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Combined therapeutic use of umbilical cord blood serum and amniotic membrane in diabetic wounds 脐带血血清和羊膜在糖尿病伤口中的联合治疗应用。
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.07.012
C. Montague , Y. Holt , M. Vlok , P. Dhanraj , K. Boodhoo , M. Maartens , K. Buthelezi , C.U. Niesler , M. van de Vyver
Diabetic wounds are hard-to-heal due to complex multifactorial dysregulation within the micro-environment, necessitating the development of novel regenerative approaches to stimulate healing. This study investigated whether the combined therapeutic application of two novel cellular tissue products, namely a decellularized collagen-rich amniotic membrane (AmR) and growth factor-rich umbilical cord blood serum (UCBS) could have a positive synergistic effect on long-term healing outcomes by stimulating both superficial wound closure and wound bed regeneration. Full thickness excisional wounds were induced on obese diabetic mice (B6.Cg-lepob/J, ob/ob, n = 23) and treated with either: 1) Standard wound care (control); 2) UCBS; 3) AmR or 4) UCBS + AmR. Macroscopic wound closure was assessed on days 0, 3, 7, 10 and 14 post wounding. To determine the potential impact on wound recurrence, endpoint analysis was performed to determine both the overall quality of healing histologically as well as the molecular state of the wounds on day 14 via proteomic analysis. The data demonstrated the presence of both healers and non-healers. Re-epithelization took place in the healers of all treatment groups, but underlying tissue regeneration was far more pronounced following application of the combined treatment (UCBS + AmR), suggesting improved quality of healing and potentially a reduced change of recurrence long term. In non-healers, wounds failed to heal due to excessive slough formation and a reduction in LTB4 expression, suggesting impaired antimicrobial activity. Care should thus be taken since the cellular tissue product therapy could pose an increased risk for infection in some patients.
由于微环境中复杂的多因素失调,糖尿病伤口很难愈合,因此有必要开发新型再生方法来刺激伤口愈合。本研究探讨了两种新型细胞组织产品(即富含脱细胞胶原的羊膜(AmR)和富含生长因子的脐带血血清(UCBS))的联合治疗应用能否通过刺激表层伤口闭合和伤口床再生对长期愈合结果产生积极的协同作用。在肥胖糖尿病小鼠(B6.Cg-lepob/J,ob/ob,n=23)身上诱发全厚切除伤口,并用以下两种方法之一进行处理:1)标准伤口护理(对照组);2)UCBS;3)AmR 或 4)UCBS+AmR。在伤口愈合后的第 0、3、7、10 和 14 天评估宏观伤口闭合情况。为了确定对伤口复发的潜在影响,进行了终点分析,以确定组织学上的整体愈合质量,以及通过蛋白质组分析确定伤口在第 14 天的分子状态。数据显示存在愈合和未愈合两种情况。所有治疗组的愈合者都出现了再上皮化,但联合治疗(UCBS+AmR)后的潜在组织再生更为明显,这表明愈合质量有所改善,并可能降低长期复发的可能性。在未愈合组中,由于痂皮形成过多和 LTB4 表达减少,伤口无法愈合,这表明抗菌活性受损。因此,细胞组织产品疗法可能会增加某些患者的感染风险,因此应小心谨慎。
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引用次数: 0
Exosomes, circadian rhythms, and cancer precision medicine: New frontiers 外泌体、昼夜节律和癌症精准医学:新前沿。
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.07.010
Naveen Soni, Bhawana Bissa
"The environment shapes people's actions," a well-known proverb, strongly dictates that a change in our way of life changes our behavior. Circadian rhythms have been identified as a mechanism for maintaining homeostasis in the body, which, if disrupted by sleeping patterns, could result in significant metabolic alterations that adversely affect our health. The changes induced by circadian rhythm alter the secretion and cargo selection in exosomes which are nanovesicles important for intercellular communication. Exosomes were formerly known as "junk particles" but are now recognized as miniature copies of a cell's genetic material. Dysregulation of circadian rhythm has shown that it changes the gene expression of a cell to some extent and significantly alters the exosomal release. Meanwhile, cells secrete exosomes continuously to align the rhythmicity of the biological clock. In this study, we integrate circadian rhythms and exosomes with precision medicines to find better approaches to early diagnosis and treatment of disease.
