Frontiers in Molecular Biosciences最新文献

{"title":"Candidate proteins interacting with cytoskeleton in cells from the basal airway epithelium in vitro","authors":"Olusola A. Olatona, Sayantan R. Choudhury, Ray Kresman, Carol A. Heckman","doi":"10.3389/fmolb.2024.1423503","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1423503","url":null,"abstract":"Introduction: The cytoskeleton consists of actin, microtubules, septins, and intermediate filaments and, in most cells, is anchored to an extracellular matrix. Each cell has a unique arrangement of this network and readjusts it from time to time. To investigate the regulation of these reorganizations, we identified interactors from extracts of four cultured lines representing basal cells from the airway epithelium.Methods: After immunoprecipitation with an antibody against keratin 17, samples were processed by liquid chromatography and tandem mass spectrometry. Samples not undergoing antibody-mediated capture were processed in parallel.Results: The main keratins of basal cells, namely, Krt14 (type I) and Krt5 (type II), constituted 67% of the total keratin recovered. Several other intermediate filament proteins, nestin, lamin-B1, and prelamin A/C, were present but not enriched upon immunoprecipitation. Although the class of armadillo-repeat proteins was represented by beta-catenin1 and plakoglobin, other desmosome plaque constituents were absent. Large cytolinkers were represented by the spectraplakin, microtubule-actin cross-linking factor (Macf1), which was enriched by immunoprecipitation, and the plakin, plectin, which was not enriched. Subunits of actin filaments and microtubules, along with numerous proteins associated with them, were recovered in both immunoprecipitated samples and those lacking the capture step. Coefficients of determination were computed based on abundance. The actin-associated proteins, alpha-spectrin and brain-specific angiogenesis inhibitor (Baiaip2l), were modestly correlated with keratin abundance but highly correlated with one another and with the keratin-binding protein, annexin A2. This interaction network resembled the pedestal formed by pathogenic <jats:italic>Escherichia coli</jats:italic>. Microtubule-associated proteins, dynamin 1-like protein and cytoplasmic dynein 1 heavy chain (Dync1h1), were enriched by immunoprecipitation, suggesting association with keratins, whereas kinesin-1 heavy chain and microtubule-associated protein retinitis pigmentosa 1 (EB1), were not enriched. Dync1h1 abundance was negatively correlated with that of all the septins, suggesting resemblance to a known antagonistic septin-dynein 1 relationship on microtubules.Conclusion: The cell lines showed remarkable uniformity with respect to the candidates interacting with cytoskeleton. The alpha-spectrin-Baiap2l network may link actin filaments to keratin precursor particles. A smaller interaction network centered on Dync1h1 was negatively correlated with all spectrin-Baiap2l constituents, suggesting that it and its binding partners are excluded from the pedestal-like domain.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141864941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gelatin-based nanoparticles and antibiotics: a new therapeutic approach for osteomyelitis?","authors":"Ali Sherafati Chaleshtori, Zeynab Marzhoseyni, Negin Saeedi, Rosita Azar Bahadori, Samaneh Mollazadeh, Hossein Pourghadamyari, Esmaeil Sajadimoghadam, Kazem Abbaszadeh‐Goudarzi, Amin Moradi Hasan-Abad, Reza Sharafati Chaleshtori","doi":"10.3389/fmolb.2024.1412325","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1412325","url":null,"abstract":"The result of infection of bone with microorganisms is osteomyelitis and septic arthritis. Methicillin-resistant <jats:italic>Staphylococcus aureus</jats:italic> (MRSA) is responsible for most of its cases (more than 50%). Since MRSA is resistant to many treatments, it is accompanied by high costs and numerous complications, necessitating more effective new treatments. Recently, development of gelatin nanoparticles have attracted the attention of scientists of biomedicine to itself, and have been utilized as a delivery vehicle for antibiotics because of their biocompatibility, biodegradability, and cost-effectiveness. Promising results have been reported with gelatin modification and combinations with chemical agents. Although these findings have been suggested that gelatin has the potential to be a suitable option for continuous release of antibiotics in osteomyelitis and septic arthritis treatment, they still have not become routine in clinical practices. The most deliver antibiotic using gelatin-derived composites is vancomycin which is showed the good efficacy. To date, a number of pre-clinical studies evaluated the utility of gelatin-based composites in the management of osteomyelitis. Gelatin-based composites were found to have satisfactory performance in the control of infection, as well as the promotion of bone defect repair in chronic osteomyelitis models. This review summarized the available evidence which provides a new insight into gelatin-derived composites with controlled release of antibiotics.