在2020年4月至2022年12月在印度三级护理中心收治的连续肝硬化AKI患者中进行的。详细信息,包括历史记录,检查结果,并记录实验室调查的结果。
    本研究共纳入243例患者。大多数(91.3%)的患者是男性。肝硬化最常见的病因是58.4%(n=142)的酒精,其次是10.3%(n=25)的乙型肝炎。54.4%(n=132)的患者存在肾前型AKI,21.8%(n=53)的患者存在肝肾综合征(HRS)。IgA肾病是内源性肾脏疾病无反应者中最常见的(n=6)肾小球病理。大多数患者属于II期(46.9%)和I期AKI(37%),而只有16.1%的人患有III期AKI。AKI的各个阶段与Child-Turcotte-Pugh(CTP)评分和终末期肝病模型(MELD)-Na评分显着相关(P<0.05)。总体住院死亡率为18.5%(n=45)。
    肾功能障碍是肝硬化患者常见的并发症。肾前因素是肝硬化患者AKI的最常见原因。AKI分期与肝脏预后评分显著相关。对治疗无反应的患者应考虑肾活检,指导进一步的管理。
    UNASSIGNED: Patients with cirrhosis are susceptible to development of acute kidney injury (AKI), which leads to poor outcome. We conducted a study to evaluate the spectrum of AKI in patients with cirrhosis.
    UNASSIGNED: This study was conducted in consecutive cirrhotic patients with AKI admitted in a tertiary care center of India from April 2020 to December 2022. Details including history, examination findings, and results of laboratory investigations were recorded.
    UNASSIGNED: A total of 243 patients were enrolled in this study. The majority (91.3%) of the patients were males. The most common etiology of cirrhosis was alcohol in 58.4% (n = 142) followed by hepatitis B in 10.3% (n = 25) of patients. Pre-renal form of AKI was present in 54.4% (n = 132) of patients and hepatorenal syndrome (HRS) in 21.8% (n = 53) of patients. IgA nephropathy was the commonest (n = 6) glomerular pathology in nonresponders with intrinsic renal disease. Majority of the patients belonged to stage II (46.9%) and stage I AKI (37%), while only 16.1% had stage III AKI. Various stages of AKI showed a significant correlation (P < 0.05) with Child-Turcotte-Pugh (CTP) score and Model for End-stage Liver Disease (MELD)-Na score. The overall in-hospital mortality rate was found to be 18.5% (n = 45).
    UNASSIGNED: Renal dysfunction is a frequent complication among cirrhotic patients. Pre-renal factors were the most common cause of AKI in cirrhotics. Stages of AKI showed significant correlation with liver prognostic scores. Renal biopsy should be considered in patients not responding to treatment, to guide further management.
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  • 文章类型: Journal Article
    没有可用的摘要。
    No abstract available.
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  • 文章类型: Journal Article
    背景:基于酒精的手擦(ABHR)是手部卫生(HH)的黄金标准,并且是感染预防和控制(IPC)策略的基石。然而,几个因素影响卫生工作者对ABHR的有效使用。这项研究评估了卫生工作者对本地生产的ABHR产品和HH行为的耐受性和可接受性。
    方法:根据WHO的标准化方案进行了一项基于医院的纵向干预研究,以评估ABHR的耐受性和可接受性(方法1)。塞拉利昂4家医院的60名卫生工作者在30天的时间内接受了训练有素的观察员的三次单独访问(第1天、第3-5天和第30天)的观察。感兴趣的结果包括使用主观和客观测量评估的皮肤耐受性和产品可接受性。
    结果:客观和主观评价显示出较强的皮肤耐受性和产品的高可接受性。在所有三次访问中,经过培训的观察者评估的皮肤耐受性评分<2,≥97%的参与者,超过WHO基准评分(BMS=<2in≥75%)。参与者对整体皮肤完整性的自我评估为97%(第2次访问)和98%(第3次访问),得分>4(BMS=>4,≥75%)。主要可接受性标准在第3次就诊时增加到95%(颜色)和88%(气味)(BMS=>4,≥50%)。尽管可接受性很高,在第2次和第3次访问期间,产品的干燥效果分别为52%和58%(BMS=>4in≥75%)。有积极的HH行为(n=53,88%),其中一半以上(n=38,63%)几乎在每个HH时刻都表现出HH。平均ABHR明显较高(76.1ml,标准差±35),特别是在护士(平均=80.1毫升)和医生(平均=74.0毫升)。
    结论:世界卫生组织制定的,本地生产的ABHR耐受性良好,并被卫生工作者接受.这些发现支持持续利用基于证据的,在资源有限的环境中进行具有成本效益的手卫生干预。高手擦消耗和频繁的HH实践是明显的HH行为。建议进一步研究以优化皮肤干燥的产品配方,并研究ABHR消耗与手部卫生依从性之间的关联。
    BACKGROUND: Alcohol-based handrub (ABHR) is the gold standard for hand hygiene (HH) and is a cornerstone of infection prevention and control (IPC) strategies. However, several factors influence the efficient use of ABHR by health workers. This study evaluated the tolerability and acceptability of a locally produced ABHR product and HH behaviour among health workers.
