Frontiers in Molecular Biosciences最新文献

筛选
英文 中文
First-trimester metabolic profiling of gestational diabetes mellitus: insights into early-onset and late-onset cases compared with healthy controls.
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2025-01-15 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1452312
Danuta Dudzik, Vangeliya Atanasova, Coral Barbas, Jose Luis Bartha
{"title":"First-trimester metabolic profiling of gestational diabetes mellitus: insights into early-onset and late-onset cases compared with healthy controls.","authors":"Danuta Dudzik, Vangeliya Atanasova, Coral Barbas, Jose Luis Bartha","doi":"10.3389/fmolb.2024.1452312","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1452312","url":null,"abstract":"<p><strong>Introduction: </strong>Gestational diabetes mellitus (GDM) is a global health concern with significant short and long-term complications for both mother and baby. Early prediction of GDM, particularly late-onset, is crucial for implementing timely interventions to mitigate adverse outcomes. In this study, we conducted a comprehensive metabolomic analysis to explore potential biomarkers for early GDM prediction.</p><p><strong>Methods: </strong>Plasma samples were collected during the first trimester from 60 women: 20 with early-onset GDM, 20 with late-onset GDM, and 20 with normal glucose tolerance. Using advanced analytical techniques, including liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS), we profiled over 150 lipid species and central carbon metabolism intermediates.</p><p><strong>Results: </strong>Significant metabolic alterations were observed in both early- and late-onset GDM groups compared to healthy controls, with a specific focus on glycerolipids, fatty acids, and glucose metabolism. Key findings revealed a 4.0-fold increase in TG(44:0), TG(46:0), TG(46:1) with <i>p</i>-values <0.001 and TG(46:2) with 4.7-fold increase and <i>p</i>-value <0.0001 as well as changes in several phospholipids as PC(38:3), PC(40:4) with 1.4-fold increase, <i>p</i> < 0.001 and PE(34:1), PE(34:2) and PE(36:2) with 1.5-fold change, <i>p</i> < 0.001 in late-onset GDM.</p><p><strong>Discussion: </strong>Observed lipid changes highlight disruptions in energy metabolism and inflammatory pathways. It is suggested that lipid profiles with distinct fatty acid chain lengths and degrees of unsaturation can serve as early biomarkers of GDM risk. These findings underline the importance of integrating metabolomic insights with clinical data to develop predictive models for GDM. Such models could enable early risk stratification, allowing for timely dietary, lifestyle, or medical interventions aimed at optimizing glucose regulation and preventing complications such as preeclampsia, macrosomia, and neonatal metabolic disorders. By focusing on metabolic disruptions evident in the first trimester, this approach addresses a critical window for improving maternal and fetal outcomes. Our study demonstrates the value of metabolomics in understanding the metabolic perturbations associated with GDM. Future research is needed to validate these biomarkers in larger cohorts and assess their integration into clinical workflows for personalized pregnancy care.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1452312"},"PeriodicalIF":3.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Enhanced intestinal epithelial co-culture model with orbital mechanical stimulation: a proof-of-concept application in food nanotoxicology.
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2025-01-13 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1529027
Mattia Santoni, Giovanni Piccinini, Giovanni Liguori, Maria Roberta Randi, Massimo Baroncini, Liliana Milani, Francesca Danesi
{"title":"Enhanced intestinal epithelial co-culture model with orbital mechanical stimulation: a proof-of-concept application in food nanotoxicology.","authors":"Mattia Santoni, Giovanni Piccinini, Giovanni Liguori, Maria Roberta Randi, Massimo Baroncini, Liliana Milani, Francesca Danesi","doi":"10.3389/fmolb.2024.1529027","DOIUrl":"10.3389/fmolb.2024.1529027","url":null,"abstract":"<p><strong>Introduction: </strong>Current <i>in vitro</i> intestinal models lack the mechanical forces present in the physiological environment, limiting their reliability for nanotoxicology studies. Here, we developed an enhanced Caco-2/HT29-MTX-E12 co-culture model incorporating orbital mechanical stimulation to better replicate intestinal conditions and investigate nanoparticle interactions.</p><p><strong>Methods: </strong>We established co-cultures under static and dynamic conditions, evaluating their development through multiple approaches including barrier integrity measurements, gene expression analysis, and confocal microscopy. We introduced novel quantitative analysis of dome formation as a differentiation marker and demonstrated the model application by investigating cellular responses to titanium dioxide (TiO₂) nanoparticles in a digested food matrix.</p><p><strong>Results: </strong>Dynamic conditions accelerated epithelial differentiation, achieving functional barrier properties by day 14 rather than day 21, with enhanced mucin production and more organized three-dimensional structure. Mechanical stimulation selectively promoted goblet cell differentiation without affecting general epithelial markers. The optimized model successfully detected concentration-dependent oxidative stress responses to TiO₂ exposure, revealing cellular dysfunction preceding membrane damage.</p><p><strong>Discussion: </strong>This improved co-culture system provides a better physiological platform for nanotoxicology studies. By incorporating mechanical forces, each cell type exhibits more representative behavior, creating a more realistic experimental setup. The model bridges the gap between simple monocultures and complex 3D systems, offering a practical approach for investigating nanoparticle-epithelium interactions in a food-relevant context.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1529027"},"PeriodicalIF":3.9,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Metabolomics insights into doxorubicin and 5-fluorouracil combination therapy in triple-negative breast cancer: a xenograft mouse model study.
