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NLRP3-Inflammasome Gene Variations in the Risk of Type 2 Diabetes. nlrp3 -炎性小体基因变异与2型糖尿病的风险
C. Ozbayer, H. Kurt, Emine Yagci, M. Kebapçı, H. Gunes, I. Degirmenci
Inflammation is the natural immunological response of an organism against any harmful, foreign or destructive effect to heal and repair damaged tissue. The nod-like receptor pyrin domain-containing-3 (NLRP3) inflammasome is one of the main components of the inflammatory mechanism and is associated with many inflammatory diseases, but it is also closely related to metabolic abnormalities, such as type 2 diabetes mellitus (T2DM), insulin resistance and obesity. NLRP3 activates inflammation and causes interleukin-1β release, exogenous and endogenous danger signals, as well as insulin resistance. In this direction, we focus on the gene structure of NLRP3 in diabetes and accordingly, we aim to determine the relationship between eight gene variations in the NLRP3 gene and T2DM. We investigated the rs10802501, rs10733113, rs10754558, rs10925026, rs10925027, rs35829419, rs4612666 and rs4925659 single-nucleotide polymorphisms of NLRP3 gene using the Sequenom MassARRAY system in 100 T2DM patients and 100 control individuals. There were no significant differences between T2DM risk and the genotype frequencies of rs10802501, rs10733113, rs35829419 and rs10925026 variants (p > 0.05). However, significant genotype frequencies were determined for rs10925027 (p = 0.0013) and rs4925659 (p < 0.001). For the risk allele G of the rs10754558 variant, significant differences were found in the heterozygous and dominant model (p = 0.036, p = 0.033). The genotype distribution of the rs4612666 variant was significant only in the heterozygous model (p = 0.047). In this hospital-based case-control study, rs10925027, rs4925659 and rs10754558 variants were found to be closely related to T2DM risk. The rs10925027 CC genotype, rs4925659 GG genotype, rs10754558 GG and GC+GG genotypes of the NLRP3 were determined as important risk factors for the T2DM.
炎症是机体对任何有害、外来或破坏性影响的自然免疫反应,目的是愈合和修复受损组织。淋巴结样受体pyrin结构域-3 (NLRP3)炎症小体是炎症机制的主要组成部分之一,与许多炎症性疾病有关,但它也与代谢异常密切相关,如2型糖尿病(T2DM)、胰岛素抵抗和肥胖。NLRP3激活炎症,引起白细胞介素-1β释放,外源性和内源性危险信号,以及胰岛素抵抗。在这个方向上,我们将重点研究NLRP3在糖尿病中的基因结构,从而确定NLRP3基因的8个基因变异与T2DM的关系。采用Sequenom MassARRAY系统对100例T2DM患者和100例对照进行NLRP3基因rs10802501、rs10733113、rs10754558、rs10925026、rs10925027、rs35829419、rs4612666和rs4925659单核苷酸多态性研究。rs10802501、rs10733113、rs35829419、rs10925026变异基因型频率与T2DM风险无显著差异(p > 0.05)。然而,rs10925027 (p = 0.0013)和rs4925659 (p < 0.001)的基因型频率显著。rs10754558变异的风险等位基因G在杂合模型和显性模型中存在显著差异(p = 0.036, p = 0.033)。rs4612666变异的基因型分布仅在杂合模式下显著(p = 0.047)。在这项以医院为基础的病例对照研究中,发现rs10925027、rs4925659和rs10754558变异与T2DM风险密切相关。NLRP3的rs10925027 CC基因型、rs4925659 GG基因型、rs10754558 GG和GC+GG基因型被确定为T2DM的重要危险因素。
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引用次数: 3
Structural Features of Coronavirus and the COVID-19 Pandemic's Impact in India. 冠状病毒的结构特征和COVID-19大流行对印度的影响。
Ankur Jaiswal, V. Babu, M. Sethi, Basant Baishya, Pallavi Jaiswal, R. Joshi, Sudhir Jugran, B. Ramola, Avnish Kumar
The rapid transmission of COVID-19 infection around the world in a brief timeframe has caused an exponential decline in street traffic and other industrial activities in various parts of the world. The confined human collaboration with the nature at the time of this emergency has shown up as an advantage for Mother Nature after COVID-19 flare because the air present in the atmosphere and water flowing in river streams is upgrading and untamed life is blossoming. India, being consistently seen as the center of contamination due to a tremendous population, overwhelming road traffic and industries which contribute to heavy pollution prompting rise in air quality index for almost all the big cities of the country. However, after the announcement of lockdown because of COVID-19, the air quality begun to upgrade and other environmental variables, for example, water quality in streams and waterways have begun offering a positive hint towards restoration. This review gives a brief knowledge on the structure and genomic organization of novel coronavirus as well as it focuses on alterations in air and water quality along with its environmental consequences at specific locations of the country during lockdown due to this pandemic circumstance.