"环境影响人的行为",这句众所周知的谚语有力地说明,生活方式的改变会改变我们的行为。昼夜节律被认为是维持体内平衡的一种机制,如果睡眠模式被打乱,就会导致新陈代谢发生重大变化,从而对我们的健康产生不利影响。昼夜节律引起的变化会改变外泌体的分泌和货物选择,而外泌体是对细胞间通信非常重要的纳米微粒。外泌体以前被称为 "垃圾颗粒",但现在被认为是细胞遗传物质的微型拷贝。昼夜节律失调表明,它会在一定程度上改变细胞的基因表达,并显著改变外泌体的释放。同时,细胞会不断分泌外泌体,以调整生物钟的节律性。在这项研究中,我们将昼夜节律和外泌体与精准医疗相结合,以找到更好的早期诊断和治疗疾病的方法。
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引用次数: 0
Characterization of the Arabidopsis thaliana chromatin remodeler DEK3 for its interaction with histones and DNA 拟南芥染色质重塑器 DEK3 与组蛋白和 DNA 相互作用的特征。
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.07.018
Rajivgandhi Sundaram , Surajit Gandhi , Claudia Jonak , Dileep Vasudevan
Chromatin structure and dynamics regulate all DNA-templated processes, such as transcription, replication, and repair. Chromatin binding factors, chromatin architectural proteins, and nucleosome remodelers modulate chromatin structure and dynamics and, thereby, the various DNA-dependent processes. Arabidopsis thaliana DEK3, a member of the evolutionarily conserved DEK domain-containing chromatin architectural proteins, is an important factor for chromatin structure and function, involved in transcriptional programming to regulate flowering time and abiotic stress tolerance. AtDEK3 contains an uncharacterized N-terminal domain, a middle SAF domain (winged helix-like domain), and a C-terminal DEK domain, but their role in the interaction of AtDEK3 with histones and DNA remained poorly understood. Using biochemical and biophysical analyses, we provide a comprehensive in vitro characterization of the different AtDEK3 domains for their interaction with histone H3/H4 and DNA. AtDEK3 directly interacts with histone H3/H4 tetramers through its N-terminal domain and the C-terminal DEK domain in a 1:1 stoichiometry. Upon interaction with H3/H4, the unstructured N-terminal domain of AtDEK3 undergoes a conformational change and adopts an alpha-helical conformation. In addition, the in-solution envelope structures of the AtDEK3 domains and their complex with H3/H4 have been characterized. The SAF and DEK domains associate with double-stranded and four-way junction DNA. As DEK3 possesses a histone-interacting domain at the N- and the C-terminus and a DNA-binding domain in the middle and at the C-terminus, the protein might play a complex role as a chromatin remodeler.
染色质结构和动态调控着所有以 DNA 为模板的过程,如转录、复制和修复。染色质结合因子、染色质结构蛋白和核小体重塑因子调节染色质结构和动态,从而调节各种 DNA 依赖过程。拟南芥 DEK3 是进化保守的含 DEK 结构域的染色质结构蛋白的一员,是染色质结构和功能的重要因子,参与转录编程以调控开花时间和非生物胁迫耐受性。AtDEK3含有一个未定性的N端结构域、一个中间的SAF结构域(翼螺旋样结构域)和一个C端DEK结构域,但它们在AtDEK3与组蛋白和DNA相互作用中的作用仍然鲜为人知。通过生化和生物物理分析,我们对 AtDEK3 不同结构域与组蛋白 H3/H4 和 DNA 的相互作用进行了全面的体外鉴定。AtDEK3 通过其 N 端结构域和 C 端 DEK 结构域以 1:1 的比例直接与组蛋白 H3/H4 四聚体相互作用。与 H3/H4 相互作用时,AtDEK3 的非结构化 N 端结构域会发生构象变化,并采用α-螺旋构象。此外,AtDEK3结构域的溶液包膜结构及其与H3/H4的复合物也得到了表征。SAF和DEK结构域与双链和四向连接DNA有联系。由于 DEK3 在 N 端和 C 端具有组蛋白相互作用结构域,在中间和 C 端具有 DNA 结合结构域,因此该蛋白可能扮演着染色质重塑者的复杂角色。
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引用次数: 0
CD38/NAD+ glycohydrolase and associated antigens in chronic lymphocytic leukaemia: From interconnected signalling pathways to therapeutic strategies 慢性淋巴细胞白血病中的 CD38/NAD+糖水解酶和相关抗原:从相互关联的信号通路到治疗策略。
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.07.006
Brigitte Bauvois , Florence Nguyen-Khac , Hélène Merle-Béral , Santos A. Susin
