Biochimie最新文献_第7页

The complex post-transcriptional regulation of genes coding for methionine adenosyl transferase: New insights for liver cancer 蛋氨酸腺苷转移酶基因编码的复杂转录后调控：肝癌的新见解。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2025-11-01 DOI: 10.1016/j.biochi.2025.05.001

Amina Doudou Tellai , Vincent Haghnejad , Justine Antoine , Basma Khemiri Merouani , Jean-Pierre Bronowicki , Natacha Dreumont

Methionine adenosyltransferases (MATs) catalyze the synthesis of S-adenosylmethionine (SAM), the universal methyl donor involved in methylation reactions, redox balance, and polyamine synthesis. In mammals, three MAT genes, MAT1A, MAT2A, and MAT2B, exhibit tissue-specific expression, with MAT1A predominating in healthy liver and MAT2A/MAT2B upregulated during liver injury and malignancy. A shift from MAT1A to MAT2A/MAT2B expression is a hallmark of hepatocellular carcinoma (HCC), contributing to decreased SAM levels and promoting tumorigenesis.

Recent findings highlight the pivotal role of post-transcriptional regulation in controlling MAT gene expression. N6-methyladenosine (m6A) modification, the most prevalent internal mRNA modification, plays a dynamic role in determining the fate of MAT2A mRNA. m6A marks regulate MAT2A mRNA splicing and stability in response to stress and metabolic changes. Additionally, RNA-binding proteins (RBPs) such as ELAVL1 and hnRNPD bind to MAT mRNAs, modulating their stability and translation. Dysregulation of these RBPs in liver disease alters MAT expression profiles. Non-coding RNAs, including microRNAs such as miR-29, miR-21, and miR-485, and long non-coding RNAs such as LINC00662 and SNGH6, modulate MAT expression post-transcriptionally by targeting MAT transcripts directly or influencing RNA-binding proteins (RBPs) and m6A writers/readers. Together, these mechanisms form a complex and intricate post-transcriptional regulatory network that governs MAT activity in physiological and pathological states.

This review examines emerging insights into MAT post-transcriptional regulation, focusing on its implications for liver cancer, and opens new avenues for developing therapies that target these regulatory mechanisms.

蛋氨酸腺苷转移酶（Methionine adenosyltransferases, MATs）催化s -腺苷蛋氨酸（S-adenosylmethionine， SAM）的合成，SAM是参与甲基化反应、氧化还原平衡和多胺合成的通用甲基供体。在哺乳动物中，MAT1A、MAT2A和MAT2B这三个MAT基因表现出组织特异性表达，其中MAT1A在健康肝脏中占主导地位，而MAT2A/MAT2B在肝损伤和恶性肿瘤中上调。从MAT1A到MAT2A/MAT2B表达的转变是肝细胞癌（HCC）的一个标志，有助于降低SAM水平并促进肿瘤发生。最近的研究结果强调了转录后调控在控制MAT基因表达中的关键作用。n6 -甲基腺苷（m6A）修饰是最常见的mRNA内部修饰，在决定MAT2A mRNA的命运中起着动态作用。m6A标记调节MAT2A mRNA的剪接和稳定性，以应对应激和代谢变化。此外，rna结合蛋白（rbp）如ELAVL1和hnRNPD与MAT mrna结合，调节其稳定性和翻译。肝脏疾病中这些rbp的失调会改变MAT的表达谱。非编码rna，包括microrna，如miR-29、miR-21和miR-485，以及长链非编码rna，如LINC00662和SNGH6，通过直接靶向MAT转录物或影响rna结合蛋白（rbp）和m6A写/读体，在转录后调节MAT表达。总之，这些机制形成了一个复杂的转录后调控网络，在生理和病理状态下控制MAT活性。本综述探讨了MAT转录后调控的新见解，重点关注其对肝癌的影响，并为开发针对这些调控机制的治疗方法开辟了新的途径。