COVID-19感染在短时间内迅速在世界各地传播,导致世界各地的街道交通和其他工业活动呈指数级下降。在这次紧急情况下,人类与自然的有限合作在COVID-19爆发后成为自然母亲的优势,因为大气中的空气和河流中的水流正在升级,未驯服的生命正在开花。印度一直被视为污染中心,因为人口众多,道路交通拥挤,工业造成了严重污染,导致该国几乎所有大城市的空气质量指数都在上升。然而,在新冠肺炎疫情宣布封锁后,空气质量开始改善,溪流和水道水质等其他环境变量开始提供积极的恢复信号。这篇综述简要介绍了新型冠状病毒的结构和基因组组织,并重点介绍了由于这种大流行的情况,在封锁期间,该国特定地区空气和水质的变化及其对环境的影响。
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引用次数: 0
Abies spectabilis-Mediated Silver Nanoparticles Inhibits Cell Growth and Promotes Apoptosis in Breast Cancer MCF-7 Cells. 冷杉介导的银纳米颗粒抑制乳腺癌MCF-7细胞生长并促进细胞凋亡。
Guanghui Ren, Xiaoyan Hao, Shuyi Yan, Jun Chen, Guobin Qiu, K. Ang, Mohd Islahuddin Mohd Tamrin
Breast cancer is the second most cause of mortality among women worldwide due to the uncontrolled proliferation of tumor cells in the mammary epithelial tissues. The silver nanoparticles were formulated from the Abies spectabilis leaf (AS-AgNPs) and characterized by various practices like UV-vis spectroscopy, FTIR, SEM, and XRD. The in vitro anticancer potential of fabricated AS-AgNPs against the MCF-7 cells were analyzed. The MTT test was executed to investigate the cytotoxic nature of fabricated AS-AgNPs against MCF-7 cells. The magnitudes of ROS accumulation and MMP level in the AS-AgNPs supplemented MCF-7 cells were studied using fluorescent staining techniques. Caspase activities were studied using assay kits. The contents of oxidative stress and antioxidant biomarker (TBARS, SOD, CAT, and GSH) levels were scrutinized by standard methods. The expressions of apoptotic markers like Bax and Bcl-2 in the AS-AgNPs administered MCF-7 cells were detected by RT-PCR assay. The MTT findings showed that both extract and fabricated AS-AgNPs remarkably decreased the MCF-7 cells. Nonetheless, both plant extract and AS-AgNPs did not affect the cell viability of MCF-10A cells. Furthermore, the fabricated AS-AgNPs improved the ROS accumulation, and depleted the MMP status in the MCF-7 cells. AS-AgNPs administered MCF-7 cells demonstrated the improved TBARS content and depleted antioxidants. The treatment with AS-AgNPs considerably elevated the caspase-9 and -3 activities and Bax expression, while decreasing the Bcl-2 expression in MCF-7 cells. Hence the current investigation reports that the formulated AS-AgNPs exhibited remarkable in vitro anticancer action against MCF-7 cells through increased ROS, oxidative stress, and apoptotic protein expression. The fabricated AS-AgNPs could be a possible anticancer remedy in the future.