Chronic lymphocytic leukaemia (CLL) is a heterogenous disease characterized by the accumulation of neoplastic CD5+/CD19+ B lymphocytes. The spreading of the leukaemia relies on the CLL cell's ability to survive in the blood and migrate to and proliferate within the bone marrow and lymphoid tissues. Some patients with CLL are either refractory to the currently available therapies or relapse after treatment; this emphasizes the need for novel therapeutic strategies that improving clinical responses and overcome drug resistance. CD38 is a marker of a poor prognosis and governs a set of survival, proliferation and migration signals that contribute to the pathophysiology of CLL. The literature data evidence a spatiotemporal association between the cell surface expression of CD38 and that of other CLL antigens, such as the B-cell receptor (BCR), CD19, CD26, CD44, the integrin very late antigen 4 (VLA4), the chemokine receptor CXCR4, the vascular endothelial growth factor receptor-2 (VEGF-R2), and the neutrophil gelatinase-associated lipocalin receptor (NGAL-R). Most of these proteins contribute to CLL cell survival, proliferation and trafficking, and cooperate with CD38 in multilayered signal transduction processes. In general, these antigens have already been validated as therapeutic targets in cancer, and a broad repertoire of specific monoclonal antibodies and derivatives are available. Here, we review the state of the art in this field and examine the therapeutic opportunities for cotargeting CD38 and its partners in CLL, e.g. by designing novel bi-/trispecific antibodies.
慢性淋巴细胞白血病(CLL)是一种以肿瘤性 CD5+/CD19+ B 淋巴细胞聚集为特征的异质性疾病。白血病的扩散依赖于 CLL 细胞在血液中存活、迁移到骨髓和淋巴组织并在其中增殖的能力。一些 CLL 患者对现有疗法难治或治疗后复发;这就强调了对新型治疗策略的需求,以改善临床反应并克服耐药性。CD38 是预后不良的标志物,它控制着一系列生存、增殖和迁移信号,这些信号对 CLL 的病理生理学起着重要作用。文献数据证明,CD38 与其他 CLL 抗原(如 B 细胞受体 (BCR)、CD19、CD26、CD44、整合素晚期抗原 4 (VLA4)、趋化因子受体 CXCR4、血管内皮生长因子受体-2 (VEGF-R2) 和中性粒细胞明胶酶相关脂质体受体 (NGAL-R))的细胞表面表达存在时空关联。这些蛋白大多有助于 CLL 细胞的存活、增殖和迁移,并在多层信号转导过程中与 CD38 相互合作。一般来说,这些抗原已被确认为癌症的治疗靶点,并且有多种特异性单克隆抗体和衍生物可供使用。在此,我们回顾了这一领域的研究现状,并探讨了在CLL中共同靶向CD38及其伙伴(例如通过设计新型双/三特异性抗体)的治疗机会。
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引用次数: 0
Polyamines putrescine and spermidine as modulators of protein aggregation rate: The effect on DTT-induced aggregation of α-lactalbumin 作为蛋白质聚集率调节剂的多胺--腐胺和亚精胺:对 DTT 诱导的 α-乳清蛋白聚集的影响。
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.07.011
Dmitriy A. Kara , Vera A. Borzova , Svetlana G. Roman , Sergey Yu. Kleymenov , Natalia A. Chebotareva
Protein aggregation is undesirable for cells due to its possible toxicity, and is also undesirable in biotechnology and pharmaceuticals. Polyamines are known to be capable of both suppressing and stimulating protein aggregation. In the present work polyamines (spermidine, putrescine) have been shown to alter the pathway of α-lactalbumin aggregation induced by dithiothreitol, leading to the formation of larger protein particles during the initial stages of aggregation and promoting the later stage of sticking of aggregates. According to the aggregation kinetics data, polyamines accelerate protein aggregation in a concentration-dependent manner, with a maximum at 50 mM spermidine and 100 mM putrescine. With a further increase in polyamines concentration the effect of aggregation acceleration decreased, thus, the modulation of the aggregation rate by polyamines was shown. A comparison of the aggregation kinetics and hydrodynamic radii growth data registered by dynamic light scattering with the data obtained by asymmetric flow field-flow fractionation and analytical ultracentrifugation allowed us to describe the early stages of aggregation and formation of initial α-lactalbumin clusters. Our results provide a deeper insight into the mechanism of amorphous aggregation of α-lactalbumin and polyamines action on protein aggregation and protein-protein interaction in general.
