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Nrf2/HO-1 Mediated Protective Activity of Genistein Against Doxorubicin-Induced Cardiac Toxicity. Nrf2/HO-1介导染料木素对阿霉素诱导的心脏毒性的保护作用。
Miao Chen, V. P. Samuel, Yi Wu, Minyan Dang, Yukiat Lin, R. Sriramaneni, S. Sah, Gopala Krishna Chinnaboina, Guang-lin Zhang
The current study evaluated the cardioprotective activity of genistein in cases of doxorubicin-(Dox) induced cardiac toxicity and a probable mechanism underlying this protection, such as an antioxidant pathway in cardiac tissues. Animals used in this study were categorized into four groups. The first group was treated with sodium carboxymethylcellulose (0.3%; CMC-Na) solution. The second group received Dox (3.0 mg/kg, i.p.) on days 6, 12, 18, and 24. The third and fourth groups received Dox (3 mg/kg, i.p.) on days 6, 12, 18, and 24 and received protective doses of genistein (100 [group 3] and 200 [group 4] mg/kg/day, p.o.) for 30 days. Treatment with genistein significantly improved the altered cardiac function markers and oxidative stress markers. This was coupled with significant improvement in cardiac histopathological features. Genistein enhanced the Nrf2 and HO-1 expression, which showed protection against oxidative insult induced by Dox. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed substantial inhibition of apoptosis by genistein in myocardia. The study showed that genistein has a strong reactive oxygen species scavenging property and potentially (P ≤ .001) decreases the lipid peroxidation as well as inhibits DNA damage in cardiac toxicity induced by Dox. In conclusion, the potential antioxidant effect of genistein may be because of its modulatory effect on Nrf2/HO-1 signalling pathway and by this means exhibits cardioprotective effects from Dox-induced oxidative injury.
目前的研究评估了染料木素在阿霉素(Dox)诱导的心脏毒性病例中的心脏保护活性,以及这种保护的可能机制,如心脏组织中的抗氧化途径。本研究中使用的动物被分为四组。第一组用羧甲基纤维素钠(0.3%;CMC-Na)解决方案。第二组于第6、12、18、24天给予Dox (3.0 mg/kg, ig)。第三组和第四组在第6、12、18和24天给予Dox (3 mg/kg, ig),同时给予染料木素保护剂量(100[3组]和200[4组]mg/kg/天,口服),持续30天。染料木素治疗可显著改善改变的心功能指标和氧化应激指标。这与心脏组织病理学特征的显著改善相结合。染料木素提高Nrf2和HO-1的表达,对Dox诱导的氧化损伤具有保护作用。末端脱氧核苷酸转移酶dUTP缺口末端标记实验显示染料木素对心肌细胞凋亡有明显的抑制作用。本研究表明染料木素具有较强的活性氧清除能力,并可能(P≤0.001)降低Dox引起的心脏毒性中脂质过氧化和抑制DNA损伤。综上所述,染料木黄酮的潜在抗氧化作用可能是由于其对Nrf2/HO-1信号通路的调节作用,从而在dox诱导的氧化损伤中表现出心脏保护作用。
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引用次数: 16
Atractylenolide III Enhances the Anti-Neoplastic Efficacy of Docetaxel in Gastric Cancer Cell by Inhibiting Fibroblast Growth Factor Receptors 1, -2, and -4 Expression. 白术内酯III通过抑制成纤维细胞生长因子受体1、2和-4的表达增强多西紫杉醇对胃癌细胞的抗肿瘤作用
Yanxia Ji, Zhenqiao Kang, Ning Kang, Yanzheng Zhao, Q. Guo, Yongge Chen
BACKGROUND Natural active components have been reported to serve as adjuvant medications in the clinical practice of cancer therapeutics. However, the antineoplastic roles of atractylenolide III (ATL) are rarely reported. In the present study, we assessed the functions of ATL combined with docetaxel in gastric cancer cells. METHODS Cell viability and cytotoxic activity were evaluated using CCK-8 and LDH-based cytotoxicity assays, respectively. Protein expression levels were measured by western blotting analysis. Annexin V-FITC/PI staining was used to evaluate cell apoptosis using flow cytometry. RESULTS AGS and SGC-7901 cell viability was significantly inhibited in ATL combined with docetaxel group compared with docetaxel treatment alone. The levels of LDH, apoptosis rate, and the ratio of BAX to Bcl-2 were significantly elevated in combination treatment group compared to docetaxel treatment alone. Intriguingly, docetaxel combined with ATL resulted in a significant decrease in FGFR1, FGFR2, and FGFR4 protein expression compared with docetaxel treatment alone. Knockout of FGFR1, -2, and -4 exhibited a similar role of medications to inhibit growth and induce apoptosis in AGS and SGC-7901 cells. CONCLUSIONS ATL and docetaxel treatment performed the synergistic effects on the inhibition of growth and induction of apoptosis in gastric cancer cells, and the underlying mechanism was mediated, at least partially, through the inhibition of FGFR1, -2, and -4.
