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Comprehensive Analysis of Epigenetic Associated Genes on Differential Gene Expression and Prognosis in Hepatocellular Carcinoma. 肝细胞癌差异基因表达及预后的表观遗传相关基因综合分析。
Cong Li, Jing Ding, Jianmin Mei
BACKGROUND Early detection of hepatocellular carcinoma (HCC) is significantly effective in clinical management. This study aimed to identify potential HCC biomarkers. METHODS Analysis of expression profiles in HCC clinical samples downloaded from the cancer genome atlas (TCGA) and the gene expression omnibus (GEO) datasets was performed to identify differentially expressed genes (DEGs) using R packages. The epigenetic differentially expressed genes (epiDEGs) were obtained after intersections of genes between DEGs and epigenetic factors (EFs). The biological functions of epiDEGs were annotated by gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. Protein-protein interaction and expression correlation were performed to investigate the interactions among epiDEGs by the STRING online tool and R packages. The epiDEGs associated with overall survival (OS) were identified as patient prognosis using the Cox regression analysis. The levels of gene expression were validated by RT-qPCR and Western blot between HCC cell lines, (HepG2, and Huh-7) and normal cell lines (THLE-2). RESULTS Thirty-five epiDEGs were obtained, including 25 upregulated genes and 10 downregulated genes. Functional enrichment and PPI analysis indicated the development of HCC is a complicated process involving various genes and proteins. Survival analysis showed nine epiDEGs associated with the OS of patients and these might be the independent prognostic biomarkers for HCC. The expressions of most epiDEGs were significantly higher in HCC patients with stage II and III compared with stage I. Furthermore, the expression of these epiDEGs between HCC cell lines with normal cell lines was shown to be consistent with the TCGA and GEO datasets except PBK. CONCLUSIONS Eight hub epiDEGs, including EZH2, CDK1, CENPA, RAD54L, HELLS, HJURP, AURKA, and AURKB, were associated with the overall survival of HCC patients and could be potential biomarkers to predict prognosis.
背景:肝细胞癌(HCC)的早期检测在临床治疗中具有显著的疗效。本研究旨在确定潜在的HCC生物标志物。方法使用R软件包分析从癌症基因组图谱(TCGA)和基因表达综合(GEO)数据集下载的HCC临床样本的表达谱,鉴定差异表达基因(DEGs)。将表观遗传差异表达基因(eggs)与表观遗传因子(EFs)相互交叉,得到表观遗传差异表达基因(eggs)。通过基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,对epgs的生物学功能进行了注释。利用STRING在线工具和R软件包对epgs进行蛋白-蛋白相互作用和表达相关性分析。通过Cox回归分析,确定与总生存期(OS)相关的epgs为患者预后。通过RT-qPCR和Western blot验证HCC细胞系(HepG2和Huh-7)和正常细胞系(THLE-2)之间的基因表达水平。结果共获得35个eggs,其中上调基因25个,下调基因10个。功能富集和PPI分析提示HCC的发生是一个涉及多种基因和蛋白的复杂过程。生存分析显示9个eggs与患者OS相关,这些可能是HCC的独立预后生物标志物。在II期和III期HCC患者中,大多数epgs的表达明显高于i期。此外,除了PBK外,这些epgs在HCC细胞系与正常细胞系之间的表达与TCGA和GEO数据集一致。结论EZH2、CDK1、CENPA、RAD54L、HELLS、HJURP、AURKA、AURKB等8个枢纽eggs与HCC患者的总生存期相关,可作为预测预后的潜在生物标志物。
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引用次数: 2
Exosomal circRNA_104948 Enhances the Progression of Glioma by Regulating miR-29b-3p and DNMT3B/MTSS1 Signaling. 外泌体circRNA_104948通过调控miR-29b-3p和DNMT3B/MTSS1信号增强胶质瘤的进展
Shoudan Zhang, Ning Guan, Xin Mao, Jingwen Cui, Xin Sui, Wenshi Guo

Glioma is a common type of malignancy in the central nervous system. The pathogenesis of glioma is complex and the underlying mechanisms remain largely unknown. In our study, exosomes were exacted from patient samples, and the isolated exosomes were confirmed by transmission electron microscope. The expression of circRNA_104948, miR-29b-3p and DNMT3B were determined using RT-qPCR. Proliferative activity of cell was examined using CCK-8 assay. Cell apoptotic rate was evaluated by flow cytometry. The expression levels of proliferation or apop-tosis markers were determined using western blotting. Our data suggested that circRNA_104948 was upregulated in plasma exosomes/tissue samples of glioma patients and glioma cell lines. Furthermore, cell proliferation was enhanced and apoptosis was suppressed in normal astrocytes treated with exosomal circRNA_104948, and the effects were reversed by sh-circRNA_104948. In addition, miR-29b-3p is a novel target of circRNA_104948, and DNMT3B is a putative downstream molecule of miR-29b-3p. circRNA_104948 could regulate the proliferation/apoptosis of astrocytes through miR-29b-3p/DNMT3B/MTSS1 signaling, and the biological behavior changes induced by glioma-Exo were reversed by miR-29b-3p mimics; upregulated cell growth caused by miR-29b-3p inhibitors was abrogated by the knockdown of DNMT3B; the effects induced by miR-29b-3p mimics were abolished by the overexpression of DNMT3B. Our findings revealed the important roles of circRNA_104948 on the development of glioma, and circRNA_104948/miR-29b-3p/MTSS1/DNMT3B pathway may be a potential candidate for the target therapy of glioma patients.

