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GLUT1 and prorenin receptor mediate differential regulation of TGF-β and CTGF in renal inner medullary collecting duct cells during high glucose conditions. GLUT1 和肾素受体介导了高糖条件下肾内髓集合管细胞对 TGF-β 和 CTGF 的不同调控。
IF 4.3 2区 生物学
Biological Research Pub Date : 2024-11-07 DOI: 10.1186/s40659-024-00560-8
Paulina E Larenas, Pilar Cárdenas, Monserrat Aguirre-Delgadillo, Carlos Moris, Dulce E Casarini, Zoe Vallotton, Minolfa C Prieto, Alexis A Gonzalez
{"title":"GLUT1 and prorenin receptor mediate differential regulation of TGF-β and CTGF in renal inner medullary collecting duct cells during high glucose conditions.","authors":"Paulina E Larenas, Pilar Cárdenas, Monserrat Aguirre-Delgadillo, Carlos Moris, Dulce E Casarini, Zoe Vallotton, Minolfa C Prieto, Alexis A Gonzalez","doi":"10.1186/s40659-024-00560-8","DOIUrl":"10.1186/s40659-024-00560-8","url":null,"abstract":"<p><strong>Background: </strong>During diabetes, prorenin is highly produced by the renal collecting ducts. The binding of prorenin to (pro)renin receptor (PRR) on the apical plasma membrane triggers intracellular profibrotic genes, including TGF-β and CTGF. However, the underlying mechanisms contributing to the stimulation of these pathways remain unclear. Hence, we hypothesize that the glucose transporter-1 (GLUT1) favors the PRR-dependent stimulation of TGF-β and CTGF in the distal nephron segments during high glucose (HG) conditions.</p><p><strong>Methods: </strong>To test this hypothesis, primary cultured renal inner medullary collecting duct (IMCD) cells were treated with normal glucose (NG, 5 mM) or high glucose (HG, 25 mM) for 48 h in the presence or absence of the GLUT1-specific inhibitor BAY 876 (2 nM). Additionally, IMCD cells were treated with the PRR antagonist PRO20. The expression of TGF-β and CTGF was quantified by immunoblot and qRT-PCR.</p><p><strong>Results: </strong>HG increased GLUT1 mRNA and protein abundance, while BAY 876 inhibited these responses. HG treatment upregulated PRR, but the concomitant treatment with BAY 876 partially prevented this effect. TGF-β and CTGF expressions were augmented in IMCD cells treated with HG. However, PRO20 prevented the increases in TGF-β but not those of CTGF. GLUT1 inhibition partially prevented the increases in reactive oxygen species (ROS) during HG while PRO20 did not. ROS scavenging impaired CTGF upregulation during HG conditions. Additionally, long-term exposure to HG increases lipid peroxidation and reduced cell viability.</p><p><strong>Conclusions: </strong>The data indicate that glucose transportation via GLUT1 is implicated in the PRR-dependent upregulation of TGF-β while CTGF is mediated mainly via a mechanism depending on ROS formation in renal medullary collecting duct cells.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"81"},"PeriodicalIF":4.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590092","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
Advances in genomic tools for plant breeding: harnessing DNA molecular markers, genomic selection, and genome editing. 用于植物育种的基因组工具的进展:利用 DNA 分子标记、基因组选择和基因组编辑。
IF 4.3 2区 生物学
Biological Research Pub Date : 2024-11-07 DOI: 10.1186/s40659-024-00562-6
Rahul Kumar, Sankar Prasad Das, Burhan Uddin Choudhury, Amit Kumar, Nitish Ranjan Prakash, Ramlakhan Verma, Mridul Chakraborti, Ayam Gangarani Devi, Bijoya Bhattacharjee, Rekha Das, Bapi Das, H Lembisana Devi, Biswajit Das, Santoshi Rawat, Vinay Kumar Mishra
