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Phosphorylated Adapter RNA Export Protein Is Methylated at Lys 381 by an Methyltransferase-like 21C (METTL21C) 磷酸化适配器 RNA 输出蛋白在 Lys 381 处被甲基转移酶样 21C (METTL21C) 甲基化
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-21 DOI: 10.3390/ijms25010145
Meiling Ke, Xiaoke Yu, Yuanyuan Sun, Shuai Han, Ling Wang, Tao Zhang, Wenxian Zeng, Hongzhao Lu
Methyltransferase-like 21C (METTL21C) is a member of the non-histone methyltransferase superfamily, which mainly mediates the methylation of lysine (Lys) residues. The main types of modification are Lys dimethylation and trimethylation. However, at present, most of the studies on METTL21C are focused on humans and mice, and there are few reports on poultry. Therefore, chicken embryo fibroblasts (DF-1) were selected as the object of study. To explore the function of chicken METTL21C (chMETTL21C) in the proliferation of DF-1 cells, flow cytometry and qPCR were used to detect the function of chicken METTL21C in the proliferation of DF-1 cells. The results showed that overexpression of METTL21C blocked the cell cycle in the G1max S phase, thus inhibiting cell proliferation. In addition, based on proteomic analysis, stable overexpression of METTL21C may inhibit the proliferation of DF-1 cells by mediating lysine trimethylation of proliferation-related proteins phosphorylated adapter RNA export protein (PHAX), nucleoside diphosphate kinases (NDPKs), eukaryotic transcription extension factor (eukaryotic translation elongation factor 1A,e EF1A), and inversin (Invs). Through immunoprecipitation (co-IP) and liquid chromatography-mass spectrometry (LC-MS/MS) analysis, METTL21C-mediated PHAX Lys-381 methylation was confirmed to be involved in the regulation of DF-1 cell proliferation. The results of this study provide a reference for analyzing the methylation function of METTL21C and the mechanism of regulating the growth and development of chicken cells.
甲基转移酶样 21C (METTL21C)是非组蛋白甲基转移酶超家族的成员,主要介导赖氨酸(Lys)残基的甲基化。主要的修饰类型是赖氨酸二甲基化和三甲基化。然而,目前有关 METTL21C 的研究大多集中在人类和小鼠身上,有关家禽的报道很少。因此,我们选择了鸡胚成纤维细胞(DF-1)作为研究对象。为了探索鸡 METTL21C(chMETTL21C)在 DF-1 细胞增殖中的功能,研究人员采用流式细胞仪和 qPCR 检测鸡 METTL21C 在 DF-1 细胞增殖中的功能。结果表明,过表达 METTL21C 会阻滞细胞周期的 G1max S 期,从而抑制细胞增殖。此外,根据蛋白质组学分析,METTL21C的稳定过表达可能通过介导磷酸化适配器RNA导出蛋白(PHAX)、核苷二磷酸激酶(NDPKs)、真核转录延伸因子(真核翻译延伸因子1A,e EF1A)和变构蛋白(Invs)的赖氨酸三甲基化来抑制DF-1细胞的增殖。通过免疫沉淀(co-IP)和液相色谱-质谱(LC-MS/MS)分析,证实了 METTL21C 介导的 PHAX Lys-381 甲基化参与了 DF-1 细胞增殖的调控。该研究结果为分析 METTL21C 的甲基化功能和调控鸡细胞生长发育的机制提供了参考。
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引用次数: 0
Ferroptosis, Metabolic Rewiring, and Endometrial Cancer 铁蛋白沉积、代谢重构与子宫内膜癌
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-20 DOI: 10.3390/ijms25010075
Eglė Žalytė
Ferroptosis is a newly discovered form of regulated cell death. The main feature of ferroptosis is excessive membrane lipid peroxidation caused by iron-mediated chemical and enzymatic reactions. In normal cells, harmful lipid peroxides are neutralized by glutathione peroxidase 4 (GPX4). When GPX4 is inhibited, ferroptosis occurs. In mammalian cells, ferroptosis serves as a tumor suppression mechanism. Not surprisingly, in recent years, ferroptosis induction has gained attention as a potential anticancer strategy, alone or in combination with other conventional therapies. However, sensitivity to ferroptosis inducers depends on the metabolic state of the cell. Endometrial cancer (EC) is the sixth most common cancer in the world, with more than 66,000 new cases diagnosed every year. Out of all gynecological cancers, carcinogenesis of EC is mostly dependent on metabolic abnormalities. Changes in the uptake and catabolism of iron, lipids, glucose, and glutamine affect the redox capacity of EC cells and, consequently, their sensitivity to ferroptosis-inducing agents. In addition to this, in EC cells, ferroptosis-related genes are usually mutated and overexpressed, which makes ferroptosis a promising target for EC prediction, diagnosis, and therapy. However, for a successful application of ferroptosis, the connection between metabolic rewiring and ferroptosis in EC needs to be deciphered, which is the focus of this review.
