Axin2基因对肝癌细胞中Wnt/β-catenin信号通路相关分子表达的调控及机制

目的探讨Axin2基因对肝癌细胞中Wnt/β-catenin信号通路相关分子表达的调控及其机制。方法通过TOPflash试验检测Axin2基因对Wnt/β-catenin信号通路的影响;荧光定量PCR(Quantitative Real-time PCR,QPCR)法检测Axin2基因在正常肝细胞LO2及3种肝癌细胞HepG2、HHCC、HB611中的表达水平;对肝癌细胞HepG2中Axin2的表达进行干扰,并检测Wnt/β-catenin信号通路相关基因(β-catenin、Cyclin A、CDK2、Wnt5a、STAT3、EGFR、APC)mRNA转录水平及相关蛋白(β-catenin、Cyclin A、CDK2、APC)的表达量。结果 Axin2对Wnt/β-catenin信号通路有显著抑制作用,且呈剂量依赖性(P 0. 05);3种肝癌细胞Axin2的表达水平显著低于正常肝细胞LO2(P 0. 05);干扰HepG2细胞中Axin2基因表达后,Axin2基因m RNA转录及蛋白表达水平降低,Wnt信号通路下游基因β-catenin、Cyclin A、CDK2、Wnt5a、STAT3和EGFR基因mRNA转录水平及β-catenin、Cyclin A、CDK2蛋白表达量均上升,而APC基因mRNA转录水平及蛋白表达量降低。结论 Axin2基因通过调控Wnt/β-catenin信号通路相关基因的表达抑制肝癌细胞的生成,本研究为寻找新的肝癌治疗靶点及防治药物提供了实验依据。     

二氢青蒿素通过调控PTEN/Akt信号通路对肝癌HepG-2细胞增殖的影响

目的:探讨不同浓度的二氢青蒿素(DHA)对肝癌HepG-2细胞生长的影响,以及影响其增殖可能的作用机制。方法:体外培养人肝癌细胞HepG-2,将实验分成加药实验组和空白对照组。加药组加入不同浓度的二氢青蒿素(25μM、50μM、100μM、150μM、200μM)干预。利用CCK8法检测不同浓度的二氢青蒿素对肝癌HepG-2细胞增殖抑制的情况,采用Western blot检测细胞内PTEN/Akt信号通路中PTEN、Akt、CyclinD1、P27相关蛋白的表达情况。结果:由CCK8的结果得出的结果,二氢青蒿素可以抑制肝癌HepG-2细胞的生长,并呈一定的浓度和时间依赖性抑制。二氢青蒿素处理48 h后,通过Western blot的结果显示,PTEN、P27表达量升高,CyclinD1和Akt表达量降低(P0.05)。结论:二氢青蒿素抑制肝癌细胞HepG-2的增殖可能与抑制PTEN/Akt信号通路,阻滞细胞生长周期有关。     

基于JAK2/STAT3信号通道为靶点的中药抗肿瘤作用研究进展

据统计肿瘤已经成为人类健康的最大的威胁。JAK2/STAT3是JAK/STAT通路中的一个重要组成部分,它在肿瘤中的持续性激活可以通过影响细胞的生长、凋亡、周期等起到促进肿瘤发生发展的作用。多种实体瘤中JAK2-STAT3信号通道均处于持续激活状态,因此针对JAK2-STAT3信号通路的靶向治疗成为目前的研究热点。研究发现许多中草药或中草药中的某些化学成分如黄连素、紫檀芪、白花蛇舌草、复方守宫散、岩大戟内酯B等可以作用于JAK2/STAT3信号通道起到抗肿瘤的功效。     

