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Studies on the mechanisms of action and development of resistance to class II bacteriocins of Gram-positive bacteria 关于革兰氏阳性细菌第二类细菌素的作用机制和抗药性发展的研究
Pub Date : 2024-01-15 DOI: 10.18388/pb.2021_517
Aleksandra Tymoszewska, Tamara Aleksandrzak-Piekarczyk
Bacteriocins are peptides or proteins produced by bacteria to kill or inhibit the growth of other bacteria inhabiting the same ecological niche. The growing interest in bacteriocins reflects their potential use in food preservation and treatment of infections caused by antibiotic-resistant pathogenic bacteria, among other applications. The number of published studies on the identification of new bacteriocin-producing strains is constantly increasing. At the same time, there is a noticeable lack of research describing the mechanisms of action of most newly identified bacteriocins, as well as the mechanisms leading to the development of resistance to these bacteriocins and cross-resistance to antibiotics. Detailed understanding of these issues will allow to develop guidelines ensuring the most effective, safe and long-term use of bacteriocins without the risk of resistance development. This work describes the main assumptions of the doctoral dissertation of Aleksandra Tymoszewska, which objectives were to characterize the mechanisms of action and of resistance to class II bacteriocins of Gram-positive bacteria. Using the model bacterium Lactococcus lactis, two groups of bacteriocins were examined: (i) garvicins Q, A, B and C, and BacSJ; and (ii) aureocin A53 (AurA53)- and enterocin L50 (EntL50)-like bacteriocins. Bacteriocins of group (i) have been shown to recognize susceptible cells and form pores in the cell membrane using a specific receptor, the mannose-specific phosphotransferase system (Man-PTS), and sensitive bacteria have been shown to acquire resistance to the these bacteriocins by modifying the structure of Man-PTS. On the other hand, the acquisition of resistance to group (ii) membrane-targeting and receptor-independent bacteriocins occurs through changes in the structure of the bacterial cell wall and membrane, which are induced by changes in the expression of proteins involved in lipid metabolism or components of the YsaCB-KinG-LlrG regulatory system. The results shed new light on previous views on the mechanisms of action of bacteriocins and open up opportunities for their further study.
细菌素是细菌产生的肽或蛋白质,可杀死或抑制栖息在同一生态位的其他细菌的生长。人们对细菌素的兴趣与日俱增,这反映了细菌素在食品保鲜和治疗由抗生素致病菌引起的感染等方面的潜在用途。已发表的关于鉴定新细菌素生产菌株的研究报告数量不断增加。与此同时,关于大多数新发现的细菌素的作用机制,以及导致对这些细菌素产生抗药性和对抗生素产生交叉抗药性的机制的研究却明显不足。对这些问题的详细了解将有助于制定指导方针,确保最有效、安全和长期地使用细菌素,同时避免产生抗药性的风险。本论文介绍了亚历山大-泰莫谢夫斯卡(Aleksandra Tymoszewska)博士论文的主要假设,其目的是描述革兰氏阳性菌对第二类细菌素的作用机制和耐药性。论文以乳酸乳球菌(Lactococcus lactis)为模型,研究了两类细菌素:(i) 加维素 Q、A、B 和 C 以及 BacSJ;(ii) 金黄色葡萄球菌素 A53 (AurA53) 和肠球菌素 L50 (EntL50) 类细菌素。研究表明,(i)类细菌素能识别易感细胞,并利用甘露糖特异性磷酸转移酶系统(Man-PTS)这一特异性受体在细胞膜上形成孔。另一方面,对第(ii)类膜靶向和不依赖受体的细菌素的耐药性是通过改变细菌细胞壁和细胞膜的结构而获得的,这种改变是由参与脂质代谢的蛋白质或 YsaCB-KinG-LlrG 调控系统成分的表达变化所诱导的。这些结果对以前关于细菌素作用机制的观点有了新的启示,并为进一步研究细菌素提供了机会。
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引用次数: 0
Znaczenie kwasów żółciowych w terapii wybranych chorób 胆汁酸在治疗某些疾病中的重要性
Pub Date : 2024-01-05 DOI: 10.18388/pb.2021_506
Aleksandra Boguszewska, Anna Kiersztan
The main function of bile acids (BA) is participation in the emulsification of dietary fats. Recently it has been discovered that BAs can also act as signaling molecules regulating the processes of their own synthesis and metabolism, as well as glucose and lipid metabolism. In addition, they affect the motility of the digestive tract and food intake. BA also interacts with the gut microbiota, a major player in their metabolism. Most of the regulatory actions of BAs are mediated by their receptors, the most important of which are the farnesoid X receptor (FXR) and the G protein-coupled receptor -TGR5, found in large amounts in the intestine, liver, adipose tissue and other tissues of the body. Recently, much attention has been paid to the influence of BA on various diseases and the possibility of using them in the treatment of e.g. inflammatory bowel disease, liver diseases, type 2 diabetes and obesity.