由于乳腺上皮组织中肿瘤细胞不受控制的增殖,乳腺癌是全世界妇女死亡的第二大原因。银纳米颗粒由冷杉叶片(AS-AgNPs)配制而成,并通过紫外可见光谱、FTIR、SEM和XRD等多种方法进行了表征。分析了制备的AS-AgNPs对MCF-7细胞的体外抗癌潜力。MTT试验研究了制备的AS-AgNPs对MCF-7细胞的细胞毒性。采用荧光染色技术研究AS-AgNPs补充后MCF-7细胞中ROS积累量和MMP水平。用检测试剂盒检测Caspase活性。采用标准方法检测氧化应激和抗氧化生物标志物(TBARS、SOD、CAT和GSH)水平。采用RT-PCR法检测AS-AgNPs给药MCF-7细胞中凋亡标志物Bax、Bcl-2的表达。MTT实验结果表明,提取液和制备的AS-AgNPs均能显著降低MCF-7细胞的凋亡。然而,植物提取物和AS-AgNPs均未影响MCF-10A细胞的细胞活力。此外,制备的AS-AgNPs改善了MCF-7细胞中的ROS积累,并减少了MMP状态。给予AS-AgNPs的MCF-7细胞显示出TBARS含量的提高和抗氧化剂的减少。AS-AgNPs显著提高了MCF-7细胞中caspase-9和-3活性以及Bax的表达,降低了Bcl-2的表达。因此,目前的研究报告表明,配方AS-AgNPs通过增加ROS、氧化应激和凋亡蛋白表达,在体外对MCF-7细胞表现出显著的抗癌作用。制备的AS-AgNPs在未来可能成为一种抗癌药物。
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引用次数: 2
Molecular Targets of Nimbolide for Anti-Cancer Therapy: An Updated Review. Nimbolide用于抗癌治疗的分子靶点:最新综述。
P. Elumalai, D. Ezhilarasan, S. Raghunandhakumar
Cancer is a major cause of death worldwide with an increasing incidence rate and is considered a major public health problem. Distance metastasis to other tissues, high toxicity, and drug resistance of cancer cells to chemotherapy demand novel therapeutic approaches to treat cancer. Natural compounds from medicinal plants have been studied for therapeutic use in various malignancies. Nimbolide is an active principal compound from Azadirachta indica, which is an Asian traditional medicinal plant utilized historically as a remedy for a variety of diseases due to its antioxidant, anti-inflammatory, anti-cancer, and antimicrobial properties. It is a limonoid triterpene possessing potent anti-cancer effects in various types of cancers. It has been reported to induce multiple cytotoxic effects in tumor cells by modulating the cell proliferation, cell cycle, apoptosis, and metastasis by altering the various molecular signaling pathways. In the present review, we summarized all the in vitro and in vivo studies reporting the molecular targets of nimbolide for the therapeutic approaches in different types of cancer cells. We analyzed research publications up to September 2021 on the effect of nimbolide in various malignancies and the molecular mechanism of action. Nimbolide targets different signaling pathways including epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), insulin like growth factor (IGF), Wingless and INT-1 (Wnt)/β-catenin, mitogen-activated protein kinases (MAPK)/c-Jun N-terminal kinases (JNK), phosphoinositide 3-kinase (PI3K)/AKT, tumor necrosis factor-α (TNF-α)/nuclear factor kappa B (NF-κβ), and death receptor 5 (DR5) in several cancer cells. Nimbolide's widespread availability and absence of side effects, as well as understanding the molecular mechanism of nimbolide's action, will be useful to develop a therapeutic agent against cancer.
癌症是全世界死亡的主要原因,发病率不断上升,被认为是一个主要的公共卫生问题。肿瘤细胞的远距离转移、高毒性以及对化疗的耐药等特点需要新的治疗方法。从药用植物中提取的天然化合物已被研究用于治疗各种恶性肿瘤。Nimbolide是一种来自印楝的活性主要化合物,印楝是一种亚洲传统药用植物,由于其抗氧化、抗炎、抗癌和抗菌特性,在历史上被用作治疗多种疾病的药物。它是一种类柠檬三萜,对各种类型的癌症具有有效的抗癌作用。据报道,它通过改变多种分子信号通路,调节细胞增殖、细胞周期、凋亡和转移,从而诱导肿瘤细胞的多种细胞毒性作用。在本文中,我们对nimbolide在不同类型癌细胞治疗方法中的分子靶点进行了综述。我们分析了截至2021年9月关于nimbolide在各种恶性肿瘤中的作用和分子作用机制的研究出版物。Nimbolide靶向多种肿瘤细胞中不同的信号通路,包括表皮生长因子(EGF)、血管内皮生长因子(VEGF)、胰岛素样生长因子(IGF)、无翼和INT-1 (Wnt)/β-catenin、丝裂原活化蛋白激酶(MAPK)/c-Jun n-末端激酶(JNK)、磷酸肌肽3-激酶(PI3K)/AKT、肿瘤坏死因子-α (TNF-α)/核因子κ B (NF-κβ)和死亡受体5 (DR5)。Nimbolide的广泛可用性和无副作用,以及了解Nimbolide作用的分子机制,将有助于开发抗癌药物。
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引用次数: 1
Ginsenoside Rk2 Protects against Ulcerative Colitis via Inactivating ERK/MEK Pathway by SIRT1. 人参皂苷Rk2通过SIRT1灭活ERK/MEK通路来预防溃疡性结肠炎。
Xiaodong Huang, Jianwei Xiao, Mudan Wen, Jing-Tao Liang
BACKGROUND Chinese traditional medicine is widely used in the treatment of ulcerative colitis (UC). Ginsenoside Rk2 is a newly discovered dammarane triterpenoid saponin isolated from ginseng. Our study aimed to investigate the effects of Ginsenoside Rk2 on UC. METHODS Human clones of colorectal adenocarcinoma Caco-2 cells and human intestinal epithelial THP-1 cells were co-cultured to establish a UC model in vitro. Cell viability and apoptosis were analyzed by cell counting kit 8 (CCK-8) and flow cytometry assay, respectively. Inflammatory cytokines' mRNA levels were measured by real-time quantitative polymerase chain reaction (RT-qPCR). Western blot was applied to examine the protein expression of apoptosis-associated proteins and the activation of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MEK) pathway. Furthermore, fisetin, an ERK kinase activator, was used to carry out rescue experiment. SRT1720, an activator of SIRT1, was applied to increase the SIRT1 protein levels while SIRT1 inhibitor nicotinamide (NAM) exerted the opposite effect. RESULTS Ginsenoside Rk2 promoted cell viability, suppressed cell apoptosis, and reduced the release of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α (TNF-α) of HT-29 cells in UC model in a concentration-dependent manner. Meanwhile, the inhibitory effects of Ginsenoside Rk2 on the ERK/MEK pathway strengthened with the increase of concentration, and was verified by fisetin application. Furthermore, the upregulation of SIRT1 induced by Ginsenoside Rk2 prompted dephosphorylation of ERK and MEK to attenuate ERK/MEK pathway activation and reduced inflammatory progress, which was confirmed by SRT1720 as well as NAM. CONCLUSIONS Ginsenoside Rk2 inactivated ERK/MEK pathway by regulating SIRT1 to restore the cellular function of human intestinal epithelial THP-1 cells. Therefore, Ginsenoside Rk2 may be effective in the treatment of UC.
