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目的基于UHPLC-Q-Exactive-Orbitrap-MS技术阐明树舌灵芝主要成分,结合网络药理学探讨其防治新型冠状病毒肺炎的作用机制。方法采用UHPLC-Q-Exactive-Orbitrap-MS技术鉴定树舌灵芝的主要成分;采用Swiss Target Prediction数据平台对鉴定成分进行靶点预测,对核心靶基因进行GO和KEGG富集分析,运用Cytoscape 3.8.0绘制关联网络图,同时通过分子对接评价树舌灵芝核心成分与血管紧张素转化酶Ⅱ(ACE2)及3种新型冠状病毒(SARS-CoV-2)蛋白的结合作用。结果该研究从树舌灵芝中鉴定化合物62个;30个活性化合物主要作用在IL-6、PTGS2和MAPK1等32个核心靶点,通过PI3K/Akt、TNF及肺结核等多条与肺损伤保护相关通路,发挥防治COVID-19的作用;分子对接显示小白菊内酯、1,4-二羟基-2-萘甲酸和瑞香素等核心成分与ACE2及3种SARS-CoV-2蛋白的亲和作用较好。结论该研究初步阐明树舌灵芝的化学成分及潜在作用机制,为筛选树舌灵芝防治COVID-19的药效成分及深入阐明作用机制提供了科学的理论依据。  相似文献   
3.
Metastatic brain disease frequently complicates extra central nervous system (CNS) neoplastic disease, with an increase in reported incidence over time. Brain parenchyma is the commonest anatomical site, with other lesions involving the spinal cord, dura and tissues surrounding the CNS. Metastases are usually characterised by a well-defined border with surrounding brain, although some can show an infiltrative edge. The use of appropriate immunohistochemical panels can help identify the origin of most tumours, and molecular testing should be performed according to the site of origin even if performed on a previous specimen due to potential changes in molecular characteristics. Reliable detection of leptomeningeal metastasis using CSF cytology relies on examination of an adequate volume of fluid; immunocytochemistry and flow cytometry can also be useful in the correct settings. Advances in the field include liquid biopsies, where circulating biomarkers are examined, and the use of methylation profiling to identify primary tumours.  相似文献   
4.
目的 基于网络药理学方法和分子对接技术探究冬虫夏草抗肿瘤的作用机制。方法 利用TCMSP、CNKI、PubMed、Drugbank、Stitch和Swiss target prediction等平台检索冬虫夏草的化学成分和作用靶点;通过GeneCards、OMIM等数据库筛选肿瘤相关基因,运用Cytoscape 3.7.2构建冬虫夏草活性成分-靶点网络,通过String数据库对关键靶点构建网络互作(PPI)网络,并进行基因本体(GO)基因和京都基因和基因组百科全书(KEGG)通路富集分析,最后利用AutoDock Vina软件和Pymol软件对药物有效活性成分和关键靶点进行分子对接验证。结果 共得到冬虫夏草22个化合物,86个抗肿瘤共同靶点,主要包括环加氧酶(PTGS)2、丝裂原活化蛋白激酶3(MAPK3)、过氧化物酶体增生激活受体γ(PPARG)、胱天蛋白酶3(CASP3)、JUN基因等关键靶点。GO分析与KEGG通路结果显示,冬虫夏草抗肿瘤涉及到多种生物学过程以及PPAR、花生四烯代谢、5-羟色胺信号通路等多种信号通路。将关键化合物和靶点进行分子对接,提示冬虫夏草抗肿瘤可能的前5个主要活性成分11,14-二十碳二烯酸、花生四烯酸、黄豆黄素、胆甾醇和豆甾醇与关键靶点PTGS2、PTGS1、PGR、HMGCR和CNR1均能自发结合。结论 初步探讨了冬虫夏草抗肿瘤的主要活性成分、相关靶点及相关通路,发现冬虫夏草可以通过多成分、多靶点、多通路抗肿瘤,为后期实验验证提供了参考依据。  相似文献   
5.
