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The role of the circular RNAs in multiple sclerosis and other neuroimmune disorders 环状rna在多发性硬化症和其他神经免疫疾病中的作用
Q3 Medicine Pub Date : 2022-08-24 Print Date: 2022-09-30 DOI: 10.18388/pb.2021_444
Anna Żurawska

In recent years non-coding RNAs have received increasing attention as an important epigenetic mechanism, with particular role of micro RNAs. As the regulation of miRNA expression is highly dynamic and complex, growing evidence suggests the existence of another higher level of regulatory mechanism involved in miRNA activity – circular RNAs (circRNAs). circRNAs represent novel, unique class of endogenous ncRNAs controlling the expression and function of miRNA. They are called natural miRNA “sponges”. Accumulating evidence reveals circRNAs role in physiological and pathological processes including CNS and immune regulation. Previous studies implicated miRNAs in regulation of autoimmune demyelination in MS. Multiple sclerosis is a chronic neurological inflammatory demyelinating disorder of the central nervous system. While the etiology of MS is still not fully understood, accumulating evidence suggests that it is a multifactorial entity with significant involvement of autoimmune processes.

近年来,非编码rna作为一种重要的表观遗传机制受到越来越多的关注,尤其是微rna的作用。由于miRNA表达的调控是高度动态和复杂的,越来越多的证据表明存在另一种更高水平的参与miRNA活性的调控机制-环状rna (circRNAs)。circRNAs代表了一类新的、独特的内源性ncRNAs,它们控制着miRNA的表达和功能。它们被称为天然的miRNA“海绵”。越来越多的证据表明,环状rna在包括中枢神经系统和免疫调节在内的生理和病理过程中发挥作用。多发性硬化症是一种中枢神经系统慢性神经炎症性脱髓鞘疾病。虽然多发性硬化症的病因尚不完全清楚,但越来越多的证据表明,多发性硬化症是一种多因素的疾病,与自身免疫过程密切相关。
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引用次数: 0
Parental ageing and Assisted Reproduction Technologies: analysis of risk of chronic diseases in the progeny 父母老龄化和辅助生殖技术:后代慢性疾病风险分析
Q3 Medicine Pub Date : 2022-08-23 Print Date: 2022-09-30 DOI: 10.18388/pb.2021_457
Maria Florencia Heber, Hafsa Gulzar, Richard Musson, Simona Bisogno, Kinga Fic, Grażyna Ewa Ptak

Conception of a child at advanced parental age (> 35 years) has been steadily increasing in recent decades, especially in developed countries. Socio-economic factors, effective contraceptives, and the availability of Assisted Reproduction Technologies (ART) have a direct impact on postponing the decision to have a baby. ART enables reproductive success for people diagnosed as infertile or with reduced possibilities of becoming pregnant due to concomitant pathologies. Epidemiological studies indicate that both advanced parental age and ART are associated with pathologies of pregnancy, such as gestational diabetes, risk of pre-eclampsia, miscarriage, placental abruption, preterm labor, stillbirth, neurodevelopmental disorders and chronic disease of the offspring. In our work, we will focus on the available information on metabolic changes that increase the risk of developing cardiovascular diseases in the offspring of parents at an advanced age and conceived through ART. Finally, we will address the sources of the observed disturbances at the gamete and embryo level, related to oxygen stress, epigenetic modifications and DNA damage, considering possible rescue actions.

近几十年来,特别是在发达国家,高龄怀孕(> 35岁)一直在稳步增加。社会经济因素、有效的避孕药具和辅助生殖技术(ART)的可用性对推迟生育决定有直接影响。抗逆转录病毒疗法使被诊断为不孕症或因伴随疾病而怀孕可能性降低的人能够成功生殖。流行病学研究表明,父母高龄和抗逆转录病毒治疗都与妊娠病理有关,如妊娠糖尿病、先兆子痫、流产、胎盘早剥、早产、死胎、神经发育障碍和后代慢性疾病的风险。在我们的工作中,我们将重点关注代谢变化的现有信息,这些信息会增加父母高龄并通过抗逆转录病毒技术受孕的后代患心血管疾病的风险。最后,我们将讨论在配子和胚胎水平上观察到的干扰的来源,与氧应激、表观遗传修饰和DNA损伤有关,并考虑可能的救援措施。
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引用次数: 0
DNA-based prediction of human phenotypic traits for the medico-legal and forensic purposes. 基于dna的人类表型性状预测,用于医学法律和法医目的。
Q3 Medicine Pub Date : 2022-07-21 Print Date: 2022-09-30 DOI: 10.18388/pb.2021_449
Maria Agnieszka Kaczmarek, Wojciech Zysek