苦参碱对人急性红白血病细胞株TF-1SALL4基因及Wnt/β-catenin信号通路下游靶基因表达的影响

目的探讨苦参碱对人急性红白血病细胞株TF-1 SALL4基因及Wnt/β-catenin信号通路下游靶基因表达的影响。方法用不同浓度的苦参碱(0.5、1.0、2.0 g/L)处理TF-1细胞,另设对照组(不加苦参碱)。苦参碱作用48 h后,采用实时荧光定量PCR法检测各组TF-1细胞中SALL4基因及Wnt/β-catenin信号通路下游靶基因β-catenin、C-myc、Cyclin DI的表达水平,并分析SALL4基因与β-catenin、C-myc及Cyclin DI表达的相关性;Western blot法检测各组TF-1细胞中SALL4蛋白的表达水平。结果经不同浓度苦参碱处理48 h后,TF-1细胞中SALL4、β-catenin、C-myc、Cyclin DI基因的表达水平及SALL4蛋白的表达水平与对照组相比,均明显下降,且呈浓度依赖性(P<0.05);SALL4基因与β-catenin、C-myc、Cyclin DI基因的表达明显相关(r s值分别为0.912、0.818和0.832,P均<0.01)。结论苦参碱对TF-1细胞中SALL4基因和蛋白表达及Wnt/β-catenin信号通路下游靶基因β-catenin、C-myc、Cyclin DI的抑制可能在抑制细胞增殖、诱导细胞凋亡过程中起重要作用。     

白藜芦醇基于PI3K/Akt通路对人结肠癌细胞HCT-116凋亡的影响

目的：探究白藜芦醇基于PI3K/Akt通路对人结肠癌细胞HCT-116凋亡的影响及其相关分子机制。方法：通过MTT实验检测白藜芦醇对HCT-116细胞的增殖抑制效应;流式细胞仪检测白藜芦醇对HCT-116的促凋亡效应;蛋白免疫印迹实验检测HCT-116细胞中Caspase-3、Bcl-2、Bax、PI3K、Akt表达情况的影响。结果：白藜芦醇对HCT-116有明显的抑制增殖作用,并有效促进了其凋亡,且引起Caspase-3与Bax表达上调,Bcl-2表达下调并抑制了PI3K和Akt的磷酸化。结论：白藜芦醇可诱导HCT-116细胞发生凋亡,且与抑制PI3K/Akt信号通路的激活相关。     

cAMP-PKA-CREB信号通路在骨形态发生蛋白9诱导小鼠间充质干细胞成骨分化中的作用

目的探讨cAMP-PKA-CREB信号通路在骨形态发生蛋白9(bone morphogenetic protein 9,BMP9)诱导小鼠间充质干细胞(mesenchymal stem cells,MSCs)C3H10T1/2成骨分化过程中的作用及其机制。方法将C3H10T1/2细胞分别加入不同浓度的cAMP-PKA-CREB信号通路抑制剂H89(1、2.5、5和10μmol/L),检测其对碱性磷酸酶(alkaline phosphatase,ALP)活性的影响;通过ALP定量和钙盐沉积试验分别检测H89对BMP9诱导C3H10T1/2细胞早期和晚期成骨分化的影响;经Western blot法检测H89对C3H10T1/2细胞中磷酸化CREB、骨钙素(Osteocalcin,OCN)和成骨关键转录因子Runx2表达水平的影响;通过Wentern blot及荧光素酶活性的检测,观察H89对经典信号通路BMPs-smad1/5/8的影响。结果随着H89浓度的增加,对BMP9诱导的C3H10T1/2细胞ALP的抑制作用明显增强(P0.05),且呈剂量依赖性;ALP定量和钙盐沉积试验结果表明,H89可明显抑制BMP9诱导的C3H10T1/2细胞早期及晚期成骨分化;H89可显著抑制BMP9诱导的C3H10T1/2细胞中磷酸化CREB、OCN及Runx2蛋白的表达(P0.05),与AdBMP9组比较,H89对经典BMPs-smad1/5/8信号通路无明显影响(P0.05)。结论阻断cAMP-PKA-CREB信号通路可抑制BMP9诱导的MSCs C3H10T1/2的成骨分化,为BMP9的临床应用奠定了理论基础。     