{"title":"Advances in genomic tools for plant breeding: harnessing DNA molecular markers, genomic selection, and genome editing.","authors":"Rahul Kumar, Sankar Prasad Das, Burhan Uddin Choudhury, Amit Kumar, Nitish Ranjan Prakash, Ramlakhan Verma, Mridul Chakraborti, Ayam Gangarani Devi, Bijoya Bhattacharjee, Rekha Das, Bapi Das, H Lembisana Devi, Biswajit Das, Santoshi Rawat, Vinay Kumar Mishra","doi":"10.1186/s40659-024-00562-6","DOIUrl":"10.1186/s40659-024-00562-6","url":null,"abstract":"<p><p>Conventional pre-genomics breeding methodologies have significantly improved crop yields since the mid-twentieth century. Genomics provides breeders with advanced tools for whole-genome study, enabling a direct genotype-phenotype analysis. This shift has led to precise and efficient crop development through genomics-based approaches, including molecular markers, genomic selection, and genome editing. Molecular markers, such as SNPs, are crucial for identifying genomic regions linked to important traits, enhancing breeding accuracy and efficiency. Genomic resources viz. genetic markers, reference genomes, sequence and protein databases, transcriptomes, and gene expression profiles, are vital in plant breeding and aid in the identification of key traits, understanding genetic diversity, assist in genomic mapping, support marker-assisted selection and speeding up breeding programs. Advanced techniques like CRISPR/Cas9 allow precise gene modification, accelerating breeding processes. Key techniques like Genome-Wide Association study (GWAS), Marker-Assisted Selection (MAS), and Genomic Selection (GS) enable precise trait selection and prediction of breeding outcomes, improving crop yield, disease resistance, and stress tolerance. These tools are handy for complex traits influenced by multiple genes and environmental factors. This paper explores new genomic technologies like molecular markers, genomic selection, and genome editing for plant breeding showcasing their impact on developing new plant varieties.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"80"},"PeriodicalIF":4.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590087","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
The sodium/ascorbic acid co-transporter SVCT2 distributes in a striated membrane-enriched domain at the M-band level in slow-twitch skeletal muscle fibers. 钠/抗坏血酸共转运体 SVCT2 分布于慢肌骨骼肌纤维 M 带水平的横纹肌膜富集区。
IF 4.3 2区 生物学
Biological Research Pub Date : 2024-11-06 DOI: 10.1186/s40659-024-00554-6
Daniel Sandoval, Jessica Mella, Jorge Ojeda, Francisca Bermedo-García, Marcela Low, Sylvain Marcellini, Maite A Castro, Mariana Casas, Enrique Jaimovich, Juan Pablo Henríquez
{"title":"The sodium/ascorbic acid co-transporter SVCT2 distributes in a striated membrane-enriched domain at the M-band level in slow-twitch skeletal muscle fibers.","authors":"Daniel Sandoval, Jessica Mella, Jorge Ojeda, Francisca Bermedo-García, Marcela Low, Sylvain Marcellini, Maite A Castro, Mariana Casas, Enrique Jaimovich, Juan Pablo Henríquez","doi":"10.1186/s40659-024-00554-6","DOIUrl":"10.1186/s40659-024-00554-6","url":null,"abstract":"<p><strong>Background: </strong>Vitamin C plays key roles in cellular homeostasis, functioning as a potent antioxidant and a positive regulator of cell differentiation. In skeletal muscle, the vitamin C/sodium co-transporter SVCT2 is preferentially expressed in oxidative slow fibers. SVCT2 is up-regulated during the early fusion of primary myoblasts and decreases during initial myotube growth, indicating the relevance of vitamin C uptake via SVCT2 for early skeletal muscle differentiation and fiber-type definition. However, our understanding of SVCT2 expression and function in adult skeletal muscles is still limited.</p><p><strong>Results: </strong>In this study, we demonstrate that SVCT2 exhibits an intracellular distribution in chicken slow skeletal muscles, following a highly organized striated pattern. A similar distribution was observed in human muscle samples, chicken cultured myotubes, and isolated mouse myofibers. Immunohistochemical analyses, combined with biochemical cell fractionation experiments, reveal a strong co-localization of SVCT2 with intracellular detergent-soluble membrane fractions at the central sarcomeric M-band, where it co-solubilizes with sarcoplasmic reticulum proteins. Remarkably, electrical stimulation of cultured myofibers induces the redistribution of SVCT2 into a vesicular pattern.</p><p><strong>Conclusions: </strong>Our results provide novel insights into the dynamic roles of SVCT2 in different intracellular compartments in response to functional demands.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"79"},"PeriodicalIF":4.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590095","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