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2025-01-13 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1517289
Mai M Hassanein, Yousra A Hagyousif, Ruba A Zenati, Hamza M Al-Hroub, Farman Matloob Khan, Ahmad Y Abuhelwa, Karem H Alzoubi, Nelson C Soares, Waseem El-Huneidi, Eman Abu-Gharbieh, Hany Omar, Dana M Zaher, Yasser Bustanji, Mohammad H Semreen
{"title":"Metabolomics insights into doxorubicin and 5-fluorouracil combination therapy in triple-negative breast cancer: a xenograft mouse model study.","authors":"Mai M Hassanein, Yousra A Hagyousif, Ruba A Zenati, Hamza M Al-Hroub, Farman Matloob Khan, Ahmad Y Abuhelwa, Karem H Alzoubi, Nelson C Soares, Waseem El-Huneidi, Eman Abu-Gharbieh, Hany Omar, Dana M Zaher, Yasser Bustanji, Mohammad H Semreen","doi":"10.3389/fmolb.2024.1517289","DOIUrl":"10.3389/fmolb.2024.1517289","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is one of the most prevalent malignancies and a leading cause of death among women worldwide. Among its subtypes, triple-negative breast cancer (TNBC) poses significant clinical challenges due to its aggressive behavior and limited treatment options. This study aimed to investigate the effects of doxorubicin (DOX) and 5-fluorouracil (5-FU) as monotherapies and in combination using an established MDA-MB-231 xenograft model in female BALB/C nude mice employing advanced metabolomics analysis to identify molecular alterations induced by these treatments.</p><p><strong>Methods: </strong>We conducted comprehensive plasma and tumor tissue sample profiling using ultra-high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS).</p><p><strong>Results: </strong>Each treatment group exhibited unique metabolic profiles in plasma and tumor analysis. Univariate and enrichment analyses identified alterations in metabolic pathways. The combination treatment of DOX + 5-FU induced the most extensive metabolic alterations disrupting key pathways including purine, pyrimidine, beta-alanine, and sphingolipid metabolism. It significantly reduced critical metabolites such as guanine, xanthine, inosine, L-fucose, and sphinganine, demonstrating enhanced cytotoxic effects compared to individual treatments. The DOX treatment uniquely increased ornithine levels, while 5-FU altered sphingolipid metabolism, promoting apoptosis.</p><p><strong>Significance: </strong>This <i>in vivo</i> study highlights TNBC's metabolic alterations to chemotherapeutics, identifying potential biomarkers like L-fucose and beta-alanine, and provides insights for improving treatment strategies.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1517289"},"PeriodicalIF":3.9,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Identification of crucial pathways and genes linked to endoplasmic reticulum stress in PCOS through combined bioinformatic analysis.