背景:据报道,天然活性成分在癌症治疗的临床实践中可作为辅助药物。然而,白术内酯III (ATL)的抗肿瘤作用很少被报道。在本研究中,我们评估了ATL联合多西紫杉醇对胃癌细胞的作用。方法采用CCK-8细胞毒法和ldh细胞毒法分别评价细胞活力和细胞毒活性。western blotting检测蛋白表达水平。Annexin V-FITC/PI染色采用流式细胞术检测细胞凋亡情况。结果ATL联合多西紫杉醇组ags和SGC-7901细胞活力明显低于单药组。联合治疗组LDH水平、细胞凋亡率、BAX / Bcl-2比值均明显高于单独治疗组。有趣的是,与单独多西紫杉醇治疗相比,多西紫杉醇联合ATL导致FGFR1、FGFR2和FGFR4蛋白表达显著降低。在AGS和SGC-7901细胞中,敲除FGFR1、-2和-4表现出与药物抑制生长和诱导凋亡相似的作用。结论satl和多西紫杉醇在抑制胃癌细胞生长和诱导凋亡方面具有协同作用,其潜在机制至少部分是通过抑制FGFR1、-2和-4介导的。
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引用次数: 9
Anti-Inflammatory and Apoptotic Signaling Effect of Fucoxanthin on Benzo(A)Pyrene-Induced Lung Cancer in Mice. 岩藻黄素对苯并(A)芘诱导小鼠肺癌的抗炎和凋亡信号传导作用。
Weiwei Chen, Hongjing Zhang, Yue Liu
Fucoxanthin, a potent carotenoid present in various natural sources especially from seaweeds; it exhibits several biological effects like anti-neoplastic, anti-mutagenic, anti-diabetic, anti-obesity and anti-inflammatory actions. Fucoxanthin role in chemoprevention of lung cancer in mouse model induced using benzo(a)pyrene [B(a)P] has been presented here. Oral administration of fucoxanthin with and without B(a)P were studied, the results from our study shows that fucoxanthin significantly decreased tumor progression in mice exposed to B(a)P, the obtained data were correlated with increased antioxidant, apoptosis and decreased tumour marker and anti-apoptotic molecules. With respect to apoptosis, fucoxanthin treated animals shows increased apoptosis compared to tumor induced mice by increased expression of caspase 9 and 3 and decreased expression of anti-apoptotic Bcl2 protein. Finally, histopathological and immuno histochemical analysis also revealed that fucoxanthin shows potent anticancer agent by bringing back the damaged tissue treated with B(a)P and also decreases the expression of PCNA in cancer induced mice. The anticancer effect of fucoxanthin may be attributed by several independent mechanisms which play a important roles in the prevention of cancer development, there is also substantial evidences to show that fucoxanthin acts indirectly by increasing the antioxidant capacity of affected tissue and prepared to cope up with oxidative stress which is proved in our study. Thus from our study it is clearly established that fucoxanthin act as a persuasive anticancer drug against lung cancer.
