Frontiers in Molecular Biosciences最新文献

{"title":"Integrated analysis of abnormal metabolic homeostasis for decoding tumor microenvironment.","authors":"Qiang Yang, Ying Cai, Shi Qiu, Aihua Zhang","doi":"10.3389/fmolb.2024.1443642","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1443642","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1443642"},"PeriodicalIF":3.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11518789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544651","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":"Editorial: Celebrating women's contribution to protein folding, misfolding, and degradation in honor of Susan Lindquist (1949-2016).","authors":"Anat Ben-Zvi, Serena Carra, Esti Yeger-Lotem","doi":"10.3389/fmolb.2024.1504059","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1504059","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1504059"},"PeriodicalIF":3.9,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521552","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":"How lactate affects immune strategies in lymphoma.","authors":"Yuehan Zhou, Jinzhan Lou, Yuqin Tian, Jinlei Ding, Xiaobo Wang, Bo Tang","doi":"10.3389/fmolb.2024.1480884","DOIUrl":"10.3389/fmolb.2024.1480884","url":null,"abstract":"<p><p>Tumor cells undergo metabolic reprogramming through shared pathways, resulting in a hypoxic, acidic, and highly permeable internal tumor microenvironment (TME). Lactate, once only regarded as a waste product of glycolysis, has an inseparable dual role with tumor immunity. It can not only provide a carbon source for immune cells to enhance immunity but also help the immune escape through a variety of ways. Lymphoma also depends on the proliferation signal of TME. This review focuses on the dynamic process of lactate metabolism and immune function changes in lymphoma and aims to comprehensively summarize and explore which genes, transcription factors, and pathways affect the biological changes and functions of immune cells. To deeply understand the complex and multifaceted role of lactate metabolism and immunity in lymphoma, the combination of lactate targeted therapy and classical immunotherapy will be a promising development direction in the future.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1480884"},"PeriodicalIF":3.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142516364","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":"Exploration of phytoconstituents of Medhya Rasayana herbs to identify potential inhibitors for <i>cerebroside sulfotransferase</i> through high-throughput screening.","authors":"Nivedita Singh, Anil Kumar Singh","doi":"10.3389/fmolb.2024.1476482","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1476482","url":null,"abstract":"<p><p><i>Cerebroside sulfotransferase</i> (CST) is a key enzyme in sulfatide biosynthesis and regulation of the myelin sheath in the nervous system. To counter sulfatide accumulation with the deficiency of aryl sulfatase A, CST is considered a target protein in substrate reduction therapy in metachromatic leukodystrophy. In this study, 461 phytoconstituents from four herbs of Medhya Rasayana were screened using multi-pronged virtual screening methods including molecular docking, molecular dynamics (MD) simulation, and reverse pharmacophore analysis. The initial screening of the top 15 hits was based on the binding affinity of the compounds toward the CST substrate-binding site using the lowest free energy of a binding score cutoff of ≤ -7.5 kcal/mol, with the number of conformations in the largest cluster more than 75. The absorption, distribution, metabolism, and excretion (ADME) and toxicity-based pharmacokinetic analysis delivered the top four hits: 18alpha-glycyrrhetinic acid, lupeol, alpha carotene, and beta-carotene, with high blood-brain barrier permeability and negligible toxicity. Furthermore, a 100-ns simulation of protein-ligand complexes with a trajectory analysis of structural deviation, compactness, intramolecular interactions, principal component analysis, free energy landscape, and dynamic cross-correlation analysis showed the binding potential and positioning of the four hits in the binding pocket. Thus, an in-depth analysis of protein-ligand interactions from pre- and post-molecular dynamics simulation, along with reverse pharmacophore mapping, suggests that 18alpha-glycyrrhetinic acid is the most potent and specific CST inhibitor, while beta-carotene could be considered the second most potent compound for CST inhibition as it also exhibited overall stability throughout the simulation. Therefore, the computational drug screening approach applied in this study may contribute to the development of oral drugs as a therapeutic option for metachromatic leukodystrophy.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1476482"},"PeriodicalIF":3.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498157","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":"Corrigendum: Comprehensive analysis of the prognostic and immunological role of PAFAH1B in pan-cancer.","authors":"Yixiao Yuan, Xiulin Jiang, Lin Tang, Juan Wang, Lincan Duan","doi":"10.3389/fmolb.2024.1497296","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1497296","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fmolb.2021.799497.].