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2025-01-09 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1504015
Yan Zhang, Xiujuan Chen, Yuan Lin, Xiaoqing Liu, Xiumei Xiong
{"title":"Identification of crucial pathways and genes linked to endoplasmic reticulum stress in PCOS through combined bioinformatic analysis.","authors":"Yan Zhang, Xiujuan Chen, Yuan Lin, Xiaoqing Liu, Xiumei Xiong","doi":"10.3389/fmolb.2024.1504015","DOIUrl":"10.3389/fmolb.2024.1504015","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic condition impacting millions of women worldwide. This study sought to identify granulosa cell endoplasmic reticulum stress (GCERS)-related differentially expressed genes (DEGs) between women with PCOS and those without PCOS using bioinformatics and to investigate the related molecular mechanisms.</p><p><strong>Methods: </strong>Two datasets were downloaded from GEO and analysed using the limma package to identify DEGs in two groups-PCOS and normal granulosa cells. Enrichment analyses, including GO, KEGG, and GSEA, were then conducted on the DEGs. Differential immune infiltration was assessed using CIBERSORT and correlations with immune cell biomarkers were evaluated. Networks for protein-protein interactions, transcription factor-target genes, miRNA-target genes, and drug-target genes were constructed and visualized using Cytoscape to identify key hub gene nodes. Finally, key genes were analysed for differential expression and correlated.</p><p><strong>Results: </strong>Overall, 127 co-DEGs were identified in the two datasets. Our study revealed that these DEGs were primarily associated with cell cycle arrest, p53-mediated signal transduction, drug response, and gland development, with molecular functions enriched in growth factor binding, collagen binding, and receptor protein kinase activity. GSEA revealed that the co-DEGs were primarily associated with immune and inflammatory pathways. Eleven hub genes-<i>MMP9</i>, <i>SPI1</i>, <i>IGF2R</i>, <i>GPBAR1</i>, <i>PDGFA</i>, <i>BMPR1A</i>, <i>LIFR</i>, <i>PRKAA1</i>, <i>MSH2</i>, <i>CDC25C</i>, and <i>KCNH2</i>-were identified through the PPI, TF target genes, miRNA target genes, and drug target gene networks.</p><p><strong>Conclusion: </strong>We identified several crucial genes and pathways linked to the onset and development of PCOS. Our findings offer a clear connection between PCOS and GCERS, clarify the molecular mechanisms driving PCOS progression, and offer new perspectives for discovering valuable therapeutic targets and potential biomarkers for the condition.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1504015"},"PeriodicalIF":3.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Recent advances of lysine lactylation in prokaryotes and eukaryotes.
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2025-01-09 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1510975
Wenjuan Zhao, Jiayi Xin, Xin Yu, Zhifang Li, Nan Li
{"title":"Recent advances of lysine lactylation in prokaryotes and eukaryotes.","authors":"Wenjuan Zhao, Jiayi Xin, Xin Yu, Zhifang Li, Nan Li","doi":"10.3389/fmolb.2024.1510975","DOIUrl":"10.3389/fmolb.2024.1510975","url":null,"abstract":"<p><p>Lysine lactylation is a newly discovered protein post-translational modification that plays regulatory roles in cell metabolism, growth, reprogramming, and tumor progression. It utilizes lactate as the modification precursor, which is an end product of glycolysis while functioning as a signaling molecule in cells. Unlike previous reviews focused primarily on eukaryotes, this review aims to provide a comprehensive summary of recent knowledge about lysine lactylation in prokaryotes and eukaryotes. The current identification and enrichment strategies for lysine lactylation are introduced, and the known readers, writers, and erasers of this modification are summarized. In addition, the physiological and pathological implications of lysine lactylation are reviewed for different organisms, especially in prokaryotic cells. Finally, we end with a discussion of the limitations of the studies so far and propose future directions for lysine lactylation investigations.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1510975"},"PeriodicalIF":3.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Dissecting the biophysical mechanisms of oleate hydratase association with membranes.