岩藻黄素,一种有效的类胡萝卜素,存在于各种天然来源中,特别是来自海藻;具有抗肿瘤、抗诱变、抗糖尿病、抗肥胖、抗炎等生物学效应。岩藻黄素在苯并(a)芘诱导的小鼠肺癌模型中的化学预防作用[B(a)P]已经在这里提出。对含B(a)P和不含B(a)P的岩藻黄素口服进行了研究,我们的研究结果表明,岩藻黄素显著降低了B(a)P暴露小鼠的肿瘤进展,所获得的数据与抗氧化、细胞凋亡和肿瘤标志物和抗凋亡分子的减少有关。在细胞凋亡方面,岩藻黄素处理动物与肿瘤诱导小鼠相比,通过增加caspase 9和3的表达,降低抗凋亡Bcl2蛋白的表达,细胞凋亡增加。最后,组织病理学和免疫组织化学分析也显示岩藻黄素具有较强的抗癌作用,可使B(a)P处理后的受损组织恢复,并降低肿瘤诱导小鼠PCNA的表达。岩藻黄素的抗癌作用可能有几个独立的机制,它们在预防癌症的发展中起着重要的作用,也有大量证据表明岩藻黄素通过增加受影响组织的抗氧化能力来间接起作用,并准备应对氧化应激,这在我们的研究中得到了证实。因此,从我们的研究中可以清楚地确定岩藻黄素作为一种有说服力的抗癌药物治疗肺癌。
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引用次数: 20
Low-Magnitude, High-Frequency Vibration Promotes Osteogenic Differentiation via Intensifying miRNA-335-5p Expression. 低强度、高频振动通过增强miRNA-335-5p表达促进成骨分化。
Wei Zhao, Yi Tang, Yang Yang, Min Wang, Haiyang Yu
Certain mechanical stimuli-particularly low-magnitude, high-frequency vibration-could induce bone marrow stem cell osteogenic differentiation and promote bone formation via Wnt signaling pathway, although the molecular mechanism is still unclear. In this study, we found that miR-335-5p is significantly upregulated after low-magnitude, high-frequency vibration, which suppresses the expression of the Wnt signaling inhibitor Dickkopf-related protein 1. Inhibition of miR-335-5p greatly reduced the osteogenic differentiation. Furthermore, the increase of miR-335-5p level was also confirmed in vivo after LMHF vibration in rabbit. Our study elucidates the prominent role of miRNAs that links the LMHF vibration and osteogenic differentiation.
某些机械刺激,特别是低强度、高频振动,可通过Wnt信号通路诱导骨髓干细胞成骨分化,促进骨形成,但其分子机制尚不清楚。在本研究中,我们发现miR-335-5p在低强度、高频振动后显著上调,从而抑制Wnt信号抑制因子dickkopf相关蛋白1的表达。抑制miR-335-5p可显著降低成骨分化。此外,在家兔LMHF振动后,体内也证实了miR-335-5p水平的升高。我们的研究阐明了连接LMHF振动和成骨分化的mirna的突出作用。
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引用次数: 4
Role of Herbal Medicine in the Management of Urolithiasis- A Review for Future Perspectives. 草药在尿石症治疗中的作用——展望未来。
Ajay Patle, K. Hatware, K. Patil, Sanjay Sharma, G. Gupta
BACKGROUND Urolithiasis is the most common renal system pathology; it affects the health of a many people. Because urolithiasis leads to severe pain, it influences the patient in many aspects. The management of urolithiasis is essential. Herein, we discuss the limitations of the management of urolithiasis with conventional drugs and the possibilities of using natural or herbal pharmacologically active agents beyond conventional drugs. PURPOSE The drugs presently used for the treatment of urolithiasis have many adverse side effects; therefore, alternatives are needed. Traditional literature suggests that many herbal or natural medicines can be easily made available for the management of urolithiasis and its consequences. METHOD The data used for this study were collected from various research /review articles, Internet sources, and text books. Literature regarding epidemiology and pharmacological studies performed by various researchers were taken into consideration in this review. The data from the last few decades, reported in different formats, were analyzed. CONCLUSION The present review reveals the severity of the progression of the occurrence of urolithiasis worldwide. The epidemiology gave in this review clearly indicates that stress-related factors and dietary complications, the key factors in the development of urolithiasis. are increasing. In this review, we acknowledge the limitations of conventional therapy. Many natural drug options are abundantly available throughout the world and can be useful for the management of urolithiasis. Future Perspectives: The development of a suitable formulation of bioactive components obtained from natural sources is being widely researched. However, traditional remedies that are very helpful in the management of urolithiasis and its related complications require scientific support and appropriate standardization for the assessment of their quality and dosage.