胶质瘤是中枢神经系统常见的一种恶性肿瘤。胶质瘤的发病机制十分复杂,其潜在机制在很大程度上仍不为人所知。我们的研究从患者样本中提取了外泌体,并通过透射电子显微镜对分离出的外泌体进行了确认。利用 RT-qPCR 测定了 circRNA_104948、miR-29b-3p 和 DNMT3B 的表达。细胞增殖活性采用 CCK-8 法检测。细胞凋亡率通过流式细胞术进行评估。增殖或细胞凋亡标志物的表达水平通过 Western 印迹法进行测定。我们的数据表明,circRNA_104948在胶质瘤患者和胶质瘤细胞系的血浆外泌体/组织样本中上调。此外,用外泌体circRNA_104948处理正常星形胶质细胞后,细胞增殖增强,凋亡被抑制,而sh-circRNA_104948能逆转这些影响。此外,miR-29b-3p 是 circRNA_104948 的一个新靶点,而 DNMT3B 是 miR-29b-3p 的推定下游分子。circRNA_104948可通过miR-29b-3p/DNMT3B/MTSS1信号转导调控星形胶质细胞的增殖/凋亡,miR-29b-3p模拟物可逆转胶质瘤-Exo诱导的生物学行为变化;敲除DNMT3B可减轻miR-29b-3p抑制剂导致的细胞生长上调;过表达DNMT3B可取消miR-29b-3p模拟物诱导的效应。我们的研究结果揭示了circRNA_104948在胶质瘤发病过程中的重要作用,circRNA_104948/miR-29b-3p/MTSS1/DNMT3B通路可能是胶质瘤患者靶向治疗的潜在候选通路。
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引用次数: 5
Mechanistic Episodes on SARS-CoV-2-Mediated Neurological Manifestations and Their Possible Therapeutic Interventions. sars - cov -2介导的神经系统表现的机制发作及其可能的治疗干预措施
Sobia Nida, Hemalatha Srinivisan, A. Pandurangan, M. Waseem
Recently, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been critically recognized and spread rapidly on this planet. Considerable recognition of SARS-CoV-2 has been known with a range of viruses that are more capable to cause diseases in avian and mammals including humans. The virus was found as a main culprit for major defects in respiratory system and thereby caused severe acute respiratory syndrome disease. This has led to depict the mortality in human population. Nevertheless, compromised reports on SARS-CoV-2 has also shown neurological complications in both central nervous system (CNS) and peripheral nervous system (PNS). This virus has notified with neurological defects as stroke, encephalopathy, cerebral edema, erythema, seizures, meningitis, ischemic, ageusia, loss of smell, myalgia and Guillain Barre Syndrome. In this review, we focused on COVID-19 mediated neurodegeneration and its mechanistic episodes on affected patients. We also discuss the possible available therapeutic interventions with clinically investigated drugs against COVID-19 mediated neurological impairment in patients and experimental in vitro and in vivo research models required for the development of drugs and/or vaccines against COVID-19 mediated neurological complications.
