Microenvironment

微环境
  • 文章类型: Journal Article
    背景:该研究旨在研究缺氧诱导因子(HIF)在发育中的作用,programming,和胶质母细胞瘤的治疗潜力。
    方法:研究,遵循PRISMA准则,使用MEDLINE(PubMed)系统地检查胶质母细胞瘤中的缺氧和HIF,WebofScience,还有Scopus.共有104项相关研究进行了数据提取。
    结果:在104项研究中,全球贡献是多种多样的,中国领先23.1%。产出最高的一年是2019年,占比11.5%。低氧诱导因子1α(HIF1α)经常被研究,其次是缺氧诱导因子2α(HIF2α),骨桥蛋白,和cavolin-1.常见的相关因子和途径包括葡萄糖转运蛋白1(GLUT1)和葡萄糖转运蛋白3(GLUT3)受体,血管内皮生长因子(VEGF),磷酸肌醇3-激酶(PI3K)-Akt-雷帕霉素(mTOR)途径,和活性氧(ROS)。HIF表达与各种胶质母细胞瘤标志相关,包括进展,生存,新生血管形成,葡萄糖代谢,迁移,和入侵。
    结论:克服诸如治疗耐药性和缺乏生物标志物的挑战对于将HIF相关疗法有效整合到胶质母细胞瘤的治疗中,以优化患者的预后至关重要。
    BACKGROUND: The study aims to investigate the role of hypoxia-inducible factors (HIFs) in the development, progression, and therapeutic potential of glioblastomas.
    METHODS: The study, following PRISMA guidelines, systematically examined hypoxia and HIFs in glioblastoma using MEDLINE (PubMed), Web of Science, and Scopus. A total of 104 relevant studies underwent data extraction.
    RESULTS: Among the 104 studies, global contributions were diverse, with China leading at 23.1%. The most productive year was 2019, accounting for 11.5%. Hypoxia-inducible factor 1 alpha (HIF1α) was frequently studied, followed by hypoxia-inducible factor 2 alpha (HIF2α), osteopontin, and cavolin-1. Commonly associated factors and pathways include glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) receptors, vascular endothelial growth factor (VEGF), phosphoinositide 3-kinase (PI3K)-Akt-mechanistic target of rapamycin (mTOR) pathway, and reactive oxygen species (ROS). HIF expression correlates with various glioblastoma hallmarks, including progression, survival, neovascularization, glucose metabolism, migration, and invasion.
    CONCLUSIONS: Overcoming challenges such as treatment resistance and the absence of biomarkers is critical for the effective integration of HIF-related therapies into the treatment of glioblastoma with the aim of optimizing patient outcomes.
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  • 文章类型: Journal Article
    乳酸以前被认为是代谢的副产品。然而,对癌症发展的复杂性的广泛研究揭示了它对肿瘤生长的重要贡献,迁移,和入侵。在组蛋白和非组蛋白蛋白中广泛观察到涉及乳酸的翻译后修饰,这些修饰通过共价连接乳酰和蛋白质中的赖氨酸残基在调节基因表达中起着至关重要的作用。这一发现大大增强了我们对乳酸参与疾病发病机制的理解。在这篇文章中,我们对乳酸与肿瘤免疫之间的复杂关系进行了全面的综述,在恶性肿瘤中发生乳酸化,以及在肿瘤免疫治疗中靶向乳酸-乳酸化的开发。此外,我们讨论了未来的研究方向,旨在提供新颖的见解,可以为调查提供信息,诊断,以及相关疾病的治疗。
    Lactic acid was formerly regarded as a byproduct of metabolism. However, extensive investigations into the intricacies of cancer development have revealed its significant contributions to tumor growth, migration, and invasion. Post-translational modifications involving lactate have been widely observed in histone and non-histone proteins, and these modifications play a crucial role in regulating gene expression by covalently attaching lactoyl groups to lysine residues in proteins. This discovery has greatly enhanced our comprehension of lactic acid\'s involvement in disease pathogenesis. In this article, we provide a comprehensive review of the intricate relationship between lactate and tumor immunity, the occurrence of lactylation in malignant tumors, and the exploitation of targeted lactate-lactylation in tumor immunotherapy. Additionally, we discuss future research directions, aiming to offer novel insights that could inform the investigation, diagnosis, and treatment of related diseases.