铁中毒是一种新发现的调节性细胞死亡形式。铁变态反应的主要特征是由铁介导的化学和酶反应引起的膜脂质过氧化。在正常细胞中,有害的脂质过氧化物被谷胱甘肽过氧化物酶 4(GPX4)中和。当 GPX4 受到抑制时,就会发生铁变态反应。在哺乳动物细胞中,铁氧化是一种肿瘤抑制机制。近年来,诱导铁氧化作为一种潜在的抗癌策略,单独使用或与其他常规疗法结合使用,受到人们的关注,这并不奇怪。然而,对铁蛋白沉降诱导剂的敏感性取决于细胞的代谢状态。子宫内膜癌(EC)是全球第六大常见癌症,每年新确诊病例超过 66,000 例。在所有妇科癌症中,子宫内膜癌的发生主要取决于代谢异常。铁、脂质、葡萄糖和谷氨酰胺的摄取和分解变化会影响癌细胞的氧化还原能力,进而影响其对铁变态反应诱导剂的敏感性。此外,在心肌细胞中,与铁突变相关的基因通常会发生突变和过度表达,这使得铁突变成为心肌细胞预测、诊断和治疗的一个很有前景的靶点。然而,要成功应用铁蛋白沉积,还需要破译心肌细胞中代谢重构与铁蛋白沉积之间的联系,这也是本综述的重点。
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引用次数: 0
Evaluation of the Expression and Localization of the Multifunctional Protein CacyBP/SIP and Elements of the MAPK Signaling Pathway in the Adrenal Glands of Rats with Primary and Secondary Hypertension 评估原发性和继发性高血压大鼠肾上腺多功能蛋白 CacyBP/SIP 的表达和定位以及 MAPK 信号通路的要素
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-20 DOI: 10.3390/ijms25010084
Magdalena Smereczańska, N. Domian, Maryla Młynarczyk, Anna Pędzińska-Betiuk, Irena Kasacka
Hypertension is a global civilization disease and one of the most common causes of death in the world. Organ dysfunction is a serious health consequence of hypertension, which involves damage to the heart, kidneys and adrenals. The interaction of recently discovered multifunctional protein-CacyBP/SIP with ERK1/2 and p38 kinases by regulating the activity and intracellular localization of these kinases may play an important role in the signaling pathways involved in the pathogenesis of hypertension. Due to the lack of data on this subject, we decided to investigate the localization, expression and possible relationship between the studied parameters in the adrenals under arterial hypertension. The study was conducted on the adrenals of rats with spontaneous and DOCA-salt hypertension. The expression of CacyBP/SIP, p-ERK1/2 and p-p38 was detected by immunohistochemistry and qRT-PCR. The results show a statistically significant decrease in CacyBP/SIP expression in the adrenal glands of hypertensive rats. With ERK1/2, there was a decrease in cortical immunoreactivity and an increase in the adrenal medulla of primary hypertensive rats. In contrast, in the adrenals of DOCA-salt rats, ERK1/2 immunoreactivity increased in the cortex and decreased in the medulla. In turn, p38 expression was higher in the adrenal glands of rats with primary and secondary hypertension. The obtained results may suggest the involvement of CacyBP/SIP in the regulation of signaling pathways in which MAP kinases play an important role and provide new insight into molecular events in hypertension. Moreover, they show the participation of CacyBP/SIP in response to oxidative stress.