背景:肾结石是最常见的肾脏系统病理;它影响了许多人的健康。由于尿石症会导致剧烈的疼痛,因此对患者的影响是多方面的。尿石症的治疗是必要的。在此,我们讨论了常规药物治疗尿石症的局限性,以及在常规药物之外使用天然或草药药理活性药物的可能性。目的目前用于治疗尿石症的药物存在许多不良反应;因此,需要替代方案。传统文献表明,许多草药或天然药物可以很容易地用于治疗尿石症及其后果。方法本研究的数据来源于各种研究/评论文章、网络资源和教科书。关于流行病学和药理学研究的文献,由不同的研究人员进行了考虑在这篇综述。对过去几十年以不同格式报告的数据进行了分析。结论本综述揭示了世界范围内尿石症发生进展的严重程度。从流行病学角度分析,应激相关因素和饮食并发症是尿石症发生的关键因素。正在增加。在这篇综述中,我们承认常规治疗的局限性。许多天然药物在世界各地大量可用,可用于尿石症的管理。未来展望:从天然来源获得的生物活性成分的合适配方的开发正在被广泛研究。然而,传统疗法对尿石症及其相关并发症的治疗非常有帮助,需要科学的支持和适当的标准化来评估其质量和剂量。
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引用次数: 12
Oxidative Stress Parameters, Selenium Levels, DNA Damage, and Phthalate Levels in Plastic Workers. 塑料工人的氧化应激参数、硒水平、DNA损伤和邻苯二甲酸盐水平。
Gulru Gurdemir, P. Erkekoğlu, Aylin Balcı, Unzile Sur, Gizem Ozkemahli, E. Tutkun, H. Yılmaz, A. Asci, B. Kocer-Gumusel
Di(2-ethylhexyl)phthalate (DEHP) is the most widely used phthalate. DEHP is highly used in PVC floorings and PVC windows and carpeting. The objective of this study was to determine sex hormone levels, oxidative stress parameters, selenium levels, DNA damage, and phthalate levels in plastics workers (n = 24, age = 20-58 years) working in the production of rubber mechanical goods and exposed to DEHP in workplace. The control group (n = 29, age = 25-54, all male) was selected from age-matched healthy adults. Antioxidant parameters and DNA damage were determined by spectrophotometry. Selenium levels were determined by atomic absorption spectroscopy. Plasma hormone levels were measured by chemiluminescence microparticle immunoassay. Plasma phthalate levels were determined by high-pressure liquid chromatography. Plastic workers had lower serum testosterone and free T4 levels and higher follicle-stimulating hormone levels vs. controls. Liver enzyme activities were markedly higher in workers vs. controls. There were also increases in plasma glutathione peroxidase levels and marked decreases in plasma selenium and erythrocyte total glutathione levels in plastics workers (P < 0.05 vs. control). Plasma 8-hydroxy-2'-deoxyguanosine levels were 14-fold higher in plastics workers than in controls. Plasma DEHP and mono(2-ethylhexyl)phthalate were also markedly higher in workers vs. controls. The results of this study show that occupational exposure to DEHP may lead to disturbances in sex hormones, increased liver problems, higher oxidative stress and DNA damage levels, and lower trace element concentrations in workers. More comprehensive and mechanistic studies with higher numbers of subjects are needed to show the unwanted effects of occupational exposure to DEHP.