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2025-01-08 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1504373
William A Lathram, Robert J Neff, Ashley N Zalla, James D Brien, Vivekanandan Subramanian, Christopher D Radka
{"title":"Dissecting the biophysical mechanisms of oleate hydratase association with membranes.","authors":"William A Lathram, Robert J Neff, Ashley N Zalla, James D Brien, Vivekanandan Subramanian, Christopher D Radka","doi":"10.3389/fmolb.2024.1504373","DOIUrl":"10.3389/fmolb.2024.1504373","url":null,"abstract":"<p><p>This study investigates the dynamics of oleate hydratase (OhyA), a bacterial flavoenzyme from <i>Staphylococcus aureus</i>, and its interactions with lipid membranes, focusing on the factors influencing membrane binding and oligomerization. OhyA catalyzes the hydration of unsaturated fatty acids, playing a key role in bacterial pathogenesis by neutralizing host antimicrobial fatty acids. OhyA binds the membrane bilayer to access membrane-embedded substrates for catalysis, and structural studies have revealed that OhyA forms oligomers on membrane surfaces, stabilized by both protein-protein and protein-lipid interactions. Using fluorescence correlation spectroscopy (FCS), we examined the effects of membrane curvature and lipid availability on OhyA binding to phosphatidylglycerol unilamellar vesicles. Our results reveal that OhyA preferentially binds to vesicles with moderate curvature, while the presence of substrate fatty acids slightly enhanced the overall interaction despite reducing the binding affinity by 3- to 4-fold. Complementary phosphorus-31 (<sup>31</sup>P) NMR spectroscopy further demonstrated two distinct binding modes: a fast-exchange interaction at lower protein concentrations and a longer lasting interaction at higher protein concentrations, likely reflecting cooperative oligomerization. These findings highlight the reversible, non-stoichiometric nature of OhyA•membrane interactions, with dynamic binding behaviors influenced by protein concentration and lipid environment. This research provides new insights into the dynamic behavior of OhyA on bacterial membranes, highlighting that initial interactions are driven by lipid-mediated protein binding, while sustained interactions are primarily governed by the protein:lipid molar ratio rather than the formation of new, specific lipid-protein interactions. These findings advance our understanding of the biophysical principles underlying OhyA's role in bacterial membrane function and virulence.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1504373"},"PeriodicalIF":3.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Artificial molecular motors in biological applications.
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2025-01-08 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1510619
Fuli Fan, Songshen Liu, Yuting Yan, Peng Zhang, Kui Che
{"title":"Artificial molecular motors in biological applications.","authors":"Fuli Fan, Songshen Liu, Yuting Yan, Peng Zhang, Kui Che","doi":"10.3389/fmolb.2024.1510619","DOIUrl":"10.3389/fmolb.2024.1510619","url":null,"abstract":"<p><p>Molecular motors are the cornerstone for the maintenance of living systems and mediate almost all fundamental processes involved in cellular trafficking. The intricate mechanisms underlying natural molecular motors have been elucidated in detail, inspiring researchers in various fields to construct artificial systems with multi-domain applications. This review summarises the characteristics of molecular motors, biomimetic approaches for their design and operation, and recent biological applications.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1510619"},"PeriodicalIF":3.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Deciphering olfactory receptor binding mechanisms: a structural and dynamic perspective on olfactory receptors.
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2025-01-08 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1498796
Jingtao Wang, Qidong Zhang, Wu Fan, Qingzhao Shi, Jian Mao, Jianping Xie, Guobi Chai, Chenglei Zhang
{"title":"Deciphering olfactory receptor binding mechanisms: a structural and dynamic perspective on olfactory receptors.","authors":"Jingtao Wang, Qidong Zhang, Wu Fan, Qingzhao Shi, Jian Mao, Jianping Xie, Guobi Chai, Chenglei Zhang","doi":"10.3389/fmolb.2024.1498796","DOIUrl":"10.3389/fmolb.2024.1498796","url":null,"abstract":"<p><p>Olfactory receptors, classified as G-protein coupled receptors (GPCRs), have been a subject of scientific inquiry since the early 1950s. Historically, investigations into the sensory mechanisms of olfactory receptors were often confined to behavioral characteristics in model organisms or the expression of related proteins and genes. However, with the development of cryo-electron microscopy techniques, it has gradually become possible to decipher the specific structures of olfactory receptors in insects and humans. This has provided new insights into the binding mechanisms between odor molecules and olfactory receptors. Furthermore, due to the rapid advancements in related fields such as computer simulations, the prediction and exploration of odor molecule binding to olfactory receptors have been progressively achieved through molecular dynamics simulations. Through this comprehensive review, we aim to provide a thorough analysis of research related to the binding mechanisms between odor molecules and olfactory receptors from the perspectives of structural biology and molecular dynamics simulations. Finally, we will provide an outlook on the future of research in the field of olfactory receptor sensory mechanisms.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1498796"},"PeriodicalIF":3.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 N17 domain of huntingtin as a multifaceted player in Huntington's disease.