高血压是一种全球性文明病,也是世界上最常见的死亡原因之一。器官功能障碍是高血压对健康造成的严重后果,包括对心脏、肾脏和肾上腺的损害。最近发现的多功能蛋白-CacyBP/SIP 与 ERK1/2 和 p38 激酶相互作用,调节这些激酶的活性和细胞内定位,可能在高血压发病机制的信号通路中发挥重要作用。由于缺乏这方面的数据,我们决定研究动脉高血压肾上腺中这些研究参数的定位、表达及其可能的关系。研究对象是自发性高血压和 DOCA 盐性高血压大鼠的肾上腺。通过免疫组化和 qRT-PCR 检测了 CacyBP/SIP、p-ERK1/2 和 p-p38 的表达。结果显示,CacyBP/SIP 在高血压大鼠肾上腺中的表达明显减少。对于 ERK1/2,原发性高血压大鼠肾上腺髓质的皮质免疫活性降低,而肾上腺髓质的免疫活性升高。相反,在 DOCA 盐大鼠的肾上腺中,ERK1/2 的免疫反应在皮质中增加,在髓质中减少。而在原发性和继发性高血压大鼠的肾上腺中,p38 的表达较高。研究结果表明,CacyBP/SIP 参与了信号通路的调控,而 MAP 激酶在其中发挥了重要作用,这为研究高血压的分子事件提供了新的视角。此外,研究还表明 CacyBP/SIP 参与了对氧化应激的反应。
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引用次数: 0
Sensitivity of Human Induced Pluripotent Stem Cells and Thereof Differentiated Kidney Proximal Tubular Cells towards Selected Nephrotoxins 人类诱导多能干细胞及其分化的肾近曲小管细胞对特定肾毒素的敏感性
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-20 DOI: 10.3390/ijms25010081
Isaac Musong Mboni-Johnston, Nazih Mohamed Zakari Kouidrat, Cornelia Hirsch, Andreas Georg Weber, Alexander Meißner, James Adjaye, Nicole Schupp
Proximal tubular epithelial cells (PTEC) are constantly exposed to potentially toxic metabolites and xenobiotics. The regenerative potential of the kidney enables the replacement of damaged cells either via the differentiation of stem cells or the re-acquisition of proliferative properties of the PTEC. Nevertheless, it is known that renal function declines, suggesting that the deteriorated cells are not replaced by fully functional cells. To understand the possible causes of this loss of kidney cell function, it is crucial to understand the role of toxins during the regeneration process. Therefore, we investigated the sensitivity and function of human induced pluripotent stem cells (hiPSC), hiPSC differentiating, and hiPSC differentiated into proximal tubular epithelial-like cells (PTELC) to known nephrotoxins. hiPSC were differentiated into PTELC, which exhibited similar morphology to PTEC, expressed prototypical PTEC markers, and were able to undergo albumin endocytosis. When treated with two nephrotoxins, hiPSC and differentiating hiPSC were more sensitive to cisplatin than differentiated PTELC, whereas all stages were equally sensitive to cyclosporin A. Both toxins also had an inhibitory effect on albumin uptake. Our results suggest a high sensitivity of differentiating cells towards toxins, which could have an unfavorable effect on regenerative processes. To study this, our model of hiPSC differentiating into PTELC appears suitable.
