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Exploring the impact of immune response on tumor heterogeneity through mathematical modeling 通过数学建模探索免疫反应对肿瘤异质性的影响
Pub Date : 2024-07-18 DOI: 10.37349/ei.2024.00149
Diksha Gautam, Sanjeev Kumar, Rashmi Sharma, Deepshikha Dixit
Aim: This article presents an investigation into various mathematical models for cell population growth, including tumor cells, and their dynamics.Methods: We classify the models into five categories: exponential, logistic, time-tested, heterogeneous, and immunology. Mathematical modeling provides insights into the development of tumors over time and how their proliferation rate becomes more dangerous. To explore the impact of immune response on tumor heterogeneity, we develop a reaction-diffusion model of tumor growth that incorporates tumor-immune interactions and a mechanism for tumor mutation and clonal expansion. We use numerical simulations to investigate how variation in immune response affects tumor heterogeneity.Results: Our findings show that a stronger immune response leads to greater homogeneity in the tumor population, which suggests that enhancing immune response could reduce tumor heterogeneity and improve treatment outcomes.Conclusions: These results have important implications for the development of therapeutic strategies targeting the immune system to combat tumor heterogeneity.
目的:本文对包括肿瘤细胞在内的各种细胞群体增长数学模型及其动态进行了研究:我们将模型分为五类:指数模型、逻辑模型、时间检验模型、异质模型和免疫学模型。通过数学建模,我们可以了解肿瘤随着时间的推移是如何发展的,以及肿瘤的增殖率是如何变得更加危险的。为了探索免疫反应对肿瘤异质性的影响,我们建立了一个肿瘤生长的反应-扩散模型,其中包含肿瘤-免疫相互作用以及肿瘤突变和克隆扩张机制。我们利用数值模拟来研究免疫反应的变化如何影响肿瘤的异质性:我们的研究结果表明,免疫反应越强,肿瘤群体的同质性越高,这表明增强免疫反应可以降低肿瘤异质性,改善治疗效果:这些结果对开发针对免疫系统的治疗策略以对抗肿瘤异质性具有重要意义。
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引用次数: 0
The immune response of nano carbon-based photic-driving vaccines to severe acute respiratory syndrome coronavirus 2 纳米碳基光驱动疫苗对严重急性呼吸系统综合征冠状病毒 2 的免疫反应
Pub Date : 2024-05-17 DOI: 10.37349/ei.2024.00143
Junming Chen, Qiang Wang, Fenfen Zhang, Jianshe Yang
As the most severe novel infectious disease in this century, coronavirus disease 2019 (COVID-19) faces tremendous challenges due to the hysteresis of drugs and vaccine development. Elucidating the panoramic mechanism of coronavirus-host immune interaction is a strategy for disease surveillance, diagnosis, treatment, prevention, and immunity assessment of COVID-19. A robust carbon nanotube (CNT)-based photic vaccine technology contributes to address the core scientific issues of these challenges. This perspective states the latest prevention and control strategy of CNT-based photic vaccine and its broad-spectrum resistance to high transmissible and pathogenic variants. Furthermore, this perspective covers the potential immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) under the CNT-based photic vaccine intervention and finally evaluates its efficacy and the underlying interactive mechanisms. In the future, findings of the highly efficient and conservative T cell epitopes depending on an intelligent chem-physical modulation would provide a promising basis for the development of next generation vaccines. Ideally, these next generation vaccines are prone to be with the function of dynamic allostery responding to the chem-physical changing and present the allosteric epitopes which are affinity to the viral variation.