Objective: Breast cancer is the second most common cancer in the world. Many metastasis suppressor genes were identified, including the KISS1 gene which encodes for a 145 amino acid protein (kisspeptin-145), which undergoes proteolytic cleavage resulting in kisspeptin-14, -13 and -10. All of these proteins can activate KISS1 receptor (KISS1R). The role of KP/KISS1R signaling in breast cancer remains controversial. The present study aimed to measure mRNA gene expression of KISS1 receptor in healthy and cancerous breast tissue and to evaluate the association of its level with the available molecular subtypes and the traditional clinico-pathological variables. Methods: The study was done on 41 operable primary breast cancer patients. Biopsies from both tumor tissue and surrounding healthy mammary tissue were taken from all patients. KISS1R mRNA expression level was measured using a quantitative real time PCR.   Results: KISS1R mRNA expression was significantly higher in stage III patients compared to stage II patients. At a cut-off value for KISS1R mRNA expression of 1.75, stage II was discriminated from stage III. A significant positive correlation was found between KISS1R mRNA expression and tumor size as well as lymph nodes metastasis. KISS1R mRNA was highly expressed in ER negative cases compared to ER positive ones, and in PR negative cases compared to PR positive ones. There was a statistically significant difference in KISS1R mRNA expression levels and different molecular subtypes being over-expressed in HER2 and triple negative cancer cases. Conclusion: This study supports other studies suggesting that KISS1/KISS1R may not be acting as a metastasis suppressor in breast cancer. KISS1R mRNA is over expressed in advanced stages of breast cancer and hence it can be used as a prognostic marker for aggressiveness of breast cancer. Also being over expressed in triple negative patients, KISS1R could represent a promising therapeutic target in triple negative cases.  相似文献   
6.
目的:探讨不同起始时间使用咖啡因防治极低出生体质量早产儿呼吸暂停的疗效和安全性。方法:检索PubMed、Cochrane Library、Embase、中国期刊全文数据库(CNKI)、万方数据、生物医学文献(CBM)及维普等数据库,收集各数据库从建库至2020年6月有关极低出生体质量早产儿早期应用咖啡因防治呼吸暂停的病例对照研究,并采用Cochrane系统评价手册5.1.0和Newcastle-Ottawa量表(NOS)对不同类型研究进行质量评价,采用RevMan 5.3进行系统评价。结果:10项文献中,包括5项随机临床对照研究(RCT)和5项回顾性队列研究,文献质量评价结果显示,5项RCT质量等级为B级,5项回顾性队列研究NOS评分为7~9分。共2 665例患儿,其中早期用药组1 515例,晚期用药1 150例。Meta分析结果显示,早期用药组呼吸暂停(AOP)发生率(RR=0.48,95%CI 0.38~0.60,P<0.01)、吸氧时间(SMD=-0.97,95%CI -1.13~-0.80,P<0.01)、机械通气时间(SMD=-0.82,95%CI -1.06~-0.58,P<0.01)、咖啡因用药时间(SMD=-0.42,95%CI -0.56~-0.28,P<0.01)、支气管肺发育不良(BPD)发生率(RR=0.50,95%CI 0.41~0.60,P<0.01)、动脉导管未封闭(PDA)发生率(RR=0.56,95%CI 0.44~0.70,P<0.01)、早产儿视网膜病(ROP)发生率(RR=0.59,95%CI 0.47~0.74,P<0.01)、脑室内出血(IVH)发生率(RR=0.66,95%CI 0.54~0.81,P<0.01)和坏死性小肠结肠炎(NEC)发生率(RR=0.70,95%CI 0.55~0.91,P<0.01)显著低于晚期用药组,而病死率(RR=1.15,95%CI 0.73~1.81,P=0.55)与晚期用药组比较差异无统计学意义。结论:极低出生体质量早产儿早期使用咖啡因能显著降低呼吸暂停发生率、BPD、ROP、PDA、IVH和NEC发生率,减少机械通气、吸氧和咖啡因用药时间,但对病死率无影响。  相似文献   
7.
五味子乙素是五味子中主要活性成分之一,具有多种药理作用。长期研究表明五味子乙素具有保护肝脏、肾脏、肺和心脑血管等作用。五味子乙素的多器官保护作用通过不同的途径起效,作用机制包括抗氧化、抗炎、抗纤维化、促进热休克反应、调节脂质代谢、抑制细胞凋亡。就五味子乙素对各器官的保护作用的分子机制进行了总结,为推进其药理研究和分子机制的阐明以及临床应用提供参考。  相似文献   
8.
