γ-radiation

γ - 辐射
  • 文章类型: Journal Article
    我们最近报道了重组凝血酶原激活剂ecarin(RAPClot™)在血液诊断中的潜在应用。在一项新研究中,我们将RAPClot™描述为一种添加剂,以开发一种新型血液收集原型管,该原型管可以产生最高质量的血清,以进行准确的生化分析物测定。RAPClot™管的干燥过程对凝血酶原激活剂的酶活性产生最小的影响。根据凝血酶活性和血浆凝血的生物测定,γ-辐射(>25kGy)导致RAPClot™管的酶活性损失30-40%。然而,目测血液凝固分析显示,经γ辐射灭菌的RAPClot™管在5分钟内显示出高剂量肝素化血液(8U/mL)的高凝固能力.这通过血栓弹力图(TEG)得到证实,表明抗凝条件下的完全凝血效率。在室温(RT)下储存超过12个月的RAPClot™管可在342秒内保留肝素化血液的有效凝血活性。用电子束(EB)灭菌的RAPClot™管的酶活性明显高于γ辐射。在室温下储存251天的EB灭菌的RAPClot™管保留超过70%的酶活性,并在682天后在340秒内凝结肝素化血液。初步临床研究在两项试验中揭示了5种常见分析物(K,Glu,乳酸脱氢酶(LD),Fe,和Phos)或在第二次研究中在γ灭菌的RAPClot™管中确定的33种分析物与商业管中的相似。总之,研究结果表明,新型RAPClot™血液收集原型管比目前的血清或肝素锂血浆管有显著优势,用于测量生化分析物。证实了RAPClot™在临床医学中的有希望的应用。
    We recently reported the potential application of recombinant prothrombin activator ecarin (RAPClot™) in blood diagnostics. In a new study, we describe RAPClot™ as an additive to develop a novel blood collection prototype tube that produces the highest quality serum for accurate biochemical analyte determination. The drying process of the RAPClot™ tube generated minimal effect on the enzymatic activity of the prothrombin activator. According to the bioassays of thrombin activity and plasma clotting, γ-radiation (>25 kGy) resulted in a 30-40% loss of the enzymatic activity of the RAPClot™ tubes. However, a visual blood clotting assay revealed that the γ-radiation-sterilized RAPClot™ tubes showed a high capacity for clotting high-dose heparinized blood (8 U/mL) within 5 min. This was confirmed using Thrombelastography (TEG), indicating full clotting efficiency under anticoagulant conditions. The storage of the RAPClot™ tubes at room temperature (RT) for greater than 12 months resulted in the retention of efficient and effective clotting activity for heparinized blood in 342 s. Furthermore, the enzymatic activity of the RAPClot™ tubes sterilized with an electron-beam (EB) was significantly greater than that with γ-radiation. The EB-sterilized RAPClot™ tubes stored at RT for 251 days retained over 70% enzyme activity and clotted the heparinized blood in 340 s after 682 days. Preliminary clinical studies revealed in the two trials that 5 common analytes (K, Glu, lactate dehydrogenase (LD), Fe, and Phos) or 33 analytes determined in the second study in the γ-sterilized RAPClot™ tubes were similar to those in commercial tubes. In conclusion, the findings indicate that the novel RAPClot™ blood collection prototype tube has a significant advantage over current serum or lithium heparin plasma tubes for routine use in measuring biochemical analytes, confirming a promising application of RAPClot™ in clinical medicine.