作为本世纪最严重的新型传染病,冠状病毒病2019(COVID-19)因药物和疫苗研发的滞后而面临巨大挑战。阐明冠状病毒与宿主免疫相互作用的全景机制是COVID-19疾病监测、诊断、治疗、预防和免疫评估的策略。基于碳纳米管(CNT)的光疫苗技术有助于解决这些挑战的核心科学问题。本视角阐述了基于碳纳米管的光疫苗的最新防控策略及其对高传播性和致病性变种的广谱抗性。此外,本视角还涵盖了在基于 CNT 的光疫苗干预下对严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)的潜在免疫反应,并最终评估了其功效和潜在的相互作用机制。未来,通过智能化学物理调控发现高效、保守的 T 细胞表位将为下一代疫苗的开发奠定良好基础。理想情况下,这些下一代疫苗应具有响应化学物理变化的动态异位功能,并呈现与病毒变异具有亲和力的异位表位。
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引用次数: 0
Recent advances in the study of the structure and function of the epididymis 附睾结构和功能研究的最新进展
Pub Date : 2024-05-17 DOI: 10.37349/ei.2024.00142
Chuxiong Wang, Ye Xie, Jiang Liu, Qinying Xie, Yafei Kang, Xinyi Dong, Donghui Huang
Testicular sperm maturation is critical for establishing male fertility. Spermatozoa undergo remodeling of sperm proteins and changes in lipid and ribonucleic acid composition during transport in the epididymal ducts, which play an important role in sperm maturation. The anatomy, epithelial cell types, physiological functions, and epigenetic inheritance of the epididymis are explored, and recent findings in epididymal research are analyzed. Suggesting possible directions for future research on the epididymis. Using the keywords “epididymis”, “sperm”, and “sperm maturation”, a search of the epididymis was performed through databases and official websites of journals related to reproduction. The epididymis was searched in databases and on the official websites of journals related to reproduction. This review introduces the characteristics of the epididymis, as well as the biological functions of cell types such as principal cells, clear cells, and basal cells, providing a detailed description of the overall physiological functions of the epididymis. It highlights current research hotspots in the field of epididymis, including single-cell analysis, epigenetics, and extracellular vesicles, aiming to offer a comprehensive understanding for beginners. The review emphasizes the importance of the epididymis, its impact on sperm maturation and subsequent embryo development, and how it advances research on epididymal diseases while providing new directions for the study and treatment strategies of infertility.
睾丸精子成熟对男性生育能力的建立至关重要。精子在附睾管中的运输过程中,精子蛋白质会发生重塑,脂质和核糖核酸的组成也会发生变化,这在精子成熟过程中起着重要作用。该书探讨了附睾的解剖结构、上皮细胞类型、生理功能和表观遗传,并分析了附睾研究的最新发现。提出未来附睾研究的可能方向。以 "附睾"、"精子"、"精子成熟 "为关键词,通过与生殖相关的数据库和期刊官方网站对附睾进行检索。在数据库和生殖相关期刊的官方网站上对附睾进行了检索。这篇综述介绍了附睾的特征,以及主细胞、透明细胞和基底细胞等细胞类型的生物学功能,详细描述了附睾的整体生理功能。书中重点介绍了当前附睾领域的研究热点,包括单细胞分析、表观遗传学和细胞外囊泡等,旨在为初学者提供一个全面的认识。综述强调了附睾的重要性、附睾对精子成熟和随后胚胎发育的影响,以及附睾疾病的研究进展,同时为不育症的研究和治疗策略提供了新的方向。
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引用次数: 0
Targeted treatments for immune dysregulation in inborn errors of immunity 先天性免疫错误中免疫失调的靶向治疗
Pub Date : 2024-04-23 DOI: 10.37349/ei.2024.00138
N. Makkoukdji, Valishti Pundit, M. Wyke, Jheison Giraldo, Travis Satnarine, Gary I. Kleiner, Melissa Gans
Primary immune regulatory disorders (PIRDs) constitute a subset of inborn errors of immunity and are characterized by lymphoproliferation, autoimmunity, malignancy, and infection. Unlike classical primary immune deficiencies, initial symptoms of PIRDs can manifest as autoimmunity such as cytopenias or enteropathy, which can often prove resistant to conventional treatments and occur years prior to the onset of infectious complications. Raising awareness about PIRDs among specialists and adopting a multidisciplinary approach is crucial for early diagnosis, intervention, and potential prevention of severe organ damage. Significant progress has been made in identifying several PIRDs, which has contributed to a more comprehensive comprehension of their underlying immunological mechanisms. This knowledge has paved the way for targeted therapies focusing on specific molecules, which tend to offer superior disease control compared to traditional immunosuppressants. This review, informed by the latest literature, explores prevalent PIRDs, detailing their clinical manifestations and recent advancements in treatment modalities.