最近,严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)的出现得到了人们的高度认可,并在这个星球上迅速传播。人们对SARS-CoV-2有相当程度的认识,这些病毒更有能力在禽类和包括人类在内的哺乳动物中引起疾病。该病毒被发现是呼吸系统重大缺陷的罪魁祸首,从而导致严重的急性呼吸综合征疾病。这导致了对人口死亡率的描述。然而,关于SARS-CoV-2的不完整报告也显示出中枢神经系统(CNS)和周围神经系统(PNS)的神经系统并发症。该病毒已引起中风、脑病、脑水肿、红斑、癫痫、脑膜炎、缺血性、老年痴呆、嗅觉丧失、肌痛和格林-巴利综合征等神经系统缺陷。在这篇综述中,我们重点关注COVID-19介导的神经变性及其在受影响患者中的机制发作。我们还讨论了针对COVID-19介导的患者神经功能损伤的临床研究药物可能的治疗干预措施,以及开发针对COVID-19介导的神经系统并发症的药物和/或疫苗所需的体外和体内实验研究模型。
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引用次数: 0
Essential Trace Metals as Countermeasure for Lead Toxicity. 必需微量金属作为铅中毒的对策。
S. Bhattacharya
Lead (Pb) is the most common toxic heavy metal that is physiologically non-essential and imposes health complications in animals and humans. Chelation therapy is considered as the definite therapy for acute lead toxicity; clinical uses of chelating agents are not recommended in long-term lead toxicity and in children. Research reveals that essential trace metals can counteract empirical Pb toxicity. This article collates the prototypical evidence of the preventive action of essential trace metals towards Pb toxicity in animals. Zinc, selenium, and their combinations are effective here. The key mechanisms of homeostasis of essential metals and cytoprotection are: modulation of signal transduction pathways of apoptosis, inflammation and immune functions (for selenium), attenuation of oxidative stress by augmenting non-enzymatic and enzymatic antioxidative systems and interference in lead accumulation in the body. By means of these mechanisms, these essential trace metals may counteract long-term lead toxicity for susceptible subjects. These mineral nutritional supplementation can easily be employed with no or less adverse effects compared to the typical chelation treatment.
铅(Pb)是最常见的有毒重金属,在生理上不是必需的,对动物和人类造成健康并发症。螯合治疗被认为是急性铅中毒的确定治疗方法;螯合剂的临床应用不推荐长期铅中毒和儿童。研究表明,必需微量金属可以抵消经验铅毒性。本文整理了必需微量金属对动物铅中毒预防作用的典型证据。锌,硒和它们的组合在这里是有效的。必需金属体内平衡和细胞保护的关键机制包括:调节细胞凋亡、炎症和免疫功能的信号转导途径(对于硒),通过增强非酶和酶抗氧化系统来减弱氧化应激,以及干扰体内铅的积累。通过这些机制,这些必需的微量金属可以抵消易感受试者的长期铅毒性。与典型的螯合治疗相比,这些矿物质营养补充剂可以很容易地使用,没有或较少的副作用。
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引用次数: 2
STAT3, VEGF, and PSMA Expression Patterns in Malignant Peripheral Nerve Sheath Tumors, Malignant Melanomas, and Glioblastomas: Does Staining Percentage and Intensity Have an Effect on Survival? STAT3、VEGF和PSMA在恶性周围神经鞘肿瘤、恶性黑色素瘤和胶质母细胞瘤中的表达模式:染色百分比和强度对生存率有影响吗?
Sinem Coskun, M. Gamsızkan, U. Yalçınkaya, M. Sungur
Malignant peripheral nerve sheath tumors (MPNSTs), glioblastomas (GBMs), and malignant melanomas (MMs) are neural crest-originating aggressive tumors with a poor prognosis. Signal transducer and transcription activator 3 (STAT3) plays a role in many biological processes, including cell life and proliferation, the acute phase response, chronic inflammation, autoimmunity, metabolism, and cancer progression, It is also known to be a prooncogenic transcription factor. Vascular endothelial growth factor (VEGF) is one of the most potent proangiogenic stimuli ever identified. It mediates tumor neovascularization, and is associated with angiogenesis and lymphangiogenesis. The prostate-specific membrane antigen (PSMA) folate hydrolase I, despite its name, has been found in tissues other than the prostate. It is overexpressed in prostate cancer cells and several other cancers, and has the potential to be a target for radioligand therapy. We investigated the value of STAT3, VEGF and PSMA immunohistochemical expression patterns and their effects on survival in MPNSTs, GBMs, and MMs. Their expression patterns were evaluated in 25 MPNSTs, 27 GBMs, and 25 MM cases. All GBM cases stained positively for STAT3 and VEGF. In the other groups, the staining patterns were heterogeneous. None of the cases showed positive staining with PSMA. There was no statistically significant difference in survival between cases with differing VEGF and STAT3 staining patterns in the MPSNT and MM groups, but there was an increase in mortality as the VEGF score increased in the GBM group. The suppression of VEGF and STAT3 may be a promising avenue for treatment of MPNSTs, GBMs, and MMs, although further research is needed.