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  • 文章类型: Journal Article
    细胞培养是组织工程的基石,在组织再生中起着至关重要的作用,药物筛选,和疾病机制的研究。在各种培养技术中,3D文化系统,特别是那些利用悬浮纤维支架的,提供比传统2D单层培养更生理相关的环境。这些3D支架增强了细胞生长,分化,通过模拟体内细胞环境进行增殖。本文综述了悬浮纤维支架在组织工程中的关键作用。我们比较了3D悬浮纤维支架与2D培养系统的有效性,讨论它们在组织再生方面的各自益处和局限性。此外,探讨了悬浮纤维支架的制备方法及其潜在应用。该综述最后考虑了未来的研究方向,以优化悬浮纤维支架,以解决组织再生中的具体挑战。强调了他们在推进组织工程和再生医学方面的重要前景。
    Cell culturing is a cornerstone of tissue engineering, playing a crucial role in tissue regeneration, drug screening, and the study of disease mechanisms. Among various culturing techniques, 3D culture systems, particularly those utilizing suspended fiber scaffolds, offer a more physiologically relevant environment than traditional 2D monolayer cultures. These 3D scaffolds enhance cell growth, differentiation, and proliferation by mimicking the in vivo cellular milieu. This review focuses on the critical role of suspended fiber scaffolds in tissue engineering. We compare the effectiveness of 3D suspended fiber scaffolds with 2D culture systems, discussing their respective benefits and limitations in the context of tissue regeneration. Furthermore, we explore the preparation methods of suspended fiber scaffolds and their potential applications. The review concludes by considering future research directions for optimizing suspended fiber scaffolds to address specific challenges in tissue regeneration, underscoring their significant promise in advancing tissue engineering and regenerative medicine.
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  • 文章类型: Journal Article
    全球范围内,肝癌在癌症相关死亡率方面排名第四,是第六常见的癌症。大约80%的肝癌是肝细胞癌(HCC)。这是癌症死亡的主要原因。众所周知,HCC可以非常快速地发展对可用的化疗治疗的抗性。为癌症患者提供适当护理的最大障碍之一是耐药性。据报道,超过90%的癌症特异性死亡是由治疗耐药性引起的。通过与靶信使RNA(mRNA)的3'-非翻译区结合,microRNAs(miRNAs),一组大约17到25个核苷酸长的非编码RNA,调控靶基因表达。此外,它们在信号通路的控制中发挥作用,细胞增殖,细胞死亡。因此,miRNA通过改变免疫表型在肝癌微环境中发挥重要作用,缺氧条件,酸化,以及血管生成和细胞外基质成分。此外,HCC中miRNA水平的变化可以通过影响各种细胞过程(如自噬)来有效抵抗癌细胞对化疗,凋亡,和膜转运蛋白活性。在目前的工作中,我们叙述了miRNA在肝癌中的作用,特别关注肿瘤微环境和耐药性。
    Globally, hepatic cancer ranks fourth in terms of cancer-related mortality and is the sixth most frequent kind of cancer. Around 80% of liver cancers are hepatocellular carcinomas (HCC), which are the leading cause of cancer death. It is well known that HCC may develop resistance to the available chemotherapy treatments very fast. One of the biggest obstacles in providing cancer patients with appropriate care is drug resistance. According to reports, more than 90% of cancer-specific fatalities are caused by treatment resistance. By binding to the 3\'-untranslated region of target messenger RNAs (mRNAs), microRNAs (miRNAs), a group of noncoding RNAs which are around 17 to 25 nucleotides long, regulate target gene expression. Moreover, they play role in the control of signaling pathways, cell proliferation, and cell death. As a result, miRNAs play an important role in the microenvironment of HCC by changing immune phenotypes, hypoxic conditions, and acidification, as well as angiogenesis and extracellular matrix components. Moreover, changes in miRNA levels in HCC can effectively resist cancer cells to chemotherapy by affecting various cellular processes such as autophagy, apoptosis, and membrane transporter activity. In the current work, we narratively reviewed the role of miRNAs in HCC, with a special focus on tumor microenvironment and drug resistance.