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2025-01-07 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1527313
Hyunju Cho
{"title":"The N17 domain of huntingtin as a multifaceted player in Huntington's disease.","authors":"Hyunju Cho","doi":"10.3389/fmolb.2024.1527313","DOIUrl":"10.3389/fmolb.2024.1527313","url":null,"abstract":"<p><p>Huntington's disease (HD) is primarily caused by the aberrant aggregation of the N-terminal exon 1 fragment of mutant huntingtin protein (mHttex1) with expanded polyglutamine (polyQ) repeats in neurons. The first 17 amino acids of the N-terminus of Httex1 (N17 domain) immediately preceding the polyQ repeat domain are evolutionarily conserved across vertebrates and play multifaceted roles in the pathogenesis of HD. Due to its amphipathic helical properties, the N17 domain, both alone and when membrane-associated, promotes mHttEx1 aggregation. Diverse post-translational modifications (PTMs) in the N17 domain alter the aggregation state, thus modulating the cellular toxicity of mHttex1. Furthermore, the N17 domain serves as a nuclear export signal (NES) and mediates the cytoplasmic localization of mHttex1. This review summarizes the four main roles of the N17 domain in regulating HD pathology and discusses potential therapeutic approaches targeting this N17 domain to mitigate HD progression.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1527313"},"PeriodicalIF":3.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Anticarcinogenic cationic peptides derived from tryptic hydrolysis of β-lactoglobulin.
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2025-01-07 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1444457
Eman Ibrahem, Ali Osman, Hefnawy Taha, Mohamed F Abo El-Maati, Basel Sitohy, Mahmoud Sitohy
{"title":"Anticarcinogenic cationic peptides derived from tryptic hydrolysis of β-lactoglobulin.","authors":"Eman Ibrahem, Ali Osman, Hefnawy Taha, Mohamed F Abo El-Maati, Basel Sitohy, Mahmoud Sitohy","doi":"10.3389/fmolb.2024.1444457","DOIUrl":"10.3389/fmolb.2024.1444457","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigated the tryptic hydrolysis of β-lactoglobulin (BLG) for 30, 60, 90, and 120 min at 1/200 E/S (enzyme/substrate ratio, w/w) to prepare potentially anticarcinogenic peptides.</p><p><strong>Methods: </strong>The properties of hydrolysates were characterized, including degree of hydrolysis, free amino acids, SDS-PAGE, FTIR, and antioxidant activity employing DPPH-assay, β-carotene/linoleic acid, and FRAP assay.</p><p><strong>Results: </strong>BLG tryptic hydrolysate produced after 60 min hydrolysis recorded the highest antioxidant activity, and LCMS analysis revealed 162 peptides of molecular masses ranging from 800 to 5671Da, most of them are of hydrophobic nature. Within the low-MW peptide group (24 peptides), there were nine hydrophobic basic (HB) and seven hydrophobic acidic (HA), representing 38% and 29%, respectively. The HB peptides may be responsible for the considerable biological activity of the hydrolysate. With dominant basic character supporting the carcinogenic activity of this hydrolysate. The <i>in vitro</i> anticancer activity against Mcf-7, Caco-2, and A-549 human cancer cell lines proliferation by MTT assay recorded IC<sub>50%</sub> at 42.8, 76.92, and 45.93 μg/mL, respectively. Treating each cell line with IC<sub>50%</sub> of the hydrolysate for 24 h increased the apoptosis by enhancing the expression of caspase-9 by 5.66, 7.97, and 3.28 folds over the untreated control and inhibited angiogenesis by reducing VEGFR-2 expression by about 56, 76, and 70%, respectively, indicating strong anticancer and antiangiogenic actions on human cancer cells. BLG tryptic hydrolysate may serve as a natural anticarcinogenic agent. The results of this study demonstrated that BLG hydrolysates have direct anticancer and antiangiogenic effects on human cancer cells. The chemical composition and characteristics of the BLG tryptic hydrolysate influence these biological and anticancer activities. The tryptic hydrolysates were generally effective against the three cancer cell lines studied (Mcf-7, Caco-2, and A-549). This effectiveness was assessed by measuring cell proliferation using the MTT assay and by evaluating their impact on angiogenesis through inhibition of VEGFR-2 activity.</p><p><strong>Discussion: </strong>Future studies may focus on enhancing the anticarcinogenic effectiveness of the peptides by isolating and evaluating the most prominent individual peptide and varying the treatment conditions.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1444457"},"PeriodicalIF":3.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信