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  • 文章类型: Journal Article
    电离辐射对生物体产生有害影响。本研究已进行,以研究槲皮素(Quer)和姜黄素(Cur)治疗大鼠的预防和治疗效果,这是两种以抗氧化活性而闻名的草药,可抵抗全身分馏伽马射线辐射引起的损害。大鼠暴露于全身γ射线照射诱导红细胞(RBC)显着减少,白细胞(WBC),血小板计数(Plt),血红蛋白浓度(Hb),血细胞比容(Hct%),平均红细胞血红蛋白(MCH),平均红细胞血红蛋白浓度(MCHC),和平均红细胞体积(MCV);血浆硫代巴比妥酸反应性物质(TBARS)的高度增加;血清谷胱甘肽(GSH)的平均值无统计学意义的降低;血浆丙氨酸转移酶(ALT)的显着增加,天冬氨酸转移酶(AST),碱性磷酸盐(ALP),血清总蛋白,血清总胆固醇水平,总甘油三酯水平,高密度脂蛋白(HDL),和低密度脂蛋白(LDL)水平;并且通过傅立叶变换红外(FTIR)测量具有明显的组织学变化和结构变化。在暴露于γ辐射之前和之后应用槲皮素和姜黄素显示所有研究参数均有显着改善。通过在辐射暴露之前共同施用姜黄素和槲皮素,极大地减轻了γ辐射对细胞的损伤。
    Ionizing radiation produces deleterious effects on living organisms. The present investigation has been carried out to study the prophylactic as well as the therapeutic effects of treated rats with quercetin (Quer) and curcumin (Cur), which are two medicinal herbs known for their antioxidant activities against damages induced by whole-body fractionated gamma irradiation. Exposure of rats to whole-body gamma irradiation induced a significant decrease in erythrocyte (RBC), leukocyte (WBCs), platelet count (Plt), hemoglobin concentration (Hb), hematocrit (Hct %), mean erythrocyte hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and mean erythrocyte volume (MCV); a high increase in plasma thiobarbituric acid reactive substances (TBARS); a nonsignificant statistical decrease in the mean value of serum glutathione (GSH); a significant increase in plasma alanine transferase (ALT), aspartate transferase (AST), alkaline phosphates (ALP), serum total protein, serum total cholesterol levels, total triglycerides levels, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels; and with marked histological changes and structural changes measured by Fourier transform infrared (FTIR). Applying both quercetin and curcumin pre- and postexposure to gamma radiation revealed a remarkable improvement in all the studied parameters. The cellular damage by gamma radiation is greatly mitigated by the coadministration of curcumin and quercetin before radiation exposure.
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  • 文章类型: Journal Article
    使用显性致死突变的方法,我们评估了在不同剂量和暴露模式下联合暴露于电离γ辐射和非电离脉冲磁场的情况下,果蝇胚胎的死亡频率.联合暴露的诱变作用本质上是拮抗的。使用以下暴露方式时,拮抗作用更为明显:暴露于非电离脉冲磁场5小时,然后暴露于3、10和60Gy剂量的γ辐射。如果曝光顺序相反,在暴露于3和10Gy剂量的γ辐射后,拮抗作用具有统计学意义,而在20Gy的剂量下,注意到协同相互作用。
    Using the method of dominant lethal mutations, we assessed the frequency of the death of Drosophila melanogaster embryos under combined exposure to ionizing γ-radiation and non-ionizing pulsed magnetic field at various doses and modes of exposure. Mutagenic effect of combined exposure is antagonistic in nature. The antagonism is more pronounced when the following mode of exposure was used: exposure to non-ionizing pulsed magnetic field for 5 h followed by exposure to γ-radiation at doses of 3, 10, and 60 Gy. In case of reverse sequence of exposures, the antagonistic effect was statistically significant after exposure to γ-radiation at doses of 3 and 10 Gy, whereas at a dose of 20 Gy, a synergistic interaction was noted.