</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1497296"},"PeriodicalIF":3.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498156","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":"Navigating directed evolution efficiently: optimizing selection conditions and selection output analysis.","authors":"Paola Handal-Marquez, Hoai Nguyen, Vitor B Pinheiro","doi":"10.3389/fmolb.2024.1439259","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1439259","url":null,"abstract":"<p><p>Directed evolution is a powerful tool that can bypass gaps in our understanding of the sequence-function relationship of proteins and still isolate variants with desired activities, properties, and substrate specificities. The rise of directed evolution platforms for polymerase engineering has accelerated the isolation of xenobiotic nucleic acid (XNA) synthetases and reverse transcriptases capable of processing a wide array of unnatural XNAs which have numerous therapeutic and biotechnological applications. Still, the current generation of XNA polymerases functions with significantly lower efficiency than the natural counterparts and retains a significant level of DNA polymerase activity which limits their <i>in vivo</i> applications. Although directed evolution approaches are continuously being developed and implemented to improve XNA polymerase engineering, the field lacks an in-depth analysis of the effect of selection parameters, library construction biases and sampling biases. Focusing on the directed evolution pipeline for DNA and XNA polymerase engineering, this work sets out a method for understanding the impact of selection conditions on selection success and efficiency. We also explore the influence of selection conditions on fidelity at the population and individual mutant level. Additionally, we explore the sequencing coverage requirements in directed evolution experiments, which differ from genome assembly and other <i>-omics</i> approaches. This analysis allowed us to identify the sequencing coverage threshold for the accurate and precise identification of significantly enriched mutants. Overall, this study introduces a robust methodology for optimizing selection protocols, which effectively streamlines selection processes by employing small libraries and cost-effective NGS sequencing. It provides valuable insights into critical considerations, thereby enhancing the overall effectiveness and efficiency of directed evolution strategies applicable to enzymes other than the ones considered here.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1439259"},"PeriodicalIF":3.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498158","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":"Corrigendum: Deepening insights into cholinergic agents for intraocular pressure reduction: systems genetics, molecular modeling, and <i>in vivo</i> perspectives.","authors":"Minjae J Kim, Mohamed M Ibrahim, Monica M Jablonski","doi":"10.3389/fmolb.2024.1490100","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1490100","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fmolb.2024.1423351.].</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1490100"},"PeriodicalIF":3.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11486731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142462119","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":"Causal relationship between plasma metabolites and carpal tunnel syndrome risk: evidence from a mendelian randomization study.","authors":"Wenbao Wu, Daofeng Fan, Chong Zheng, Binfu Que, Qing Qing Lian, Yangui Chen, Rui Qiu","doi":"10.3389/fmolb.2024.1431329","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1431329","url":null,"abstract":"<p><strong>Background: </strong>Carpal tunnel syndrome (CTS) is a common symptom of nerve compression and a leading cause of pain and hand dysfunction. However, the underlying biological mechanisms are not fully understood. The aim of this study was to reveal the causal effect of circulating metabolites on susceptibility to CTS.</p><p><strong>Methods: </strong>We employed various Mendelian randomization (MR) methods, including Inverse Variance Weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Model, to examine the association between 1,400 metabolites and the risk of developing CTS. We obtained Single-nucleotide polymorphisms (SNPs) associated with 1,400 metabolites from the Canadian Longitudinal Study on Aging (CLSA) cohort. CTS data was derived from the FinnGen consortium, which included 11,208 cases and 1,95,047 controls of European ancestry.</p><p><strong>Results: </strong>The results of the two-sample MR study indicated an association between 77 metabolites (metabolite ratios) and CTS. After false discovery rate (FDR) correction, a strong causal association between glucuronate levels (odd ratio (OR) [95% CI]: 0.98 [0.97-0.99], p _FDR = 0.002), adenosine 5'-monophosphate (AMP) to phosphate ratio (OR [95% CI]:0.58 [0.45-0.74], p _FDR = 0.009), cysteinylglycine disulfide levels (OR [95% CI]: 0.85 [0.78-0.92], p _FDR = 0.047) and CTS was finally identified.