背景中药在溃疡性结肠炎(UC)的治疗中被广泛应用。人参皂苷Rk2是从人参中分离得到的一种新发现的达玛烷型三萜皂苷。本研究旨在探讨人参皂苷Rk2对UC的影响。方法将人结直肠癌Caco-2细胞克隆与人肠上皮细胞THP-1细胞共培养,建立UC体外模型。采用细胞计数试剂盒8 (CCK-8)和流式细胞术分析细胞活力和凋亡情况。采用实时定量聚合酶链反应(RT-qPCR)检测炎症因子mRNA水平。Western blot检测凋亡相关蛋白的表达和细胞外信号调节激酶(ERK)/丝裂原活化蛋白激酶(MEK)通路的激活情况。采用ERK激酶激活剂非瑟酮进行抢救实验。SRT1720是SIRT1的激活剂,用于提高SIRT1蛋白水平,而SIRT1抑制剂烟酰胺(NAM)则起到相反的作用。结果人参皂苷Rk2提高UC模型HT-29细胞的细胞活力,抑制细胞凋亡,降低促炎因子IL -1β、IL-6、IL-10、肿瘤坏死因子-α (TNF-α)的释放,并呈浓度依赖性。同时,人参皂苷Rk2对ERK/MEK通路的抑制作用随着浓度的增加而增强,并通过非瑟酮应用得到验证。此外,人参皂苷Rk2诱导SIRT1上调,促使ERK和MEK去磷酸化,从而减弱ERK/MEK通路的激活,减缓炎症进程,SRT1720和NAM证实了这一点。结论人参皂苷Rk2通过调节SIRT1灭活ERK/MEK通路,恢复人肠上皮THP-1细胞的功能。因此,人参皂苷Rk2可能对UC的治疗有效。
{"title":"Ginsenoside Rk2 Protects against Ulcerative Colitis via Inactivating ERK/MEK Pathway by SIRT1.","authors":"Xiaodong Huang, Jianwei Xiao, Mudan Wen, Jing-Tao Liang","doi":"10.1615/jenvironpatholtoxicoloncol.2021039648","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021039648","url":null,"abstract":"BACKGROUND Chinese traditional medicine is widely used in the treatment of ulcerative colitis (UC). Ginsenoside Rk2 is a newly discovered dammarane triterpenoid saponin isolated from ginseng. Our study aimed to investigate the effects of Ginsenoside Rk2 on UC. METHODS Human clones of colorectal adenocarcinoma Caco-2 cells and human intestinal epithelial THP-1 cells were co-cultured to establish a UC model in vitro. Cell viability and apoptosis were analyzed by cell counting kit 8 (CCK-8) and flow cytometry assay, respectively. Inflammatory cytokines' mRNA levels were measured by real-time quantitative polymerase chain reaction (RT-qPCR). Western blot was applied to examine the protein expression of apoptosis-associated proteins and the activation of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MEK) pathway. Furthermore, fisetin, an ERK kinase activator, was used to carry out rescue experiment. SRT1720, an activator of SIRT1, was applied to increase the SIRT1 protein levels while SIRT1 inhibitor nicotinamide (NAM) exerted the opposite effect. RESULTS Ginsenoside Rk2 promoted cell viability, suppressed cell apoptosis, and reduced the release of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α (TNF-α) of HT-29 cells in UC model in a concentration-dependent manner. Meanwhile, the inhibitory effects of Ginsenoside Rk2 on the ERK/MEK pathway strengthened with the increase of concentration, and was verified by fisetin application. Furthermore, the upregulation of SIRT1 induced by Ginsenoside Rk2 prompted dephosphorylation of ERK and MEK to attenuate ERK/MEK pathway activation and reduced inflammatory progress, which was confirmed by SRT1720 as well as NAM. CONCLUSIONS Ginsenoside Rk2 inactivated ERK/MEK pathway by regulating SIRT1 to restore the cellular function of human intestinal epithelial THP-1 cells. Therefore, Ginsenoside Rk2 may be effective in the treatment of UC.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84974243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Construction and Characterization of Cadherin 6 (CDH6)-Targeting Chimeric Antigen Receptor (CAR) Modified T Cells. Cadherin 6 (CDH6)靶向嵌合抗原受体修饰T细胞的构建与表征
Li Pang, Fang Ren, Xiaoxuan Xu, Lingyang Fu, Tifang Wang, Zhiqiang Guo