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引用次数: 0

Design of competitive inhibitory peptides for 3-hydroxy-3-Methylglutaryl coenzyme A reductase 3-羟基-3-甲基戊二酰辅酶A还原酶竞争性抑制肽的设计

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2025-11-01 DOI: 10.1016/j.biochi.2025.10.017

Valeriy V. Pak , Shomansur Sh Sagdullaev , Aleksandr V. Pak

The effectiveness of statins in preventing hypercholesterolemia and associated cardiovascular diseases has been confirmed for a long time. Statins are competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR). This enzyme plays a key role in the reaction that represents the rate-limiting step in cholesterol biosynthesis. Numerous studies on the properties of food-derived peptides have revealed various bioactivities that influence human health, including the modulation of endogenous cholesterol levels. Ongoing studies have shown that some peptides function using the same mechanism as statins and can be considered another class of compounds for HMGR inhibition.To date, the competitive inhibition of HMGR by peptides has been confirmed for 36 of them. The half-maximal inhibitory concentration (IC₅₀) of the most active food-derived peptide was found to be 12.8 μM, which is significantly lower than statin activity. This review presents approaches for modeling peptides to enhance their activity. Analysis of the peptides' physicochemical characteristics revealed the potential to design a more active peptide by adjusting a single parameter. The most active designed peptide exhibited 700 times the activity of an isolated peptide found in food. These studies demonstrate the potential of using peptides to develop nutraceuticals or drugs that prevent hypercholesterolemia.

他汀类药物预防高胆固醇血症及相关心血管疾病的有效性早已得到证实。他汀类药物是3-羟基-3-甲基戊二酰辅酶A还原酶（HMGR）的竞争性抑制剂。这种酶在代表胆固醇生物合成限速步骤的反应中起着关键作用。对食物来源多肽特性的大量研究揭示了影响人类健康的各种生物活性，包括调节内源性胆固醇水平。正在进行的研究表明，一些肽的作用机制与他汀类药物相同，可以被认为是抑制HMGR的另一类化合物。迄今为止，已证实其中36种多肽对HMGR有竞争性抑制作用。食源性肽的半最大抑制浓度（IC50）为12.8 μM，明显低于他汀类药物的活性。本文综述了建立多肽模型以增强其活性的方法。对多肽理化特性的分析揭示了通过调整单个参数来设计更有活性的多肽的潜力。设计出的活性最高的肽的活性是食品中分离肽活性的700倍。这些研究证明了利用多肽开发预防高胆固醇血症的营养品或药物的潜力。

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引用次数: 0

Inhibition of proteolytic activity of Bothrops alternatus venom by two small molecules and docking analysis against a snake venom metalloproteinase 两个小分子抑制蛇毒蛋白水解活性及其与蛇毒金属蛋白酶的对接分析。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2025-11-01 DOI: 10.1016/j.biochi.2025.08.009

Silvina M. Echeverría , Giuliana C. Blanco , María del Carmen Gauna Pereira , Silvana L. Maruñak , José M. Ferreras , Claudia C. Gay

The only effective treatment against snakebites is the administration of antivenom. Snake venom metalloproteinases (SVMPs) play a key role in the pathogenesis of envenomation. In this work, the ability of two molecules to inhibit the proteolytic activity of Bothrops alternatus venom and its PIII SVMP (baltergin) was studied: a dye (alizarin red S: Az) and a vitamin (l-ascorbic acid: AA). Neutralization of hemorrhage and docking analysis were also carried out. The inhibition of the proteolytic activity, showed the IC₅₀ for Az (3.6 mM) was 52 times lower than for AA (188.2 mM). Az was not only able to inhibit casein degradation but also a milk protein compatible with beta-lactoglobulin, meanwhile AA was only capable of inhibit the degradation of casein. Both molecules were able to completely inhibit the action of baltergin on casein degradation. It was also observed that the antioxidant activity of Az increased, while the activity of AA decreased after exposition to visible radiation. As a result, Az induced an increase in its proteolytic inhibitory potential, although no significant changes were observed with AA. A partial neutralization of hemorrhage was observed, representing 46 % of inhibition, only for Az at a venom:molecule ratio (m:m) of 1:4. It was demonstrated that Az interacts with PIII SVMPs through more bonds than with AA, which makes it fit better in the vicinity of the catalytic site. Natural (or synthetic) dyes open up a new range of possibilities for exploring alternatives for the complementary treatment of snakebites.