Wnt信号通路与人类疾病相关性的研究进展

Wnt信号传导通路是一条广泛存在于多细胞生物体内且具有高度进化保守性的信号通路。该通路对细胞增殖、分化、凋亡、细胞极性及细胞的迁移和侵入产生影响,在多种器官的发育形成过程以及成体状态下病理生理过程中发挥重要作用。目前已有大量研究表明,Wnt信号通路的改变与肿瘤的形成和发生、退行性疾病的发展以及干细胞功能的改变密切相关。有更多新的研究表明,该通路与炎症发生、新生血管形成、免疫功能的维持以及创伤愈合和组织再生也有潜在性的联系。该通路正作为一个关键热点应用于上述各个领域的基础应用及药物开发研究中。本文在检索Pub Med上关于Wnt信号通路与人类疾病文献的基础上,从Wnt信号通路的组成及其与人类纤维化疾病、代谢综合征、眼部疾病、肿瘤和骨相关疾病等方面的相关性,阐明Wnt信号传导通路在细胞的增殖、分化、凋亡等过程中发挥的重要调节作用及对维持诸多器官的正常发育和形成所起的至关重要的作用。     

微量元素硒调节细胞信号传导的研究进展

概述了硒调节细胞信号传导的功能,认为其调节信号通路有：促分裂原激活蛋白激酶信号通路、蛋白激酶C信号通路、核糖体S6蛋白激酶信号通路、转录因子NF-kB和AP-1等。同时认为氧化还原修饰信号分子是硒调节信号传导的主要机制。硒通过作用于信号传导通路而调节细胞的分化、生长、增殖和凋亡,使硒具有生物多样性。     

影响皮肤光老化信号通路的植物提取物

人体衰老过程中伴随着皮肤形态和生理的恶化，并随着年龄的增长而逐渐表现出来，如色素沉积、皱纹、干燥等。光老化是导致皮肤老化的主要原因，因此，研究光老化的信号通路以及探究相关的影响信号通路延缓皮肤衰老的植物提取物具有非常重要的意义。论文综述了调控皮肤光老化的主要信号通路，包括TGF-β1/Smad信号通路、NF-KB信号通路、Nrf2/ARE信号通路和MAPK信号通路，并重点介绍通过调控各种信号通路延缓皮肤衰老的植物提取物。通过对植物提取物抗光老化成分的详细阐述，以期为植物提取物更好地应用到抗衰老化妆品中提供借鉴。     

促红细胞生成素对心肺复苏后大鼠脑保护的研究与PI3K/AKT信号通路的相关性

目的:是探讨促红细胞生成素(EPO)对心肺复苏后大鼠脑保护的作用疗效和促红细胞生成素是否可以通过磷脂酰肌醇3激酶/蛋白激酶B(PI3K/AKT)信号通路对大鼠心肺复苏后具有脑保护作用。方法:将60只健康雄性大鼠随机分为实验组和对照组,全部氯化钾致颤(10%kcl 0.3m L/kg脉冲式静脉注射诱发心搏骤停),立即行心肺复苏及气管插管等治疗,实验组给予促红细胞生成素,对照组给与同等量的生理盐水。观察不同时间点神经功能缺损评分;免疫组织化学染色观察半胱氨酸水解酶-3(caspase-3)、磷酸化蛋白激酶B(p-AKT)的表达;用HE染色方法观察脑组织受损情况。结果:实验组与对照组比较,caspase-3阳性细胞表达数量相对减少(P0.05),p-AKT阳性细胞表达数量相对增加(P0.05);实验组与对照组比较,神经细胞排列较整齐,细胞变形数量减少,细胞受损相对减轻。结论:促红细胞生成素对心肺复苏后大鼠具有脑保护作用,其机制可能与PI3K/AKT信号通路激活,抑制细胞凋亡有关,降低神经功能缺损评分,减轻神经元病理形态的损伤。     

Target of Rapamycin Signaling Involved in the Regulation of Photosynthesis and Cellular Metabolism in Chlorella sorokiniana