胆汁酸(BA)的主要功能是参与食物脂肪的乳化。最近人们发现,胆汁酸还可以作为信号分子调节自身的合成和代谢过程,以及葡萄糖和脂质的代谢。此外,它们还会影响消化道的蠕动和食物的摄入。BA 还与肠道微生物群相互作用,是它们新陈代谢的主要参与者。BA 的大部分调节作用都是由其受体介导的,其中最重要的是类雌激素 X 受体(FXR)和 G 蛋白偶联受体--TGR5,它们大量存在于肠道、肝脏、脂肪组织和人体的其他组织中。最近,人们开始关注 BA 对各种疾病的影响,以及将其用于治疗炎症性肠病、肝病、2 型糖尿病和肥胖症等疾病的可能性。
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引用次数: 0
Biologiczne wspomaganie leczenia ortopedycznego 骨科治疗的生物支持
Pub Date : 2023-12-28 DOI: 10.18388/pb.2021_505
M. Pawlak, Joanna Wałecka, P. Bąkowski, A. Tyczewska, Kamilla Grzywacz
Damage to the musculoskeletal system significantly impairs mobility and quality of life, limiting everyday activities. For a successful orthopedic treatment, anatomical, physiological and biomechanical factors must be taken into account as they all influence tissue healing. It is therefore of crucial importance to support traditional treatment with biological therapies, as they facilitate the regeneration of the tissue microarchitecture. Such orthobiologics work at the cellular level (orthobiologics rich in mesenchymal cells or growth factors) or at the tissue level (matrices for repairing e.g. cartilage). In this review, we describe the most frequently used orthobiologics rich in mesenchymal cells (bone marrow, autologous adipose tissue, tenocytes, umbilical cord, urine and bursa) and growth factors, presenting the molecular basis of their functioning and their clinical effectiveness.
肌肉骨骼系统受损会严重影响活动能力和生活质量,限制日常活动。要想成功进行矫形治疗,必须考虑解剖、生理和生物力学因素,因为它们都会影响组织愈合。因此,以生物疗法支持传统治疗至关重要,因为生物疗法有助于组织微结构的再生。此类矫形生物制剂可在细胞层面(富含间充质细胞或生长因子的矫形生物制剂)或组织层面(用于修复软骨等的基质)发挥作用。在这篇综述中,我们将介绍最常用的富含间充质细胞(骨髓、自体脂肪组织、腱细胞、脐带、尿液和滑囊)和生长因子的骨生物制品,介绍其功能的分子基础及其临床效果。
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引用次数: 0
Białko CD14 jako modulator odpowiedzi zapalnej 作为炎症反应调节剂的 CD14 蛋白质
Pub Date : 2023-12-28 DOI: 10.18388/pb.2021_501
A. Ciesielska, Ichrak Ben Amor, Katarzyna Kwiatkowska
CD14 is one of the key proteins involved in the activation of the inflammatory response of immune cells. CD14 binds bacterial lipopolysaccharide (LPS) and transfers its molecules to the complex of Toll-like receptor 4 (TLR4) and MD-2 protein, which in turn triggers pro-inflammatory signaling pathways necessary to combat infection. CD14 determines the final shape of the pro-inflammatory reaction of cells to LPS, serving as a transporter of this endotoxin and also as a regulator of TLR4 activity. In addition, CD14 transports other molecules of microbial or endogenous origin to their target receptors/proteins, participating in the activation of pro-inflammatory signaling pathways triggered by the presence of pathogens, as well as tissue damage. Currently, more attention is paid to the role of the CD14 protein in the development of non-infectious diseases such as autoimmune diseases, metabolic diseases and cardiovascular diseases.
CD14 是参与激活免疫细胞炎症反应的关键蛋白之一。CD14 与细菌脂多糖(LPS)结合,并将其分子转移到 Toll 样受体 4(TLR4)和 MD-2 蛋白的复合物中,进而触发抗感染所需的促炎信号通路。CD14 决定着细胞对 LPS 的促炎反应的最终形态,它既是这种内毒素的转运体,也是 TLR4 活性的调节器。此外,CD14 还能将其他微生物或内源性分子转运至其靶受体/蛋白,参与激活由病原体存在和组织损伤引发的促炎信号通路。目前,人们更多地关注 CD14 蛋白在自身免疫性疾病、代谢性疾病和心血管疾病等非传染性疾病的发病过程中的作用。
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引用次数: 0
Genetyczne i molekularne podłoża rozwoju glejaka 胶质瘤发展的基因和分子基础
Pub Date : 2023-12-18 DOI: 10.18388/pb.2021_495
Przemysław Panek, Aleksandra Jezela-Stanek
Stage IV glioblastoma is the most frequently diagnosed and the worst prognosis tumor of the central nervous system (CNS). Patients suffering from this type of cancer usually survive several months with the use of surgical treatment, radiotherapy and chemotherapy. The development of glioblastoma is determined by a number of mutations, the most common of which are the p16, p19, p53, pRB, PTEN, PDGFR, CDK4 and EGFR protein genes as well as the loss of heterozygosity on chromosomes 10, 17 and 19. The occurrence of mutations within the IDH1 and IDH2 genes and increased methylation of MGMT promoter improves patient survival, but few patients live more than 3 years after diagnosis. The most important cell signaling pathways in glioblastoma are PI3K/Akt/mTOR and Wnt/β-catenin, which play a key role in tumor cell function. However, these cells are highly resistant to anticancer drugs, including inhibitors of cell signaling pathways. Currently, the potential methods of effectively combating malignant gliomas are alternating electric field therapy and the implementation of new immunotherapeutic strategies.