对付蛇咬伤唯一有效的方法是注射抗蛇毒血清。蛇毒金属蛋白酶（SVMPs）在蛇毒的发病机制中起着关键作用。本研究研究了两种分子：染料（茜素红S: Az）和维生素（l -抗坏血酸：AA）对交替肉毒虫毒液及其PIII SVMP （baltergin）蛋白水解活性的抑制作用。并进行出血中和和对接分析。结果表明，Az （3.6 mM）的IC50比AA （188.2 mM）低52倍。Az不仅能抑制酪蛋白的降解，而且是与β -乳球蛋白相容的乳蛋白，而AA仅能抑制酪蛋白的降解。两种分子都能完全抑制蛋白蛋白对酪蛋白的降解。可见辐射处理后，Az的抗氧化活性增加，AA的抗氧化活性降低。结果，Az诱导了其蛋白水解抑制电位的增加，尽管AA没有观察到明显的变化。在毒液：分子比（m:m）为1:4时，观察到出血的部分中和，占抑制的46%。结果表明，Az通过更多的键与PIII SVMPs相互作用，这使得它更适合于催化位点附近。天然（或合成）染料为探索替代蛇咬伤的补充治疗开辟了新的可能性范围。

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引用次数: 0

Ribosome biogenesis and homeostasis: in the front line to cope with cellular stress 核糖体生物发生与体内平衡：在应对细胞应激的第一线。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2025-11-01 DOI: 10.1016/j.biochi.2025.08.016

Emilie L. Cerezo , Yves Henry, Anthony K. Henras, Yves Romeo

Cells must continuously adapt to both internal and environmental stresses by finely tuning their molecular and metabolic activities. One of the most regulated energy-consuming processes is ribosome biogenesis, essential for gene expression modulation. While the focus is often on the regulation of this process during growth and proliferation, this review incorporates exciting recent findings describing molecular checkpoints and signaling that converge to and derive from ribosomes under stress conditions, in both yeast and mammals. Special emphasis is placed on the roles of transcription factors and ribosome-binding proteins in repressing ribosomal gene expression and pre-ribosome maturation, as well as on the translational reprogramming that occurs through mechanisms such as eIF2α phosphorylation, specialized ribosome, and ribosome hibernation. In addition, we examine the interplay between ribosome homeostasis and key signaling cascades that ultimately determine cell fate. We especially focus on regulations mediated by conserved signaling pathways such as the Integrated Stress Response, the Ribotoxic Stress Response and the AMP-activated protein kinase cascade. Lastly, we discuss the p53 signaling pathway as a central integrator of nucleolar stress, linking ribosome biogenesis impairment to critical cell fate decisions, such as cell cycle arrest, senescence, or apoptosis. Together, these insights provide a comprehensive overview of stress-response integration onto ribosomes and underscore the central role of ribosome homeostasis in cellular adaptation across the eukaryotic systems.