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141864939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AlphaFold2 in biomedical research: facilitating the development of diagnostic strategies for disease","authors":"Hong Zhang, Jiajing Lan, Huijie Wang, Ruijie Lu, Nanqi Zhang, Xiaobai He, Jun Yang, Linjie Chen","doi":"10.3389/fmolb.2024.1414916","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1414916","url":null,"abstract":"Proteins, as the primary executors of physiological activity, serve as a key factor in disease diagnosis and treatment. Research into their structures, functions, and interactions is essential to better understand disease mechanisms and potential therapies. DeepMind’s AlphaFold2, a deep-learning protein structure prediction model, has proven to be remarkably accurate, and it is widely employed in various aspects of diagnostic research, such as the study of disease biomarkers, microorganism pathogenicity, antigen-antibody structures, and missense mutations. Thus, AlphaFold2 serves as an exceptional tool to bridge fundamental protein research with breakthroughs in disease diagnosis, developments in diagnostic strategies, and the design of novel therapeutic approaches and enhancements in precision medicine. This review outlines the architecture, highlights, and limitations of AlphaFold2, placing particular emphasis on its applications within diagnostic research grounded in disciplines such as immunology, biochemistry, molecular biology, and microbiology.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141864938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of calpastatin hcast 3-25 and activity of the calpain/calpastatin system in human glioblastoma stem cells: possible involvement of hcast 3-25 in cell differentiation","authors":"Sonia Spinelli, Federica Barbieri, Monica Averna, Tullio Florio, Marco Pedrazzi, Beatrice F. Tremonti, Michela Capraro, Roberta De Tullio","doi":"10.3389/fmolb.2024.1359956","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1359956","url":null,"abstract":"Glioblastoma (GBM) is the most malignant brain tumor, characterized by cell heterogeneity comprising stem cells (GSCs) responsible for aggressiveness. The calpain/calpastatin (calp/cast) proteolytic system is involved in critical physiological processes and cancer progression. In this work we showed the expression profile of hcast 3-25 (a Type III calpastatin variant devoid of inhibitory units) and the members of the system in several patient-derived GSCs exploring the relationship between hcast 3-25 and activation/activity of calpains. Each GSC shows a peculiar calp/cast mRNA and protein expression pattern, and hcast 3-25 is the least expressed. Differentiation promotes upregulation of all the calp/cast system components except hcast 3-25 mRNA, which increased or decreased depending on individual GSC culture. Transfection of hcast 3-25-V5 into two selected GSCs indicated that hcast 3-25 effectively associates with calpains, supporting the digestion of selected calpain targets. Hcast 3-25 possibly affects the stem state promoting a differentiated, less aggressive phenotype.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141864937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating adipose-tissue miRNAs in gastrointestinal cancer patients and their association with the level and type of adiposity at body composition analysis","authors":"Federica Tambaro, Giovanni Imbimbo, Valentina Pace, Maria Ida Amabile, Veronica Rizzo, Simona Orlando, Giulia Lauteri, Cesarina Ramaccini, Carlo Catalano, Giuseppe Nigri, Maurizio Muscaritoli, Alessio Molfino","doi":"10.3389/fmolb.2024.1449197","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1449197","url":null,"abstract":"BackgroundAdipose tissue (AT) wasting in cancer is an early catabolic event with negative impact on outcomes. Circulating miRNAs may promote body weight loss and cachexia. We measured circulating miRNAs linked to AT alterations and compared their levels between i) gastrointestinal (GI) cancer patients and controls, ii) cachectic and non-cachectic cancer patients, and iii) according to adiposity level and its distribution.MethodsPatients with GI cancer and subjects with benign diseases as controls were considered. Cachexia was assessed and adiposity evaluated by CT-scan for subcutaneous AT area (SAT), visceral AT area and the total AT area (TAT). MiRNAs involved were measured in