邻苯二甲酸二(2-乙基己基)酯(DEHP)是应用最广泛的邻苯二甲酸酯。DEHP广泛用于PVC地板、PVC窗户和地毯。本研究的目的是确定从事橡胶机械产品生产并在工作场所暴露于DEHP的塑料工人(n = 24,年龄= 20-58岁)的性激素水平、氧化应激参数、硒水平、DNA损伤和邻苯二甲酸盐水平。对照组29例,年龄25-54岁,均为男性。分光光度法测定抗氧化参数和DNA损伤。用原子吸收光谱法测定硒的含量。采用化学发光微粒免疫法测定血浆激素水平。采用高压液相色谱法测定血浆邻苯二甲酸酯水平。与对照组相比,整形工人的血清睾酮和游离T4水平较低,促卵泡激素水平较高。工人的肝酶活性明显高于对照组。塑料工人血浆谷胱甘肽过氧化物酶水平升高,血浆硒和红细胞总谷胱甘肽水平明显降低(P < 0.05)。塑料工人的血浆8-羟基-2'-脱氧鸟苷水平比对照组高14倍。工人血浆DEHP和邻苯二甲酸单(2-乙基己基)也明显高于对照组。本研究结果表明,职业性接触DEHP可能导致性激素紊乱、肝脏问题增加、氧化应激和DNA损伤水平升高,以及工人体内微量元素浓度降低。需要对更多的研究对象进行更全面和更机械的研究,以显示职业性接触DEHP的不良影响。
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引用次数: 5
Rutin Protects against Doxorubicin-Induced Cognitive Dysfunction While Retaining the Anticancer Potential of Dox in a Murine Model of N-Methyl-N-Nitrosourea - Induced Mammary Carcinoma. 在n-甲基- n-亚硝基脲诱导的小鼠乳腺癌模型中,芦丁对阿霉素诱导的认知功能障碍有保护作用,同时保留了阿霉素的抗癌潜力。
G. Ramalingayya, K. Gourishetti, P. Nayak, C. Rao, A. Kishore, S. Alnaseer, S. Hussain, K. Nandakumar
Chemobrain is a significant post-chemotherapy complication for which no approved treatments are available. We had previously identified that rutin inhibits doxorubicin (Dox-) -induced cognitive decline in healthy rats. However, it was important to also establish that it does so in rats with mammary carcinoma without compromising Dox's antitumor potential. Mammary carcinoma was induced in female rats by intraperitonial administration of N-methyl-N-nitrosourea (i.p.). Rats that developed mammary carcinoma were treated with Dox after pretreatment with vehicle or rutin. After Dox exposure (50 days), episodic and spatial memory was assessed using the novel object recognition task and the Morris water maze, respectively. Tumor progression was evaluated by measurement of tumor weight and volume and histological analysis. Blood samples were collected to estimate hematological parameters. Oxidative status and TNF-α levels were estimated in brain homogenates. Dox treatment significantly reduced tumor size and volume. Pretreatment with rutin did not significantly alter Dox's tumor suppression potential, suggesting that it does not influence Dox's anticancer activity. In addition, rutin ameliorated Dox-induced cognitive decline, myelosuppression, and brain oxidative stress. The present study indicates that rutin protects against Dox-induced cognitive decline and myelosuppression without affecting its antitumor potential.