细胞必须不断地通过微调分子和代谢活动来适应内部和环境的压力。核糖体生物发生是最受调节的能量消耗过程之一，对基因表达调节至关重要。虽然重点通常是在生长和增殖过程中对这一过程的调节，但本综述结合了令人兴奋的最新发现，描述了酵母和哺乳动物在应激条件下收敛于核糖体并源自核糖体的分子检查点和信号。特别强调转录因子和核糖体结合蛋白在抑制核糖体基因表达和核糖体前成熟中的作用，以及通过eIF2α磷酸化、特化核糖体和核糖体冬眠等机制发生的翻译重编程。此外，我们还研究了核糖体稳态和最终决定细胞命运的关键信号级联之间的相互作用。我们特别关注由保守信号通路介导的调控，如综合应激反应、核糖体毒性应激反应和amp激活的蛋白激酶级联反应。最后，我们讨论了p53信号通路作为核仁应激的中心整合器，将核糖体生物发生损伤与关键的细胞命运决定（如细胞周期阻滞、衰老或凋亡）联系起来。总之，这些见解提供了对核糖体的应激反应整合的全面概述，并强调了核糖体稳态在真核系统细胞适应中的核心作用。

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引用次数: 0

Are Traditional mutant controls sufficient to identify true RNA G-quadruplex binding proteins? 传统的突变控制是否足以识别真正的RNA g -四重结合蛋白？

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2025-11-01 DOI: 10.1016/j.biochi.2025.10.018

Marc-Antoine Turcotte, Louise Dao Josépha Crespo, Jean-Pierre Perreault

G-quadruplexes (G4s) are stable non-canonical RNA structures involved in various regulatory processes, whose recognition by G4-binding proteins (G4BPs) is often studied using affinity purification and biochemical validation. A critical factor in validating true G4BPs lies in the choice of negative controls, which are frequently limited to simple G-to-A point mutations. Here, we reassess the classification of Guanine Nucleotide-Binding Protein-Like 1 (GNL1), previously identified as an RNA G4BP (rG4BP), by employing 7-deazaguanine (7dG) substitutions and salt variation strategies. Using fluorescence assays with N-methyl mesoporphyrin IX (NMM) and electrophoretic mobility shift assays (EMSAs), we show that GNL1 binds wild-type and 7dG-modified RNAs with comparable affinities. Additional experiments using potassium and lithium ions further that GNL1 binding is independent of G4 structure. Finally, truncation of PRKN RNA to its G4 core significantly reduced GNL1 binding, indicating that the protein does not interact with the folded G4 itself. These results collectively demonstrate that GNL1 binds guanine-containing sequences rather than true G4s, and that its prior classification as a G4BP was likely due to insufficient controls. Our findings highlight the importance of using robust negative controls, such as 7dG substitution and ionic condition modulation, in the accurate identification of bona fide G4BPs.

g -四plex （G4s）是参与多种调控过程的稳定非规范RNA结构，其被g4结合蛋白（g4bp）识别的研究经常使用亲和纯化和生化验证。验证真正g4bp的一个关键因素在于阴性对照的选择，阴性对照通常仅限于简单的G-to-A点突变。在这里，我们重新评估了鸟嘌呤核苷酸结合蛋白样1 （GNL1）的分类，以前鉴定为RNA G4BP (rG4BP)，采用7-去氮鸟嘌呤（7dG）取代和盐变化策略。通过n -甲基间卟啉IX （NMM）荧光分析和电泳迁移迁移分析（EMSAs），我们发现GNL1结合野生型和7dg修饰的rna具有相当的亲和力。另外使用钾离子和锂离子的实验进一步证明了GNL1的结合与G4结构无关。最后，将PRKN RNA截断至其G4核心显著降低了GNL1的结合，表明该蛋白不与折叠的G4本身相互作用。这些结果共同表明，GNL1结合的是含有鸟嘌呤的序列，而不是真正的G4s，而且其先前被分类为G4BP可能是由于控制不足。我们的研究结果强调了使用强大的阴性对照，如7dG取代和离子条件调制，在准确鉴定真正的g4bp中的重要性。

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引用次数: 0

Inside front cover-EDB 内部前盖- edb

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2025-11-01 DOI: 10.1016/S0300-9084(25)00238-X

引用次数: 0

Post-transcriptional modifications and regulation of mRNAs in human mitochondria 人线粒体mrna转录后修饰和调控

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2025-11-01 DOI: 10.1016/j.biochi.2025.06.015