蛋白质聚集对细胞来说是不可取的,因为它可能具有毒性,在生物技术和制药领域也是不可取的。众所周知,多胺既能抑制蛋白质聚集,也能刺激蛋白质聚集。在本研究中,多胺(亚精胺、腐胺)改变了二硫苏糖醇诱导的α-乳清蛋白聚集的途径,在聚集的初始阶段导致形成较大的蛋白质颗粒,并促进聚集体后期的粘连。根据聚集动力学数据,多胺以浓度依赖的方式加速蛋白质的聚集,在 50 mM 亚精胺和 100 mM 腐胺时达到最大值。随着多胺浓度的进一步增加,加速聚集的效果减弱,因此多胺对聚集速率的调节作用显现出来。将动态光散射记录的聚集动力学和流体力学半径增长数据与非对称流场-流动分馏和分析超速离心法获得的数据进行比较,使我们能够描述聚集的早期阶段和初始 α 乳清蛋白簇的形成。我们的研究结果让我们更深入地了解了 α-乳白蛋白无定形聚集的机理以及多胺对蛋白质聚集和蛋白质-蛋白质相互作用的一般作用。
{"title":"Polyamines putrescine and spermidine as modulators of protein aggregation rate: The effect on DTT-induced aggregation of α-lactalbumin","authors":"Dmitriy A. Kara ,&nbsp;Vera A. Borzova ,&nbsp;Svetlana G. Roman ,&nbsp;Sergey Yu. Kleymenov ,&nbsp;Natalia A. Chebotareva","doi":"10.1016/j.biochi.2024.07.011","DOIUrl":"10.1016/j.biochi.2024.07.011","url":null,"abstract":"<div><div>Protein aggregation is undesirable for cells due to its possible toxicity, and is also undesirable in biotechnology and pharmaceuticals. Polyamines are known to be capable of both suppressing and stimulating protein aggregation. In the present work polyamines (spermidine, putrescine) have been shown to alter the pathway of α-lactalbumin aggregation induced by dithiothreitol, leading to the formation of larger protein particles during the initial stages of aggregation and promoting the later stage of sticking of aggregates. According to the aggregation kinetics data, polyamines accelerate protein aggregation in a concentration-dependent manner, with a maximum at 50 mM spermidine and 100 mM putrescine. With a further increase in polyamines concentration the effect of aggregation acceleration decreased, thus, the modulation of the aggregation rate by polyamines was shown. A comparison of the aggregation kinetics and hydrodynamic radii growth data registered by dynamic light scattering with the data obtained by asymmetric flow field-flow fractionation and analytical ultracentrifugation allowed us to describe the early stages of aggregation and formation of initial α-lactalbumin clusters. Our results provide a deeper insight into the mechanism of amorphous aggregation of α-lactalbumin and polyamines action on protein aggregation and protein-protein interaction in general.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 182-192"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A new isoxazolyl-urea derivative induces apoptosis, paraptosis, and ferroptosis by modulating MAPKs in pancreatic cancer cells 一种新的异噁唑基脲衍生物通过调节胰腺癌细胞中的 MAPKs,诱导细胞凋亡、副凋亡和铁凋亡。
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.08.001
Young Yun Jung , Rajaghatta N. Suresh , Chakrabhavi Dhananjaya Mohan , Kachigere B. Harsha , Chilkunda Sannaiah Shivakumara , Kanchugarakoppal S. Rangappa , Kwang Seok Ahn
MAPK pathway regulates the major events including cell division, cell death, migration, invasion, and angiogenesis. Small molecules that modulate the MAPK pathway have been demonstrated to impart cytotoxicity in cancer cells. Herein, the synthesis of a new isoxazolyl-urea derivative (QR-4) has been described and its effect on the growth of pancreatic cancer cells has been investigated. QR-4 reduced the cell viability in a panel of pancreatic cancer cells with minimal effect on normal hepatocytes. QR-4 induced the cleavage of PARP and procaspase-3, reduced the expression of antiapoptotic proteins, increased SubG1 cells, and annexin V/PI-stained cells indicating the induction of apoptosis. QR-4 also triggered paraptosis as witnessed by the reduction of mitochondrial membrane potential, decrease in the expression of Alix, increase in the levels of ATF4 and CHOP, and enhanced ER stress. QR-4 also modulated ferroptosis-related events such as elevation in iron levels, alteration in GSH/GSSG ratio, and increase in the expression of TFRC with a parallel decrease in the expression of GPX4 and SLC7A11. The mechanistic approach revealed that QR-4 increases the phosphorylation of all three forms of MAPKs (JNK, p38, and ERK). Independent application of specific inhibitors of these MAPKs resulted in a partial reversal of QR-4-induced effects. Overall, these reports suggest that a new isoxazolyl-urea imparts cell death via apoptosis, paraptosis, and ferroptosis by regulating the MAPK pathway in pancreatic cancer cells.
