Biomolecules最新文献_第5页

Targeting APC/C Ubiquitin E3-Ligase Activation with Pyrimidinethylcarbamate Apcin Analogues for the Treatment of Breast Cancer. 用嘧啶基乙基氨基甲酸酯 Apcin 类似物靶向激活 APC/C 泛素 E3 连接酶治疗乳腺癌

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-11-12 DOI: 10.3390/biom14111439

Maria Kapanidou, Natalie L Curtis, Sandra S Diaz-Minguez, Sandra Agudo-Alvarez, Alfredo Rus Sanchez, Ammar Mayah, Rosette Agena, Paul Brennan, Paula Morales, Raul Benito-Arenas, Agatha Bastida, Victor M Bolanos-Garcia

{"title":"Targeting APC/C Ubiquitin E3-Ligase Activation with Pyrimidinethylcarbamate Apcin Analogues for the Treatment of Breast Cancer.","authors":"Maria Kapanidou, Natalie L Curtis, Sandra S Diaz-Minguez, Sandra Agudo-Alvarez, Alfredo Rus Sanchez, Ammar Mayah, Rosette Agena, Paul Brennan, Paula Morales, Raul Benito-Arenas, Agatha Bastida, Victor M Bolanos-Garcia","doi":"10.3390/biom14111439","DOIUrl":"10.3390/biom14111439","url":null,"abstract":"Activation of the ubiquitin ligase APC/C by the protein Cdc20 is an essential requirement for proper cell division in higher organisms, including humans. APC/C is the ultimate effector of the Spindle Assembly Checkpoint (SAC), the signalling system that monitors the proper attachment of chromosomes to microtubules during cell division. Defects in this process result in genome instability and cancer. Interfering with APC/C substrate ubiquitylation in cancer cells delays mitotic exit, which induces cell death. Therefore, impairing APC/C function represents an opportunity for the treatment of cancer and malignancies associated with SAC dysregulation. In this study, we report a new class of pyrimidinethylcarbamate apcin analogues that interfere with APC/C activity in 2D and 3D breast cancer cells. The new pyrimidinethylcarbamate apcin analogues exhibited higher cytotoxicity than apcin in all breast cancer cell subtypes investigated, with much lower cytotoxicity observed in fibroblasts and RPE-1 cells. Further molecular rationalisation of apcin and its derivatives was conducted using molecular docking studies. These structural modifications selected from the in silico studies provide a rational basis for the development of more potent chemotypes to treat highly aggressive breast cancer and possibly other aggressive tumour types of diverse tissue origins.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fasting as an Adjuvant Therapy for Cancer: Mechanism of Action and Clinical Practice. 禁食作为癌症的辅助疗法：作用机制与临床实践。

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-11-12 DOI: 10.3390/biom14111437

Yichun Xie, Huabin Ye, Zhongjun Liu, Zhiqing Liang, Jinrong Zhu, Rongxin Zhang, Yan Li

{"title":"Fasting as an Adjuvant Therapy for Cancer: Mechanism of Action and Clinical Practice.","authors":"Yichun Xie, Huabin Ye, Zhongjun Liu, Zhiqing Liang, Jinrong Zhu, Rongxin Zhang, Yan Li","doi":"10.3390/biom14111437","DOIUrl":"10.3390/biom14111437","url":null,"abstract":"The fundamental biological characteristics of tumor cells are characterized by irregularities in signaling and metabolic pathways, which are evident through increased glucose uptake, altered mitochondrial function, and the ability to evade growth signals. Interventions such as fasting or fasting-mimicking diets represent a promising strategy that can elicit distinct responses in normal cells compared to tumor cells. These dietary strategies can alter the circulating levels of various hormones and metabolites, including blood glucose, insulin, glucagon, growth hormone, insulin-like growth factor, glucocorticoids, and epinephrine, thereby potentially exerting an anticancer effect. Additionally, elevated levels of insulin-like growth factor-binding proteins and ketone bodies may increase tumor cells' dependence on their own metabolites, ultimately leading to their apoptosis. The combination of fasting or fasting-mimicking diets with radiotherapy or chemotherapeutic agents has demonstrated enhanced anticancer efficacy. This paper aims to classify fasting, elucidate the mechanisms that underlie its effects, assess its impact on various cancer types, and discuss its clinical applications. We will underscore the differential effects of fasting on normal and cancer cells, the mechanisms responsible for these effects, and the imperative for clinical implementation.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Organoids as Tools for Investigating Skin Aging: Mechanisms, Applications, and Insights. 有机体作为研究皮肤老化的工具：机制、应用和见解。

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-11-12 DOI: 10.3390/biom14111436

Xin-Yu Wang, Qian-Nan Jia, Jun Li, He-Yi Zheng

引用次数: 0

Biotechnological and Biomedical Applications of Enzymes Involved in the Synthesis of Nucleosides and Nucleotides-2nd Edition. 参与核苷和核苷酸合成的酶的生物技术和生物医学应用--第 2 版。