Louise Lambert , Amandine Moretton , Géraldine Farge

Mitochondria contain their own circular genome (mtDNA), which encodes essential components of the oxidative phosphorylation (OXPHOS) system. Mitochondrial DNA transcription is a unique and relatively simple process, requiring a specialized transcription machinery that consists of a RNA polymerase (POLRMT), two transcription factors (TFAM and TFB2M), and an elongation factor (TEFM). During transcription, a non-canonical initiating nucleotide (NCIN) can be incorporated as the first nucleotide, serving as a 5’ cap. Mitochondrial transcription produces large polycistronic transcripts, which are subsequently processed by ribonucleases to generate individual messenger RNAs (mt-mRNAs), ribosomal RNAs (mt-rRNAs), and transfer RNAs (mt-tRNAs). This review will specifically focus on the maturation and regulation of mt-mRNAs. Following their release from the primary transcript, mt-mRNAs undergo various post-transcriptional modifications, including methylation, pseudouridylation, and polyadenylation. These modifications play a crucial role in determining mt-mRNAs fate by influencing their stability, translation efficiency, and overall mitochondrial function. Additionally, the spatial organization of these processes within mitochondrial RNA granules (MRGs) suggests a compartmentalized system for mitochondrial gene regulation, ensuring precise coordination between transcription, processing, and translation. A deeper understanding of these post-transcriptional modifications provides valuable insights into mitochondrial gene expression and its broader impact on cellular metabolism.

线粒体含有自己的环状基因组（mtDNA），其编码氧化磷酸化（OXPHOS）系统的基本成分。线粒体DNA转录是一个独特且相对简单的过程，需要一个专门的转录机制，包括RNA聚合酶（POLRMT），两个转录因子（TFAM和TFB2M）和一个延伸因子（TEFM）。在转录过程中，非规范起始核苷酸（NCIN）可以作为第一个核苷酸，作为5'帽。线粒体转录产生大的多顺反子转录物，随后由核糖核酸酶加工产生单个信使rna （mt- mrna）、核糖体rna （mt- rrna）和转移rna （mt-tRNAs）。本文将特别关注mt- mrna的成熟和调控。从初级转录物释放后，mt- mrna经历各种转录后修饰，包括甲基化、假尿嘧啶化和聚腺苷化。这些修饰通过影响mt- mrna的稳定性、翻译效率和整体线粒体功能，在决定它们的命运中起着至关重要的作用。此外，这些过程在线粒体RNA颗粒（MRGs）中的空间组织表明，线粒体基因调控存在区隔化系统，确保转录、加工和翻译之间的精确协调。对这些转录后修饰的深入了解为线粒体基因表达及其对细胞代谢的广泛影响提供了有价值的见解。

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引用次数: 0

Ribosome biogenesis is a therapeutic vulnerability in pediatric neuroblastoma 核糖体生物发生是小儿神经母细胞瘤的治疗弱点。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2025-11-01 DOI: 10.1016/j.biochi.2025.07.018

Camille Jouines , Piero Lo Monaco , Angéline Gaucherot , Marie-Ambre Monet , Isabelle Iacono Di Cacito , Valentin Simioni , Déborah Monchiet , Jean-Jacques Diaz , Valérie Combaret , Virginie Marcel , Frédéric Catez

Neuroblastoma is a heterogeneous malignant pediatric tumor, the prognosis of which depends on patient age and disease stage. Current treatment strategies rely on four key diagnostic criteria: age, histological stage, genomic profile, and MYCN gene status. The oncogenic activity of MYC depends on ribosome biogenesis, which is hyperactivated in cancer cells to support their high proliferative capacity, and which may thus represent a vulnerability in neuroblastoma and constitute a therapeutic target. Here, using the well-established IMR-32 cell line along with a previously established panel of patient-derived neuroblastoma cell lines with varying MYCN status, we show that RNA polymerase I inhibition following exposure to CX-5461 and BMH-21 suppressed cell proliferation at nanomolar concentrations and induced ribosomal stress, leading to the activation of apoptosis and the p21 pathway. Furthermore, analysis of expression of ribosome biogenesis factors using publicly available datasets and RT-qPCR data from an in-house neuroblastoma cohort, we identified FBL as a marker of poor prognosis in neuroblastoma. Consistently, FBL knockdown reduced neuroblastoma cell proliferation, supporting its relevance as a therapeutic target. In conclusion, our study reinforces the therapeutic potential of ribosome biogenesis inhibition in neuroblastoma and expands the list of potential targets to include rRNA maturation factors. These findings highlight the relevance of targeting ribosome biogenesis as a novel approach for neuroblastoma treatment.