恶性周围神经鞘瘤(MPNSTs)、胶质母细胞瘤(GBMs)和恶性黑色素瘤(mm)是神经嵴源性侵袭性肿瘤,预后较差。信号换能器和转录激活因子3 (STAT3)在许多生物学过程中发挥作用,包括细胞生命和增殖、急性期反应、慢性炎症、自身免疫、代谢和癌症进展,它也是一种已知的致癌转录因子。血管内皮生长因子(VEGF)是迄今为止发现的最有效的促血管生成刺激之一。它介导肿瘤新生血管,并与血管生成和淋巴管生成有关。前列腺特异性膜抗原(PSMA)叶酸水解酶I,尽管它的名字,已经在前列腺以外的组织中发现。它在前列腺癌细胞和其他几种癌症中过度表达,有可能成为放射配体治疗的靶点。我们研究了STAT3、VEGF和PSMA免疫组织化学表达模式的价值及其对MPNSTs、GBMs和mm中生存的影响。在25例mpnst、27例GBMs和25例MM病例中评估了它们的表达模式。所有GBM病例STAT3和VEGF均呈阳性。在其他组中,染色模式是不均匀的。所有病例均未见PSMA阳性染色。在MPSNT组和MM组中,不同VEGF和STAT3染色模式的患者的生存率无统计学差异,但在GBM组中,随着VEGF评分的增加,死亡率增加。虽然还需要进一步的研究,但抑制VEGF和STAT3可能是治疗MPNSTs、GBMs和mm的一种有希望的途径。
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引用次数: 1
Assessment of the Therapeutic Effects of Fucoxanthin by Attenuating Inflammation in Ovalbumin-Induced Asthma in an Experimental Animal Model. 岩藻黄素对蛋清蛋白诱导哮喘炎症的治疗作用的实验动物模型评价。
Xinjun Yang, G. Guo, Minyan Dang, Lei Yan, Xin Kang, Kunjin Jia, Hongrui Ren
Asthma has affected more than 300 million people worldwide and is considered one of the most debilitating global public health problems based on a recent statistical report from the Global Initiative for Asthma. Inflammation of the airways leads to the various interrelated mechanisms of innate and adaptive immunity acting mutually with the epithelium of the respiratory organ. Fucoxanthin is an orange or brown pigment which is naturally found in various seaweeds. To the best of our knowledge, there are no scientific claims or evidence of the curative effects of fucoxanthin against asthma. Hence, this present research was designed to investigate the curative activity of fucoxanthin against ovalbumin-induced asthma in a mouse model. Fucoxanthin (50 mg/kg) showed significant (P < 0.001) antiasthma activity. It effectively decreased intracellular secretion of reactive oxygen species and increased antioxidant enzyme activity. Fucoxanthin also decreased inflammatory cytokine markers in bronchoalveolar lavage fluid. Because fucoxanthin showed effective antiasthma activity against ovalbumin-induced asthma in experimental animals, further research on this natural antioxidant could lead to development of a novel drug for the treatment of asthma in humans.
