Li Ji, Anqi Deng, Huiying Chen, Shuangyan Guo, Pingyu Wang, Ruiyi Zhang, Wenyang Chen, Taotao Fan, Lijuan Jiang, Bing Shen
{"title":"Role of Ca<sup>2+</sup>/calmodulin and PI3K/AKT signaling pathways and active ingredients of BaoTaiYin in treatment of recurrent miscarriage.","authors":"Li Ji, Anqi Deng, Huiying Chen, Shuangyan Guo, Pingyu Wang, Ruiyi Zhang, Wenyang Chen, Taotao Fan, Lijuan Jiang, Bing Shen","doi":"10.3389/fmolb.2025.1573294","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1573294","url":null,"abstract":"<p><strong>Introduction: </strong>BaoTaiyin (BTY) is a traditional Chinese medicine decoction. It has been used to treat recurrent miscarriage (RM). However, there are no comprehensive systematic studies to identify the chemical compositions of BTY and molecular mechanisms on RM. Finding the chemical components of BTY and clarifying the underlying processes in the treatment of RM were the goals of the study.</p><p><strong>Methods: </strong>We used ultra-high-performance liquid chromatography coupled with triple quadruple time-of-flight tandem mass spectrometry to analyze the chemical components of BTY, network analysis to predict the pharmacological effects of the identified active ingredients, and cell experiments to identify potential molecular mechanisms.</p><p><strong>Results: </strong>We found 12 active ingredients among 61 components identified in BTY. These identified activities were linked to regulatory effects on 127 key signaling pathways, targeting 107 proteins. Through network analysis, we determined that insulin-like growth factor 1 receptor, matrix metalloproteinases, PI3K, and STAT3 may be the core targets of BTY's therapeutic effects on RM. We further explored this mechanism to find that aqueous extracts of BTY significantly enhanced IGFBP2 and CaMKK2 expression and trophoblast proliferation, whereas inhibitors of IGF1R/PI3K/AKT pathway or CaMKK2 blocked the effect of BTY on trophoblast proliferation. In addition, IGFBP2 siRNA suppressed BTY-induced CaMKK2 expression. Caffeic acid, as one of components of BTY, increased intracellular Ca<sup>2+</sup> concentration and proliferation in trophoblast.</p><p><strong>Conclusion: </strong>Our research showed that BTY may have therapeutic benefits on RM through multiple targets and pathways, such as the IGF1R/PI3K/AKT and Ca<sup>2+</sup>/calmodulin signaling pathways.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1573294"},"PeriodicalIF":3.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810929","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}
Lian Zhu, Liu Xie, Ziming Wang, Kai-Lin Li, Wei Cai
{"title":"Mass spectrometry-based metabolomics reveal the effects and potential mechanism of isochlorogenic acid A in MC3T3-E1 cells.","authors":"Lian Zhu, Liu Xie, Ziming Wang, Kai-Lin Li, Wei Cai","doi":"10.3389/fmolb.2025.1518873","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1518873","url":null,"abstract":"<p><strong>Introduction: </strong>The bioactive compound 3,5-DiCQA, derived from Duhaldea nervosa, has been traditionally utilized in folk remedies for bone fractures and osteoporosis. However, its therapeutic mechanisms remain unclear.</p><p><strong>Methods: </strong>We employed UHPLC-Q Exactive Orbitrap MS-based cell metabolomics to investigate the molecular mechanisms of 3,5-DiCQA in MC3T3-E1 cells. Cell proliferation was assessed via MTT assay, differentiation by alkaline phosphatase (ALP) activity, and mineralization through alizarin red staining and cetylpyridinium chloride quantification. Metabolomic profiling compared drug-treated and control groups.</p><p><strong>Results: </strong>Results from MTT assays demonstrated that 3,5-DiCQA significantly promoted cell proliferation at 100 μM. Alkaline phosphatase (ALP) assays and alizarin red staining revealed enhanced osteoblast differentiation and mineralization, respectively. Calcification deposition was significantly increased in the calcified stained cells by cetylpyridinium chloride quantization, indicating that 3,5-DiCQA can promote the mineralization of MC3T3-E1 cells. Metabolomic analysis identified key metabolic changes, including the downregulation of phytosphingosine and upregulation of sphinganine and citric acid.</p><p><strong>Discussion: </strong>These findings suggest that 3,5-DiCQA promotes osteoblast proliferation, differentiation and mineralization through pathways such as sphingolipid metabolism, arginine and proline metabolism, mucin type O-glycan biosynthesis and the citrate cycle (TCA cycle). This study provides insights into the therapeutic potential of 3,5-DiCQA for osteoporosis and highlights the utility of metabolomics in elucidating traditional Chinese medicine (TCM).</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1518873"},"PeriodicalIF":3.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810917","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 to quantify magic spots - a brief overview of (p)ppGpp detection and quantitation methods.","authors":"Filip Gąsior, Wiktoria Klasa, Katarzyna Potrykus","doi":"10.3389/fmolb.2025.1574135","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1574135","url":null,"abstract":"<p><p>Guanosine tetra- and penta-phosphates, collectively known as (p)ppGpp, are well-known second messengers of cellular stress responses in bacteria and plants. Their intracellular concentration is tightly regulated and can vary widely-from undetectable levels under optimal growth conditions, through intermediate concentrations, to extremely high levels that match or even exceed GTP concentrations when cells are exposed to severe stress. Importantly, the effects exerted by (p)ppGpp are often concentration-dependent, making their quantitative analysis a crucial aspect of studying cellular responses to stress. To gain a deeper understanding of the regulatory mechanisms associated with (p)ppGpp, it is essential to monitor its accumulation <i>in vivo</i> and conduct detailed molecular studies <i>in vitro</i>. Various methods have been developed for detecting and quantifying (p)ppGpp, enabling researchers to track its levels in living cells and analyse its function under controlled laboratory conditions. In this work, we provide an overview of the available techniques for (p)ppGpp detection and quantification. We present their advantages, limitations, and potential applications in research on metabolic regulation and cellular stress responses.