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  • 文章类型: Journal Article
    草药香料由于其独特的香气和味道以及无数的经济和健康价值而被广泛用作食品添加剂。包括月桂叶在内的四种主要香料的香气特征,黑胡椒,辣椒,并使用HS-SPME/GC-MS对茴香进行了测试,以响应最广泛使用的香料加工方法,包括低剂量和高剂量的高压灭菌和γ辐射。此外,使用总需氧计数测试了加工对香料微生物污染的影响。GC-MS分析鉴定了月桂叶中的22种挥发物,34黑胡椒,23在辣椒中,和24茴香。所有确定的挥发物都属于氧化物/酚/醚,酯类,酮,酒精,倍半萜和单萜烃。大约在所有测试的香料中检测到高水平的氧化物/苯酚/醚。44、28.2、48.8、61.1%,在月桂叶,黑胡椒,辣椒,还有茴香,分别是总混合物,并表示它们作为香料的典型用途。总的氧化物/苯酚/醚显示,在暴露于γ辐射后,月桂叶从44%增加到47.5%,虽然高压灭菌后黑胡椒中的单萜烃从对照的11.4富集到高剂量和低剂量高压灭菌的65.9%和82.6%,分别。在月桂叶中检测到桉树脑的含量为17.9%,在高剂量高压灭菌和γ辐射(两种剂量)下,其含量增加了29-31%。高压灭菌和γ辐射均明显影响所检查香料的香气。Further,使用多变量数据分析(MVA)评估了响应处理的挥发性变化,揭示了与对照相比,高压灭菌和γ辐射样品之间的明显分离。在115°C下高压灭菌15分钟和10kGy辐射消除了所有测试香料中检测到的生物负载,即将微生物计数降低到检测限(<10cfu/g)以下。
    Herbal spices are widely consumed as food additives owing to their distinct aroma and taste as well as a myriad of economic and health value. The aroma profile of four major spices including bay leaf, black pepper, capsicum, and fennel was tested using HS-SPME/GC-MS and in response to the most widely used spices´ processing methods including autoclaving and γ-radiation at low and high doses. Additionally, the impact of processing on microbial contamination of spices was tested using total aerobic count. GC-MS analysis led to the identification of 22 volatiles in bay leaf, 34 in black pepper, 23 in capsicum, and 24 in fennel. All the identified volatiles belonged to oxides/phenols/ethers, esters, ketones, alcohols, sesquiterpene and monoterpene hydrocarbons. Oxides/phenol/ethers were detected at high levels in all tested spices at ca. 44, 28.2, 48.8, 61.1%, in bay leaves, black pepper, capsicum, and fennel, respectively of the total blend and signifying their typical use as spices. Total oxides/phenol/ethers showed an increase in bay leaf upon exposure to γ-radiation from 44 to 47.5%, while monoterpene hydrocarbons were enriched in black pepper upon autoclaving from 11.4 in control to reach 65.9 and 82.6% for high dose and low dose of autoclaving, respectively. Cineole was detected in bay leaf at 17.9% and upon exposure to autoclaving at high dose and γ-radiation (both doses) its level increased by 29-31%. Both autoclaving and γ-radiation distinctly affected aroma profiles in examined spices. Further, volatile variations in response to processing were assessed using multivariate data analysis (MVA) revealing distinct separation between autoclaved and γ-radiated samples compared to control. Both autoclaving at 115 °C for 15 min and radiation at 10 kGy eliminated detected bioburden in all tested spices i.e., reduced the microbial counts below the detection limit (< 10 cfu/g).