This study aims to present the current state of knowledge on the DNA-based prediction of human externally visible characteristics of an unknown person based on the crime scene biological material left behind. This DNA sample is referred to as a “biological witness” and the procedure itself is called forensic DNA phenotyping (FDP). The analytic part of this work is based on scholarly articles published between 2015 and 2021. The electronic search of relevant references was conducted according to the PRISMA methodology in March 2021 at EBSCO Discovery Service (EDS) at the Adam Mickiewicz University library and Google Scholar. The molecular basis of FDP, DNA markers used to predict sex, age, biogeographic origin and externally visible traits such as pigmentation (skin, eye and hair colour), hair morphology, facial morphology, presence of freckles, body height, body weight (obesity), male pattern baldness and myopia were described. Furthermore, methodological difficulties resulting from the polygenic inheritance of the studied traits, as well as social and ethical problems accompanying forensic DNA phenotyping were discussed. Finally, key themes for future research related to forensic DNA phenotyping were outlined.

本研究旨在介绍基于犯罪现场遗留生物材料的基于dna的未知人的外部可见特征预测的知识现状。这种DNA样本被称为“生物学证人”,其过程本身被称为法医DNA表型(FDP)。本工作的分析部分基于2015年至2021年间发表的学术文章。相关文献的电子检索于2021年3月在Adam Mickiewicz大学图书馆的EBSCO Discovery Service (EDS)和Google Scholar上根据PRISMA方法进行。描述了FDP的分子基础,用于预测性别、年龄、生物地理来源和外部可见特征的DNA标记,如色素沉着(皮肤、眼睛和头发颜色)、头发形态、面部形态、雀斑的存在、身高、体重(肥胖)、男性型秃顶和近视。此外,还讨论了由于所研究性状的多基因遗传而导致的方法上的困难,以及伴随法医DNA表型的社会和伦理问题。最后,概述了未来法医DNA表型相关研究的关键主题。
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引用次数: 0
CRISPR/Cas as the intelligent immune system of bacteria and archea CRISPR/Cas作为细菌和古细菌的智能免疫系统
Q3 Medicine Pub Date : 2022-07-21 Print Date: 2022-09-30 DOI: 10.18388/pb.2021_453
Dalia Blicharska, Izabela Szućko-Kociuba, Ewa Filip, Lidia Skuza

The invention of CRISPR is considered to be one of the most breakthrough discoveries in recent years in the history of biology, biotechnology, medicine, as well as the pharmaceutical and agricultural industries. The methods developed using CRISPR create new, previously unattainable possibilities that can significantly improve the quality of life. From the invention of this intelligent immune system to the present day, much research has been done using the CRISPR/Cas systems. The result of these studies was the development of a modern tool for genetic manipulation, which allows for the introduction of many modifications within the DNA, which may contribute to the silencing of the expression of given genes or their overexpression through e.g. mutations or deletions. The paper describes the application of the method for genetic manipulation with the use of the second class system – CRISPR/Cas9 and the advantages of this method and its advantage over the previously used genetic engineering tools, as well as its limitations and disadvantages, which significantly limit the possibility of its application. The potential use of the method was also presented as well as the research carried out with the use of CRSPR/Cas9.

CRISPR的发明被认为是近年来生物学、生物技术、医学以及制药和农业工业历史上最具突破性的发现之一。使用CRISPR开发的方法创造了新的,以前无法实现的可能性,可以显着提高生活质量。从这种智能免疫系统的发明到现在,使用CRISPR/Cas系统进行了许多研究。这些研究的结果是现代遗传操作工具的发展,它允许在DNA中引入许多修饰,这可能有助于沉默特定基因的表达或通过突变或缺失等过度表达。本文描述了利用第二类系统CRISPR/Cas9进行基因操作的方法的应用,以及该方法的优点及其相对于以往使用的基因工程工具的优势,以及其局限性和缺点,这极大地限制了其应用的可能性。还介绍了该方法的潜在用途以及使用CRSPR/Cas9进行的研究。
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引用次数: 0
Pharmacological chaperone therapy for the treatment of inborn errors of metabolism 药物伴侣疗法治疗先天性代谢缺陷
Q3 Medicine Pub Date : 2022-07-20 Print Date: 2022-09-30 DOI: 10.18388/pb.2021_451
Patryk Lipiński, Aleksandra Jezela-Stanek, Anna Tylki-Szymańska

The article describes the mechanism of molecular and pharmacological chaperones in the treatment of inborn errors of metabolism. The literature review of the usage of ambroxol acting as a pharmacological chaperone for beta-glucocerebrosidase in Gaucher disease and Parkinson’s disease associated with GBA variants has been reviewed.