In this study, we constructed cadherin 6 (CDH6)-targeting chimeric antigen receptor (CAR) modified T cells (CAR-T cells) and investigated their target-specific recognition and tumor-specific cytocidal effect through in vitro approach. CDH6 expression at the transcriptional level and its correlation with clinicopathological parameters in various tumor types were analyzed using online bioinformatics tool. Conventional molecular cloning method was used to construct the lentiviral vector encoding CDH6-specific CAR and the lentivirus was prepared using 3-plasmid transient cotransfection method. CDH6-targeting CAR-T cells were prepared using centrifugal infection method, and the specific recognition and cytocidal effects of CAR-T cell targets were investigated through in vitro co-culture experiments. At the transcription level, CDH6 was significantly overexpressed in ovarian cancer tissues (P < 0.05). Although it was not correlated with tumor stage and patient's prognosis, the overexpression of CDH6 was positively associated with the expression of paired-box 8 (PAX8), a lineage-specific transcription factor. In the present study, we successfully established CDH6-targeting CAR-T cells that can secrete effector cytokines and produce specific cytocidal effects after being co-cultured with CDH6-positive ovarian cancer cells in vitro. Thus, CDH6, as a lineage-specific factor of ovarian tissue, may be an ideal target for CAR-T cell therapy of ovarian cancer.
在本研究中,我们构建了cadherin 6 (CDH6)靶向CAR修饰的T细胞(CAR-T细胞),并通过体外方法研究了其靶向特异性识别和肿瘤特异性杀细胞作用。利用在线生物信息学工具分析不同类型肿瘤中CDH6转录水平的表达及其与临床病理参数的相关性。采用传统的分子克隆方法构建编码cdh6特异性CAR的慢病毒载体,采用3质粒瞬时共转染法制备慢病毒。采用离心感染法制备靶向cdh6的CAR-T细胞,并通过体外共培养实验研究CAR-T细胞靶细胞的特异性识别和细胞杀伤作用。在转录水平上,CDH6在卵巢癌组织中显著过表达(P < 0.05)。虽然与肿瘤分期和患者预后无关,但CDH6的过表达与谱系特异性转录因子PAX8的表达呈正相关。在本研究中,我们成功建立了靶向cdh6的CAR-T细胞,该细胞与cdh6阳性卵巢癌细胞体外共培养后,可分泌效应细胞因子并产生特异性杀细胞作用。因此,CDH6作为卵巢组织的谱系特异性因子,可能是CAR-T细胞治疗卵巢癌的理想靶点。
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引用次数: 1
Anticancer Effect of Arbutin on Diethylnitrosamine-Induced Liver Carcinoma in Rats via the GRP and GADD Pathway. 熊果苷通过GRP和GADD途径对二乙基亚硝胺诱导的大鼠肝癌的抗癌作用。
Xiangting Zeng, Haipeng Liu, Zeping Huang, Peng Dong, Xiao Chen
Liver cancer is the third most common cancer, with increasing morbidity and mortality rates worldwide. Despite the increasing occurrence of liver cancer, it has a poor prognosis and potential treatment options are still lacking. The current study aimed to explore the anticancer potential of arbutin against diethylnitrosamine (DEN)-triggered liver carcinogenesis in rats. Liver cancer was initiated in rats via the administration of DEN (200 mg/kg) and then treated with 30 mg/kg of arbutin. Albumin, globulin, and total protein were quantified using kits. Antioxidant, liver injury marker, and tumor biomarker contents were quantified using marker-specific assay kits. The inflammatory markers c-JNK, TRAIL, caspase-8, and p53 contents were also detected using kits. Reverse transcription PCR analysis was used to study the expression of chaperones GRP78, GRP94, and PDIA4 as well as ERDJ4, ATF4, and GADD34. Liver histology was studied microscopically. The arbutin treatment effectively improved body weight and reduced liver weight in animals with DEN-provoked liver cancer. The treatment also improved the albumin, globulin, and total protein contents and antioxidants. In addition, arbutin reduced liver injury marker enzyme function and improved c-JNK, TRAIL, caspase-8, and p53 contents. Arbutin supplementation also decreased the expression of GRP78, PDIA4, GRP94, ERDJ4, ATF4, and GADD34 in the liver tissues of DEN-provoked animals. Arbutin effectively ameliorated the DEN-provoked histological alterations. Altogether, our findings show that arbutin has anti-inflammatory, antioxidant, and anticarcinogenic activities against DEN-provoked liver cancer in rats.