Target of rapamycin (TOR) is a serine/threonine protein kinase that plays a central regulating role in cell proliferation, growth, and metabolism, but little is known about the TOR signaling pathway in Chlorella sorokiniana. In this study, a Chlorella sorokiniana DP-1 strain was isolated and identified, and its nutritional compositions were analyzed. Based on homologous sequence analysis, the conserved CsTOR protein was found in the genome of Chlorella sorokiniana. In addition, the key components of TOR complex 1 (TORC1) were present, but the components of TORC2 (RICTOR and SIN1) were absent in Chlorella sorokiniana. Pharmacological assays showed that Chlorella sorokiniana DP-1 was insensitive to rapamycin, Torin1 and KU0063794, whereas AZD8055 could significantly inhibit the growth of Chlorella sorokiniana. RNA-seq analysis showed that CsTOR regulated various metabolic processes and signal transduction pathways in AZD8055-treated Chlorella sorokiniana DP-1. Most genes involved in photosynthesis and carbon fixation in Chlorella sorokiniana DP-1 were significantly downregulated under CsTOR inhibition, indicating that CsTOR positively regulated the photosynthesis in Chlorella sorokiniana. Furthermore, CsTOR controlled protein synthesis and degradation by positively regulating ribosome synthesis and negatively regulating autophagy. These observations suggested that CsTOR plays an important role in photosynthesis and cellular metabolism, and provide new insights into the function of CsTOR in Chlorella sorokiniana.     

Predominant Role of mTOR Signaling in Skin Diseases with Therapeutic Potential

The serine/threonine kinase mechanistic target of rapamycin (mTOR) plays a pivotal role in the regulation of cell proliferation, survival, and motility in response to availability of energy and nutrients as well as mitogens. The mTOR signaling axis regulates important biological processes, including cellular growth, metabolism, and survival in many tissues. In the skin, dysregulation of PI3K/AKT/mTOR pathway may lead to severe pathological conditions characterized by uncontrolled proliferation and inflammation, including skin hyperproliferative as well as malignant diseases. Herein, we provide an update on the current knowledge regarding the pathogenic implication of the mTOR pathway in skin diseases with inflammatory features (such as psoriasis, atopic dermatitis, pemphigus, and acne) and malignant characteristics (such as cutaneous T cell lymphoma and melanoma) while we critically discuss current and future perspectives for therapeutic targeting of mTOR axis in clinical practice.     

Studies on the incorporation of trans-polyoctenylene in polystyrene and PVC blends

trans-Polyoctenylene rubber, TOR, has been melt blended with PVC and with polystyrene, PS, in various proportions. PVC/TOR and PS/TOR blends were rigid, lending support to the claim that TOR improves dimensional stability of polymer and rubber blends. A processability study of PVC/TOR blends using a Brabender Plasti-corder showed that TOR is a suitable processing aid for PVC.     

DNA Synthesis during Endomitosis Is Stimulated by Insulin via the PI3K/Akt and TOR Signaling Pathways in the Silk Gland Cells of Bombyx mori

Silk gland cells undergo multiple endomitotic cell cycles during silkworm larval ontogeny. Our previous study demonstrated that feeding is required for continued endomitosis in the silk gland cells of silkworm larvae. Furthermore, the insulin signaling pathway is closely related to nutritional signals. To investigate whether the insulin signaling pathway is involved in endomitosis in silk gland cells, in this study, we initially analyzed the effects of bovine insulin on DNA synthesis in endomitotic silk gland cells using 5-bromo-2''-deoxyuridine (BrdU) labeling technology, and found that bovine insulin can stimulate DNA synthesis. Insulin signal transduction is mainly mediated via phosphoinositide 3-kinase (PI3K)/Akt, the target of rapamycin (TOR) and the extracellular signal-regulated kinase (ERK) pathways in vertebrates. We ascertained that these three pathways are involved in DNA synthesis in endomitotic silk gland cells using specific inhibitors against each pathway. Moreover, we investigated whether these three pathways are involved in insulin-stimulated DNA synthesis in endomitotic silk gland cells, and found that the PI3K/Akt and TOR pathways, but not the ERK pathway, are involved in this process. These results provide an important theoretical foundation for the further investigations of the mechanism underlying efficient endomitosis in silk gland cells.     