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  • 文章类型: Journal Article
    子宫腺肌病(AM)是一种常见的妇科疾病,其特征是子宫肌层内存在子宫内膜腺体和基质。它与异常子宫出血(AUB)有关,痛经,和不孕症。尽管已经提出了几种机制来阐明AM,该疾病的确切原因和发展仍不清楚。最近的研究强调了微环境中巨噬细胞极化的重要性,在AM的启动和进展中起着至关重要的作用。然而,目前缺乏关于巨噬细胞极化在AM中的作用和调节机制的全面综述。因此,本文旨在总结巨噬细胞极化的表型和功能以及子宫腺肌病相关巨噬细胞(AAMs)的极化现象。阐述了AAM极化在入侵/迁移中的作用及调控机制,纤维化,血管生成,痛经,和不孕症。此外,这篇综述探讨了AAM极化的潜在分子机制,并提出了未来的研究方向。总之,本综述为理解AM的发病机制提供了新的视角,为开发通过调节AAM极化的靶向药物提供了理论基础。
    Adenomyosis (AM) is a common gynecological disorder characterized by the presence of endometrial glands and stroma within the uterine myometrium. It is associated with abnormal uterine bleeding (AUB), dysmenorrhea, and infertility. Although several mechanisms have been proposed to elucidate AM, the exact cause and development of the condition remain unclear. Recent studies have highlighted the significance of macrophage polarization in the microenvironment, which plays a crucial role in AM initiation and progression. However, a comprehensive review regarding the role and regulatory mechanism of macrophage polarization in AM is currently lacking. Therefore, this review aims to summarize the phenotype and function of macrophage polarization and the phenomenon of the polarization of adenomyosis-associated macrophages (AAMs). It also elaborates on the role and regulatory mechanism of AAM polarization in invasion/migration, fibrosis, angiogenesis, dysmenorrhea, and infertility. Furthermore, this review explores the underlying molecular mechanisms of AAM polarization and suggests future research directions. In conclusion, this review provides a new perspective on understanding the pathogenesis of AM and provides a theoretical foundation for developing targeted drugs through the regulation of AAM polarization.
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  • 文章类型: Journal Article
    在食管鳞状细胞癌(ESCC)患者中,我国ESCC的发病率和死亡率也高于世界其他地区。尽管治疗部门方法取得了进展,患者生存率没有明显提高,这通常会导致治疗阻塞和癌症重复。ESCC具有自我更新和分化能力的特殊细胞,称为癌症干细胞样细胞(CSLCs),这反映了癌症的发展过程和预后。在这次审查中,我们评估了CSLCs,从ESCC中细胞表面标志物的表达鉴定。通过激发EMT参与肿瘤的迁移和侵袭,干细胞促进肿瘤再分化。一些因素可以通过EMT相关途径抑制ESCC的迁移和侵袭。我们在这里总结了CSLCs表面标记的研究进展,EMT通路,以及肿瘤生长过程中的微环境。因此,这些数据可能对临床应用更有价值。
    In patients with esophageal squamous cell carcinoma (ESCC), the incidence and mortality rate of ESCC in our country are also higher than those in the rest of the world. Despite advances in the treatment department method, patient survival rates have not obviously improved, which often leads to treatment obstruction and cancer repeat. ESCC has special cells called cancer stem-like cells (CSLCs) with self-renewal and differentiation ability, which reflect the development process and prognosis of cancer. In this review, we evaluated CSLCs, which are identified from the expression of cell surface markers in ESCC. By inciting EMTs to participate in tumor migration and invasion, stem cells promote tumor redifferentiation. Some factors can inhibit the migration and invasion of ESCC via the EMT-related pathway. We here summarize the research progress on the surface markers of CSLCs, EMT pathway, and the microenvironment in the process of tumor growth. Thus, these data may be more valuable for clinical applications.
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  • 文章类型: Journal Article
    胶质母细胞瘤(GB)是肿瘤学中最不利的诊断之一。复杂电流治疗导致15个月的中位生存期。对治疗的抗性与癌症干细胞(CSC)的存在有关。本综述旨在分析CSC可塑性的机制,显示β-连环蛋白在调节CSCs重要功能中的特殊作用,并描述了Wnt非依赖性β-连环蛋白水平增加的分子机制,受CSCs局部微环境的影响。本综述还分析了使用药物调节CSCs效果低的原因,并提出了用肿瘤细胞疫苗开发免疫治疗方案,含有能够产生多向抗肿瘤免疫反应的异质癌细胞。此外,本研究讨论了通过从健康同胞移植造血干细胞并使用氯法齐明或其他降低CSC中β-catenin浓度的再用途药物来控制淋巴细胞减少的可能性.
    Glioblastoma (GB) is one of the most adverse diagnoses in oncology. Complex current treatment results in a median survival of 15 months. Resistance to treatment is associated with the presence of cancer stem cells (CSCs). The present review aimed to analyze the mechanisms of CSC plasticity, showing the particular role of β-catenin in regulating vital functions of CSCs, and to describe the molecular mechanisms of Wnt-independent increase of β-catenin levels, which is influenced by the local microenvironment of CSCs. The present review also analyzed the reasons for the low effectiveness of using medication in the regulation of CSCs, and proposed the development of immunotherapy scenarios with tumor cell vaccines, containing heterogenous cancer cells able of producing a multidirectional antineoplastic immune response. Additionally, the possibility of managing lymphopenia by transplanting hematopoietic stem cells from a healthy sibling and using clofazimine or other repurposed drugs that reduce β-catenin concentration in CSCs was discussed in the present study.