肝癌是第三大最常见的癌症,全世界的发病率和死亡率都在上升。尽管肝癌的发病率越来越高,但其预后较差,潜在的治疗方案仍然缺乏。本研究旨在探讨熊果苷对二乙基亚硝胺(DEN)引发的大鼠肝癌的抗癌潜力。通过给药(200 mg/kg)引起大鼠肝癌,然后用30 mg/kg熊果苷治疗。白蛋白、球蛋白和总蛋白用试剂盒定量。使用标记特异性检测试剂盒定量测定抗氧化剂、肝损伤标志物和肿瘤生物标志物的含量。用试剂盒检测炎症标志物c-JNK、TRAIL、caspase-8和p53的含量。采用反转录PCR分析研究伴侣蛋白GRP78、GRP94、PDIA4以及ERDJ4、ATF4、GADD34的表达。显微镜下观察肝脏组织学。熊果苷治疗有效地改善了den引起的肝癌动物的体重并降低了肝脏重量。该处理还提高了白蛋白、球蛋白、总蛋白含量和抗氧化剂。此外,熊果苷降低肝损伤标志物酶功能,提高c-JNK、TRAIL、caspase-8和p53含量。补充熊果苷还降低了den -鼠肝组织中GRP78、PDIA4、GRP94、ERDJ4、ATF4和GADD34的表达。熊果苷有效改善了den引起的组织学改变。总之,我们的研究结果表明熊果苷对den引起的大鼠肝癌具有抗炎、抗氧化和抗癌活性。
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引用次数: 3
Sonochemical Internalization of Bleomycin Inhibits Adenocarcinoma Breast Tumor Development in an Orthotopic Rat Model. 博来霉素声化学内化抑制原位大鼠乳腺腺癌肿瘤的发展。
Lina Nguyen, Ethan-Quan Nguyen, Cassandra Tran, K. Nguyen, Ananya Devarajan, K. Berg, H. Hirschberg
One approach to reducing post-operative tumor recurrence and alleviate debilitating side effects of systemic chemotherapy, is work centered on the development of drug activation by focused and targeted externally applied physical energy thus providing site and temporal specificity. One such technique, light mediated photochemical internalization (PCI), has been shown to be a method to obtain enhanced chemotherapy efficacy for a wide variety of anti-cancer agents. A related technology, sonochemical internaization (SCI), is an extension of the PCI concept developed to overcome the limitations of poor light penetration in tissue. SCI utilizes ultrasonic energy, to activate sonosensitizers, co-administered with anti cancer agents. The purpose of the study reported here was to evaluate the inhibitory effects of SCI of bleomycin (BLM), both in vitro and in vivo, on the adenocarcinoma breast tumor rat cell line Mat B III. In vitro, the two aspects of sonication, sonoporation (SP) and sonochemical internalization (SCI) of BLM were examined. In vivo, BLM-SCI significantly inhibited tumor development, following Mat B III implantation, in an orthotopic breast tumor animal model using Fisher rats.