MAPK 通路调节细胞分裂、细胞死亡、迁移、侵袭和血管生成等主要事件。调节 MAPK 通路的小分子已被证明对癌细胞具有细胞毒性。本文介绍了一种新的异噁唑基脲衍生物(QR-4)的合成,并研究了它对胰腺癌细胞生长的影响。QR-4 降低了一组胰腺癌细胞的存活率,而对正常肝细胞的影响极小。QR-4 可诱导 PARP 和 procaspase-3 的裂解,减少抗凋亡蛋白的表达,增加 SubG1 细胞和附件素 V/PI 染色的细胞,这表明 QR-4 可诱导细胞凋亡。QR-4 还能触发凋亡,表现为线粒体膜电位降低、Alix 表达减少、ATF4 和 CHOP 水平升高以及 ER 应激增强。QR-4 还调节了铁跃迁相关事件,如铁水平升高、GSH/GSSG 比率改变、TFRC 表达增加,同时 GPX4 和 SLC7A11 表达减少。机理研究表明,QR-4 会增加所有三种形式的 MAPK(JNK、p38 和 ERK)的磷酸化。独立应用这些 MAPKs 的特异性抑制剂可部分逆转 QR-4 诱导的效应。总之,这些报告表明,一种新的异噁唑基脲通过调节胰腺癌细胞的 MAPK 通路,使细胞通过凋亡、副凋亡和铁凋亡而死亡。
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引用次数: 0
Behind the stoNE wall: A fervent activity for nuclear lipids stoNE墙的背后:核脂的狂热活动。
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.08.002
Kseniya Samardak, Janélie Bâcle, María Moriel-Carretero
The four main types of biomolecules are nucleic acids, proteins, carbohydrates and lipids. The knowledge about their respective interactions is as important as the individual understanding of each of them. However, while, for example, the interaction of proteins with the other three groups is extensively studied, that of nucleic acids and lipids is, in comparison, very poorly explored. An iconic paradigm of physical (and likely functional) proximity between DNA and lipids is the case of the genomic DNA in eukaryotes: enclosed within the nucleus by two concentric lipid bilayers, the wealth of implications of this interaction, for example in genome stability, remains underassessed. Nuclear lipid-related phenotypes have been observed for 50 years, yet in most cases kept as mere anecdotical descriptions. In this review, we will bring together the evidence connecting lipids with both the nuclear envelope and the nucleoplasm, and will make critical analyses of these descriptions. Our exploration establishes a scenario in which lipids irrefutably play a role in nuclear homeostasis.