近端肾小管上皮细胞(PTEC)经常暴露于具有潜在毒性的代谢物和异种生物中。肾脏的再生潜能可通过干细胞分化或重新获得 PTEC 的增殖特性来替换受损细胞。然而,众所周知,肾功能会衰退,这表明衰退的细胞并没有被功能完善的细胞所替代。为了了解肾细胞功能丧失的可能原因,了解毒素在再生过程中的作用至关重要。因此,我们研究了人类诱导多能干细胞(hiPSC)、分化的 hiPSC 和分化成近端肾小管上皮样细胞(PTELC)的 hiPSC 对已知肾毒素的敏感性和功能。当用两种肾毒素处理时,hiPSC 和分化型 hiPSC 比分化型 PTELC 对顺铂更敏感,而所有阶段的 hiPSC 对环孢素 A 同样敏感。我们的研究结果表明,分化细胞对毒素高度敏感,这可能会对再生过程产生不利影响。为了研究这一点,我们的 hiPSC 分化成 PTELC 的模型似乎很合适。
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引用次数: 0
Uptake and Metabolic Conversion of Exogenous Phosphatidylcholines Depending on Their Acyl Chain Structure in Arabidopsis thaliana 拟南芥对外源磷脂酰胆碱的吸收和代谢转化取决于其酰基链结构
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-20 DOI: 10.3390/ijms25010089
E. Kotlova, S. Senik, Gregory A. Pozhvanov, I. Prokopiev, I. Boldyrev, B. Manzhieva, Ekaterina Ya. Amigud, R. Puzanskiy, Anna A. Khakulova, E. B. Serebryakov
Fungi and plants are not only capable of synthesizing the entire spectrum of lipids de novo but also possess a well-developed system that allows them to assimilate exogenous lipids. However, the role of structure in the ability of lipids to be absorbed and metabolized has not yet been characterized in detail. In the present work, targeted lipidomics of phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs), in parallel with morphological phenotyping, allowed for the identification of differences in the effects of PC molecular species introduced into the growth medium, in particular, typical bacterial saturated (14:0/14:0, 16:0/16:0), monounsaturated (16:0/18:1), and typical for fungi and plants polyunsaturated (16:0/18:2, 18:2/18:2) species, on Arabidopsis thaliana. For comparison, the influence of an artificially synthesized (1,2-di-(3-(3-hexylcyclopentyl)-propanoate)-sn-glycero-3-phosphatidylcholine, which is close in structure to archaeal lipids, was studied. The phenotype deviations stimulated by exogenous lipids included changes in the length and morphology of both the roots and leaves of seedlings. According to lipidomics data, the main trends in response to exogenous lipid exposure were an increase in the proportion of endogenic 18:1/18:1 PC and 18:1_18:2 PC molecular species and a decrease in the relative content of species with C18:3, such as 18:3/18:3 PC and/or 16:0_18:3 PC, 16:1_18:3 PE. The obtained data indicate that exogenous lipid molecules affect plant morphology not only due to their physical properties, which are manifested during incorporation into the membrane, but also due to the participation of exogenous lipid molecules in the metabolism of plant cells. The results obtained open the way to the use of PCs of different structures as cellular regulators.
真菌和植物不仅能够从头合成各种脂质,而且还拥有一套完善的系统,使它们能够吸收外源脂质。然而,结构在脂质吸收和代谢能力中的作用尚未得到详细表征。在本研究中,通过对磷脂酰胆碱(PCs)和磷脂酰乙醇胺(PEs)进行有针对性的脂质组学研究,并同时进行形态学表型分析,确定了引入生长培养基的 PC 分子种类的影响差异,特别是典型的细菌饱和(14:0/14:0、16:0/16:0)、单不饱和(16:0/18:1)以及真菌和植物中典型的多不饱和(16:0/18:2、18:2/18:2)物种对拟南芥的影响。为了进行比较,研究了人工合成的(1,2-二(3-(3-己基环戊基)-丙酸)-sn-甘油-3-磷脂酰胆碱对拟南芥的影响。外源脂质刺激的表型偏差包括幼苗根和叶的长度和形态变化。根据脂质组学数据,外源脂质暴露的主要反应趋势是内源 18:1/18:1 PC 和 18:1_18:2 PC 分子物种的比例增加,C18:3(如 18:3/18:3 PC 和/或 16:0_18:3 PC、16:1_18:3 PE)物种的相对含量减少。所获得的数据表明,外源脂质分子影响植物形态的原因不仅在于它们的物理特性(在融入膜的过程中表现出来),还在于外源脂质分子参与了植物细胞的新陈代谢。研究结果为利用不同结构的多氯联苯作为细胞调节剂开辟了道路。
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引用次数: 0
Deep Learning Model for Classifying and Evaluating Soybean Leaf Disease Damage 用于分类和评估大豆叶片病害损害的深度学习模型
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-20 DOI: 10.3390/ijms25010106
Sandeep Goshika, K. Meksem, Khaled R. Ahmed, N. Lakhssassi
Soybean (Glycine max (L.) Merr.) is a major source of oil and protein for human food and animal feed; however, soybean crops face diverse factors causing damage, including pathogen infections, environmental shifts, poor fertilization, and incorrect pesticide use, leading to reduced yields. Identifying the level of leaf damage aids yield projections, pesticide, and fertilizer decisions. Deep learning models (DLMs) and neural networks mastering tasks from abundant data have been used for binary healthy/unhealthy leaf classification. However, no DLM predicts and categorizes soybean leaf damage severity (five levels) for tailored pesticide use and yield forecasts. This paper introduces a novel DLM for accurate damage prediction and classification, trained on 2930 near-field soybean leaf images. The model quantifies damage severity, distinguishing healthy/unhealthy leaves and offering a comprehensive solution. Performance metrics include accuracy, precision, recall, and F1-score. This research presents a robust DLM for soybean damage assessment, supporting informed agricultural decisions based on specific damage levels and enhancing crop management and productivity.