根据全球哮喘倡议最近的一份统计报告,哮喘已经影响了全球3亿多人,被认为是最令人衰弱的全球公共卫生问题之一。气道炎症导致先天免疫和适应性免疫与呼吸器官上皮相互作用的各种相关机制。岩藻黄素是一种橙色或棕色的色素,天然存在于各种海藻中。据我们所知,没有科学声明或证据表明岩藻黄质对哮喘有疗效。因此,本研究旨在探讨岩藻黄素对卵清蛋白诱导的哮喘小鼠模型的治疗活性。岩藻黄质(50 mg/kg)抗哮喘活性显著(P < 0.001)。有效降低细胞内活性氧的分泌,提高抗氧化酶的活性。岩藻黄素还能降低支气管肺泡灌洗液中的炎性细胞因子标志物。由于岩藻黄素在实验动物中显示出有效的抗哮喘活性,对这种天然抗氧化剂的进一步研究可能导致开发一种治疗人类哮喘的新药。
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引用次数: 9
Curcumin Modulates Hepatocellular Carcinoma by Reducing UNC119 Expression. 姜黄素通过降低UNC119表达调节肝细胞癌。
Zhenjiang Zhao, A. Malhotra, Wu Yuan Seng
UNCI 19 expression has been reported to be significantly higher in hepatic cancer cells (HCC). However, the clinical significance of modulating UNC119 expression in HCC is not well understood. The study described here aimed to explore the potential of curcumin in modulation of UNC119 expression in HCC by assessment with quantitative real-time PCR, western blot, and immune-histochemical analyses in HCC cell lines and tissues. The biological functions of UNC119 in the proliferation, growth, and cycle of tumor cells were analyzed both in vitro and in vivo. UNC119 expression was upregulated in HCC cell lines and tissues as indicated by comparison with normal liver cells and tissues. Cellular function assays showed that higher levels of UNC119 not only promoted proliferation but also enhanced HCC cell migration and invasion. UNC119 promoted progression of the cell cycle and significantly promoted HCC cell growth through the Wnt/β-catenin signal pathway, and enhanced tumor migration and invasion by the TGF-β/EMT pathway. Curcumin efficiently inhibited HCC cell proliferation by blocking the Wnt/β-catenin pathway and inhabited migration and invasion by blocking the TGF-p/EMT signal pathway. Curcumin not only was beneficial for tumor remission but also contributed to the long-term survival of HCC-bearing mice. UNC119 was significantly upregulated and promoted cell growth in hepatic cancer cells and tissues by the Wnt/β-catenin signal pathway and migration by TGF-β/EMT signal pathway. Curcumin treatment inhibited cell proliferation, growth, migration, and invasion by inhibition of those pathways.
据报道,UNCI 19在肝癌细胞(HCC)中的表达显著升高。然而,调节UNC119在HCC中的表达的临床意义尚不清楚。本研究旨在探讨姜黄素在HCC细胞系和组织中调节UNC119表达的潜力,方法包括定量实时PCR、western blot和免疫组织化学分析。体外和体内分析UNC119在肿瘤细胞增殖、生长和周期中的生物学功能。与正常肝细胞和组织相比,HCC细胞系和组织中UNC119的表达上调。细胞功能分析显示,高水平的UNC119不仅促进了细胞增殖,而且增强了HCC细胞的迁移和侵袭。UNC119通过Wnt/β-catenin信号通路促进细胞周期进展,显著促进HCC细胞生长,通过TGF-β/EMT通路增强肿瘤迁移侵袭。姜黄素通过阻断Wnt/β-catenin通路有效抑制肝癌细胞增殖,通过阻断TGF-p/EMT信号通路有效抑制肝癌细胞的迁移和侵袭。姜黄素不仅有利于肿瘤缓解,而且有助于肝癌小鼠的长期生存。UNC119在肝癌细胞和组织中通过Wnt/β-catenin信号通路显著上调,促进细胞生长,通过TGF-β/EMT信号通路促进细胞迁移。姜黄素通过抑制这些途径抑制细胞增殖、生长、迁移和侵袭。
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引用次数: 11
Therapeutic potential of Artemisia vulgaris: An insight into underlying immunological mechanisms. 寻常蒿的治疗潜力:对潜在免疫机制的洞察。
L. Soon, Phui Qi Ng, Jestin Chellian, Thiagarajan Madheswaran, Jithendra Panneerselvam, G. Gupta, S. Nammi, Nicole G. Hansbro, A. Hsu, H. Dureja, M. Mehta, S. Satija, P. Hansbro, K. Dua, T. Collet, D. Chellappan
Artemisia vulgaris is a traditional Chinese herb believed to have a wide range of healing properties; it is traditionally used to treat numerous health ailments. The plant is commonly called mugwort or riverside wormwood. The plant is edible, and in addition to its medicinal properties, it is also used as a culinary herb in Asian cooking in the form of a vegetable or in soup. The plant has garnered the attention of researchers in the past few decades, and several research studies have investigated its biological effects, including antioxidant, anti-inflammatory, anticancer, hypolipidemic, and antimicrobial properties. In this review, various studies on these biological effects are discussed along with the tests conducted, compounds involved, and proposed mechanisms of action. This review will be of interest to the researchers working in the field of herbal medicine, pharmacology, medical sciences, and immunology.