神经母细胞瘤是一种异质性的儿童恶性肿瘤，其预后取决于患者的年龄和疾病分期。目前的治疗策略依赖于四个关键的诊断标准：年龄、组织学分期、基因组谱和MYCN基因状态。MYC的致癌活性取决于核糖体的生物发生，核糖体在癌细胞中被过度激活，以支持其高增殖能力，因此可能代表神经母细胞瘤的易感性，并构成治疗靶点。在这里，我们使用已建立的IMR-32细胞系以及先前建立的具有不同MYCN状态的患者源性神经母细胞瘤细胞系，我们发现暴露于CX-5461和BMH-21后的RNA聚合酶I抑制在纳摩尔浓度下抑制细胞增殖并诱导核糖体应激，导致细胞凋亡和p21途径的激活。此外，利用公开数据集和来自内部神经母细胞瘤队列的RT-qPCR数据分析核糖体生物发生因子的表达，我们确定FBL是神经母细胞瘤预后不良的标志。一致地，FBL敲低可减少神经母细胞瘤细胞增殖，支持其作为治疗靶点的相关性。总之，我们的研究加强了核糖体生物发生抑制在神经母细胞瘤中的治疗潜力，并扩大了潜在靶点列表，包括rRNA成熟因子。这些发现突出了靶向核糖体生物发生作为神经母细胞瘤治疗新方法的相关性。

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引用次数: 0

Sequence characteristics, expression pattern, ovarian maintenance function and action mechanism of SIRT1 in Chlamys farreri 栉孔栉孔栉孔栉孔中SIRT1的序列特征、表达模式、卵巢维持功能及作用机制。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2025-11-01 DOI: 10.1016/j.biochi.2025.07.020

Yan Xing , Dongyan Luo , Xijuan Lei , Xiaoling Liu

SIRT1 (silent mating type information regulation 2 homolog 1), a histone deacetylase in Sirtuin family, regulates ovarian development and aging in higher mammals, but its role in invertebrates remains unexplored. This study investigated SIRT1 in the scallop Chlamys farreri. Its 2382 bp CDS (coding sequence) encodes 793 amino acids with the NTERM activation motif, the catalytic activity center and the ESA domain. QRT-PCR revealed that SIRT1 expression level in gonads was significantly higher than that in other tissues. In ovary, SIRT1 expression was the highest at growing stage, in the testes, the gene was highly expressed at growing stage and mature stage, suggesting it was related to the oocyte development, spermatocyte development and the sperm maturation. Furthermore, injection experiment showed resveratrol (SIRT1 activator) up-regulated SIRT1′ expression, then oocyte numbers were increased but oocytes' maturity were suppressed, while nicotinamide (SIRT1 inhibitor) down-regulated SIRT1′ expression, then oocyte numbers were reduced but oocytes’ maturity were accelerated, suggesting SIRT1 can promote the oocytes proliferation while delay the oocytes maturation to prevent ovarian aging. Yeast one-hybrid and electrophoretic mobility shift assay confirmed SIRT1 binds Chlamys farreri FOXL2 via two sequences (SIF1: +28–+35; SIF2: +53–+60). Dual-luciferase reporter system showed FOXL2 could up-regulate SIRT1. It was worth mentioning that FOXL2 expression was up-regulated when nicotinamide down-regulated SIRT1 expression in ovaries, indicating there was a positive and negative feedback regulation between SIRT1 and FOXL2 expression, we speculate that those two genes play a crucial role in the development and maintenance of Chlamys farreri ovarian function.