We discuss the second reported case of NUT carcinoma (NC) arising in the thyroid.1 NC is a rare and aggressive malignancy which usually arises in the midline head and neck structures. The tumour is defined cytogenetically by rearrangements of the NUTM1 gene, most commonly producing the BRD4-NUTM1 fusion oncogene. A 23-year-old-male had a neck mass excised by right hemithyroidectomy following two fine needle aspirates (Thy 3a and Thy 4). Following completion left thyroidectomy with bilateral central neck dissection, further surgery was required to excise recurrent disease from the thyroid bed and right lateral neck. This aggressive clinical course prompted molecular analysis which revealed a BRD4-NUTM1 fusion gene. The initial hemithyroidectomy diagnosis of solid variant papillary thyroid carcinoma with poorly differentiated areas was thus revised to NC. This is a rare site for NC to occur and illustrates the importance of considering this diagnosis in poorly differentiated neoplasms in the head and neck region.1  相似文献   
9.
Molecular markers can serve as diagnostic tools to support pathological analysis in thyroid neoplasms. However, because the same markers can be observed in some benign thyroid lesions, additional approaches are necessary to differentiate thyroid tumor subtypes, prevent overtreatment and tailor specific clinical management. This applies particularly to the recently described variant of thyroid cancer referred to as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This variant has an estimated prevalence of 4.4% to 9.1% of all papillary thyroid carcinomas worldwide. We studied 60 thyroid lesions: 20 classical papillary thyroid carcinoma (CPTC), 20 follicular variant of PTC (FVPTC) and 20 NIFTP. We examined morphological and molecular features to identify parameters that can differentiate NIFTP from the other PTC subtypes. When blindly investigating the nuclear architecture of thyroid neoplasms, we observed that NIFTP has significantly longer telomeres than CPTC and FVPTC. Super-resolved 3D-structured illumination microscopy demonstrated that NIFTP is heterogeneous and that its nuclei contain more densely packed DNA and smaller interchromatin spaces than CPTC and FVPTC, a pattern that resembles normal thyroid tissue. These data are consistent with the observed indolent biological behavior and favorable prognosis associated with NIFTP, which lacks BRAFV600E mutations. Of note, next-generation thyroid oncopanel sequencing was unable to distinguish the thyroid cancer histotypes in our study cohort. In summary, our data suggest that 3D nuclear architecture can be a powerful analytical tool to diagnose and guide clinical management of NIFTP.  相似文献   
10.
目的:优化祛湿清肺方提取工艺,并对祛湿清肺方提取液进行体外抗炎活性评价。方法:以绿原酸、虎杖苷、黄芩苷、汉黄芩苷、黄芩素、芦荟大黄素、汉黄芩素、大黄素成分含量及得膏率为指标,加水量及提取时间为考察因素,采用熵权法结合星点设计-效应面法对祛湿清肺方提取工艺进行优化。以脂多糖(LPS)诱导大鼠腹腔巨噬细胞(RAW264.7)为炎症模型,酶联免疫吸附法测定白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、一氧化氮(NO)的含量,蛋白质印迹法检测磷酸化NF-κB抑制蛋白激酶(phosphorylated inhibitor of NF-κB kinase,p-IKK)、磷酸化NF-κB p65(phosphorylated NF-κB p65,p-NF-κB p65)、NF-κB抑制蛋白α(inhibitor of NF-κBα,IκBα)蛋白表达水平变化,评价祛湿清肺方提取液抗炎活性。结果:星点设计-效应面法优化所得的最佳提取工艺为加水量13倍,提取2次,每次提取时间105 min。祛湿清肺方提取液能降低IL-6、IL-1β、TNF-α、NO的含量,抑制p-IKK、p-NF-κB p65蛋白表达,促进IκBα蛋白表达,具有较好的体外抗炎活性。结论:熵权法结合星点设计-效应面法优选的祛湿清肺方提取工艺稳定可行,所得提取液具有较好的抗炎活性,为祛湿清肺方开发和现代化研究提供参考奠定基础。  相似文献   
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