大豆(Glycine max (L.) Merr.)是人类食物和动物饲料中油脂和蛋白质的主要来源;然而,大豆作物面临着各种因素的损害,包括病原体感染、环境变化、施肥不当和农药使用不当,从而导致减产。识别叶片受损程度有助于产量预测、农药和肥料决策。深度学习模型(DLM)和掌握大量数据任务的神经网络已被用于二元健康/不健康叶片分类。然而,目前还没有一种深度学习模型能预测大豆叶片受损严重程度(五级)并进行分类,以进行有针对性的农药使用和产量预测。本文介绍了一种用于准确预测和分类损害的新型 DLM,它是在 2930 幅近田大豆叶片图像上训练而成的。该模型可量化损害严重程度,区分健康/不健康叶片,并提供全面的解决方案。性能指标包括准确度、精确度、召回率和 F1 分数。这项研究提出了一种用于大豆损害评估的稳健 DLM,可支持基于特定损害程度的明智农业决策,并提高作物管理水平和生产率。
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引用次数: 0
Role of Single-Nucleotide Polymorphisms in Genes Implicated in Capecitabine Pharmacodynamics on the Effectiveness of Adjuvant Therapy in Colorectal Cancer 卡培他滨药效学相关基因的单核苷酸多态性对结直肠癌辅助治疗效果的影响
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-20 DOI: 10.3390/ijms25010104
Y. Cura, Almudena Sánchez-Martín, Noelia Márquez-Pete, E. González-Flores, Fernando Martínez-Martínez, C. Pérez-Ramírez, A. Jiménez-Morales
Colorectal cancer (CRC) is a highly prevalent form of neoplasm worldwide. Capecitabine, an oral antimetabolite, is widely used for CRC treatment; however, there exists substantial variation in individual therapy response. This may be due to genetic variations in genes involved in capecitabine pharmacodynamics (PD). In this study, we investigated the role of single-nucleotide polymorphisms (SNPs) related to capecitabine’s PD on disease-free survival (DFS) in CRC patients under adjuvant treatment. Thirteen SNPs in the TYMS, ENOSF1, MTHFR, ERCC1/2, and XRCC1/3 genes were genotyped in 142 CRC patients using real-time PCR with predesigned TaqMan® probes. A significant association was found between favorable DFS and the ENOSF1 rs2612091-T allele (p = 0.010; HR = 0.34; 95% CI = 0.14–0.83), as well as with the TYMS/ENOSF1 region ACT haplotype (p = 0.012; HR = 0.37; 95% CI = 0.17–0.80). Other factors such as low histological grade (p = 0.009; HR = 0.34; 95% CI = 0.14–0.79) and a family history of cancer (p = 0.040; HR = 0.48; 95% CI = 0.23–0.99) were also linked to improved DFS. Therefore, the SNP ENOSF1 rs2612091 could be considered as a predictive genetic biomarker for survival in CRC patients receiving capecitabine-based adjuvant regimens.