本文介绍了分子和药物伴侣治疗先天性代谢错误的机制。本文综述了氨溴索作为β -葡糖脑苷酶的药物伴侣在与GBA变异相关的戈谢病和帕金森病中的应用。
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引用次数: 0
Role of MCPIP1 protein in lipid metabolism, liver homeostasis and non-alcoholic fatty liver disease MCPIP1蛋白在脂质代谢、肝脏稳态和非酒精性脂肪性肝病中的作用
Q3 Medicine Pub Date : 2022-07-15 Print Date: 2022-09-30 DOI: 10.18388/pb.2021_446
Natalia Pydyn, Jerzy Kotlinowski

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of lipids in hepatocytes. Among NAFLD patients, in 25% of them this disease progress to nonalcoholic steatohepatitis, which is characterized additionally by the development of inflammation and fibrosis of liver. Currently, it is estimated that 24% of the world’s population suffers from NAFLD. MCPIP1 protein is an RNase described as a negative regulator of inflammation. Also, MCPIP1 plays a role in lipid metabolism because it inhibits the process of adipogenesis and mice with a deletion of Zc3h12a gene are characterized by dyslipidemia and reduced body fat content. In the case of ischemia-reperfusion injury in liver, MCPIP1 is protective against the inflammation and damage of this organ. Lipid accumulation by hepatocytes is associated with a decrease of Mcpip1 level. In addition, MCPIP1 may influence the PPARγ-mediated lipogenesis process. Presence of Mcpip1 in both myeloid leukocytes and liver epithelial cells is crucial for the maintenance of liver homeostasis.

非酒精性脂肪性肝病(NAFLD)以肝细胞内脂质过度积聚为特征。在NAFLD患者中,25%的患者进展为非酒精性脂肪性肝炎,其另一个特征是肝脏炎症和纤维化的发展。目前,据估计全世界24%的人口患有NAFLD。MCPIP1蛋白是一种RNase,被描述为炎症的负调节因子。此外,MCPIP1在脂质代谢中发挥作用,因为它抑制脂肪生成过程,缺失Zc3h12a基因的小鼠具有血脂异常和体脂含量降低的特征。在肝脏缺血再灌注损伤的情况下,MCPIP1对该器官的炎症和损伤具有保护作用。肝细胞脂质积累与Mcpip1水平降低有关。此外,MCPIP1可能影响ppar γ介导的脂肪生成过程。Mcpip1存在于髓系白细胞和肝上皮细胞中,对维持肝脏稳态至关重要。
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引用次数: 1
rRNA as a source of ribosomes variability and their non-translational functions rRNA作为核糖体可变性及其非翻译功能的来源
Q3 Medicine Pub Date : 2022-05-27 Print Date: 2022-06-30 DOI: 10.18388/pb.2021_440
Agnieszka Czarnocka-Cieciura

Ribosomes are macromolecular complexes responsible for translation. During last few years our understanding of their role in the cell was changed. Discoveries showing their variability in the protein composition and rRNA sequence suggested that they can play an active role in the gene regulation, selecting mRNA molecules to be translated and affecting the shape of the proteome. Populations of polimorphic ribosomes are involved in the stress response, virulence and antibiotic sensitivity. Here, I discuss the described and potential functions of ribosomes containing polymorphisms in rRNA molecules, as well as factors limiting the development of research in this field.

核糖体是负责翻译的大分子复合物。在过去的几年里,我们对它们在细胞中的作用的理解发生了变化。发现它们在蛋白质组成和rRNA序列上的可变性表明,它们可以在基因调控中发挥积极作用,选择要翻译的mRNA分子并影响蛋白质组的形状。多态核糖体种群参与应激反应、毒力和抗生素敏感性。在这里,我讨论了rRNA分子中含有多态性的核糖体的描述和潜在功能,以及限制该领域研究发展的因素。
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引用次数: 0
Nanoparticles in chemotherapy: characteristics, design strategies, mechanism of internalization and intracellular degradation 化疗中的纳米颗粒:特性、设计策略、内化机制和细胞内降解
Q3 Medicine Pub Date : 2022-05-27 Print Date: 2022-06-30 DOI: 10.18388/pb.2021_441
Joanna Pilch

Although significant advances have been made in cancer treatment, effective methods of treatment are still limited. Classical chemotherapy is one of the main cancer treatments, but it often causes many side effects that may cause non-specific drug action. This is mainly due to the lack of significant differences between cancer and normal cells as well as drug resistance. To reduce the side effects and increase the specificity and the selectivity of chemotherapeutics to cancer cells, new methods of their delivery to tumors are being sought. One of these methods is the application of nanoparticles (NPs), e.g. Quantum Dots (QDs) as drug delivery platforms. This review describes the most popular NPs in chemotherapy, including quantum dots, gold nanoparticles, dendrimers, micelles, and liposomes. The review describes also a strategy of design and synthesis of NPs, mechanism of cellular uptake, as well as intracellular degradation and toxicity of NPs.