寻常蒿是一种传统的中国草药,被认为具有广泛的治疗特性;传统上,它被用来治疗许多健康疾病。这种植物通常被称为艾草或河畔艾草。这种植物是可食用的,除了它的药用特性外,它也被用作亚洲烹饪中的蔬菜或汤中的烹饪草本植物。在过去的几十年里,这种植物引起了研究人员的注意,一些研究调查了它的生物效应,包括抗氧化、抗炎、抗癌、降血脂和抗菌特性。在这篇综述中,对这些生物效应的各种研究进行了讨论,并进行了测试,涉及的化合物,并提出了作用机制。本文对中草药、药理学、医学和免疫学领域的研究人员有一定的参考价值。
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引用次数: 10
D-Pinitol Ameliorates Imiquimod-Induced PsoriasisLike Skin Inflammation in a Mouse Model via the NF-κB Pathway. d-匹尼醇通过NF-κB途径改善吡喹莫德诱导的银屑病样皮肤炎症小鼠模型
Jing Ma, Shi-jun Feng, Dongfang Ai, Yuan Liu, Xiufang Yang
Psoriasis is an autoregulated immune and inflammation-based skin disease affecting approximately 3-4% of the worldwide population. Pinitol, conservatively used in ayurvedic medicine, has been shown to disclose an antiinflammatory effect, hold back the T-helper cells, and postpone cardiovascular diseases. In the present study we aimed to reveal the effect of D-pinitol on imiquimod (IMQ)-induced psoriasis-like skin inflammation in a mouse model via the nuclear factor-κB (NF-κB) pathway genes. In the current study, we found that D-pinitol ameliorated the skin abrasion and abridged epithelial thickness, inflammation numbers, and collagen-occupied regions in IMQ-induced psoriasis-like mice. The same results (epithelial thickness, inflammation numbers, and collagen-occupied regions) we achieved in dorsal skin regions. In addition, D-pinitol modified the lipid profile and antioxidant enzyme levels, which means that the IMQ-induced group showed elevated malondialdehyde when compared to D-pinitol. Downregulated expression of glutathione, superoxide dismutase, and catalase in the IMQ-induced group was incomparable with D-pinitol, control, and standard group. Additionally, inflammatory and NF-kB pathway gene levels in the psoriatic mouse skin, which includes tumor necrosis factor-α, interleukin [IL]-6, IL-17A, IL-23,TRAF3, NIK, IKKα, and RelB, were dramatically increased or decreased by treatment with D-pinitol. Histological and morphometric studies disclose the efficiency of D-pinitol. Finally, we found that D-pinitol reserved the TRAF3, NIK, IKKα, and RelB in the psoriatic skin, signifying that it restrains the commencement of NF-κB signaling pathways. The present results suggest that D-pinitol could prove to have tremendous preventive potential against the treatment and prevention of inflammatory disease.