plasma by RT-qPCR.Results37 naïve GI cancer patients and 14 controls were enrolled. Patients with cachexia presented with lower SAT compared to non-cachectic (<jats:italic>p</jats:italic> &amp;lt; 0.05). In cancer patients, we found higher levels of miR-26a, miR-128, miR-155 and miR-181a vs. controls (<jats:italic>p</jats:italic> &amp;lt; 0.05). Cancer patients with BMI <jats:inline-formula><mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\"><mml:mrow><mml:mo>&lt;</mml:mo></mml:mrow></mml:math></jats:inline-formula> 25 kg/m<jats:sup>2</jats:sup> showed higher levels of miR-26a vs. those with BMI <jats:inline-formula><mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\"><mml:mrow><mml:mo>≥</mml:mo></mml:mrow></mml:math></jats:inline-formula> 25 (<jats:italic>p</jats:italic> = 0.035). MiR-26a and miR-181a were higher in cachectic and non-cachectic vs. controls (<jats:italic>p</jats:italic> &amp;lt; 0.05). Differences between cachectic and controls were confirmed for miR-155 (<jats:italic>p</jats:italic> &amp;lt; 0.001) but not between non-cachectic vs. control (<jats:italic>p</jats:italic> = 0.072). MiR-155 was higher in cachectic patients with low TAT vs. those without cachexia and high TAT (<jats:italic>p</jats:italic> = 0.036).ConclusionOur data confirm a modulation of specific and different miRNAs involved in AT metabolism in cancer and cachexia. MiR-155 levels were higher in patients presenting with cachexia and low adiposity with implications in the pathogenic mechanisms and clinical consequences of GI cancer patients.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141864935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Beyond protein degradation and lysine modification: novel insights into non-canonical ubiquitination.","authors":"Aysegul Sapmaz, Jin Gan, Darragh P O'Brien, Adán Pinto-Fernández","doi":"10.3389/fmolb.2024.1461356","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1461356","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004009","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}

{"title":"Progress and trends in myocardial infarction-related long non-coding RNAs: a bibliometric analysis","authors":"Qingkun Meng, Hao Tan, Chengfu Wang, Zhijun Sun","doi":"10.3389/fmolb.2024.1382772","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1382772","url":null,"abstract":"BackgroundMyocardial infarction (MI), a critical condition, substantially affects patient outcomes and mortality rates. Long non-coding RNAs (lncRNAs) play a critical role in the onset and progression of MI. This study aimed to explore the related research on MI-related lncRNAs from a bibliometric perspective, providing new clues and directions for researchers in the field.MethodsA comprehensive search was conducted on 7 August 2023, using the Web of Science Core Collection (WoSCC) database to compile a dataset of all English-language scientific journals. The search gathered all relevant publications from January 2000 to August 2023 that pertain to MI-related lncRNAs. Data on countries, institutions, journals, authors, and keywords were collected, sorted, statistically analyzed, and visualized using CiteSpace 6.2.R4, VOSviewer 1.6.19, an online bibliometric analysis platform (<jats:ext-link>http://bibliometric.com</jats:ext-link>), and the bibliometric package in R-Studio 4.3.1. Articles were screened by two independent reviewersResultsBetween January 2000 and August 2023, a total of 1,452 papers were published in the research field of MI-related lncRNAs. The year with the most publications was 2020, accounting for 256 papers. The publication volume displayed an exponential growth trend, fitting the equation y = 2.0215e<jats:sup>0.2786x</jats:sup>, R<jats:sup>^2</jats:sup> = 0.97. In this domain, China leads in both the number of published papers (N = 1,034) and total citations, followed by the United States, Germany, Iran, and Italy. The most productive institution is Harbin Medical University (N = 144). The European Review for Medical and Pharmacological Sciences had the highest number of publications (N = 46), while Circulation Research had the most citations (TC = 4,537), indicating its irreplaceable standing in this field. Research mainly focuses on the cardiovascular system, cellular biology, physiology, etc. The most productive author is Zhang Y. Apart from “Myocardial Infarction” and “LncRNA,” the most frequent keywords include “expression,” “atherosclerosis,” and “apoptosis.” Cluster analysis suggests current research themes concentrate on cardiovascular diseases and gene expression, cardiac ischemia/reperfusion injury and protection, expression and proliferation, atherosclerosis and inflammatory response, among others. Keyword bursts indicate recent hot topics as targeting, autophagy, etc.ConclusionThis