结肠直肠癌(CRC)是一种全球高发的肿瘤。卡培他滨是一种口服抗代谢药,被广泛用于治疗结直肠癌。这可能是由于卡培他滨药效学(PD)相关基因的遗传变异造成的。在这项研究中,我们调查了与卡培他滨药效学相关的单核苷酸多态性(SNPs)对接受辅助治疗的 CRC 患者无病生存期(DFS)的影响。使用预先设计的 TaqMan® 探针进行实时 PCR,对 142 例 CRC 患者的 TYMS、ENOSF1、MTHFR、ERCC1/2 和 XRCC1/3 基因中的 13 个 SNPs 进行了基因分型。结果发现,良好的 DFS 与 ENOSF1 rs2612091-T 等位基因(p = 0.010;HR = 0.34;95% CI = 0.14-0.83)以及 TYMS/ENOSF1 区域 ACT 单倍型(p = 0.012;HR = 0.37;95% CI = 0.17-0.80)之间存在明显关联。组织学分级低(p = 0.009;HR = 0.34;95% CI = 0.14-0.79)和癌症家族史(p = 0.040;HR = 0.48;95% CI = 0.23-0.99)等其他因素也与 DFS 的改善有关。因此,SNP ENOSF1 rs2612091可被视为接受以卡培他滨为基础的辅助治疗方案的CRC患者生存率的预测性遗传生物标志物。
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引用次数: 0
Differential Effects of Lipid Bilayers on αPSM Peptide Functional Amyloid Formation 脂质双分子层对αPSM肽功能性淀粉样蛋白形成的不同影响
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-20 DOI: 10.3390/ijms25010102
Kamilla Kristoffersen, Kasper Holst Hansen, M. Andreasen
Phenol-soluble modulins (PSMs) are key virulence factors of S. aureus, and they comprise the structural scaffold of biofilm as they self-assemble into functional amyloids. They have been shown to interact with cell membranes as they display toxicity towards human cells through cell lysis, with αPSM3 being the most cytotoxic. In addition to causing cell lysis in mammalian cells, PSMs have also been shown to interact with bacterial cell membranes through antimicrobial effects. Here, we present a study on the effects of lipid bilayers on the aggregation mechanism of αPSM using chemical kinetics to study the effects of lipid vesicles on the aggregation kinetics and using circular dichroism (CD) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM) to investigate the corresponding secondary structure of the aggregates. We found that the effects of lipid bilayers on αPSM aggregation were not homogeneous between lipid type and αPSM peptides, although none of the lipids caused changes in the dominating aggregation mechanism. In the case of αPSM3, all types of lipids slowed down aggregation to a varying degree, with 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) having the most pronounced effect. For αPSM1, lipids had opposite effects, where DOPC decelerated aggregation and lipopolysaccharide (LPS) accelerated the aggregation, while 1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DOPG) had no effect. For αPSM4, both DOPG and LPS accelerated the aggregation, but only at high concentration, while DOPC showed no effect. None of the lipids was capable of inducing aggregation of αPSM2. Our data reveal a complex interaction pattern between PSMs peptides and lipid bilayers that causes changes in the aggregation kinetics by affecting different kinetic parameters along with only subtle changes in morphology.
酚溶性调节蛋白(PSMs)是金黄色葡萄球菌的关键毒力因子,它们自我组装成功能性淀粉样蛋白,构成了生物膜的结构支架。它们与细胞膜相互作用,通过细胞裂解对人体细胞产生毒性,其中αPSM3的细胞毒性最强。除了在哺乳动物细胞中导致细胞裂解外,PSMs 还能通过抗菌作用与细菌细胞膜相互作用。在此,我们利用化学动力学研究了脂质囊泡对αPSM聚集动力学的影响,并利用圆二色性(CD)光谱、傅立叶变换红外(FTIR)光谱和透射电子显微镜(TEM)研究了聚集体的相应二级结构,从而介绍了脂质双层膜对αPSM聚集机制的影响。我们发现,脂质双层膜对αPSM聚合的影响在脂质类型和αPSM肽之间并不一致,但没有一种脂质导致主导聚合机制发生变化。就 αPSM3 而言,所有类型的脂质都在不同程度上减缓了其聚集,其中 1,2-二油酰-sn-甘油-3-磷酸胆碱(DOPC)的作用最为明显。对 αPSM1 而言,脂质的作用正好相反,DOPC 会减缓聚集,而脂多糖(LPS)会加速聚集,而 1,2-二油酰-sn-甘油-3-磷酸-rac-(1-甘油)(DOPG)则没有作用。对于αPSM4,DOPG和LPS都能加速其聚集,但只有在高浓度时才会发生,而DOPC则没有影响。没有一种脂质能够诱导αPSM2的聚集。我们的数据揭示了 PSMs 肽与脂质双分子层之间复杂的相互作用模式,它通过影响不同的动力学参数而导致聚集动力学发生变化,而形态学上只有微妙的变化。
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引用次数: 0
MRI/RNA-Seq-Based Radiogenomics and Artificial Intelligence for More Accurate Staging of Muscle-Invasive Bladder Cancer 基于 MRI/RNA-Seq 的放射基因组学和人工智能为肌肉浸润性膀胱癌提供更准确分期
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-20 DOI: 10.3390/ijms25010088
T. Qureshi, Xingyu Chen, Yibin Xie, Kaoru Murakami, Toru Sakatani, Yuki Kita, Takashi Kobayashi, M. Miyake, Simon R. V. Knott, Debiao Li, Charles J. Rosser, H. Furuya