尽管在癌症治疗方面取得了重大进展,但有效的治疗方法仍然有限。经典化疗是主要的癌症治疗方法之一,但它往往会产生许多副作用,可能导致非特异性药物作用。这主要是由于癌细胞与正常细胞之间缺乏显著差异以及耐药性。为了减少副作用,增加化疗药物对癌细胞的特异性和选择性,人们正在寻找新的方法将它们输送到肿瘤中。其中一种方法是应用纳米颗粒(NPs),例如量子点(QDs)作为药物传递平台。本文综述了化疗中最常用的NPs,包括量子点、金纳米粒子、树状大分子、胶束和脂质体。本文还介绍了NPs的设计和合成策略,细胞摄取机制,以及NPs的细胞内降解和毒性。
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引用次数: 0
Effective mucosal vaccines - opportunities and challenges 有效的粘膜疫苗——机遇与挑战
Q3 Medicine Pub Date : 2022-05-24 Print Date: 2022-06-30 DOI: 10.18388/pb.2021_439
Agnieszka Razim, Sabina Górska, Andrzej Myc

Most pathogens enter the body through the surfaces of the mucous membranes, e.g. the nose or the intestines. The mucosal immune response is essential for the effective elimination of invading pathogens. Unfortunately, most vaccines which are administered intramuscularly by injection do not induce an adequate protective immune response on mucous membranes. For example, after intramuscular injection, the level of secretory IgA antibodies is low and often insufficient to successfully combat the pathogen. On the other hand, mucosal-induced immunity produces a long-lasting effect in the form of a local and systemic response to the pathogen. Moreover, the administration of such vaccines does not generate hazardous medical waste and their application does not require the presence of qualified medical personnel. Therefore, intensive research into vaccines administered via the mucosal route is ongoing. An obstacle in the development of mucosal vaccines is the natural defense mechanisms of the mucosa, the overcoming of which requires the use of specialized adjuvants. Currently, there are no such formulations on the market.

大多数病原体通过粘膜表面(如鼻子或肠道)进入人体。粘膜免疫反应是有效消除入侵病原体所必需的。不幸的是,大多数通过肌肉注射给药的疫苗不能在粘膜上引起足够的保护性免疫反应。例如,在肌肉注射后,分泌的IgA抗体水平很低,往往不足以成功地对抗病原体。另一方面,粘膜诱导的免疫以局部和全身对病原体的反应的形式产生持久的影响。此外,这种疫苗的施用不会产生危险的医疗废物,其应用也不需要有合格的医务人员在场。因此,通过粘膜途径给药的疫苗的深入研究正在进行中。黏膜疫苗开发的一个障碍是粘膜的天然防御机制,克服这一机制需要使用专门的佐剂。目前,市场上还没有这样的配方。
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引用次数: 0
GPR18 receptor – the structure and the role in the physiology and pathophysiology GPR18受体的结构及其在生理病理生理中的作用
Q3 Medicine Pub Date : 2022-05-24 Print Date: 2022-06-30 DOI: 10.18388/pb.2021_399
Michalina Jurkiewicz, Greta Steć, Adrian Szczepaniak, Jakub Fichna, Marta Zielińska

G-protein coupled receptors constitute the largest family of membrane receptors and they participate in the maintenance of the homeostasis in the body. Some of these receptors still remain orphan receptors as there is insufficient research and ambiguous evidence concerning their function and endogenous ligands. For a long time, GPR18 belonged to this group, but recently it has been classified as an endocannabinoid receptor due to its affinity to cannabinoid ligands. GPR18 receptor is expressed in the encephalon, thyroid gland, leukocytes, lungs and testicles. The modulatory role of GPR18 receptor has been proven in the regulation of intraocular pressure, neuroimmunomodulation, regulation of arterial blood pressure and in metabolic disorders. In this article we summarize the current knowledge concerning the GPR18 receptor – its expression, ligands and the in the physiological processes and the pathophysiological conditions.

g蛋白偶联受体是膜受体中最大的家族,参与机体内稳态的维持。由于对其功能和内源性配体的研究不足和证据不明确,其中一些受体仍然是孤儿受体。长期以来,GPR18属于这一类,但最近由于其对大麻素配体的亲和力而被归类为内源性大麻素受体。GPR18受体在脑、甲状腺、白细胞、肺和睾丸中表达。GPR18受体在眼压调节、神经免疫调节、动脉血压调节和代谢紊乱等方面的调节作用已被证实。本文就GPR18受体的表达、配体及其生理过程和病理生理条件等方面的研究进展进行综述。
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引用次数: 0
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Postepy biochemii
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