    METHODS: A longitudinal hospital-based intervention study was conducted in accordance with the WHO\'s standardized protocol for evaluating ABHR tolerability and acceptability (Method 1). Sixty health workers across 4 hospitals in Sierra Leone were observed over a 30-day period at three separate visits (days 1, 3-5, and 30) by trained observers. The outcomes of interest included skin tolerability and product acceptabilityevaluated using subjective and objective measures.
    RESULTS: Objective and subjective evaluations demonstrated strong skin tolerability and high acceptability with the product. At all three visits, the skin tolerability score assessed by trained observers was < 2 in ≥ 97% of participants, exceeding the WHO benchmark score (BMS = < 2 in ≥ 75%). Participants\' self-evaluations of overall skin integrity were 97% (visit 2) and 98% (visit 3) for scores > 4 (BMS = > 4 in ≥ 75%). The primary acceptability criteria increased up to 95% (colour) and 88% (smell) at visit 3 (BMS = > 4 in ≥ 50%). Despite high acceptability, the product\'s drying effect remained low at 52% and 58% during visits 2 and 3, respectively (BMS = > 4 in ≥ 75%). There were positive HH behaviours (n = 53, 88%), with more than half (n = 38, 63%) of them exhibiting HH at almost every HH moment. The mean ABHR was notably high (76.1 ml, SD ± 35), especially among nurses (mean = 80.1 ml) and doctors (mean = 74.0 ml).
    CONCLUSIONS: The WHO-formulated, locally produced ABHR was well tolerated and accepted by health workers. These findings support the continuous utilization of evidence-based, cost-effective hand hygiene interventions in resource-limited settings. High handrub consumption and frequent HH practices were noticeable HH behaviours. Further research is recommended to optimize product formulations for skin dryness and investigate the association between ABHR consumption and hand hygiene compliance.
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  • 文章类型: Journal Article
    本研究旨在确定右桂丸与五子岩宗丸(DYWWYW)的联合作用和机理,一种传统的中草药配方,在95%乙醇诱导的子宫内膜薄型小鼠模型中。
    薄型子宫内膜小鼠用孕酮(0.002mg)以及低剂量和高剂量的DYWWYW(0.05和0.5mLDYWWYW,分别,在2mL生理盐水中稀释)。进行蛋白质印迹和qRT-PCR分析以确定蛋白质和mRNA表达水平,分别,子宫组织中整合素αγβ3和白血病抑制因子(LIF)的表达。通过ELISA测定血清雌二醇和孕酮浓度。其余薄型子宫内膜小鼠与雄性小鼠交配,并计算不同组植入的胚胎数量。
    高剂量的DYWWYW可有效改善95%乙醇引起的子宫内膜损伤。雌二醇的水平,黄体酮,用高剂量DYWWYW治疗的薄型子宫内膜小鼠中的αγβ3和LIF也显着升高。此外,高剂量的DYWWYW可显着增加子宫内膜薄型小鼠的胚胎植入次数。
    DYWWYW通过提高内源性雌二醇水平对薄型子宫内膜有改善作用,黄体酮,小鼠模型中的αγβ3和LIF。
    在生殖周期中,子宫内膜厚度超过7mm被认为是成功胚胎植入的临界值.目前,虽然治疗子宫内膜厚度的改善,如西地那非,子宫内膜刮除,已经尝试了粒细胞集落刺激因子和低剂量的阿司匹林,对患者的影响并不一致。因此,有必要寻求新的治疗方法来有效增加子宫内膜厚度。本研究建立了95%乙醇诱导的子宫内膜薄型雌性ICR小鼠模型。高剂量右归丸汤联合五子延宗丸(DYWWYW)可有效改善子宫内膜损伤,并显着增加薄型子宫内膜小鼠的胚胎植入次数。此外,包括雌二醇在内的一些关键指标的水平,黄体酮,在用高剂量DYWWYW处理的薄型子宫内膜小鼠中,αγβ3和LIF也增加。因此,DYWWYW在小鼠模型中增加子宫内膜厚度方面是可行的。
    UNASSIGNED: This study aimed to determine the effect and mechanism of the Decoction of Yougui Wan combined with Wuzi Yanzong Wan (DYWWYW), a traditional Chinese herbal formula, in a mouse model with thin endometrium induced by 95% ethanol.