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  • 文章类型: Journal Article
    这项研究的目的是证明蜂花提取物(MEE)对丙基硫氧嘧啶(PTU)和/或γ辐射(IR)引起的甲状腺功能减退相关的脑损伤的神经保护作用。甲状腺功能减退诱导和/或暴露于IR导致血清T3和T4水平显著降低,与脂质过氧化终产物水平升高相关,丙二醛(MDA),脑组织匀浆中的亚硝酸盐(NO)。此外,甲状腺功能减退和/或暴露于IR通过上调蛋白激酶RNA样内质网激酶(PERK)的基因表达显着增强内质网应激,激活的转录因子6(ATF6),内质网相关降解(ERAD),脑组织匀浆中的CCAAT/增强子结合蛋白同源蛋白(CHOP)与Bax的过表达表明的促凋亡状态有关,BCl2和caspase-12最终导致脑损伤。同时,用MEE治疗的PTU和/或IR暴露的大鼠通过ATF6降低了氧化应激和ERAD。此外,MEE治疗阻止Bax和caspase-12基因表达增加。甲状腺功能减退动物的这种治疗与神经元保护有关,如脑组织中微管相关蛋白tau(MAPT)和淀粉样前体蛋白(APP)的基因表达下调所示。此外,MEE的给药改善了脑组织的组织学结构。总之,MEE可能预防甲状腺功能减退症引起的与氧化应激和内质网应激相关的脑损伤。
    The purpose of this study was to demonstrate the neuroprotective effect of Melissa officinalis extract (MEE) against brain damage associated with hypothyroidism induced by propylthiouracil (PTU) and/or γ-radiation (IR) in rats. Hypothyroidism induction and/or exposure to IR resulted in a significant decrease in the serum levels of T3 and T4 associated with increased levels of lipid peroxidation end product, malondialdehyde (MDA), and nitrites (NO) in the brain tissue homogenate. Also, hypothyroidism and /or exposure to IR markedly enhance the endoplasmic reticulum stress by upregulating the gene expressions of the protein kinase RNA-like endoplasmic reticulum kinase (PERK), activated transcription factor 6 (ATF6), endoplasmic reticulum-associated degradation (ERAD), and CCAAT/enhancer-binding protein homologous protein (CHOP) in the brain tissue homogenate associated with a proapoptotic state which indicated by the overexpression of Bax, BCl2, and caspase-12 that culminates in brain damage. Meanwhile, the PTU and /or IR-exposed rats treated with MEE reduced oxidative stress and ERAD through ATF6. Also, the MEE treatment prevented the Bax and caspase-12 gene expression from increasing. This treatment in hypothyroid animals was associated with neuronal protection as indicated by the downregulation in the gene expressions of the microtubule-associated protein tau (MAPT) and amyloid precursor protein (APP) in the brain tissue. Furthermore, the administration of MEE ameliorates the histological structure of brain tissue. In conclusion, MEE might prevent hypothyroidism-induced brain damage associated with oxidative stress and endoplasmic reticulum stress.
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  • 文章类型: Journal Article
    烟酰胺腺嘌呤二核苷酸磷酸氢(NADPH)是一种通用还原剂,在植物的细胞代谢和抗逆境反应的实施中起着重要作用。仅有几种酶确保细胞中NADPH池的形成。其中,最重要的是葡萄糖-6-磷酸脱氢酶(G6PDH,EC1.1.1.49),苹果酸脱氢酶脱羧(DMDH,苹果酸酶,EC1.1.1.40)和NADP-异柠檬酸脱氢酶(NADP-IDH,EC1.1.1.42)。本研究致力于研究NaCl和γ辐射作为非生物胁迫因素的个体和组合效应对生物识别指标和这些NADPH生成酶活性的影响,关于有机含量,和顺磁性中心的形成作为玉米(Zagatala-68基因型)芽中的防御反应。发现100mMNaCl对芽的发育具有抑制作用。相对较低剂量(50Gy和100Gy)的γ射线呈阳性,但它的高剂量(150Gy和200Gy)对这一过程有负面影响。500Gy是玉米芽的致死剂量(LD)。在所有情况下,组合应激都大大延迟了芽的发育。G6PDH在第一,然而,NADP-IDH在实验的最后几天显示出相同的活性。这三种酶,尤其是G6PDH,在胁迫因素(辐射或盐)的影响下,根和茎组织都被激活。组合胁迫(γ-辐射盐)也导致这些活动的诱导,这对于中和胁迫因素的负面影响是必要的。在所有情况下,胁迫因素对幼苗中有机质的含量也有负面影响。电离辐射,这导致了新的顺磁性中心的形成,在许多情况下,在小麦幼苗中观察到一种抗胁迫防御反应,但不是玉米芽,这清楚地表明,这些C3和C4类型的植物对γ辐射的保护机制存在一些差异。