减少术后肿瘤复发和减轻全身化疗副作用的一种方法是通过集中和靶向的外部施加物理能量来开发药物激活,从而提供部位和时间特异性。其中一种技术,光介导的光化学内化(PCI),已被证明是一种获得各种抗癌药物增强化疗效果的方法。一项相关技术,超声化学内在化(SCI),是PCI概念的延伸,旨在克服组织中光线穿透力差的局限性。SCI利用超声波能量,激活声敏剂,与抗癌药物共同施用。本文报道的研究目的是评估博来霉素(BLM)的SCI在体外和体内对乳腺腺癌大鼠肿瘤细胞系Mat B III的抑制作用。在体外研究了BLM的超声作用,即sonoporation (SP)和sonochemical internalization (SCI)。在体内,在Fisher大鼠原位乳腺肿瘤动物模型中,Mat B III植入后,BLM-SCI显著抑制肿瘤的发展。
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引用次数: 0
Effects of Allocryptopine on the Proliferation and Epithelial-Mesenchymal Transition of Oral Squamous Cell Carcinoma through m6A Mediated Hedgehog Signaling Pathway. 异隐托平通过m6A介导的Hedgehog信号通路对口腔鳞状细胞癌增殖和上皮-间质转化的影响
Junxia Gong, Chunlin Wang, Fang Zhang, Weidong Lan
BACKGROUND Allocryptopine is an isoquinoline alkaloid extracted from Macleaya cordata. This study aimed to explore the effects of allocryptopine on the growth and metastasis of oral squamous cell carcinoma (OSCC) cells. METHODS The human OSCC cell line HSC-3 and SAS were selected in this study. MTT assay was performed to measure cell viability. Western blot was used to detect protein expressions. transwell assay was conducted to determine the migrated and invaded cells. M6A modification was confirmed by methylated RNA immunoprecipitation assay. RESULTS Compared with the NC group, the cell viability, migration and invasion ability of OSCC cells were suppressed after allocryptopine treatment in a dose dependent manner. Allocryptopine upregulated the E-cadherin expression and downregulated N-cadherin and Vimentin expressions in the OSCC cells. In addition, the protein expressions of patched receptor 1 (PTCH1), smoothened co-receptor (SMO) and Gli family (GLI1) were downregulated after allocryptopine treatment. Furthermore, allocryptopine treatment decreased the expression of Methyltransferase like 3 (METTL3) and inhibited N6-methyladenosine (m6A) modification of PTCH1. Moreover, overexpression of PTCH1 reversed the effects of allocryptopine and induced the aggressiveness of OSCC cells. CONCLUSION Allocryptopine suppressed the proliferation and epithelial-mesenchymal transition (EMT) of OSCC cells via m6A mediated Hedgehog signaling pathway, relieving the carcinogenic behaviors of OSCC.
背景:异隐碱是一种从麦草属植物中提取的异喹啉类生物碱。本研究旨在探讨异隐托平对口腔鳞癌(OSCC)细胞生长和转移的影响。方法选择人OSCC细胞系HSC-3和SAS。MTT法测定细胞活力。Western blot检测蛋白表达。Transwell法检测细胞迁移和浸润情况。甲基化RNA免疫沉淀法证实M6A修饰。结果与NC组比较,异隐托平对OSCC细胞活力、迁移和侵袭能力均有一定的抑制作用,且呈剂量依赖性。异隐topine上调OSCC细胞中E-cadherin的表达,下调N-cadherin和Vimentin的表达。此外,异隐碱处理后,斑块受体1 (PTCH1)、平滑共受体(SMO)和Gli家族(GLI1)蛋白表达下调。此外,异隐碱处理降低了甲基转移酶如3 (METTL3)的表达,抑制了PTCH1的n6 -甲基腺苷(m6A)修饰。此外,PTCH1的过表达逆转了异隐托平的作用,并诱导了OSCC细胞的侵袭性。结论异隐topine通过m6A介导的Hedgehog信号通路抑制OSCC细胞的增殖和上皮间质转化(epithelial-mesenchymal transition, EMT),减轻OSCC的致癌行为。
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引用次数: 1
STAT1 Mediates the Transcription of CircIFI30 and Promotes the Progression of Triple-Negative Breast Cancer by Up-Regulating CDCA4. STAT1通过上调CDCA4介导CircIFI30转录,促进三阴性乳腺癌的进展。
Jie Zhang, Shufeng Xia, Xiao-you Liu, Deguang Qi, Xiao-song He, Daqin Chen
Signal transducers and activators of transcription 1 (STAT1) is an important transcription factor that regulates the growth, survival, differentiation and apoptosis of various tumor cells. However, the biological roles of STAT1 and potential mechanisms in triple-negative breast cancer (TNBC) remain largely unknown. The expression levels of STAT1, CircIFI30, CDCA4, and epithelial-mesenchymal transition (EMT)-associated molecules (MM2, MMP9, E-cadherin, and N-cadherin) were evaluated using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Furthermore, cell-counting kit-8 assay, Transwell assay, flow cytometry, and immunofluorescence staining were performed to investigate the biological functions of STAT1 and CircIFI30 in TNBC cells. In addition, Dual luciferase activity assay and chromatin immunoprecipitation qPCR were used to predict the interaction between STAT1 and CircIFI30 promoter. The effects of CircIFI30 on the stability of CDCA4 mRNA were also confirmed in further function study. Up-regulation of STAT1 was detected in TNBC tissues and cells, which were positively correlated with tumor metastasis, advanced clinical stage and poor survival rate. Up-regulated STAT1 could promote the proliferation, invasion, migration, EMT and inhibit the apoptosis of TNBC cells. RNA-seq indicated has_circ_0005571 (CircIFI30) was significantly down-regulated in TNBC cells after knockdown of STAT1. Moreover, STAT1 could be novel transcription factor that binds to CircIFI30 promoter to enhance its transcription. Additionally, knockdown of CirclFl30 down regulated the expression of cell division cycleassociated protein 4 (CDCA4) through reducing the stability of its mRNA. Our data revealed the STAT1/CircIFI30/CDCA4 axis could regulate the proliferation, invasion, migration, EMT and apoptosis of TNBC cells. Therefore, STAT1 may be a putative therapeutic candidate for targeted treatment of TNBC.