核酸、蛋白质、碳水化合物和脂质是四种主要的生物大分子。对它们各自相互作用的了解与对它们各自的了解同样重要。然而,虽然蛋白质与其他三类分子的相互作用已被广泛研究,但核酸和脂质的相互作用却鲜有人问津。真核生物基因组 DNA 是 DNA 与脂质之间物理(也可能是功能)接近的一个标志性范例:它被两层同心的脂质双分子层封闭在细胞核内,这种相互作用的丰富内涵,例如对基因组稳定性的影响,仍未得到充分评估。与核脂质相关的表型已被观察了 50 年,但在大多数情况下,这些表型都只是逸闻趣事。在这篇综述中,我们将汇集把脂质与核膜和核质联系起来的证据,并对这些描述进行批判性分析。我们的探索建立了一种情景,在这种情景中,脂质无可辩驳地在核稳态中发挥作用。
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引用次数: 0
Venom variation among the three subspecies of the North African mountain viper Vipera monticola Saint Girons 1953 北非山地蝰蛇三个亚种的毒液变异(Saint-Girons,1954 年)。
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.07.008
Maik Damm , Ignazio Avella , Reema Merzara , Nahla Lucchini , Jon Buldain , Frederico Corga , Abdellah Bouazza , Soumia Fahd , Roderich D. Süssmuth , Fernando Martínez-Freiría
The North African mountain viper (Vipera monticola) is a medically relevant venomous snake distributed in Morocco, Algeria, and Tunisia. Three subspecies of V. monticola, exhibiting differences in morphotypes and dietary regimes, are currently recognised: V. m. monticola, V. m. atlantica, and V. m. saintgironsi. Through the application of snake venomics, we analysed the venoms of specimens of Moroccan origin belonging to each of the three subspecies. Snake venom metalloproteinases (svMP), snake venom serine proteases (svSP), C-type lectin and C-type lectin-related proteins (CTL), and phospholipases A2 (PLA2) were predominant, with PLA2 being the most abundant toxin family overall. Disintegrins (DI) and cysteine-rich secretory proteins (CRISP) were exclusive to V. m. monticola and V. m. atlantica, while l-amino-acid oxidases (LAAO) were only found in V. m. saintgironsi. The differences detected in the venom profiles, as well as in presence/absence and relative abundances of toxin families, indicate the occurrence of intraspecific venom variation within V. monticola. The identified patterns of venom similarity between subspecies seem to align more with their phylogenetic relationships than with the reported differences in their feeding habits.
北非山地蝰蛇(Vipera monticola)是一种与医学相关的毒蛇,分布于摩洛哥、阿尔及利亚和突尼斯。目前,北非山地蝰蛇有三个亚种,形态和饮食习惯各不相同:蒙特科拉蛇、亚特兰提卡蛇和圣吉龙蛇。通过应用蛇毒组学,我们对这三个亚种的摩洛哥原产标本的毒液进行了分析。蛇毒金属蛋白酶(svMP)、蛇毒丝氨酸蛋白酶(svSP)、C型凝集素和C型凝集素相关蛋白(CTL)以及磷脂酶A2(PLA2)占主导地位,其中PLA2是含量最高的毒素家族。解体蛋白(DI)和富含半胱氨酸的分泌蛋白(CRISP)为蒙蒂科拉蛇毒和亚特兰蒂卡蛇毒所独有,而l-氨基酸氧化酶(LAAO)仅见于圣吉龙蛇毒。在毒液特征以及毒素家族的存在/不存在和相对丰度方面发现的差异表明,V. monticola存在种内毒液变异。亚种间毒液相似性的确定模式似乎更符合它们的系统发育关系,而不是它们的食性差异。
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引用次数: 0
Direct analysis by ultra-high-resolution mass spectrometry of lipid A and phospholipids from Acinetobacter baumannii cells 利用超高分辨率质谱法直接分析鲍曼不动杆菌细胞中的脂质 A 和磷脂。
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.09.012
Delphine Vergoz , Annick Schaumann , Isabelle Schmitz , Maria van Agthoven , Sara Martí , Jordi Vila , Carlos Afonso , Emmanuelle Dé , Corinne Loutelier-Bourhis , Stéphane Alexandre
Acinetobacter baumannii, classified as priority number one by the World Health Organization (WHO), is an opportunistic pathogen responsible for infection and is able to develop antibiotic resistance easily. Membranes are bacteria's first line of defense against external aggression, such as antibiotics. A chemical modification of a lipid family or a change in lipid composition can lead to resistance to antibiotics. In this work, we analyzed different A. baumannii strains from various environments with different antibiotic resistance profiles, using matrix-assisted laser desorption ionization-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FT-ICR MS). This study shows that it is possible to describe the main lipidome (phospholipids and lipid A) from the simple preparation of lysed cells, and that despite the complexity of the mixture. This ultra-high resolution mass spectrometry technique enables the separation of isobaric ion, to report a new class of lipids. Given its performance, this technique can be used to quickly and reliably characterize the lipidome of clinical strains from different environments.