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  • 文章类型: Journal Article
    针灸是有效的干预措施,特别是在神经方面,内分泌疾病和免疫性疾病。介导针刺效应的潜在机制包括抗炎和氧化应激,抑制细胞凋亡,和刺激内源性干细胞的增殖和分化。中药联合干细胞移植在疾病医治中具有协同感化。越来越多的研究发现,针灸可以促进增殖,分化,外源性干细胞的归巢和存活。本文综述了近15年来针灸和中药对内源性干细胞和外源性干细胞联合干预多种疾病的作用机制及存在的主要问题。为今后的临床研究提供参考。
    Acupuncture is effective intervention, particularly in nerve, endocrine diseases and immune diseases. The potential mechanisms mediating the effects of acupuncture include anti-inflammatory and oxidative stress, inhibition of cell apoptosis, and stimulation of the proliferation and differentiation of endogenous stem cells. Traditional Chinese medicine combined with stem cell transplantation have a synergistic effect in the treatment of diseases. Increasing studies have found that acupuncture can promote the proliferation, differentiation, homing and survival of exogenous stem cells. This article reviews the mechanism of acupuncture and Chinese herbs on endogenous stem cells and exogenous stem cells in the combined intervention of diverse disorders and the major problems in past 15 years, which will provide a reference for future clinical research.
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  • 文章类型: Journal Article
    利用免疫生物学领域的范围审查策略来识别免疫治疗靶标,评估了实施小儿脑肿瘤免疫治疗策略的知识差距.该分析表明,迄今为止,在过度依赖成人神经胶质瘤人群的观察结果的情况下,表征和理解肿瘤生物学的免疫学方面的努力有限。关于免疫治疗靶标的频率和普遍性的基础知识是一个未满足的需求领域,同时开发具有免疫能力的儿科肿瘤模型来测试治疗方法,尤其是组合治疗。在儿科肿瘤分类从组织学到具有靶向免疫治疗的分子的演变中出现了机会。
    Utilizing a Scoping Review strategy in the domain of immune biology to identify immune therapeutic targets, knowledge gaps for implementing immune therapeutic strategies for pediatric brain tumors was assessed. The analysis demonstrated limited efforts to date to characterize and understand the immunological aspects of tumor biology with an over-reliance on observations from the adult glioma population. Foundational knowledge regarding the frequency and ubiquity of immune therapeutic targets is an area of unmet need along with the development of immune-competent pediatric tumor models to test therapeutics and especially combinatorial treatment. Opportunities arise in the evolution of pediatric tumor classification from histological to molecular with targeted immune therapeutics.
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  • 文章类型: Journal Article
    骨折后发生许多生理过程,包括炎症细胞募集,血管化,愈伤组织的形成和重塑。在特殊情况下,如严重的骨缺损或骨坏死,再生微环境受到损害,使内源性干/祖细胞不能完全显示其修复潜力。因此,外部干预,如移植或增强,往往是必要的。原位骨组织工程(iBTE)采用具有微环境线索的无细胞支架,which,植入后,将内源性干/祖细胞的行为重定向到促再生炎症反应并重建血管生成-骨生成偶联。该过程最终导致血管化骨再生(VBR)。在这种情况下,提供了针对VBR靶向iBTE技术的当前技术和模式的全面回顾。
    Numerous physiological processes occur following bone fracture, including inflammatory cell recruitment, vascularization, and callus formation and remodeling. In particular circumstances, such as critical bone defects or osteonecrosis, the regenerative microenvironment is compromised, rendering endogenous stem/progenitor cells incapable of fully manifesting their reparative potential. Consequently, external interventions, such as grafting or augmentation, are frequently necessary. In situ bone tissue engineering (iBTE) employs cell-free scaffolds that possess microenvironmental cues, which, upon implantation, redirect the behavior of endogenous stem/progenitor cells towards a pro-regenerative inflammatory response and reestablish angiogenesis-osteogenesis coupling. This process ultimately results in vascularized bone regeneration (VBR). In this context, a comprehensive review of the current techniques and modalities in VBR-targeted iBTE technology is provided.
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