STAT1 (Signal transducers and activators of transcription 1)是调控多种肿瘤细胞生长、存活、分化和凋亡的重要转录因子。然而,STAT1在三阴性乳腺癌(TNBC)中的生物学作用和潜在机制在很大程度上仍然未知。采用定量逆转录聚合酶链式反应(RT-qPCR)评估STAT1、CircIFI30、CDCA4和上皮-间质转化(EMT)相关分子(MM2、MMP9、E-cadherin和N-cadherin)的表达水平。通过细胞计数试剂盒-8、Transwell、流式细胞术、免疫荧光染色等方法研究STAT1和CircIFI30在TNBC细胞中的生物学功能。此外,利用双荧光素酶活性测定和染色质免疫沉淀qPCR预测STAT1与CircIFI30启动子之间的相互作用。CircIFI30对CDCA4 mRNA稳定性的影响也在进一步的功能研究中得到证实。STAT1在TNBC组织细胞中表达上调,与肿瘤转移、临床分期和生存率呈正相关。STAT1上调可促进TNBC细胞增殖、侵袭、迁移、EMT,抑制TNBC细胞凋亡。RNA-seq显示,在敲低STAT1后,TNBC细胞中has_circ_0005571 (CircIFI30)显著下调。此外,STAT1可能是结合CircIFI30启动子增强其转录的新型转录因子。此外,敲低CirclFl30可通过降低细胞分裂周期相关蛋白4 (CDCA4) mRNA的稳定性来下调其表达。我们的数据显示STAT1/CircIFI30/CDCA4轴可以调节TNBC细胞的增殖、侵袭、迁移、EMT和凋亡。因此,STAT1可能是一种假定的靶向治疗TNBC的候选药物。
{"title":"STAT1 Mediates the Transcription of CircIFI30 and Promotes the Progression of Triple-Negative Breast Cancer by Up-Regulating CDCA4.","authors":"Jie Zhang, Shufeng Xia, Xiao-you Liu, Deguang Qi, Xiao-song He, Daqin Chen","doi":"10.1615/jenvironpatholtoxicoloncol.2021039794","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021039794","url":null,"abstract":"Signal transducers and activators of transcription 1 (STAT1) is an important transcription factor that regulates the growth, survival, differentiation and apoptosis of various tumor cells. However, the biological roles of STAT1 and potential mechanisms in triple-negative breast cancer (TNBC) remain largely unknown. The expression levels of STAT1, CircIFI30, CDCA4, and epithelial-mesenchymal transition (EMT)-associated molecules (MM2, MMP9, E-cadherin, and N-cadherin) were evaluated using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Furthermore, cell-counting kit-8 assay, Transwell assay, flow cytometry, and immunofluorescence staining were performed to investigate the biological functions of STAT1 and CircIFI30 in TNBC cells. In addition, Dual luciferase activity assay and chromatin immunoprecipitation qPCR were used to predict the interaction between STAT1 and CircIFI30 promoter. The effects of CircIFI30 on the stability of CDCA4 mRNA were also confirmed in further function study. Up-regulation of STAT1 was detected in TNBC tissues and cells, which were positively correlated with tumor metastasis, advanced clinical stage and poor survival rate. Up-regulated STAT1 could promote the proliferation, invasion, migration, EMT and inhibit the apoptosis of TNBC cells. RNA-seq indicated has_circ_0005571 (CircIFI30) was significantly down-regulated in TNBC cells after knockdown of STAT1. Moreover, STAT1 could be novel transcription factor that binds to CircIFI30 promoter to enhance its transcription. Additionally, knockdown of CirclFl30 down regulated the expression of cell division cycleassociated protein 4 (CDCA4) through reducing the stability of its mRNA. Our data revealed the STAT1/CircIFI30/CDCA4 axis could regulate the proliferation, invasion, migration, EMT and apoptosis of TNBC cells. Therefore, STAT1 may be a putative therapeutic candidate for targeted treatment of TNBC.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83782094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
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Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer
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