</p><p><strong>Conclusion: </strong>In summary, the results of this study suggest that the identified glucuronate, the ratio of AMP to phosphate, and cysteinylglycine disulfide levels can be considered as metabolic biomarkers for CTS screening and prevention in future clinical practice, as well as candidate molecules for future mechanism exploration and drug target selection.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1431329"},"PeriodicalIF":3.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142462118","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":"Shedding light on the <i>DICER1</i> mutational spectrum of uncertain significance in malignant neoplasms.","authors":"D S Bug, I S Moiseev, Yu B Porozov, N V Petukhova","doi":"10.3389/fmolb.2024.1441180","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1441180","url":null,"abstract":"<p><p>The Dicer protein is an indispensable player in such fundamental cell pathways as miRNA biogenesis and regulation of protein expression in a cell. Most recently, both germline and somatic mutations in <i>DICER1</i> have been identified in diverse types of cancers, which suggests Dicer mutations can lead to cancer progression. In addition to well-known hotspot mutations in RNAase III domains, <i>DICER1</i> is characterized by a wide spectrum of variants in all the functional domains; most are of uncertain significance and unstated clinical effects. Moreover, various new somatic <i>DICER1</i> mutations continuously appear in cancer genome sequencing. The latest contemporary methods of variant effect prediction utilize machine learning algorithms on bulk data, yielding suboptimal correlation with biological data. Consequently, such analysis should be conducted based on the functional and structural characteristics of each protein, using a well-grounded targeted dataset rather than relying on large amounts of unsupervised data. Domains are the functional and evolutionary units of a protein; the analysis of the whole protein should be based on separate and independent examinations of each domain by their evolutionary reconstruction. Dicer represents a hallmark example of a multidomain protein, and we confirmed the phylogenetic multidomain approach being beneficial for the clinical effect prediction of Dicer variants. Because Dicer was suggested to have a putative role in hematological malignancies, we examined variants of <i>DICER1</i> occurring outside the well-known hotspots of the RNase III domain in this type of cancer using phylogenetic reconstruction of individual domain history. Examined substitutions might disrupt the Dicer function, which was demonstrated by molecular dynamic simulation, where distinct structural alterations were observed for each mutation. Our approach can be utilized to study other multidomain proteins and to improve clinical effect evaluation.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1441180"},"PeriodicalIF":3.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142462029","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":"Investigating the effects of combined treatment of mesalazine with <i>Lactobacillus casei</i> in the experimental model of ulcerative colitis.","authors":"Shabnam Bahrami, Nahid Babaei, Hadi Esmaeili Gouvarchin Ghaleh, Jaleh Mohajeri Borazjani, Mahdieh Farzanehpour","doi":"10.3389/fmolb.2024.1456053","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1456053","url":null,"abstract":"<p><strong>Introduction: </strong>Ulcerative colitis (UC), a common gastrointestinal disorder in affluent nations, involves chronic intestinal mucosal inflammation. This research investigated the effects of combined probiotic treatment of <i>Lactobacillus casei</i> (L. casei) and mesalazine on disease activity index and inflammatory factors in the UC model.</p><p><strong>Methods: </strong>20 male BALB/c mice were utilized and divided into four groups. To induce UC, all groups received 100 μL of 4% acetic acid (AA) intra-rectally. The first group received phosphate-buffered saline (PBS) (as a control group), the second group was treated with L. casei, the third group was treated with mesalazine and, the fourth group was treated with L. casei and mesalazine. Treatment with L. Casei and mesalazine commenced after the manifestation of symptoms resulting from UC induction. Finally, the mice were euthanized and the disease activity index, myeloperoxidase activity, nitric oxide rate, cytokines level (IL-1β, IL-6, TNF-α) and, gene expression (iNOS, COX-2, and cytokines) were evaluated.</p><p><strong>Results: </strong>The combined treatment of L. casei and mesalazine led to a significant decrease in the levels of NO, MPO and inflammatory cytokines. In addition, the expression of cytokines, iNOS and COX-2 genes decreased in mice treated with the combination.</p><p><strong>Discussion: </strong>This study shows that combined treatment of L. casei and mesalazine improves of experimental UC, which can be attributed to the anti-inflammatory properties of L. casei and mesalazine. In conclusion, this combination therapy can be considered a suitable option for the management of UC.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1456053"},"PeriodicalIF":3.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142462124","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}