Increasing carotenoid production in Xanthophyllomyces dendrorhous/Phaffia rhodozyma: SREBP pathway activation and promoter engineering. 提高黄ophyllomyces dendrorhous/Phaffia rhodozyma 的类胡萝卜素产量:SREBP 通路激活和启动子工程。
IF 4.3 2区 生物学
Biological Research Pub Date : 2024-11-05 DOI: 10.1186/s40659-024-00559-1
Alejandro Durán, Maximiliano Venegas, Salvador Barahona, Dionisia Sepúlveda, Marcelo Baeza, Víctor Cifuentes, Jennifer Alcaíno
{"title":"Increasing carotenoid production in Xanthophyllomyces dendrorhous/Phaffia rhodozyma: SREBP pathway activation and promoter engineering.","authors":"Alejandro Durán, Maximiliano Venegas, Salvador Barahona, Dionisia Sepúlveda, Marcelo Baeza, Víctor Cifuentes, Jennifer Alcaíno","doi":"10.1186/s40659-024-00559-1","DOIUrl":"10.1186/s40659-024-00559-1","url":null,"abstract":"<p><p>The yeast Xanthophyllomyces dendrorhous synthesizes astaxanthin, a high-value carotenoid with biotechnological relevance in the nutraceutical and aquaculture industries. However, enhancing carotenoid production through strain engineering remains an ongoing challenge. Recent studies have demonstrated that carotenogenesis in X. dendrorhous is regulated by the SREBP pathway, which includes the transcription factor Sre1, particularly in the mevalonate pathway that also produces precursors used for ergosterol synthesis. In this study, we explored a novel approach to enhance carotenoid synthesis by replacing the native crtE promoter, which drives geranylgeranyl pyrophosphate synthesis (the step where carotenogenesis diverges from ergosterol biosynthesis), with the promoter of the HMGS gene, which encodes 3-hydroxy-3-methylglutaryl-CoA synthase from the mevalonate pathway. The impact of this substitution was evaluated in two mutant strains that already overproduce carotenoids due to the presence of an active Sre1 transcription factor: CBS.cyp61-, which does not produce ergosterol and strain CBS.SRE1N.FLAG, which constitutively expresses the active form of Sre1. Wild-type strain CBS6938 was used as a control. Our results showed that this modification increased the crtE transcript levels more than threefold and fourfold in CBS.cyp61<sup>-</sup>.pHMGS/crtE and CBS.SRE1N.FLAG.pHMGS/crtE, respectively, resulting in 1.43-fold and 1.22-fold increases in carotenoid production. In contrast, this modification did not produce significant changes in the wild-type strain, which lacks the active Sre1 transcription factor under the same culture conditions. This study highlights the potential of promoter substitution strategies involving genes regulated by Sre1 to enhance carotenoid production, specifically in strains where the SREBP pathway is activated, offering a promising avenue for strain improvement in industrial applications.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"78"},"PeriodicalIF":4.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575009","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
DLK1 and DLK2, two non-canonical ligands of NOTCH receptors, differentially modulate the osteogenic differentiation of mesenchymal C3H10T1/2 cells. NOTCH受体的两种非经典配体DLK1和DLK2对间充质C3H10T1/2细胞的成骨分化具有不同的调节作用。
IF 4.3 2区 生物学
Biological Research Pub Date : 2024-10-30 DOI: 10.1186/s40659-024-00561-7
María-Milagros Rodríguez-Cano, María-Julia González-Gómez, Eva-María Monsalve, María-José M Díaz-Guerra, Moustapha Kassem, Jorge Laborda, María-Luisa Nueda, Victoriano Baladrón