Accurate staging of bladder cancer assists in identifying optimal treatment (e.g., transurethral resection vs. radical cystectomy vs. bladder preservation). However, currently, about one-third of patients are over-staged and one-third are under-staged. There is a pressing need for a more accurate staging modality to evaluate patients with bladder cancer to assist clinical decision-making. We hypothesize that MRI/RNA-seq-based radiogenomics and artificial intelligence can more accurately stage bladder cancer. A total of 40 magnetic resonance imaging (MRI) and matched formalin-fixed paraffin-embedded (FFPE) tissues were available for analysis. Twenty-eight (28) MRI and their matched FFPE tissues were available for training analysis, and 12 matched MRI and FFPE tissues were used for validation. FFPE samples were subjected to bulk RNA-seq, followed by bioinformatics analysis. In the radiomics, several hundred image-based features from bladder tumors in MRI were extracted and analyzed. Overall, the model obtained mean sensitivity, specificity, and accuracy of 94%, 88%, and 92%, respectively, in differentiating intra- vs. extra-bladder cancer. The proposed model demonstrated improvement in the three matrices by 17%, 33%, and 25% and 17%, 16%, and 17% as compared to the genetic- and radiomic-based models alone, respectively. The radiogenomics of bladder cancer provides insight into discriminative features capable of more accurately staging bladder cancer. Additional studies are underway.
膀胱癌的准确分期有助于确定最佳治疗方法(如经尿道切除术与根治性膀胱切除术、保留膀胱术)。然而,目前约有三分之一的患者分期过高,三分之一的患者分期过低。我们迫切需要一种更准确的分期方法来评估膀胱癌患者,以协助临床决策。我们假设,基于磁共振成像/RNA-seq的放射基因组学和人工智能可以更准确地对膀胱癌进行分期。共有 40 份磁共振成像(MRI)和匹配的福尔马林固定石蜡包埋(FFPE)组织可供分析。其中 28 例磁共振成像样本及其匹配的 FFPE 组织可用于训练分析,12 例匹配的磁共振成像样本和 FFPE 组织可用于验证分析。对 FFPE 样本进行了大量 RNA-seq,然后进行了生物信息学分析。在放射组学中,提取并分析了数百个基于核磁共振成像的膀胱肿瘤图像特征。总体而言,该模型在区分膀胱内癌和膀胱外癌方面的平均灵敏度、特异度和准确度分别为 94%、88% 和 92%。与单独基于基因和放射组学的模型相比,所提出的模型在三个矩阵中分别提高了 17%、33% 和 25%,以及 17%、16% 和 17%。膀胱癌放射基因组学深入揭示了能够更准确地对膀胱癌进行分期的鉴别特征。其他研究正在进行中。
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引用次数: 0
The p66Shc Redox Protein and the Emerging Complications of Diabetes p66Shc 氧化还原蛋白与新出现的糖尿病并发症
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-20 DOI: 10.3390/ijms25010108
G. Biondi, N. Marrano, Anna Borrelli, Martina Rella, R. D'Oria, V. A. Genchi, C. Caccioppoli, A. Cignarelli, Sebastio Perrini, L. Laviola, Francesco Giorgino, A. Natalicchio
Diabetes mellitus is a chronic metabolic disease, the prevalence of which is constantly increasing worldwide. It is often burdened by disabling comorbidities that reduce the quality and expectancy of life of the affected individuals. The traditional complications of diabetes are generally described as macrovascular complications (e.g., coronary heart disease, peripheral arterial disease, and stroke), and microvascular complications (e.g., diabetic kidney disease, retinopathy, and neuropathy). Recently, due to advances in diabetes management and the increased life expectancy of diabetic patients, a strong correlation between diabetes and other pathological conditions (such as liver diseases, cancer, neurodegenerative diseases, cognitive impairments, and sleep disorders) has emerged. Therefore, these comorbidities have been proposed as emerging complications of diabetes. P66Shc is a redox protein that plays a role in oxidative stress, apoptosis, glucose metabolism, and cellular aging. It can be regulated by various stressful stimuli typical of the diabetic milieu and is involved in various types of organ and tissue damage under diabetic conditions. Although its role in the pathogenesis of diabetes remains controversial, there is strong evidence regarding the involvement of p66Shc in the traditional complications of diabetes. In this review, we will summarize the evidence supporting the role of p66Shc in the pathogenesis of diabetes and its complications, focusing for the first time on the emerging complications of diabetes.