Silencing DTX3L Inhibits the Progression of Cervical Carcinoma by Regulating PI3K/AKT/mTOR Signaling Pathway

Cervical carcinoma (CC) is the second most prevalent gynecologic cancer in females across the world. To obtain a better understanding of the mechanisms underlying the development of CC, high-resolution label-free mass spectrometry was performed on CC and adjacent normal tissues from eight patients. A total of 2631 proteins were identified, and 46 significant differently expressed proteins (DEPs) were found between CC and normal tissues (p < 0.01, fold change >10 or <0.1). Ingenuity pathway analysis revealed that the majority of the proteins were involved in the regulation of eIF4 and p70S6K signaling and mTOR signaling. Among 46 DEPs, Integrinβ6 (ITGB6), PPP1CB, TMPO, PTGES3 (P23) and DTX3L were significantly upregulated, while Desmin (DES) was significantly downregulated in CC tissues compared with the adjacent normal tissues. In in vivo and in vitro experiments, DTX3L knockdown suppressed CC cell proliferation, migration, invasion and xenograft tumorigenesis, and enhanced cell apoptosis. Combination of silencing DTX3L and cisplatin treatment induced higher apoptosis percentage compared to cisplatin treatment alone. Moreover, DTX3L silencing inhibited the PI3K/AKT/mTOR signal pathway. Thus, our results suggested DTX3L could regulate CC progression through the PI3K/AKT/mTOR signal pathway and is potentially a novel biomarker and therapeutic target for CC.     

Mechanical and Morphological Properties of PP/LLPDE/NR Blends—Effects of Polyoctenamer

In this study, impact-modified polypropylene (PP) ternary blends based on PP/natural rubber (NR)/linear low-density polyethylene (LLDPE) with ratios of 72/10/18 and 64/20/16 were produced by a twin-screw extruder with polyoctenamer (TOR) as the compatibilizer. The mechanical properties of the blends were determined on injection-molded specimens in tensile, flexural, and impact testing. The impact strength and elongation at break of the blend increased significantly while the flexural modulus and tensile strength decreased slightly with increasing TOR content. The impact strength improved with the increasing TOR due the increase of interfacial adhesion resulting in finer dispersion of the rubbery minor phase in the PP matrix. The improvement in compatibility with the addition of TOR into PP/NR/LLDPE blends is being supported by both scanning electron microscopy (SEM) and dynamic mechanical analysis (DMA).     

Pharmacological Effects of Polyphenol Phytochemicals on the Intestinal Inflammation via Targeting TLR4/NF-κB Signaling Pathway

TLR4/NF-κB is a key inflammatory signaling transduction pathway, closely involved in cell differentiation, proliferation, apoptosis, and pro-inflammatory response. Toll like receptor 4 (TLR4), the first mammalian TLR to be characterized, is the innate immune receptor that plays a key role in inflammatory signal transductions. Nuclear factor kappa B (NF-κB), the TLR4 downstream, is the key to accounting for the expression of multiple genes involved in inflammatory responses, such as pro-inflammatory cytokines. Inflammatory bowel disease (IBD) in humans is a chronic inflammatory disease with high incidence and prevalence worldwide. Targeting the TLR4/NF-κB signaling pathway might be an effective strategy to alleviate intestinal inflammation. Polyphenol phytochemicals have shown noticeable alleviative effects by acting on the TLR4/NF-κB signaling pathway in intestinal inflammation. This review summarizes the pharmacological effects of more than 20 kinds of polyphenols on intestinal inflammation via targeting the TLR4/NF-κB signaling pathway. We expected that polyphenol phytochemicals targeting the TLR4/NF-κB signaling pathway might be an effective approach to treat IBD in future clinical research applications.