    UNASSIGNED: Thin endometrium mice were treated with progynova (0.002 mg) as well as a low and high dose of DYWWYW (0.05 and 0.5 mL DYWWYW, respectively, diluted in 2 mL normal saline). Western blotting and qRT-PCR analyses were performed to determine the protein and mRNA expression levels, respectively, of integrin αγβ3 and leukaemia inhibitor factor (LIF) in uterus tissues. Serum oestradiol and progesterone concentrations were determined via ELISA. The remaining thin endometrium mice were mated with male mice, and the number of embryos implanted in the different groups was calculated.
    UNASSIGNED: A high dose of DYWWYW effectively ameliorated the injury of endometrium caused by 95% ethanol. The levels of oestradiol, progesterone, αγβ3 and LIF in thin endometrium mice treated with a high dose of DYWWYW were also significantly elevated. Additionally, a high dose of DYWWYW remarkably increased the number of embryo implantations in mice with thin endometrium.
    UNASSIGNED: DYWWYW has improvement effects on thin endometrium by elevating the levels of endogenous oestradiol, progesterone, αγβ3, and LIF in a mouse model.
    During the reproductive cycle, endometrium thickness of more than 7 mm is considered as a cut-off value for successful embryo implantation. Currently, although therapies for the improvement of endometrium thickness such as sildenafil, endometrial scraping, granulocyte colony-stimulating factor and low dose of aspirin have been tried, the effects on patients are not consistent. Consequently, it is necessary to seek novel therapies to increase endometrium thickness effectively. A 95% ethanol-induced thin endometrium female ICR mouse model was established in this study. High dose of Decoction of Yougui Wan combined with Wuzi Yanzong Wan (DYWWYW) effectively ameliorated the injury of endometrium and remarkably increased the number of embryo implantations in thin endometrium mice. Additionally, the levels of some key indicators including oestradiol, progesterone, αγβ3, and LIF were also increased in thin endometrium mice treated with high dose of DYWWYW. Therefore, DYWWYW was feasible in increasing endometrium thickness in a mouse model.
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  • 文章类型: Journal Article
    已知同时滥用酒精-可卡因会导致肝脏中更强,更不可预测的细胞损伤,心,和大脑。然而,可卡因和酒精在肝损伤中的作用机制仍不清楚.这些发现揭示了可卡因诱导的小鼠和小鼠的肝损伤和炎症。值得注意的是,与单独治疗相比,在小鼠中同时服用可卡因和乙醇会导致更严重的肝损伤。代谢组学分析证实,马尿酸(HA)是可卡因消耗后血清中最丰富的代谢物,并且在原代猴肝细胞中形成。HA,可卡因的代谢产物,增加线粒体DNA泄漏,随后通过Kupffer细胞(KCs)中的STING信号增加促炎因子的产生。此外,可卡因处理的KC通过酒精诱导的TNFR1诱导的肝细胞坏死的条件培养基。最后,体内STING信号传导的中断改善了酒精和可卡因诱导的肝损伤和炎症的共同给药。这些发现假设HA-STING-TNFR1轴的干预作为治疗酒精和可卡因诱导的过度肝损伤的新策略。
    The simultaneous abuse of alcohol-cocaine is known to cause stronger and more unpredictable cellular damage in the liver, heart, and brain. However, the mechanistic crosstalk between cocaine and alcohol in liver injury remains unclear. The findings revealed cocaine-induced liver injury and inflammation in both marmosets and mice. Of note, co-administration of cocaine and ethanol in mice causes more severe liver damage than individual treatment. The metabolomic analysis confirmed that hippuric acid (HA) is the most abundant metabolite in marmoset serum after cocaine consumption and that is formed in primary marmoset hepatocytes. HA, a metabolite of cocaine, increases mitochondrial DNA leakage and subsequently increases the production of proinflammatory factors via STING signaling in Kupffer cells (KCs). In addition, conditioned media of cocaine-treated KC induced hepatocellular necrosis via alcohol-induced TNFR1. Finally, disruption of STING signaling in vivo ameliorated co-administration of alcohol- and cocaine-induced liver damage and inflammation. These findings postulate intervention of HA-STING-TNFR1 axis as a novel strategy for treatment of alcohol- and cocaine-induced excessive liver damage.