    Being a universal reducing agent nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) plays an important role in the cellular metabolism and the implementation of anti-stress reactions in plants. There are only a few enzymes that ensure the NADPH pool formation in cells. Among them, the most important are glucose-6-phosphate dehydrogenase (G6PDH, EC 1.1.1.49), malate dehydrogenase decarboxylating (DMDH, malic enzyme, EC 1.1.1.40) and NADP-isocitrate dehydrogenase (NADP-IDH, EC 1.1.1.42). The presented investigation is devoted to studying the influence of the individual and combinative effects of NaCl and γ-radiation as abiotic stress factors on biometric indicators and activity of these NADPH-generating enzymes, on organic content, and the formation of paramagnetic centers as defense reaction in corn (Zagatala-68 genotype) sprouts. It was found that 100 mM NaCl had an inhibitory effect on the development of sprouts. Relatively lower doses (50 Gy and 100 Gy) of γ-radiation had a positive, but its higher doses (150 Gy and 200 Gy) had a negative effect on this process. 500 Gy was a lethal dose (LD) for the corn sprouts. Combinative stress in all cases considerably delayed the development of sprouts. G6PDH showed the highest activity in the first, whereas, NADP-IDH showed the same activity in the last days of the experiment. All three enzymes, especially the G6PDH, have been activated in both root and stem tissues under the influence of stress factors (either radiation or salt). Combinative stress (γ-radiation + salt) also led to an induction of these activities which was necessary to neutralize the negative consequences of stress factors. Stress factors in all cases also had a negative effect on the content of organic matter in seedlings. Ionizing gamma radiation, which resulted in the formation of new paramagnetic centers as an anti-stress defense reaction in many cases was observed in wheat seedlings, but not in corn sprouts, which clearly shows that there are some differences in the protective mechanisms of these C3- and C4-types of plants to γ-radiation.
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  • 文章类型: Journal Article
    在这项研究中,使用原子力显微镜检查了CuBi2O4薄膜的形成过程,能量色散分析和X射线衍射分析方法。通过在3.5V的电位差下从硫酸溶液中进行电化学沉积来合成膜。将膜生长的持续时间设定为10至90分钟,以评估受控膜生长的可能性并在长时间的生长过程中保持其结构性能的稳定性。通过X射线衍射获得的数据的分析表明,所得薄膜样品是具有四方CuBi2O4相的高度有序结构。获得了CuBi2O4膜的厚度与取决于膜沉积时间的强度性能之间的联系的结果。获得了使用CuBi2O4薄膜对低能γ量子的屏蔽效率的结果。
    In this research, the formation processes of CuBi2O4 films were examined using atomic force microscopy, energy dispersive analysis and X-ray diffraction analysis methods. The films were synthesized through electrochemical deposition from sulfuric acid solutions at a potential difference of 3.5 V. The duration of film growth was set to between 10 and 90 min to assess the possibility of controlled film growth and preserve the stability of their structural properties during growth over an extended period. An analysis of the data obtained by X-ray diffraction revealed that the resulting film samples are highly ordered structures with a tetragonal CuBi2O4 phase. The results of the connection between the thickness of CuBi2O4 films and strength properties depending on the time of film deposition were obtained. The results of the shielding efficiency of low-energy γ-quanta using CuBi2O4 films were obtained.