{"title":"DLK1 and DLK2, two non-canonical ligands of NOTCH receptors, differentially modulate the osteogenic differentiation of mesenchymal C3H10T1/2 cells.","authors":"María-Milagros Rodríguez-Cano, María-Julia González-Gómez, Eva-María Monsalve, María-José M Díaz-Guerra, Moustapha Kassem, Jorge Laborda, María-Luisa Nueda, Victoriano Baladrón","doi":"10.1186/s40659-024-00561-7","DOIUrl":"10.1186/s40659-024-00561-7","url":null,"abstract":"<p><strong>Background: </strong>C3H10T1/2 is a mesenchymal cell line capable of differentiating into osteoblasts, adipocytes and chondrocytes. The differentiation of these cells into osteoblasts is modulated by various transcription factors, such as RUNX2. Additionally, several interconnected signaling pathways, including the NOTCH pathway, play a crucial role in modulating their differentiation into mature bone cells. We have investigated the roles of DLK1 and DLK2, two non-canonical inhibitory ligands of NOTCH receptors, in the osteogenic differentiation of C3H10T1/2 cells.</p><p><strong>Results: </strong>Our results corroborate existing evidence that DLK1 acts as an inhibitor of osteogenesis. In contrast, we demonstrate for the first time that DLK2 enhances this differentiation process. Additionally, our data suggest that NOTCH2, 3 and 4 receptors may promote osteogenesis, as indicated by their increased expression during this process, whereas NOTCH1 expression, which decreases during cell differentiation, might inhibit osteogenesis. Moreover, treatment with DAPT, a NOTCH signaling inhibitor, impeded osteogenic differentiation. We have confirmed the increase in ERK1/2 MAPK and p38 MAPK phosphorylation in C3H10T1/2 cells induced to differentiate to osteoblasts. Our new findings reveal increased ERK1/2 MAPK phosphorylation in differentiated C3H10T1/2 cells with a decrease in DLK1 expression or an overexpression of DLK2, which is coincident with the behavior of those transfectants where we have detected an increase in osteogenic differentiation. Additionally, p38 MAPK phosphorylation increases in differentiated C3H10T1/2 cells with reduced DLK1 levels.</p><p><strong>Conclusions: </strong>Our results suggest that DLK1 may inhibit osteogenesis, while DLK2 may promote it, by modulating NOTCH signaling and the phosphorylation of ERK1/2 and p38 MAPK pathways. Given the established inhibitory effect of DLK proteins on NOTCH signaling, these new insights could pave the way for developing future therapeutic strategies aimed at treating bone diseases.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"77"},"PeriodicalIF":4.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543563","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
Landscape transcriptomic analysis of bovine follicular cells during key phases of ovarian follicular development. 在卵泡发育的关键阶段对牛卵泡细胞进行横向转录组分析。
IF 4.3 2区 生物学
Biological Research Pub Date : 2024-10-28 DOI: 10.1186/s40659-024-00558-2
Henry David Mogollón García, Rodrigo de Andrade Ferrazza, Julian Camilo Ochoa, Flávia Florencio de Athayde, Pedro Marcus Pereira Vidigal, Milo Wiltbank, John Patrick Kastelic, Roberto Sartori, João Carlos Pinheiro Ferreira
{"title":"Landscape transcriptomic analysis of bovine follicular cells during key phases of ovarian follicular development.","authors":"Henry David Mogollón García, Rodrigo de Andrade Ferrazza, Julian Camilo Ochoa, Flávia Florencio de Athayde, Pedro Marcus Pereira Vidigal, Milo Wiltbank, John Patrick Kastelic, Roberto Sartori, João Carlos Pinheiro Ferreira","doi":"10.1186/s40659-024-00558-2","DOIUrl":"10.1186/s40659-024-00558-2","url":null,"abstract":"<p><strong>Background: </strong>There are many gaps in our understanding of the mechanisms involved in ovarian follicular development in cattle, particularly regarding follicular deviation, acquisition of ovulatory capacity, and preovulatory changes. Molecular evaluations of ovarian follicular cells during follicular development in cattle, especially serial transcriptomic analyses across key growth phases, have not been reported. This study aims to address this gap by analyzing gene expression using RNA-seq in granulosa and antral cells recovered from ovarian follicular fluid during critical phases of ovarian follicular development in Holstein cows.