糖尿病是一种慢性代谢性疾病,其发病率在全球范围内不断上升。这种疾病通常伴有致残性并发症,降低了患者的生活质量和预期寿命。糖尿病的传统并发症一般被描述为大血管并发症(如冠心病、外周动脉疾病和中风)和微血管并发症(如糖尿病肾病、视网膜病变和神经病变)。近来,由于糖尿病管理的进步和糖尿病患者预期寿命的延长,糖尿病与其他病症(如肝病、癌症、神经退行性疾病、认知障碍和睡眠障碍)之间出现了密切的相关性。因此,这些合并症被认为是糖尿病的新并发症。P66Shc 是一种氧化还原蛋白,在氧化应激、细胞凋亡、糖代谢和细胞衰老中发挥作用。它可受到糖尿病环境中各种典型的应激刺激的调节,并参与糖尿病条件下各种器官和组织的损伤。尽管 p66Shc 在糖尿病发病机制中的作用仍存在争议,但有确凿证据表明它参与了糖尿病传统并发症的发生。在这篇综述中,我们将总结支持 p66Shc 在糖尿病及其并发症的发病机制中发挥作用的证据,并首次将重点放在新出现的糖尿病并发症上。
{"title":"The p66Shc Redox Protein and the Emerging Complications of Diabetes","authors":"G. Biondi, N. Marrano, Anna Borrelli, Martina Rella, R. D'Oria, V. A. Genchi, C. Caccioppoli, A. Cignarelli, Sebastio Perrini, L. Laviola, Francesco Giorgino, A. Natalicchio","doi":"10.3390/ijms25010108","DOIUrl":"https://doi.org/10.3390/ijms25010108","url":null,"abstract":"Diabetes mellitus is a chronic metabolic disease, the prevalence of which is constantly increasing worldwide. It is often burdened by disabling comorbidities that reduce the quality and expectancy of life of the affected individuals. The traditional complications of diabetes are generally described as macrovascular complications (e.g., coronary heart disease, peripheral arterial disease, and stroke), and microvascular complications (e.g., diabetic kidney disease, retinopathy, and neuropathy). Recently, due to advances in diabetes management and the increased life expectancy of diabetic patients, a strong correlation between diabetes and other pathological conditions (such as liver diseases, cancer, neurodegenerative diseases, cognitive impairments, and sleep disorders) has emerged. Therefore, these comorbidities have been proposed as emerging complications of diabetes. P66Shc is a redox protein that plays a role in oxidative stress, apoptosis, glucose metabolism, and cellular aging. It can be regulated by various stressful stimuli typical of the diabetic milieu and is involved in various types of organ and tissue damage under diabetic conditions. Although its role in the pathogenesis of diabetes remains controversial, there is strong evidence regarding the involvement of p66Shc in the traditional complications of diabetes. In this review, we will summarize the evidence supporting the role of p66Shc in the pathogenesis of diabetes and its complications, focusing for the first time on the emerging complications of diabetes.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":"1 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138954952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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