原发性免疫调节紊乱(PIRDs)是先天性免疫错误的一个分支,其特点是淋巴细胞增殖、自身免疫、恶性肿瘤和感染。与传统的原发性免疫缺陷不同,PIRD 的初期症状可表现为细胞减少症或肠病等自身免疫症状,这些症状通常会对常规治疗产生抗药性,并在感染性并发症发生前数年出现。提高专科医生对 PIRD 的认识并采用多学科方法对于早期诊断、干预和预防严重器官损伤至关重要。在确定几种 PIRD 方面已经取得了重大进展,这有助于更全面地了解其潜在的免疫机制。这些知识为针对特定分子的靶向治疗铺平了道路,与传统的免疫抑制剂相比,靶向治疗往往能提供更好的疾病控制效果。本综述以最新文献为基础,探讨了流行的 PIRD,详细介绍了它们的临床表现和治疗方法的最新进展。
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引用次数: 0
Physical activity, immune system and hypertension: reflections and challenges for future pandemics based on learning from coronavirus disease 2019 体育锻炼、免疫系统和高血压:基于对 2019 年冠状病毒疾病的学习,对未来流行病的思考与挑战
Pub Date : 2024-04-17 DOI: 10.37349/ei.2024.00137
Francisco Pitanga
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引用次数: 0
Dendritic cell and co-stimulatory molecule targeted therapy for autoimmune diseases: a review of the newly implemented strategies 针对自身免疫性疾病的树突状细胞和共刺激分子靶向疗法:新实施策略综述
Pub Date : 2024-04-02 DOI: 10.37349/ei.2024.00136
Mazen El Jamal, Farah Shibli
Dendritic cells (DCs) play an important role in the formation of the immune response, and they are involved in the pathogenesis of autoimmune diseases. Targeting DCs has thus emerged as a new therapeutic modality in the management of inflammatory and autoimmune diseases. DCs can be manipulated ex vivo and then injected back into humans to suppress the immune response. They can also be manipulated in vivo by delivering specific molecules into the DCs. Co-stimulatory molecules that shape DCs interaction with T cells can also be targeted to suppress immunity. This review tackles the latest advances in each of the 3 presented approaches.
树突状细胞(DC)在免疫反应的形成过程中发挥着重要作用,并参与了自身免疫性疾病的发病机制。因此,靶向树突状细胞已成为治疗炎症和自身免疫性疾病的一种新疗法。可以在体外操纵 DCs,然后将其注射回人体,以抑制免疫反应。还可以通过向直流电中输送特定分子,在体内对其进行操纵。还可以针对影响 DC 与 T 细胞相互作用的共刺激分子抑制免疫。本综述探讨了上述三种方法的最新进展。
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引用次数: 0
Cancer stem cell, chromosomal instability, and cancer immunity 癌症干细胞、染色体不稳定性和癌症免疫力
Pub Date : 2024-04-02 DOI: 10.37349/ei.2024.00135
Laxmi Kumari, Saloni Munjal, Reena Yadav, Y. Kumar, Alka Bhatia
Cancer stem cells (CSCs) are a unique population of tumor cells with stem cell-like properties. They are believed to be involved in drug resistance, potential therapy failure, tumor relapse after treatment, and ultimately reduced overall survival of cancer patients. One of the causal factors that may lead to CSC formation is chromosomal instability (CIN), a dynamic event leading to numerical and structural changes in the chromosomes. The CIN is also proposed to aid the maintenance of CSCs, contribute towards their heterogeneity, and facilitate their immune escape. However, the role of CIN in the modulation of the immune system in tumors remains contradictory. Studies have revealed that it can lead to both activation and suppression of the immune system. Previous literature suggests that the CIN, CSCs, and cancer immunity (3Cs), interact with and complement each other to create a pro-tumor environment. However, the mechanisms underlying such an interaction are poorly understood. So, in this review article, an attempt has been made to understand the nature of the interaction between the triad of CIN, CSC, and the immune response in tumors and some of the pathways governing the same. Understanding the above may be a positive step towards the complete cure for malignant diseases.
癌症干细胞(CSCs)是一种独特的肿瘤细胞群,具有类似干细胞的特性。它们被认为与耐药性、潜在治疗失败、治疗后肿瘤复发以及最终降低癌症患者的总体生存率有关。染色体不稳定性(CIN)是可能导致 CSC 形成的因果因素之一,它是导致染色体数量和结构变化的动态事件。CIN 还被认为有助于 CSCs 的维持、促进其异质性并促进其免疫逃逸。然而,CIN 在调节肿瘤免疫系统中的作用仍然相互矛盾。研究表明,它既能导致免疫系统的激活,也能导致免疫系统的抑制。以往的文献表明,CIN、CSCs 和癌症免疫(3Cs)相互作用并相互补充,从而创造出有利于肿瘤的环境。然而,人们对这种相互作用的机制知之甚少。因此,在这篇综述文章中,我们试图了解肿瘤中 CIN、CSC 和免疫反应三者之间相互作用的本质,以及支配这种相互作用的一些途径。对上述问题的理解可能是朝着彻底治愈恶性疾病迈出的积极一步。
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引用次数: 0
Periodontitis and lipopolysaccharides: How far have we understood? 牙周炎与脂多糖:我们了解了多少?