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  • 文章类型: Journal Article
    为了提高马铃薯片的干燥质量,这项研究采用了微波加热(MH)结合乙醇渗透脱水(EOD)预处理策略,以提高爆炸膨化干燥(EPD)的质量。本文系统地研究了不同预处理方法的效果(不处理,HAD,MH,EOD,MHEOD)对进行CO2-EPD的马铃薯切片的质量和理化性质。结果表明,经过MH和EOD预处理,马铃薯切片的内部孔表现出均匀的多孔结构。MH+EOD+CO2-EPD处理表现出优异的膨胀,脆度,硬度,和颜色,维生素C和蛋白质的保留率较高。测量结果为2.15的膨胀比,1290.01g的硬度,脆度745.94克,ΔE为6.54,蛋白质含量为1.99g/100g,VC含量为17.33mg/100g。此外,这项研究探索了微波功率的影响,微波干燥时间,乙醇浓度,和乙醇浸泡时间对膨胀比的影响,硬度,脆度,蛋白质含量,VC内容,和颜色。MH+EOD+CO2-EPD是一种环境可持续和高效的解决方案,具有广泛的工业应用潜力,可提高加工质量和经济效益。
    To enhance the drying quality of potato slices, this investigation employed a microwave heating (MH) combined with ethanol osmotic dehydration (EOD) pretreatment strategy to improve the quality of explosion puffing drying (EPD). This paper systematically investigated the effects of different pretreatment methods (no treatment, HAD, MH, EOD, MH+EOD) on the quality and physicochemical properties of potato slices subjected to CO2-EPD. The results showed that after MH and EOD pretreatments, the internal pores of the potato slices exhibited a uniform porous structure. The MH+EOD+CO2-EPD treatment demonstrated superior expansion, crispness, hardness, and color, with higher retention rates of vitamin C and protein. The measurements were an expansion ratio of 2.15, hardness of 1290.01 g, crispness of 745.94 g, ΔE of 6.54, protein content of 1.99 g/100 g, and VC content of 17.33 mg/100 g. Additionally, the study explored the effects of microwave power, microwave drying time, ethanol concentration, and ethanol soaking time on the expansion ratio, hardness, crispness, protein content, VC content, and color. MH+EOD+CO2-EPD is an environmentally sustainable and efficient solution with potential for widespread industrial application to enhance processing quality and economic benefits.
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  • 文章类型: Journal Article
    在生物炼制的背景下,研究人员一直在寻找木质纤维素生物质和理想的处理方法来生产经济上可行的生物燃料。在这种情况下,竹秆表现为具有巨大潜力的植物基质,纤维素含量高,结晶度低。因此,这项工作的目的和差异是确定从竹秆中提取的纤维素的酶水解的最佳条件,并评估其在通过分离水解和发酵(SHF)以及糖化和同时发酵(SSF)生产生物乙醇中的潜在应用。通过CRISPR/Cas9修饰的酿酒酵母。平均纤维素提取率为41.87%,提取效率为86.76%。总的来说,随着水解时间的增加,在几乎所有的分析中都观察到葡萄糖产生的增加,在72h时具有较高的水解效率值。结果范围为2.09至19.8g/L的葡萄糖,效率值为10.47至99%。在测试5中发现了最佳条件(36°C的温度和pH5.0,只有10FPU/g的底物CellicCtec2Novozymes®鸡尾酒)。观察到,对于所有水解时间,在水解效率下,自变量pH和温度均显着。表现出负面影响,指示相同的较高值促进响应变量的较低值。对于生物乙醇生产,发酵4小时后,SSH过程的最大浓度为7.84g/L,而对于SSF过程,发酵24小时后为12.6g/L,表明同时过程的巨大潜力以及竹秆生物质在高产量生物燃料中的应用。
    In the context of biorefinery, researchers have been looking for lignocellulosic biomasses and ideal treatments to produce economically viable biofuels. In this scenario, the bamboo culm appears as a plant matrix of great potential, given the high cellulose content of low crystallinity. Thus, the objective and differential of this work was to determine the best conditions for enzymatic hydrolysis of cellulose extracted from bamboo culm and to evaluate its potential application in the production of bioethanol through Separate Hydrolysis and Fermentation (SHF) and Saccharification and Simultaneous Fermentation (SSF) by Saccharomyces cerevisiae modified via CRISPR/Cas9. The average cellulose extraction yield was 41.87 % with an extraction efficiency of 86.76 %. In general, as the hydrolysis time increased, an increase in glucose production was observed in almost all assays, with higher hydrolysis efficiency values at 72 h. The results ranged from 2.09 to 19.8 g/L of glucose obtained with efficiency values of 10.47 to 99 %. The best conditions were found in test 5 (temperature of 36 °C and pH 5.0, with only 10 FPU/g of substrate Cellic Ctec2 Novozymes ® cocktail). It is observed that for all hydrolysis times the independent variables pH and temperature were significant under the hydrolysis efficiency, showing a negative effect, indicating that higher values of the same promote lower values of the response variable. For bioethanol production, a maximum concentration of 7.84 g/L was observed for the SSH process after 4 h of fermentation, while for the SSF process it was 12.6 g/L after 24 h of fermentation, indicating the large potential of the simultaneous process together with the application of bamboo culm biomass for high production of biofuel.