化疗脑是一种重要的化疗后并发症,目前尚无批准的治疗方法。我们之前已经发现,芦丁抑制阿霉素(Dox-)诱导的健康大鼠认知能力下降。然而,重要的是要确定它在患有乳腺癌的大鼠中起作用,而不影响Dox的抗肿瘤潜力。用n -甲基-n -亚硝基脲(i.p)腹腔灌胃诱导雌性大鼠乳腺癌。发生乳腺癌的大鼠在用对照物或芦丁预处理后再用阿霉素治疗。Dox暴露后(50天),分别使用新的对象识别任务和Morris水迷宫评估情景记忆和空间记忆。通过测量肿瘤的重量、体积和组织学分析来评估肿瘤的进展。采集血样估计血液学参数。测定脑匀浆的氧化状态和TNF-α水平。Dox治疗显著减小了肿瘤的大小和体积。芦丁预处理未显著改变Dox的抑瘤潜能,提示其不影响Dox的抗癌活性。此外,芦丁还能改善dox诱导的认知能力下降、骨髓抑制和脑氧化应激。目前的研究表明,芦丁对dox诱导的认知能力下降和骨髓抑制有保护作用,但不影响其抗肿瘤潜能。
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引用次数: 10
Analysis of Lead, Cadmium, and Nickel in Blood Donors in Relation to Smoking-A Comparative Study. 献血者中铅、镉和镍与吸烟的关系分析——一项比较研究。
Achummantakath Hashim, Haneena Fathima, R. Muhammed, D. R. D. Neevan
Donor blood is usually screened for some risk factors, such as hepatitis, HIV, and malarial parasites, but it is not routinely screened for heavy metals although their adverse effects on the human body have been proved by a number of studies. In this study, an attempt was made to determine the effect of smoking on concentration of cadmium, nickel, and lead in donor blood. A semistructured questionnaire was prepared and given to participants. It showed that 79% (two groups: 65 smokers and 65 nonsmokers) smoked at least one cigarette per day. Collected blood samples were then subjected to atomic absorption spectrometry (AAS). In comparing blood levels between smoking and nonsmoking participants, we noted a high positive correlation between lead and nickel concentrations. There were statistically significant correlations between cadmium, lead, and nickel concentrations in the blood of smokers and nonsmokers. Moreover, because a substantial percentage of blood donors may be smokers and blood donation does not always meet demand, it would be difficult to completely exclude smokers from donating blood. Our findings indicate the need to screen for heavy metals when transfusing blood to the elderly, neonates, and infants, and to avoid transfusion of blood and blood products if levels are in the toxic range.
通常对献血者的血液进行一些危险因素的筛查,如肝炎、艾滋病毒和疟疾寄生虫,但并不常规筛查重金属,尽管它们对人体的不利影响已被许多研究证明。在这项研究中,试图确定吸烟对供体血液中镉、镍和铅浓度的影响。准备了一份半结构化的问卷并发给参与者。研究显示,79%的人(两组:65名吸烟者和65名非吸烟者)每天至少抽一支烟。采集血液样本,然后进行原子吸收光谱法(AAS)。在比较吸烟和不吸烟参与者的血液水平时,我们注意到铅和镍浓度之间的高度正相关。吸烟者和非吸烟者血液中的镉、铅和镍浓度有统计学意义的相关性。此外,由于相当大比例的献血者可能是吸烟者,而献血并不总是满足需求,因此很难完全排除吸烟者献血。我们的研究结果表明,在向老年人、新生儿和婴儿输血时,需要对重金属进行筛查,如果血液和血液制品的含量在有毒范围内,则应避免输血。
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引用次数: 9
AgNPs from Nigella sativa Control Breast Cancer: An In Vitro Study. 黑草AgNPs控制乳腺癌:一项体外研究。
B. Rohini, T. Akther, M. Waseem, Jasim Khan, M. Kashif, S. Hemalatha
In our current study, we synthesized silver nanoparticles (AgNPs) from an aqueous seed extract of Nigella sativa. The seed extract contains phytochemical compounds including phenols, terpenoids, and flavonoids that may act as reducing agents and are able to convert metal ions to metal nanoparticles. The formation of synthesized AgNPs was characterized using UV-visible spectroscopy, Fourier transform infra-red spectroscopy (FT-IR), scanning electron microscopy (SEM) and energy dispersive analysis of X-rays (EDX). The efficacy of N-AgNPs against human breast cancer (MCF-7) cells was tested. The synthesized AgNPs displayed dose-dependent cytotoxicity (1-200 µg/mL) against MCF-7 cells. Morphological alterations of the cells also appeared as bright field images. Treatment of synthesized AgNPs altered the expression of Bax and Bcl-2 (apoptotic proteins) and COX-2 (inflammatory marker) in MCF-7 cells. To our knowledge, this is the first report demonstrating that N-AgNPs from Nigella sativa can induce apoptosis in MCF-7 cells.