Pub Date : 2024-02-29 DOI: 10.37349/ei.2024.00133
S. Banavar, E. Tan, F. Davamani, S. Khoo
Periodontitis is a ubiquitous chronic inflammatory worldwide disease. The multiplicity of gram-negative microbiomes and their endotoxins, such as lipopolysaccharides (LPS), play a crucial role in its pathogenesis. The detection and consequent effects of LPS occur either via membrane-based cluster of differentiation 14 (CD14)/myeloid differentiation factor 2 (MD2)/Toll-like receptor (TLR)-4 complex activation or through intracellular cytosolic LPS detection that further cascades its effects, resulting in a variety of cell death processes, including apoptosis, pyroptosis, necroptosis, NETosis, and their crosstalk. Irrespective of the detection of LPS, the cellular response is for protecting and resolving the inflammation. However, chronic and exaggerated responses in periodontitis result in the destruction of periodontal structures. This review summarizes the extracellular and cytosolic detection of LPS and its further consequences. Then, it sheds light on methods reported to mitigate the adverse effects of LPS.
牙周炎是一种普遍存在的全球性慢性炎症性疾病。革兰氏阴性微生物群及其内毒素(如脂多糖(LPS))的多样性在牙周炎的发病机制中起着至关重要的作用。LPS 的检测和随之产生的效应可通过膜上的分化簇 14(CD14)/髓系分化因子 2(MD2)/类托尔受体(TLR)-4 复合物激活,也可通过细胞内的细胞膜 LPS 检测,从而进一步产生级联效应,导致多种细胞死亡过程,包括细胞凋亡、嗜热细胞增多症、坏死细胞增多症、网状细胞增多症以及它们之间的相互影响。无论检测到何种 LPS,细胞反应都是为了保护和消除炎症。然而,牙周炎中的慢性和夸张反应会导致牙周结构的破坏。本综述总结了 LPS 的细胞外和细胞膜检测及其进一步的后果。然后,它揭示了所报道的减轻 LPS 负面影响的方法。
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引用次数: 0
Myelitis associated with COVID-19: clinical, radiological, and laboratory characteristics 与 COVID-19 相关的脊髓炎:临床、放射学和实验室特征
Pub Date : 2024-02-29 DOI: 10.37349/ei.2024.00132
Aleksandra Kozlova, Alina Dzharullaeva, Amir Tukhvatulin, I. Zakroyshchikova, T. Simaniv, Lola Askarova, D. Eliseeva, Natalia Stoida, I. Kochergin, E. Baydina, M. Zakharova
Aim: The current study aimed to describe various types of myelitis associated with a novel coronavirus infection [coronavirus disease 2019 (COVID-19)] as well as to analyze cytokine profiles and cerebrospinal fluid (CSF) parameters in affected patients and to compare them to patients with other immune-mediated disorders—multiple sclerosis (MS), in order to identify possible common pathogenetic pathways and consequently treatment targets.Methods: Clinical, radiological, and laboratory characteristics were studied based on patients’ history. CSF from patients with myelitis associated with COVID-19 (11 patients) was compared with CSF of healthy controls (HC) (7 patients) and patients with MS (37 patients) from the non-COVID era. CSF cytological examination, protein levels and oligoclonal bands (OCBs) evaluation, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus detection and cytokine profiling using Bio-Plex Pro Human Inflammation Panel 1, 37-Plex were performed.Results: In total 11 patients with different types of myelitis developed up to 3 months after COVID-19 were enrolled in the study. Radiological findings were diverse: short transverse myelitis (lesion of fewer than 3 segments) (n = 6), longitudinal extensive transverse myelitis (LETM) (n = 2), multifocal spinal cord lesions (n = 1), and myelitis involving dorsal and lateral columns (n = 2). The most pronounced response to treatment was observed in patients with partial transverse myelitis and patients with anti-myelin oligodendrocyte glycoprotein (MOG) antibodies (MOG Abs). Multiple comparisons have demonstrated decreased levels of interleukin-10 (IL-10), interferon-α2 (IFN-α2), IFN-β, and thymic stromal lymphopoietin (TSLP), and increased IL-19 and B cell activating factor (BAFF) in patients with COVID-19 myelitis (CM) compared to the MS group. The highest BAFF and a proliferation-inducing ligand (APRIL) concentrations were found in patients with the most profound neurological disability.Conclusions: Myelitis associated with COVID-19 is clinically and radiologically heterogeneous. Evaluation of cytokine profiles in patients with myelitis associated with COVID-19 revealed their relative similarity with ones of MS patients, except for a few cytokines. BAFF/APRIL system as well as IL-10 is well-known for the role in the development and progression of autoimmune diseases, however, their links with COVID-19 and effects on the development of immune-mediated central nervous system (CNS) disorders after SARS-CoV-2 remain to be further studied.