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  • 文章类型: Journal Article
    甲状腺功能取决于人体对碘的摄取以及暴露于各种有害环境危害(压力,电离辐射)。
    这项工作的目的是评估暴露于低剂量和中等剂量的外部γ辐射对年轻雌性大鼠在辐射后偏远时期的甲状腺结构和功能的影响。
    使用40只雌性大鼠研究了20天(每日剂量为0.1、0.25和0.5Gy)外部γ辐射暴露对功能活动(甲状腺激素水平,碘代谢)和大鼠甲状腺的形态结构)在辐射暴露后12个月。
    仅在暴露于0.25和0.5Gy的大鼠组中显示出甲状腺质量的增加和总甲状腺蛋白浓度的降低以及血液T3和T4的降低。总碘浓度及其蛋白质结合分数(1.2-1.4倍,p<.01),并且在所有受照射的动物的甲状腺中,蛋白质结合与总碘的比率均降低。0.1-Gy组显示甲状腺过氧化物酶(TPO)活性升高,过氧化氢酶活性增加,这可能表明甲状腺细胞激活了碘氧化。只有0.5-Gy组显示出碘的尿排泄减少(2.1倍,p<.01)。在0.25和0.5Gy的辐射剂量下,甲状腺功能降低的特征是微滤泡结构和实质萎缩性变化的发展,甲状腺上皮脱皮和上皮增殖增加。暴露于0.25和0.5Gy的大鼠甲状腺细胞核的直径增加,这表明甲状腺细胞的功能张力。
    我们的研究表明,一年后,暴露于0.1、0.25和0.5-Gy的外部γ辐射引起大鼠甲状腺结构和功能的变化,表现为低甲状腺炎(0.5Gy)的发展,亚临床甲状腺炎(0.25Gy)和甲状腺细胞功能紧张。甲状腺功能障碍的机制-在自由基过程激活的背景下,碘的摄取及其组织作用受损-提示钠/碘转运体(NIS)的功能紊乱,TPO和甲状腺球蛋白合成。与中间剂量相比,与早期时期(180天)相比,0.1Gy剂量的影响主要出现在偏远时期.
    UNASSIGNED: Thyroid function depends on iodine uptake by the body as well as on exposure to various harmful environmental hazards (stress, ionizing radiation).
    UNASSIGNED: The aim of the work was to assess the effect of exposure to low and intermediate doses of external γ-radiation on the thyroid structure and function in young female rats at remote periods after radiation.
    UNASSIGNED: Forty female rats were used to study remote effects of external γ-radiation exposure during 20 d (at daily doses of 0.1, 0.25 and 0.5 Gy) on the functional activity (levels of thyroid hormones, iodine metabolism) and the morphological structure of the rat thyroid) after 12 months following the radiation exposure.
    UNASSIGNED: An increase in thyroid mass and a decrease in total thyroid protein concentration along with a reduction of blood T3 and T4 was shown only in rat groups exposed to 0.25 and 0.5 Gy. Both the concentration of total iodine and its protein-bound fraction (1.2-1.4 fold, p < .01) and the protein-bound to total iodine ratio were decreased in the thyroids of all irradiated animals. The 0.1-Gy group showed elevated thyroperoxidase (TPO) activity along with increased catalase activity, which may indicate the activation of iodine oxidation by thyrocytes. Only the 0.5-Gy group demonstrated reduced urinary excretion of iodine (2.1 fold, p < .01).The reduction of thyroid function at radiation doses of 0.25 and 0.5 Gy was characterized by a microfollicular structure and the development of atrophic changes in the parenchyma, desquamation of thyroid epithelium and an increase in epithelium proliferation. The diameter of the thyrocyte nuclei was increased in rats exposed to 0.25 and 0.5 Gy, which indicates functional tension of thyrocytes.
    UNASSIGNED: Our research shows that after a year, the exposure to external γ-radiation of 0.1, 0.25 and 0.5-Gy caused changes in the structure and function of the rat thyroid which are manifested by the development of hypothyroiditis (0.5 Gy), \'subclinical\' hypothyroiditis (0.25 Gy) and functional tension of thyrocytes. The mechanisms of thyroid dysfunction - impaired- uptake of iodine and its organification against the background of activation of free radical processes - suggest disturbances in the function of the sodium/iodide symporter (NIS), TPO and thyroglobulin synthesis. In contrast to the intermediate doses, the effects of the 0.1-Gy dose were mostly found at the remote periods compared to the earlier periods (180 days).