</p><p><strong>Results: </strong>Integrated analysis of gene ontology (GO), gene set enrichment (GSEA), protein-protein interaction (PPI), and gene topology identified that differentially expressed genes (DEGs) in the largest ovarian follicles at deviation (Dev) were primarily involved in FSH-negative feedback, steroidogenesis, cell proliferation, apoptosis, and the prevention of early follicle rupture. In contrast, DEGs in the second largest follicles (DevF2) were mainly related to loss of cell viability, apoptosis, and immune cell invasion. In the dominant (PostDev) and preovulatory (PreOv) follicles, DEGs were associated with vascular changes and inflammatory responses.</p><p><strong>Conclusions: </strong>The transcriptome of ovarian follicular fluid cells had a predominance of granulosa cells in the dominant follicle at deviation, with upregulation of genes involved in cell viability, steroidogenesis, and apoptosis prevention, whereas in the non-selected follicle there was upregulation of cell death-related transcripts. Immune cell transcripts increased significantly after deviation, particularly in preovulatory follicles, indicating strong intrafollicular chemotactic activity. We inferred that immune cell invasion occurred despite an intact basal lamina, contributing to follicular maturation.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"76"},"PeriodicalIF":4.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521013","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
Enhancing late postmortem interval prediction: a pilot study integrating proteomics and machine learning to distinguish human bone remains over 15 years. 加强死后晚期间隔预测:一项将蛋白质组学和机器学习相结合的试点研究,以区分 15 年来的人类骨骼遗骸。
IF 4.3 2区 生物学
Biological Research Pub Date : 2024-10-24 DOI: 10.1186/s40659-024-00552-8
Camila Garcés-Parra, Pablo Saldivia, Mauricio Hernández, Elena Uribe, Juan Román, Marcela Torrejón, José L Gutiérrez, Guillermo Cabrera-Vives, María de Los Ángeles García-Robles, William Aguilar, Miguel Soto, Estefanía Tarifeño-Saldivia
{"title":"Enhancing late postmortem interval prediction: a pilot study integrating proteomics and machine learning to distinguish human bone remains over 15 years.","authors":"Camila Garcés-Parra, Pablo Saldivia, Mauricio Hernández, Elena Uribe, Juan Román, Marcela Torrejón, José L Gutiérrez, Guillermo Cabrera-Vives, María de Los Ángeles García-Robles, William Aguilar, Miguel Soto, Estefanía Tarifeño-Saldivia","doi":"10.1186/s40659-024-00552-8","DOIUrl":"10.1186/s40659-024-00552-8","url":null,"abstract":"<p><strong>Background: </strong>Determining the postmortem interval (PMI) accurately remains a significant challenge in forensic sciences, especially for intervals greater than 5 years (late PMI). Traditional methods often fail due to the extensive degradation of soft tissues, necessitating reliance on bone material examinations. The precision in estimating PMIs diminishes with time, particularly for intervals between 1 and 5 years, dropping to about 50% accuracy. This study aims to address this issue by identifying key protein biomarkers through proteomics and machine learning, ultimately enhancing the accuracy of PMI estimation for intervals exceeding 15 years.</p><p><strong>Methods: </strong>Proteomic analysis was conducted using LC-MS/MS on skeletal remains, specifically focusing on the tibia and ribs. Protein identification was performed using two strategies: a tryptic-specific search and a semitryptic search, the latter being particularly beneficial in cases of natural protein degradation. The Random Forest algorithm was used to model protein abundance data, enabling the prediction of PMI. A thorough screening process, combining importance scores and SHAP values, was employed to identify the most informative proteins for model's training and accuracy.