目的:本研究旨在描述与新型冠状病毒感染[冠状病毒病2019(COVID-19)]相关的各种类型的脊髓炎,分析受影响患者的细胞因子谱和脑脊液(CSF)参数,并将其与其他免疫介导疾病-多发性硬化症(MS)患者进行比较,以确定可能的共同致病途径,从而确定治疗目标:方法:根据患者病史研究其临床、放射学和实验室特征。将与 COVID-19 相关的脊髓炎患者(11 例)的脑脊液与健康对照组(7 例)和非 COVID 时代的多发性硬化症患者(37 例)的脑脊液进行比较。研究人员还进行了脑脊液细胞学检查、蛋白质水平和寡克隆带(OCBs)评估、严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)病毒检测,并使用 Bio-Plex Pro Human Inflammation Panel 1, 37-Plex 进行了细胞因子分析:共有 11 名患者在 COVID-19 后 3 个月内患上了不同类型的脊髓炎。放射学检查结果多种多样:短横贯性脊髓炎(病变少于 3 节)(6 例)、纵向广泛横贯性脊髓炎(2 例)、多灶性脊髓病变(1 例)以及累及背侧柱和侧柱的脊髓炎(2 例)。部分横贯性脊髓炎患者和抗髓鞘少突胶质细胞糖蛋白(MOG)抗体(MOG 抗体)患者对治疗的反应最为明显。多项比较显示,与 MS 组相比,COVID-19 骨髓炎(CM)患者的白细胞介素-10(IL-10)、干扰素-α2(IFN-α2)、IFN-β 和胸腺基质淋巴细胞生成素(TSLP)水平降低,IL-19 和 B 细胞活化因子(BAFF)水平升高。BAFF和增殖诱导配体(APRIL)浓度最高的患者神经系统残疾程度最严重:结论:与COVID-19相关的脊髓炎在临床和影像学上具有异质性。对 COVID-19 相关性脊髓炎患者的细胞因子谱进行评估后发现,除少数细胞因子外,它们与多发性硬化症患者的细胞因子谱相对相似。BAFF/APRIL系统和IL-10在自身免疫性疾病的发生和发展中的作用众所周知,然而,它们与COVID-19的联系以及对SARS-CoV-2后免疫介导的中枢神经系统(CNS)疾病发生的影响仍有待进一步研究。
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引用次数: 0
Immune cell dynamics in male reproductive health: orchestrating immune privilege and inflammatory responses 男性生殖健康中的免疫细胞动态:协调免疫特权和炎症反应
Pub Date : 2024-02-28 DOI: 10.37349/ei.2024.00131
Yiming Zhang, Jianhua Zhu, Mingxin Wang
Epididymitis or epididymo-orchitis is a common urological condition in males characterized by scrotal pain, swelling, and potential urinary symptoms. Although antibiotics can eliminate the causative pathogens, persistent inflammation may compromise spermatogenesis and steroidogenesis. The testis, an immune-privileged organ, possesses a specialized immune microenvironment that shields germ cells (GCs) from autoimmune attacks and orchestrates immune defenses against pathogens. This review focuses on the complex interplay between immune cells, including macrophages, dendritic cells (DCs), mast cells (MCs), and T cell subsets, in the testis. The roles of these immune cells in infection-induced orchitis were deliberated upon, emphasizing their involvement in inflammation and immune tolerance. Furthermore, the implications of testicular fibrosis and its effect on male infertility are discussed, emphasizing the role of MCs in tissue remodeling. The objective of this review is to expand comprehension of male reproductive health and foster the identification of potential therapeutic targets for epididymo-orchitis.
附睾炎或附睾睾丸炎是男性常见的泌尿系统疾病,其特点是阴囊疼痛、肿胀和潜在的泌尿系统症状。虽然抗生素可以消除致病病原体,但持续的炎症可能会损害精子生成和类固醇生成。睾丸是一个具有免疫特权的器官,它拥有专门的免疫微环境,可保护生殖细胞(GC)免受自身免疫攻击,并协调针对病原体的免疫防御。本综述将重点讨论睾丸中巨噬细胞、树突状细胞(DC)、肥大细胞(MC)和 T 细胞亚群等免疫细胞之间复杂的相互作用。研究讨论了这些免疫细胞在感染诱发的睾丸炎中的作用,强调了它们在炎症和免疫耐受中的参与。此外,还讨论了睾丸纤维化的影响及其对男性不育的影响,强调了 MCs 在组织重塑中的作用。本综述旨在加深对男性生殖健康的理解,并促进确定附睾睾丸炎的潜在治疗靶点。
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引用次数: 0
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Exploration of immunology
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