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  • 文章类型: Journal Article
    背景:非同源末端连接,一个重要的DNA双链断裂修复途径,在赋予放射治疗剂抗性方面发挥着重要作用,导致癌症进展和复发。
    目的:参与胡椒碱和许多其他植物化合物的放射增敏作用的分子分子在很大程度上仍然回避。这项研究旨在评估胡椒碱,植物生物碱可以通过调节非同源末端连接机制的表达来改变辐射抗性。
    方法:雌激素受体阳性/阴性,培养乳腺癌细胞以了解胡椒碱与放疗的协同作用。顺铂和巴泽多昔芬用作阳性对照。使用低剂量γ辐射器-2000将细胞暴露于γ-辐射。胡椒碱对雌激素受体调节的作用,DNA损伤,DNA损伤反应,细胞凋亡是通过蛋白质印迹完成的,免疫荧光,基于酵母的雌激素-受体-LacZ-报告基因测定,和核易位分析。对DNA损伤和遗传毒性进行了微核分析,使用共聚焦显微镜通过γH2AX焦点染色对DSB进行定量。进行流式细胞术分析以确定细胞周期,线粒体膜去极化,和活性氧的产生。使用Schrodinger软件进行药效团分析和蛋白质-配体相互作用研究。协同作用是通过复合统计分析计算的。用GraphPad棱镜计算标准误差/偏差/显著性。
    结果:使用胡椒碱,我们提出了一种通过雌激素受体介导的NHEJ途径调节来克服获得性放射抗性的新策略。这是第一个全面的研究阐明胡椒碱的放射增敏潜力的机制。胡椒碱增强辐射诱导的细胞死亡,增强雌激素受体β的表达和激活,雌激素受体α的表达和激活降低。此外,胡椒碱与大多数已知的雌激素激动剂和拮抗剂具有共同的药效团特征。它改变了DDR和NHEJ途径的雌激素受体α/β比例以及雌激素反应蛋白的表达。DDR蛋白表达增强,ATM,p53和具有低DNA-PK修复复合物的P-p53(包括DNA-PKcs/Ku70/Ku80),导致辐射诱导的DNA双链断裂的积累(如MNi和γH2AX-foci所证明的),最终导致细胞周期停滞和线粒体凋亡途径。
    结论:结论:我们的研究首次报道,胡椒碱通过积累DNA断裂使乳腺癌细胞对辐射敏感,通过改变DNA-PK复合物的表达,和DDR蛋白,通过选择性雌激素受体调节,提供了一种新的对抗辐射抗性的策略。
    BACKGROUND: Non-homologous end joining, an important DNA-double-stranded break repair pathway, plays a prominent role in conferring resistance to radiotherapeutic agents, resulting in cancer progression and relapse.
    OBJECTIVE: The molecular players involved in the radio-sensitizing effects of piperine and many other phytocompounds remain evasive to a great extent. The study is designed to assess if piperine, a plant alkaloid can alter the radioresistance by modulating the expression of non-homologous end-joining machinery.
    METHODS: Estrogen receptor-positive/negative, breast cancer cells were cultured to understand the synergetic effects of piperine with radiotherapy. Cisplatin and Bazedoxifene were used as positive controls. Cells were exposed to γ- radiation using Low Dose gamma Irradiator-2000. The piperine effect on Estrogen receptor modulation, DNA-Damage, DNA-Damage-Response, and apoptosis was done by western blotting, immunofluorescence, yeast-based-estrogen-receptor-LacZ-reporter assay, and nuclear translocation analysis. Micronuclei assay was done for DNA damage and genotoxicity, and DSBs were quantified by γH2AX-foci-staining using confocal microscopy. Flow cytometry analysis was done to determine the cell cycle, mitochondrial membrane depolarization, and Reactive oxygen species generation. Pharmacophore analysis and protein-ligand interaction studies were done using Schrodinger software. Synergy was computed by compusyn-statistical analysis. Standard errors/deviation/significance were computed with GraphPad prism.