</p><p><strong>Results: </strong>A minimal set of three biomarkers-K1C13, PGS1, and CO3A1-was identified, significantly improving the prediction accuracy between PMIs of 15 and 20 years. The model, based on protein abundance data from semitryptic peptides in tibia samples, achieved sustained 100% accuracy across 100 iterations. In contrast, non-supervised methods like PCA and MCA did not yield comparable results. Additionally, the use of semitryptic peptides outperformed tryptic peptides, particularly in tibia proteomes, suggesting their potential reliability in late PMI prediction.</p><p><strong>Conclusions: </strong>Despite limitations such as sample size and PMI range, this study demonstrates the feasibility of combining proteomics and machine learning for accurate late PMI predictions. Future research should focus on broader PMI ranges and various bone types to further refine and standardize forensic proteomic methodologies for PMI estimation.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"75"},"PeriodicalIF":4.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494940","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
Cisplatin-resistance and aggressiveness are enhanced by a highly stable endothelin-converting enzyme-1c in lung cancer cells. 高度稳定的内皮素转换酶-1c增强了肺癌细胞对顺铂的耐药性和侵袭性。
IF 4.3 2区 生物学
Biological Research Pub Date : 2024-10-24 DOI: 10.1186/s40659-024-00551-9
Cristopher Almarza, Karla Villalobos-Nova, María A Toro, Manuel González, Ignacio Niechi, David A Brown-Brown, Rodrigo A López-Muñoz, Eduardo Silva-Pavez, Belén Gaete-Ramírez, Manuel Varas-Godoy, Verónica A Burzio, Lilian Jara, Francisco Aguayo, Julio C Tapia
{"title":"Cisplatin-resistance and aggressiveness are enhanced by a highly stable endothelin-converting enzyme-1c in lung cancer cells.","authors":"Cristopher Almarza, Karla Villalobos-Nova, María A Toro, Manuel González, Ignacio Niechi, David A Brown-Brown, Rodrigo A López-Muñoz, Eduardo Silva-Pavez, Belén Gaete-Ramírez, Manuel Varas-Godoy, Verónica A Burzio, Lilian Jara, Francisco Aguayo, Julio C Tapia","doi":"10.1186/s40659-024-00551-9","DOIUrl":"10.1186/s40659-024-00551-9","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Lung cancer constitutes the leading cause of cancer mortality. High levels of endothelin-1 (ET-1), its cognate receptor ET&lt;sub&gt;A&lt;/sub&gt;R and its activating enzyme, the endothelin-converting enzyme-1 (ECE-1), have been reported in several cancer types, including lung cancer. ECE-1 comprises four isoforms, which only differ in their cytoplasmic N-terminus. Protein kinase CK2 phosphorylates the N-terminus of isoform ECE-1c, increasing its stability and leading to enhanced invasiveness in glioblastoma and colorectal cancer cells, which is believed to be mediated by the amino acid residue Lys-6, a conserved putative ubiquitination site neighboring the CK2-phosphorylated residues Ser-18 and Ser-20. Whether Lys-6 is linked to the acquisition of a cancer stem cell (CSC)-like phenotype and aggressiveness in human non-small cell lung cancer (NSCLC) cells has not been studied.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In order to establish the role of Lys-6 in the stability of ECE-1c and its involvement in lung cancer aggressiveness, we mutated this residue to a non-ubiquitinable arginine and constitutively expressed the wild-type (ECE-1c&lt;sup&gt;WT&lt;/sup&gt;) and mutant (ECE-1c&lt;sup&gt;K6R&lt;/sup&gt;) proteins in A549 and H1299 human NSCLC cells by lentiviral transduction. We determined the protein stability of these clones alone or in the presence of the CK2 inhibitor silmitasertib, compared to ECE-1c&lt;sup&gt;WT&lt;/sup&gt; and mock-transduced cells. In addition, the concentration of secreted ET-1 in the growth media was determined by ELISA. Expression of stemness genes were determined by Western blot and RT-qPCR. Chemoresistance to cisplatin was studied by MTS viability assay. Migration and invasion were measured through transwell and Matrigel assays, respectively, and the side-population was determined using flow cytometry.