鲍曼不动杆菌(Acinetobacter baumannii)被世界卫生组织(WHO)列为头号优先病原体,是一种造成感染的机会性病原体,很容易产生抗生素耐药性。膜是细菌抵御抗生素等外部侵袭的第一道防线。脂质家族的化学修饰或脂质成分的改变可导致对抗生素产生抗药性。在这项工作中,我们利用基质辅助激光解吸电离-傅立叶变换离子回旋共振质谱(MALDI-FT-ICR MS)分析了来自不同环境、具有不同抗生素耐药性的鲍曼不动杆菌菌株。这项研究表明,通过简单制备裂解细胞就能描述主要脂质体(磷脂和脂质 A),尽管混合物非常复杂。这种超高分辨率质谱技术能够分离等压离子,从而报告一类新的脂质。鉴于其性能,该技术可用于快速、可靠地鉴定来自不同环境的临床菌株的脂质体。
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引用次数: 0
New insights on pentadecanoic acid with special focus on its controversial essentiality: A mini-review 关于十五烷酸的新见解,特别关注其有争议的本质:微型综述。
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.10.008
Vincent Ciesielski , Philippe Legrand , Sophie Blat , Vincent Rioux
Pentadecanoic acid (C15:0, PDA) is an odd and minor fatty acid that has been neglected in the literature until the last decade. Indeed, as a specific fatty acid of dairy fat, PDA was only used as a biomarker of dairy fat consumption. Lately, PDA was first correlated negatively with the incidence of metabolic syndrome disorder, then its physiological effects have been investigated as a protective fatty acid. PDA supplementation has been demonstrated as negatively correlated with elevated levels of leptin, plasminogen activator inhibitor-1 and insulin, and has been shown to exhibit sensitizing insulin effects with activation of AMPK pathway. PDA also reduced the severity of metabolic dysfunction-associated steatohepatitis (MASH), notably through reduced alanine transaminase and pro-inflammatory cytokines levels. The final effect described for PDA is its ability to display anti-inflammatory properties in several pathology models. Hence, considering these multiple effects, the presence of PDA could be associated with a healthier physiological state, this raises the question of whether the presence of PDA in the body, in adequate quantities, is needed to participate to health maintenance. PDA is not synthesized in sufficient quantities endogenously, so it must be provided by the diet, mainly through dairy fat, although other types of food can also contribute to the dietary intake of PDA. Essential fatty acids are described as not being endogenously synthesized in sufficient and required quantities to maintain physiological health. Thus, PDA might gather both conditions to be described as essential, yet further investigations on both criteria are needed to enhance knowledge on this odd chain fatty acid with promising impact as potential protective supplement nutrient.
十五烷酸(C15:0,PDA)是一种奇特而次要的脂肪酸,直到最近十年才被文献所忽视。事实上,作为乳脂中的一种特殊脂肪酸,PDA 只被用作乳脂消耗量的生物标志物。近来,PDA 首先与代谢综合征的发病率呈负相关,然后其作为一种保护性脂肪酸的生理效应得到了研究。研究表明,补充 PDA 与瘦素、纤溶酶原激活物抑制剂-1 和胰岛素水平的升高呈负相关,并通过激活 AMPK 途径显示出对胰岛素的敏感效应。PDA 还能降低代谢功能障碍相关性脂肪性肝炎(MASH)的严重程度,特别是通过降低丙氨酸转氨酶和促炎细胞因子水平。PDA 的最后一项功效是它能在多个病理模型中显示抗炎特性。因此,考虑到这些多重效果,PDA 的存在可能与更健康的生理状态有关,这就提出了一个问题,即体内是否需要足够数量的 PDA 来参与健康维护。内源性合成的 PDA 数量不足,因此必须由膳食提供,主要是通过乳脂,尽管其他类型的食物也有助于从膳食中摄取 PDA。必需脂肪酸被描述为无法在内源性合成足够的、维持生理健康所需的数量。因此,PDA 可以同时满足这两个条件,被描述为必需脂肪酸,但还需要对这两个标准进行进一步调查,以加深对这种奇链脂肪酸的了解,因为这种脂肪酸具有潜在的保护性补充营养素的作用。
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