    RESULTS: Using piperine, we propose a new strategy for overcoming acquired radioresistance through estrogen receptor-mediated modulation of the NHEJ pathway. This is the first comprehensive study elucidating the mechanism of radio sensitizing potential of piperine. Piperine enhanced the radiation-induced cell death and enhanced the expression and activation of Estrogen receptor β, while Estrogen receptor α expression and activation were reduced. In addition, piperine shares common pharmacophore features with most of the known estrogen agonists and antagonists. It altered the estrogen receptor α/β ratio and the expression of estrogen-responsive proteins of DDR and NHEJ pathway. Enhanced expression of DDR proteins, ATM, p53, and P-p53 with low DNA-PK repair complex (comprising of DNA-PKcs/Ku70/Ku80), resulted in the accumulation of radiation-induced DNA double-stranded breaks (as evidenced by MNi and γH2AX-foci) culminating in cell cycle arrest and mitochondrial-pathway of apoptosis.
    CONCLUSIONS: In conclusion, our study for the first time reported that piperine sensitizes breast cancer cells to radiation by accumulating DNA breaks, through altering the expression of DNA-PK Complex, and DDR proteins, via selective estrogen receptor modulation, offering a novel strategy for combating radioresistance.
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  • 文章类型: Journal Article
    从首尔女子大学暴露于γ辐射的土壤样品中分离出辐射异常球菌17bor-2菌株,大韩民国。异常球菌属是革兰氏阴性,球菌形,和极端细菌,以抗辐射细菌而闻名。因此,对辐射的抗性背后的机制和负责抗性的基因可能有助于生物技术应用的详细实验研究。为了研究基因在菌株17bor-2中的紫外线抗性中的参与,使用PacificBiosciencesRSII系统对菌株的基因组DNA进行了测序和构建。此外,使用基因组专家评论(IMG-ER)系统注释和解释菌株17bor-2的完整基因组序列,以及Produal和JGIGenePRIMP分析。菌株17bor-2的基因组分析揭示了ExcinucleaseUvrABC基因的证据,它们是核苷酸切除修复(NER)机制中的关键酶,以及recA依赖性和recQ途径的基因。辐照异常球菌17bor-2菌株的基因组为环状染色体,包含3,052,043bp,GC含量为67.0%,包括2911个编码序列(CD),49个tRNA基因,和9个rRNA基因。此外,它们完整的基因组序列注释特征提供了证据,证明抗辐射基因在适应极端环境条件中起着核心作用。近几十年来,切除修复基因对于原核生物和真核生物对UV-C辐射的抗性都有相当详细的说明。
    Strain Deinococcus irradiatisoli 17bor-2 was isolated from a soil sample exposed to γ radiation at Seoul Women\'s University, Republic of Korea. The genus Deinococcus is a Gram-negative, coccus-shaped, and extremophilic bacterium, well renowned as being a radiation-resistant bacterium. Therefore, the mechanism behind the resistance to radiation and the gene responsible for the resistance could be helpful for detailed experimental studies with biotechnological applications. To study the involvement of genes in UV radiation resistance in strain 17bor-2, the genomic DNA of the strain was sequenced and constructed using the Pacific Biosciences RS II system. In addition, the complete genome sequence of strain 17bor-2 was annotated and interpreted using the Genomes-Expert Review (IMG-ER) system, along with Prodigal and JGI GenePRIMP analysis. The genome analysis of strain 17bor-2 revealed evidence of excinuclease UvrABC genes, which are key enzymes in the nucleotide excision repair (NER) mechanism, as well as genes from the recA-dependent and recQ pathways. The genome of strain Deinococcus irradiatisoli 17bor-2 was a circular chromosome comprising 3,052,043 bp with a GC content of 67.0%, including 2911 coding sequences (CDs), 49 tRNA genes, and 9 rRNA genes. In addition, their complete genome sequence annotation features provided evidence that radiation resistance genes play a central part in adaptation against extreme environmental conditions. In recent decades, excision repair genes have been indicated in considerable detail for both prokaryote and eukaryote resistance against UV-C radiation.
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