牛皮癣是一种自我调节的免疫和炎症性皮肤病,影响全球约3-4%的人口。Pinitol,保守地用于阿育吠陀医学,已经显示出抗炎作用,抑制t辅助细胞,延缓心血管疾病。在本研究中,我们旨在通过核因子-κB (NF-κB)途径基因揭示D-pinitol对咪喹莫特(IMQ)诱导的小鼠银屑病样皮肤炎症的影响。在目前的研究中,我们发现D-pinitol改善了imq诱导的牛皮癣样小鼠的皮肤磨损和缩短上皮厚度、炎症数量和胶原占据区域。我们在背侧皮肤区域获得了相同的结果(上皮厚度、炎症数量和胶原占据区域)。此外,D-pinitol改变了脂质谱和抗氧化酶水平,这意味着与D-pinitol相比,imq诱导组显示丙二醛升高。imq诱导组谷胱甘肽、超氧化物歧化酶和过氧化氢酶的表达下调与d -蒎醇、对照组和标准组无法比较。此外,银屑病小鼠皮肤中的炎症和NF-kB通路基因水平,包括肿瘤坏死因子-α、白细胞介素[IL]-6、IL- 17a、IL-23、TRAF3、NIK、IKKα和RelB,在D-pinitol治疗后显著升高或降低。组织学和形态计量学研究揭示了d -蒎醇的有效性。最后,我们发现D-pinitol在银屑病皮肤中保留了TRAF3、NIK、IKKα和RelB,这表明它抑制了NF-κB信号通路的启动。目前的结果表明,d -蒎醇在治疗和预防炎症性疾病方面具有巨大的预防潜力。
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引用次数: 5
Evaluation of LncRNA ANRIL Potential in Hepatic Cancer Progression. LncRNA ANRIL在肝癌进展中的潜力评估。
Yongjian Ji, Hao Sun, Haiqing Liang, Yong Wang, Meili Lu, Zhaoyang Guo, Zhuozhen Lv, W. Ren
BACKGROUND/AIMS LncRNAs are significant regulators in multiple cancers including hepatocellular carcinoma (HCC). Recently, lncRNA ANRIL has been reported to be elevated during multiple cancer types, exhibiting oncogenic roles. However, the exact biological mechanism of ANRIL is still poorly understood in HCC. METHODS Quantitative real-time polymerase chain reaction (qRT-PCR) assays were utilized to detect expressions of ANRIL, miR-384, and STAT3. CCK8 and EDU assays were employed to evaluate HCC cell proliferation. A flow cytometry assay was used to detect the HCC cell cycle and cell apoptosis. The scratch migration and Transwell invasion assays were performed to test cell migration and invasion, respectively. RIP and RNA pull-down assays were carried out to confirm the correlation between ANRIL and miR-384. The dual-luciferase reporter assay was used to prove the association between miR-384 and STAT3. Western blotting analysis was performed to examine protein levels of STAT3. IHC and HE staining were employed to detect Ki-67 and histopathology. RESULTS ANRIL expression was upregulated in HCC cells, including SMCC7721, HepG2, MHCC-97H, SNU449 and HUH-7 cells, in comparison to the normal human liver cells LO2. Knockdown of ANRIL suppressed HCC cell proliferation and induced cell cycle arrest and apoptosis. HCC cell migration and invasion capacity were inhibited by inhibition of ANRIL. Bioinformatics analyses revealed that ANRIL could interact with miR-384. miR-384 was significantly decreased in HCC cells, and overexpression of miR-384 repressed HCC progression. STAT3 was predicted as a target of miR-384, and miR-384 can modulate STAT3 levels negatively in vitro. ANRIL can suppress HCC development through regulating miR-384 and STAT3 in vivo. CONCLUSION ANRIL is involved in HCC progression by direct targeting of miR-384 and STAT3. Also, ANRIL could act as a potential candidate for HCC diagnosis, prognosis, and therapy.
背景/ aimslncrna是包括肝细胞癌(HCC)在内的多种癌症的重要调节因子。最近,lncRNA ANRIL被报道在多种癌症类型中升高,表现出致癌作用。然而,ANRIL在HCC中的确切生物学机制尚不清楚。方法采用定量实时聚合酶链反应(qRT-PCR)检测ANRIL、miR-384、STAT3的表达。CCK8和EDU检测HCC细胞增殖。流式细胞术检测肝癌细胞周期和细胞凋亡。采用划痕迁移法和Transwell侵袭法分别检测细胞迁移和侵袭。采用RIP和RNA拉下实验来证实ANRIL与miR-384之间的相关性。双荧光素酶报告试验被用来证明miR-384和STAT3之间的关联。Western blotting检测STAT3蛋白水平。采用免疫组化和HE染色检测Ki-67及组织病理学。结果肝癌细胞SMCC7721、HepG2、MHCC-97H、SNU449和HUH-7细胞中tsanril的表达较正常人肝细胞LO2上调。ANRIL基因敲低可抑制肝癌细胞增殖,诱导细胞周期阻滞和凋亡。抑制ANRIL可抑制肝癌细胞的迁移和侵袭能力。生物信息学分析显示ANRIL可与miR-384相互作用。miR-384在HCC细胞中显著降低,过表达miR-384可抑制HCC的进展。STAT3被预测为miR-384的靶标,miR-384可以在体外负向调节STAT3水平。ANRIL可以通过调节miR-384和STAT3在体内抑制HCC的发展。结论anril通过直接靶向miR-384和STAT3参与HCC进展。此外,ANRIL可作为HCC诊断、预后和治疗的潜在候选药物。
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引用次数: 12
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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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