SIRT1 （silent mating type information regulation 2 homolog 1）是Sirtuin家族中的一种组蛋白去乙酰化酶，在高等哺乳动物中调节卵巢发育和衰老，但其在无脊椎动物中的作用尚不清楚。本研究研究了栉孔扇贝（Chlamys farreri）中的SIRT1。其编码序列为2382 bp，编码793个氨基酸，具有NTERM激活基序、催化活性中心和ESA结构域。QRT-PCR结果显示，性腺中SIRT1的表达水平明显高于其他组织。在卵巢中，SIRT1在生长期表达量最高，在睾丸中，该基因在生长期和成熟期均高表达，提示其与卵母细胞发育、精母细胞发育和精子成熟有关。注射实验显示，白藜芦醇（SIRT1激活剂）上调SIRT1表达，使卵母细胞数量增加，但抑制卵母细胞成熟；烟酰胺（SIRT1抑制剂）下调SIRT1表达，使卵母细胞数量减少，但促进卵母细胞成熟，提示SIRT1可以促进卵母细胞增殖，延缓卵母细胞成熟，防止卵巢衰老。酵母单杂交和电泳迁移转移实验证实SIRT1通过两个序列(SIF1: +28-+35；SIF2: 60 + 53 - +)。双荧光素酶报告系统显示FOXL2可以上调SIRT1。值得一提的是，在烟酰胺下调卵巢中SIRT1表达的同时，FOXL2表达上调，说明SIRT1与FOXL2表达之间存在正负反馈调节，我们推测这两个基因在栉比栉比卵巢功能的发育和维持中起着至关重要的作用。

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引用次数: 0

Advancing antimicrobial peptides: Overcoming challenges in the era of bacterial resistance 推进抗菌肽：克服细菌耐药性时代的挑战。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2025-11-01 DOI: 10.1016/j.biochi.2025.07.019

Ratchaneewan Aunpad, Thanit Thitirungreangchai

Antimicrobial resistance (AMR) in bacteria poses a significant public health threat, necessitating the development of alternative treatments. Antimicrobial peptides (AMPs) have emerged as promising candidates to address this issue due to their potent antimicrobial activity and diverse functional properties, which provide distinct advantages over conventional antibiotics. However, the clinical application of AMPs has been hindered by several challenges, including instability in vivo, safety concerns, and varying efficacy in vivo. To overcome these limitations, innovative approaches to AMP design and modification, as well as advanced delivery systems, are being actively investigated. This article provides a comprehensive overview of the classification, structural characteristics, and mechanisms of action of AMPs. Recent advances in AMP design and modification are highlighted, with a focus on strategies aimed at enhancing their therapeutic potential. Additionally, the development of delivery systems and formulation strategies for AMPs is discussed, with an emphasis on improving bioavailability, targeted distribution, and effectiveness in combating drug-resistant bacterial infections.

细菌的抗菌素耐药性（AMR）对公共卫生构成重大威胁，需要开发替代治疗方法。抗菌肽（AMPs）已成为解决这一问题的有希望的候选人，因为它们具有强大的抗菌活性和多样化的功能特性，与传统抗生素相比具有明显的优势。然而，AMPs的临床应用一直受到一些挑战的阻碍，包括体内不稳定性、安全性问题和体内疗效不一。为了克服这些限制，正在积极研究AMP设计和修改的创新方法，以及先进的输送系统。本文就抗菌肽的分类、结构特点和作用机制作一综述。强调了AMP设计和修改的最新进展，重点是旨在提高其治疗潜力的策略。此外，还讨论了抗菌肽的给药系统和配方策略的发展，重点是提高生物利用度、靶向分配和对抗耐药细菌感染的有效性。

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引用次数: 0