bibliometric analysis reveals that research on MI-related lncRNAs has rapidly expanded between January 2000 and August 2023, primarily led by China and the United States. Our study highlights the significant biological roles of lncRNAs in the pathogenesis and progression of MI, including their involvement in gene expression regulation, atherosclerosis development, and apoptosis. These findings underscore the potential of lncRNAs as therapeutic targets and biomarkers for MI. Additionally, our study provides insights into the features and ","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141864940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes: a significant medium for regulating drug resistance through cargo delivery","authors":"Bixuan Ren, Xiaoqing Li, Zhihua Zhang, Sheng Tai, Shan Yu","doi":"10.3389/fmolb.2024.1379822","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1379822","url":null,"abstract":"Exosomes are small lipid nanovesicles with a diameter of 30–150 nm. They are present in all body fluids and are actively secreted by the majority of cells through the process of exocytosis. Exosomes play an essential role in intercellular communication and act as significant molecular carriers in regulating various physiological and pathological processes, such as the emergence of drug resistance in tumors. Tumor-associated exosomes transfer drug resistance to other tumor cells by releasing substances such as multidrug resistance proteins and miRNAs through exosomes. These substances change the cell phenotype, making it resistant to drugs. Tumor-associated exosomes also play a role in impacting drug resistance in other cells, like immune cells and stromal cells. Exosomes alter the behavior and function of these cells to help tumor cells evade immune surveillance and form a tumor niche. In addition, exosomes also export substances such as tumoricidal drugs and neutralizing antibody drugs to help tumor cells resist drug therapy. In this review, we summarize the mechanisms of exosomes in promoting drug resistance by delivering cargo in the context of the tumor microenvironment (TME).","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141865019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontiers | The downregulation of tight junction proteins and pIgR in the colonic epithelium causes the susceptibility of EpCAM+/− mice to colitis and gut microbiota dysbiosis","authors":"Ya Nie, Ting Lin, Yanhong Yang, Wanwan Liu, Qing Hu, Guibin Chen, Li Huang, Huijuan Wu, Cunjie Kong, Zili Lei, Jiao Guo","doi":"10.3389/fmolb.2024.1442611","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1442611","url":null,"abstract":"BackgroundThe genetic factors play important roles on the pathogenesis of inflammatory bowel disease (IBD). EpCAM is highly expressed in the intestinal epithelium. It is still unclear if the decrease or somatic mutation of EpCAM could cause IBD.MethodsThe WT and EpCAM+/− mice were administrated with DSS intermittently for nearly 8 weeks. The colon, liver and feces were harvested to check the morphological and histological changes, the expression of inflammatory genes and the gut microbiota via H&E staining, immunofluorescence, qPCR, western blot and 16S rDNA sequence assays.ResultsThe DSS administration induced more serious inflammation in the colon of EpCAM+/− mice than WT mice. Compared to DSS-induced WT mice, the transcriptional levels of IL-6, F4/80, Ly6g, Ly6d and Igha were significantly higher in the colon of DSS-induced EpCAM+/− mice. The protein levels of MMP7 and MMP8 and the activation of JNK, ERK1/2 and p38 were significantly increased in the colon of DSS-induced EpCAM+/− mice. The protein levels of CLDN1, CLDN2, CLDN3, CLDN7, OCLD, ZO-1 and pIgR were significantly decreased in the colon of DSS-induced EpCAM+/− mice. The serum concentration of LPS was significantly higher in the DSS-induced EpCAM+/− mice which caused the acute inflammation in the liver of them. The expression of Pigr was significantly reduced in the liver of DSS-induced EpCAM+/− mice. The ratio of Firmicutes/Bacteroidetes at the phylum level was higher in the gut microbiota of EpCAM+/− mice than WT mice.ConclusionIn conclusion, the heterozygous mutation of EpCAM increased the susceptibility to colitis, gut microbiota dysbiosis and liver injury.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141937844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Liquid biopsy in oncology: opportunity and challenges.","authors":"Ashok Kumar, Rajesh Singh, Neha Arya, Smiths Lueong, Aklank Jain","doi":"10.3389/fmolb.2024.1466938","DOIUrl":"10.3389/fmolb.2024.1466938","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11317461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972541","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}