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;ECE-1c&lt;sup&gt;K6R&lt;/sup&gt; displayed higher stability in NSCLC cells compared to ECE-1c&lt;sup&gt;WT&lt;/sup&gt;-expressing cells, but ET-1 secreted levels showed no difference up to 48 h. Most importantly, ECE-1c&lt;sup&gt;K6R&lt;/sup&gt; promoted expression of the stemness genes c-Myc, Sox-2, Oct-4, CD44 and CD133, which enhance cellular self-renewal capability. Also, the ECE-1c&lt;sup&gt;K6R&lt;/sup&gt;-expressing cells showed higher cisplatin chemoresistance, correlating with an augmented side-population abundance due to the increased expression of the ABCG2 efflux pump. Finally, the ECE-1c&lt;sup&gt;K6R&lt;/sup&gt;-expressing cells showed enhanced invasiveness, which correlated with the regulated expression of known EMT markers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Our findings suggest an important role of ECE-1c in lung cancer. ECE-1c is key in a non-canonical ET-1-independent mechanism which triggers a CSC-like phenotype, leading to enhanced lung cancer aggressiveness. Underlying this mechanism, ECE-1c is stabilized upon phosphorylation by CK2, which is upregulated in many cancers. Thus, phospho-ECE-1c may be considered as a novel prognostic biomarker of ","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"74"},"PeriodicalIF":4.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494939","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
Oviduct epithelial spheroids during in vitro culture of bovine embryos mitigate oxidative stress, improve blastocyst quality and change the embryonic transcriptome. 牛胚胎体外培养过程中的输卵管上皮细胞球减轻氧化应激、提高囊胚质量并改变胚胎转录组。
IF 4.3 2区 生物学
Biological Research Pub Date : 2024-10-22 DOI: 10.1186/s40659-024-00555-5
Thanya Pranomphon, Álvaro López-Valiñas, Carmen Almiñana, Coline Mahé, Viviane Lopes Brair, Rangsun Parnpai, Pascal Mermillod, Stefan Bauersachs, Marie Saint-Dizier
{"title":"Oviduct epithelial spheroids during in vitro culture of bovine embryos mitigate oxidative stress, improve blastocyst quality and change the embryonic transcriptome.","authors":"Thanya Pranomphon, Álvaro López-Valiñas, Carmen Almiñana, Coline Mahé, Viviane Lopes Brair, Rangsun Parnpai, Pascal Mermillod, Stefan Bauersachs, Marie Saint-Dizier","doi":"10.1186/s40659-024-00555-5","DOIUrl":"https://doi.org/10.1186/s40659-024-00555-5","url":null,"abstract":"<p><strong>Background: </strong>In vitro embryo production is increasingly used for genetic improvement in cattle but bypasses the oviduct environment and exposes the embryos to oxidative stress with deleterious effects on further development. Here we aimed to examine the effect of oviduct epithelial spheroids (OES) on embryo development and quality in terms of morphology and gene expression during two co-culture times (4 days: up to embryonic genome activation at 8-16 cell stage vs. 7 days: up to blastocyst stage) and under two oxygen levels (5% vs. 20%).</p><p><strong>Methods: </strong>Bovine presumptive zygotes produced by in vitro fertilization (day 0) using in-vitro matured oocytes were cultured in droplets of synthetic oviductal fluid (SOF) medium with or without (controls) OES for 4 or 7 days under 5% or 20% oxygen (4 treated and 2 control groups). Cleavage rates were evaluated on day 2 and blastocyst rates on days 7-8. Expanded blastocysts on days 7-8 were evaluated for total cell numbers and gene expression analysis by RNA-sequencing.</p><p><strong>Results: </strong>Under 20% oxygen, blastocyst rates and total cell numbers were significantly higher in the presence of OES for 4 and 7 days compared to controls (P < 0.05), with no difference according to the co-culture time. Under 5% oxygen, the presence of OES did not affect blastocyst rates but increased the number of cells per blastocyst after 7 days of co-culture (P < 0.05). Both oxygen level and OES co-culture had a significant impact on the embryonic transcriptome. The highest number of differentially expressed genes (DEGs) was identified after 7 days of co-culture under 20% oxygen. DEGs were involved in a wide range of functions, including lipid metabolism, membrane organization, response to external signals, early embryo development, and transport of small molecules among the most significantly impacted.