第四期胶质母细胞瘤是中枢神经系统(CNS)中最常见的肿瘤,也是预后最差的肿瘤。这种类型的癌症患者在接受手术治疗、放疗和化疗后通常能存活数月。胶质母细胞瘤的发生取决于多种基因突变,其中最常见的是 p16、p19、p53、pRB、PTEN、PDGFR、CDK4 和表皮生长因子受体蛋白基因以及 10、17 和 19 号染色体上的杂合性缺失。IDH1 和 IDH2 基因的突变以及 MGMT 启动子甲基化的增加可提高患者的生存率,但很少有患者在确诊后存活超过 3 年。胶质母细胞瘤中最重要的细胞信号通路是 PI3K/Akt/mTOR 和 Wnt/β-catenin,它们在肿瘤细胞功能中发挥着关键作用。然而,这些细胞对包括细胞信号通路抑制剂在内的抗癌药物具有很强的抗药性。目前,有效抗击恶性胶质瘤的潜在方法是交变电场疗法和实施新的免疫治疗策略。
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引用次数: 0
Sirtuin 1 as a potential molecular target of resveratrol in selected diseases Sirtuin 1 作为白藜芦醇在某些疾病中的潜在分子靶点
Pub Date : 2023-12-18 DOI: 10.18388/pb.2021_499
Hanna Frankenstein, Jakub Robak, U. Lewandowska, K. Owczarek
Cancer, type 2 diabetes, cardiovascular and neurological diseases are disorders commonly classified as diseases that have a significant impact on the length and quality of human life. Sirtuins play an important role in their pathogenesis and complications. Numerous studies indicate that modulation of the expression of these proteins can slow down the processes of aging and cell death, prevent inflammation, and regulate metabolic processes, and consequently modify the progression of the disease. One of the best-known sirtuins is sirtuin 1, whose strongest natural activator is resveratrol. The development of alternative therapies involving natural compounds such as resveratrol is highly desirable due to the significantly lower number of side effects compared to conventional therapies. Therefore, this review summarizes the possible benefits of resveratrol as a sirtuin 1 activator in the prevention and treatment of human diseases based on the results of the studies conducted so far.
癌症、2 型糖尿病、心血管疾病和神经系统疾病通常被归类为对人类生命的长度和质量有重大影响的疾病。Sirtuins 在这些疾病的发病机制和并发症中发挥着重要作用。大量研究表明,调节这些蛋白的表达可以延缓衰老和细胞死亡过程、预防炎症、调节新陈代谢过程,从而改变疾病的进展。最著名的 sirtuin 蛋白之一是 sirtuin 1,其最强的天然激活剂是白藜芦醇。与传统疗法相比,白藜芦醇等天然化合物的副作用明显降低,因此开发白藜芦醇等天然化合物的替代疗法是非常可取的。因此,本综述根据迄今为止的研究结果,总结了白藜芦醇作为 sirtuin 1 激活剂在预防和治疗人类疾病方面可能带来的益处。
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引用次数: 0
Struktura molekularna i funkcje wakuolarnych enzymów procesujących w ontogenezie roślin 植物本体发育过程中液泡加工酶的分子结构和功能
Pub Date : 2023-12-18 DOI: 10.18388/pb.2021_497
Marta Przybylak, Karolina Wleklik, Alan Stafiej, Sławomir Borek
Vacuolar processing enzymes (VPEs) are plant proteases belonging to the C13 protease family. The specific activity of VPEs was characterized by comparing them to animal caspases. VPEs perform many important functions at various stages of plant ontogenesis, playing a role not only in the proper development of the plant organism but also in plant reactions to biotic and abiotic stress factors. A particularly important role of VPEs is noted in the processing of vacuolar proteins, enabling the production of their mature and active forms. VPEs are involved in programmed cell death, but despite residual evidence, we also suggest that VPEs are involved in autophagy. Based on literature data on autophagy in yeast, we formulate a hypothesis that VPEs during autophagy in plant cells are involved in the degradation of autophagic bodies - one of the final stages of autophagy.
空泡加工酶(VPEs)是属于 C13 蛋白酶家族的植物蛋白酶。通过将 VPEs 与动物的 Caspases 进行比较,确定了它们的特异性活性。VPE 在植物本体发育的不同阶段发挥着许多重要功能,不仅在植物机体的正常发育中发挥作用,而且在植物对生物和非生物胁迫因素的反应中也发挥着作用。VPE 的一个特别重要的作用是加工液泡蛋白,使其能够产生成熟的活性形式。VPE 参与了细胞的程序性死亡,但尽管证据尚存,我们仍认为 VPE 也参与了自噬。根据有关酵母自噬的文献数据,我们提出了一个假设,即植物细胞自噬过程中的 VPE 参与了自噬体的降解--这是自噬的最后阶段之一。
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Postępy Biochemii
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