在我们目前的研究中,我们合成了银纳米粒子(AgNPs)从黑草种子的水提取物。种子提取物含有植物化学化合物,包括酚类、萜类和类黄酮,它们可以作为还原剂,并能够将金属离子转化为金属纳米粒子。利用紫外-可见光谱、傅里叶变换红外光谱(FT-IR)、扫描电镜(SEM)和x射线能谱分析(EDX)对合成AgNPs的形成进行了表征。研究了N-AgNPs对人乳腺癌(MCF-7)细胞的杀伤作用。合成的AgNPs对MCF-7细胞表现出剂量依赖性的细胞毒性(1-200µg/mL)。细胞形态变化也以亮场图像呈现。合成AgNPs的处理改变了MCF-7细胞中Bax、Bcl-2(凋亡蛋白)和COX-2(炎症标志物)的表达。据我们所知,这是第一次有报道表明来自Nigella sativa的N-AgNPs可以诱导MCF-7细胞凋亡。
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引用次数: 20
Increased Expression of TGF-β and IFN-γ in Peripheral Blood Mononuclear Cells (PBMCs) Cultured in Conditioned Medium (CM) of K562 Cell Culture. K562细胞培养条件培养基(CM)培养外周血单个核细胞(PBMCs)中TGF-β和IFN-γ的表达升高。
A. A. Mohamed Adil, Lavanya Vallinayagam, K. Chitra, Shazia Jamal, A. Pandurangan, Neesar Ahmed
In the present study, we investigated the effects of conditioned media (CM) collected from the cancer cell lines (K562, MCF-7, and HeLa) on peripheral blood mononuclear cells (PBMCs) isolated from the healthy human blood. The soluble factors in the CM are probably responsible for the differential mRNA expressions of Foxp3, Helios, Neuropilin- 1 (NRP-1), and glycoprotein A repetitions predominant (GARP), along with IFN-γ and TGF-β in PBMCs cultured with cancer cells CM. The PBMCs cultured with CM of K562 showed increased expression of Foxp3, Helios, NRP-1, GARP, IFN-γ, and TGF-β compared to PBMCs cultured with CM of MCF-7 and HeLa cells. In addition, the intracellular staining on PBMCs cultured with CM from cell lines were also evaluated for CD4, CD25, Foxp3, Helios, and NRP-1 by multicolor flow cytometry. The expression of CD4+CD25+Foxp3+, CD4+Helios+Foxp3+ and CD+NRP-1+Foxp3+ showed retarded cell population compared to control PBMCs. Our data suggest that soluble factors in CM of cancer cells may trigger the immune response in PBMCs resulting in a systematic response. Further research could lead to the identification of specific soluble factors that are involved in trafficking of cells into the immune cascades, which could be a safe and promising strategy for targeting human cancers.
在本研究中,我们研究了从癌细胞系(K562、MCF-7和HeLa)中收集的条件培养基(CM)对从健康人血液中分离的外周血单个核细胞(PBMCs)的影响。CM中的可溶性因子可能是导致Foxp3、Helios、Neuropilin- 1 (NRP-1)、糖蛋白A重复显性(GARP)以及IFN-γ和TGF-β mRNA表达差异的原因。与MCF-7和HeLa细胞的CM培养的pbmc相比,K562 CM培养的pbmc中Foxp3、Helios、NRP-1、GARP、IFN-γ和TGF-β的表达增加。此外,采用多色流式细胞术检测细胞内CD4、CD25、Foxp3、Helios和NRP-1的表达。CD4+CD25+Foxp3+、CD4+Helios+Foxp3+和CD+NRP-1+Foxp3+的表达均表现为细胞群发育迟缓。我们的数据表明,癌细胞CM中的可溶性因子可能触发pbmc的免疫反应,导致系统性反应。进一步的研究可能会导致识别特定的可溶性因子,这些因子参与了细胞进入免疫级联的运输,这可能是针对人类癌症的一种安全和有希望的策略。
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引用次数: 1
期刊
Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer
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