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-11-12 DOI: 10.3390/biom14111438

Jesús Fernández-Lucas

引用次数: 0

Differential Lipid Signatures of Lumbar and Cisternal Cerebrospinal Fluid. 腰椎和椎管内脑脊液的不同脂质特征

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-11-11 DOI: 10.3390/biom14111431

Trine L Toft-Bertelsen, Søren Norge Andreassen, Nicolas H Norager, Anja Hviid Simonsen, Steen Gregers Hasselbalch, Marianne Juhler, Nanna MacAulay

{"title":"Differential Lipid Signatures of Lumbar and Cisternal Cerebrospinal Fluid.","authors":"Trine L Toft-Bertelsen, Søren Norge Andreassen, Nicolas H Norager, Anja Hviid Simonsen, Steen Gregers Hasselbalch, Marianne Juhler, Nanna MacAulay","doi":"10.3390/biom14111431","DOIUrl":"10.3390/biom14111431","url":null,"abstract":"Background: The molecular composition of cerebrospinal fluid (CSF) is often used as a key indicator of biochemical alterations within distinct brain and spinal cord fluid compartments. The CSF protein content in lumbar CSF samples is widely employed as a biomarker matrix for diagnosing brain-related pathological conditions. CSF lipid profiles may serve as promising complementary diagnostics, but it remains unresolved if the lipid distribution is consistent along the neuroaxis.Methods: The lipid composition was determined with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) in cisternal CSF obtained from healthy subjects undergoing preventive surgery of an unruptured aneurism (n = 11) and lumbar CSF obtained from individuals referred for the clinical evaluation of cognitive dysfunction but subsequently cleared and deemed healthy (n = 19).Results: We reveal discernible variations in lipid composition along the neuroaxis, with a higher overall lipid concentration in cisternal CSF, although with different relative distributions of the various lipid classes in the two compartments. The cisternal CSF contained elevated levels of most lipid classes, e.g., sphingomyelins, lysophosphatidylcholines, plasmenylphosphatidylcholines, phosphatidic acids, and triacylglycerols, whereas a few select lipids from the classes of fatty acids, phosphatidylcholines, amides and plasmenylphosphatidylethanolamines were, oppositely, elevated in the lumbar CSF pool.Conclusions: The distinct lipid distribution along the neuroaxis illustrates that the molecular constituents in these two CSF compartments are not uniform. These findings emphasize the necessity of establishing a lumbar lipid index for the accurate interpretation of the cranial CSF lipid profile.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Loss of Sterol Biosynthesis in Economically Important Plant Pests and Pathogens: A Review of a Potential Target for Pest Control. 具有重要经济价值的植物害虫和病原体中甾醇生物合成的丧失：害虫控制的潜在目标回顾。

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-11-11 DOI: 10.3390/biom14111435

Paul Dahlin, Andrea Caroline Ruthes

{"title":"Loss of Sterol Biosynthesis in Economically Important Plant Pests and Pathogens: A Review of a Potential Target for Pest Control.","authors":"Paul Dahlin, Andrea Caroline Ruthes","doi":"10.3390/biom14111435","DOIUrl":"10.3390/biom14111435","url":null,"abstract":"Sterol biosynthesis is a crucial metabolic pathway in plants and various plant pathogens. Their vital physiological role in multicellular organisms and their effects on growth and reproduction underline their importance as membrane compounds, hormone precursors, and signaling molecules. Insects, nematodes, and oomycetes of the Peronosporales group, which harbor important agricultural pests and pathogens, have lost the ability to synthesize their own sterols. These organisms rely on the acquisition of sterols from their host and are dependent on the sterol composition of the host. It is thought that sterol-synthesizing enzymes were lost during co-evolution with the hosts, which provided the organisms with sufficient amounts of the required sterols. To meet the essential requirements of these organisms, some sterol auxotrophs retained a few remaining sterol-modifying enzymes. Several molecular and biochemical investigations have suggested promising avenues for pest and pathogen control by targeting host sterol composition, sterol uptake, or sterol modification in organisms that have lost the ability to biosynthesize sterol de novo. This review examines the loss of sterol biosynthesis de novo in insects, nematodes, and oomycetes with the aim of investigating the sterol metabolic constraints and sterol acquisition of these organisms. This will shed light on its potential as a control target for the management of sterol-dependent organisms in a comprehensive agronomic approach.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Estrogen Regulates Ca²⁺ to Promote Mitochondrial Function Through G-Protein-Coupled Estrogen Receptors During Oocyte Maturation. 雌激素在卵母细胞成熟过程中通过 G 蛋白偶联雌激素受体调节 Ca2+ 以促进线粒体功能

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-11-11 DOI: 10.3390/biom14111430