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  • 文章类型: Journal Article
    长期饮酒如何导致持续性疼痛病理的机制尚不清楚。了解短期饮酒的早期事件如何降低非疼痛刺激的阈值,被描述为异常性疼痛可能被证明是谨慎的,以了解重要的启动机制。以前,我们观察到短期低剂量酒精摄入导致女性特异性异常性疼痛和脊髓背角小胶质细胞活化增加.其他文献描述了慢性乙醇暴露如何激活Toll样受体4(TLR4)以引发炎症反应。TLR4在许多细胞类型上表达,我们的目的是研究在短期/低剂量酒精模式下,小胶质细胞上的TLR4是否足以增强异常性疼痛。我们的研究使用了一种新的遗传模型,其中TLR4的表达通过引入一个浮动的转录阻断剂(TLR4-null背景(TLR4LoxTB))从整个身体中去除,然后通过用Cx3CR1:CreERT2动物饲养TLR4LoxTB动物来限制小胶质细胞。正如以前报道的那样,单独服用乙醇14天后,我们没有观察到疼痛行为增加。然而,我们在野生型和小胶质细胞-TLR4限制性雌性小鼠足底注射亚阈值剂量前列腺素E2(PGE2)后3小时观察到显著的启动效应.我们还观察到女性特异性向促炎表型的显着转变以及腰背角小胶质细胞的形态变化。对与疼痛引发相关的神经元亚型的研究表明,雌性小鼠背角PKCγ中间神经元中c-Fos和FosB活性的增加直接对应于小胶质细胞活性的增加。这项研究揭示了TLR4在非病理性饮酒者疼痛诱导性二态中的细胞和女性特异性作用。
    The mechanisms of how long-term alcohol use can lead to persistent pain pathology are unclear. Understanding how earlier events of short-term alcohol use can lower the threshold of non-painful stimuli, described as allodynia could prove prudent to understand important initiating mechanisms. Previously, we observed that short-term low-dose alcohol intake induced female-specific allodynia and increased microglial activation in the spinal cord dorsal horn. Other literature describes how chronic ethanol exposure activates Toll-like receptor 4 (TLR4) to initiate inflammatory responses. TLR4 is expressed on many cell types, and we aimed to investigate whether TLR4 on microglia is sufficient to potentiate allodynia during a short-term/low-dose alcohol paradigm. Our study used a novel genetic model where TLR4 expression is removed from the entire body by introducing a floxed transcriptional blocker (TLR4-null background (TLR4LoxTB)), then restricted to microglia by breeding TLR4LoxTB animals with Cx3CR1:CreERT2 animals. As previously reported, after 14 days of ethanol administration alone, we observed no increased pain behavior. However, we observed significant priming effects 3 h post intraplantar injection of a subthreshold dose of prostaglandin E2 (PGE2) in wild-type and microglia-TLR4 restricted female mice. We also observed a significant female-specific shift to pro-inflammatory phenotype and morphological changes in microglia of the lumbar dorsal horn. Investigations in pain priming-associated neuronal subtypes showed an increase of c-Fos and FosB activity in PKCγ interneurons in the dorsal horn of female mice directly corresponding to increased microglial activity. This study uncovers cell- and female-specific roles of TLR4 in sexual dimorphisms in pain induction among non-pathological drinkers.
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