</p><p><strong>Conclusion: </strong>OES had beneficial effects on embryo development and quality under both 5% and 20% oxygen, mitigating oxidative stress. Stronger effects on embryo quality and transcriptome were obtained after 7 than 4 days of co-culture. This study shows the impact of OES on embryo development and reveals potential molecular targets of OES-embryo dialog involved in response to stress and early embryonic development.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"73"},"PeriodicalIF":4.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494941","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
H Antigen expression modulates epidermal Keratinocyte Integrity and differentiation. H 抗原表达调节表皮角质细胞的完整性和分化。
IF 4.3 2区 生物学
Biological Research Pub Date : 2024-10-18 DOI: 10.1186/s40659-024-00541-x
Seon-Pil Jin, Jang-Hee Oh, Namjoo Kaylee Kim, Jin Ho Chung
{"title":"H Antigen expression modulates epidermal Keratinocyte Integrity and differentiation.","authors":"Seon-Pil Jin, Jang-Hee Oh, Namjoo Kaylee Kim, Jin Ho Chung","doi":"10.1186/s40659-024-00541-x","DOIUrl":"https://doi.org/10.1186/s40659-024-00541-x","url":null,"abstract":"<p><strong>Background: </strong>ABO blood group antigens (ABH antigens) are carbohydrate chains glycosylated on epithelial and red blood cells. Recent findings suggest reduced ABH expression in psoriasis and atopic dermatitis, a chronic inflammatory skin disease with retained scale. H antigen, a precursor for A and B antigens, is synthesized by fucosyltransferase 1 (FUT1). Desmosomes, critical for skin integrity, are known to require N-glycosylation for stability. We investigate the impact of H antigens, a specific type of glycosylation, on desmosomes in keratinocytes.</p><p><strong>Method: </strong>Primary human keratinocytes were transfected with FUT1 siRNA or recombinant adenovirus for FUT1 overexpression. Cell adhesion and desmosome characteristics and their underlying mechanisms were analyzed.</p><p><strong>Result: </strong>The knockdown of FUT1, responsible for H2 antigen expression in the skin, increased cell-cell adhesive strength and desmosome size in primary cultured keratinocytes without altering the overall desmosome structure. Desmosomal proteins, including desmogleins or plakophilin, were upregulated, suggesting enhanced desmosome assembly. Reduced H2 antigen expression via FUT1 knockdown led to increased keratinocyte differentiation, evidenced by elevated expression of differentiation markers. Epidermal growth factor receptor (EGFR) has been described to be associated with FUT1 and promotes cell migration and differentiation. The effects of FUT1 knockdown were recapitulated by an EGFR inhibitor concerning desmosomal proteins and cellular differentiation. Further investigation demonstrated that the FUT1 knockdown reduced EGFR signaling by lowering the levels of EGF ligands rather than directly regulating EGFR activity. Moreover, FUT1 overexpression reversed the effects observed in FUT1 knockdown, resulting in the downregulation of desmosomal proteins and differentiation markers while increasing both mRNA and protein levels of EGFR ligands.</p><p><strong>Conclusion: </strong>The expression level of FUT1 in the epidermis appears to influence cell-cell adhesion and keratinocyte differentiation status, at least partly through regulation of H2 antigen and EGFR ligand expression. These observations imply that the fucosylation of the H2 antigen by FUT1 could play a significant role in maintaining the molecular composition and regulation of desmosomes and suggest a possible involvement of the altered H2 antigen expression in skin diseases, such as psoriasis and atopic dermatitis.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"72"},"PeriodicalIF":4.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457896","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
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