Qingyang Liu, Jingmei Li, Yanxue Li, Ming Cheng, Hui Zhang, Baohua Ma

{"title":"Estrogen Regulates Ca2+ to Promote Mitochondrial Function Through G-Protein-Coupled Estrogen Receptors During Oocyte Maturation.","authors":"Qingyang Liu, Jingmei Li, Yanxue Li, Ming Cheng, Hui Zhang, Baohua Ma","doi":"10.3390/biom14111430","DOIUrl":"10.3390/biom14111430","url":null,"abstract":"Estrogen is a steroid hormone that plays a key role in regulating many physiological processes, such as follicle activation and development and oocyte maturation in mammals. Ca2+ is crucial in oogenesis, oocyte maturation, ovulation, and fertilization. However, the mechanism by which estrogen regulates Ca2+ during oocyte maturation in mice has not been reported. This study revealed that Ca2+ levels in oocytes significantly increase during the 4-12 h period in vitro. Oocytes treated with 0.1 µM estrogen and 1 µM G1, a G-protein-coupled estrogen receptor (GPER) agonist, showed significantly increased Ca2+ levels, while treatment with 1 µM G15, an antagonist of GPER, significantly decreased Ca2+ levels. Notably, estrogen regulates Ca2+ in oocytes through the GPER pathway and promotes the expression of the Ca2+-producing protein EPAC1. In addition, estrogen alleviates the inhibitory effect of the Ca2+ chelator BAPTA-AM during oocyte maturation by promoting Ca2+ production. Furthermore, estrogen can promote the expression of the mitochondrial generation-associated protein SIRT1 through the GPER pathway, alleviate mitochondrial oxidative damage caused by BAPTA-AM, and restore the mitochondrial membrane potential level. Collectively, this study demonstrates that estrogen can regulate Ca2+ through the GPER-EPAC1 pathway and promote the expression of SIRT1, which promotes oocyte mitochondrial function during oocyte maturation.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preparation and Antibacterial Properties of Poly (l-Lactic Acid)-Oriented Microporous Materials. 以聚（l-乳酸）为导向的微孔材料的制备与抗菌特性

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-11-11 DOI: 10.3390/biom14111432

Yihong Li, Yanjun Feng, Qingyi Huang, Cenyi Luo, Wei Chen, Zhengqiu Li, Lei Liu, Jiafeng Li

引用次数: 0

Evaluation of the Efficacy of a Full-Spectrum Low-THC Cannabis Plant Extract Using In Vitro Models of Inflammation and Excitotoxicity. 利用炎症和兴奋毒性体外模型评估全谱低 THC 大麻植物提取物的功效。

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-11-11 DOI: 10.3390/biom14111434

Emily Ross-Munro, Esra Isikgel, Bobbi Fleiss

引用次数: 0

Unraveling the Immune Web: Advances in SMI Capsular Fibrosis from Molecular Insights to Preclinical Breakthroughs. 揭开免疫之网：从分子洞察到临床前突破的 SMI 囊性纤维化研究进展。

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-11-11 DOI: 10.3390/biom14111433

Ines Schoberleitner, Klaus Faserl, Michaela Lackner, Débora C Coraça-Huber, Angela Augustin, Anja Imsirovic, Stephan Sigl, Dolores Wolfram

{"title":"Unraveling the Immune Web: Advances in SMI Capsular Fibrosis from Molecular Insights to Preclinical Breakthroughs.","authors":"Ines Schoberleitner, Klaus Faserl, Michaela Lackner, Débora C Coraça-Huber, Angela Augustin, Anja Imsirovic, Stephan Sigl, Dolores Wolfram","doi":"10.3390/biom14111433","DOIUrl":"10.3390/biom14111433","url":null,"abstract":"Breast implant surgery has evolved significantly, yet challenges such as capsular contracture remain a persistent concern. This review presents an in-depth analysis of recent advancements in understanding the immune mechanisms and clinical implications associated with silicone mammary implants (SMIs). The article systematically examines the complex interplay between immune responses and capsular fibrosis, emphasizing the pathophysiological mechanisms of inflammation in the etiology of this fibrotic response. It discusses innovations in biomaterial science, including the development of novel anti-biofilm coatings and immunomodulatory surfaces designed to enhance implant integration and minimize complications. Emphasis is placed on personalized risk assessment strategies, leveraging molecular insights to tailor interventions and improve patient outcomes. Emerging therapeutic targets, advancements in surgical techniques, and the refinement of post-operative care are also explored. Despite notable progress, challenges such as the variability in immune responses, the long-term efficacy of new interventions, and ethical considerations remain. Future research directions are identified, focusing on personalized medicine, advanced biomaterials, and bridging preclinical findings with clinical applications. As we advance from bench to bedside, this review illuminates the path forward, where interdisciplinary collaboration and continued inquiry weave together to enhance the art and science of breast implant surgery, transforming patient care into a realm of precision and excellence.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0