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1574135"},"PeriodicalIF":3.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810915","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":"Single-cell RNA sequencing advances in revealing the development and progression of MASH: the identifications and interactions of non-parenchymal cells.","authors":"Meng Ning, Donghui Lu, Dong Liang, Pei-Gen Ren","doi":"10.3389/fmolb.2025.1513993","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1513993","url":null,"abstract":"<p><p>Developing drugs for the treatment of Metabolic Associated Steatohepatitis (MASH) has always been a significant challenge. Researchers have been dedicated to exploring drugs and therapeutic strategies to alleviate disease progression, but treatments remain limited. This is partly due to the complexity of the pathophysiological processes, and inadequate knowledge of the cellular and molecular mechanisms in MASH. Especially, the liver non-parenchymal cells (NPCs) like Kupffer cells, hepatic stellate cells and sinusoidal endothelial cells which play critical roles in live function, immune responses, fibrosis and disease progression. Deciphering how these cells function in MASH, would help understand the pathophysiological processes and find potential drug targets. In recent years, new technologies have been developed for single-cell transcriptomic sequencing, making cell-specific transcriptome profiling a reality in healthy and diseased livers. In this review, we discussed how the use of single-cell transcriptomic sequencing provided us with an in-depth understanding of the heterogeneous, cellular interactions among non-parenchymal cells and tried to highlight recent discoveries in MASH by this technology. It is hoped that the summarized features and markers of various subclusters in this review could provide a technical reference for further experiments and a theoretical basis for clinical applications.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1513993"},"PeriodicalIF":3.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810931","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}
Francesco Tavanti, Giorgia Brancolini, Roberto Perris
{"title":"Computational analysis of the structural-functional dynamics of a Co-receptor proteoglycan.","authors":"Francesco Tavanti, Giorgia Brancolini, Roberto Perris","doi":"10.3389/fmolb.2025.1549177","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1549177","url":null,"abstract":"<p><p>Nerve-Glial Antigen 2/Chondroitin Sulphate Proteoglycan 4 (NG2/CSPG4) is the largest membrane-intercalated cell surface component of the human proteome known to date. NG2/CSPG4 is endowed with the capability of engaging a myriad of molecular interactions and exert co-receptor functions, of which primary ones are sequestering of growth factors and the anchoring of cells to the extracellular matrix. However, the nature of the interactive dynamics of the proteoglycan remains veiled because of its conspicuous size and structural complexity. By leveraging on a multi-scale <i>in silico</i> approach, we have pioneered a comprehensive computational analysis of the structural-functional traits of the NG2/CSPG4 ectodomain. The modelling highlights an intricate assembly of β-sheet motifs linked together by flexible loops. Furthermore, our <i>in silico</i> predictions highlight that the previously delineated D1 domain may consistently remain more accessible for molecular interplays with respect to the D2 and D3 domains. Based on these findings, we have simulated the structural mechanism through the proteoglycan may serve as a co-receptor for growth factor FGF-2, showing that NG2/CSPG4 bends towards the receptor FGFR-1 for this growth factor and confirming the previously hypothesized trimeric complex formation promoted by FGF-2 dimers bridging the FGFR-1-proteoglycan interaction. The Chondroitin Sulphate Proteoglycan 4 is a large multi-domain transmembrane protein involved in several biological processes including pathological conditions. Despite its importance, it has never been studied at the atomistic level due to its large size. Here, we employed a multi-scale computer simulations approach to study its three-dimensional structure, its movements and co-receptor properties, showing that it can serve as mediator in the growth factor signaling process.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1549177"},"PeriodicalIF":3.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810914","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":"Identification and characterization of yeast SNF1 kinase homologs in <i>Leishmania major</i>.","authors":"Gaurav Shoeran, Namrata Anand, Upninder Kaur, Kapil Goyal, Rakesh Sehgal","doi":"10.3389/fmolb.2025.1567703","DOIUrl":"10.3389/fmolb.2025.1567703","url":null,"abstract":"<p><strong>Background: </strong>Sucrose Non Fermenting1 (SNF1) constitutes a family of protein kinases conserved in eukaryotes, plants, and fungi. SNF1 has been known to play a crucial role in stress adaptation and metabolism, enabling organisms to respond to changing environmental conditions. Initially identified in yeast, SNF1 is essential for shifting from the primary carbon source, glucose, to secondary carbon sources like sucrose. Homologs of this protein family were identified in <i>Leishmania major</i>, a protozoan parasite and we aimed to determine their role in this parasite.</p><p><strong>Methods: </strong>In the present study, we identified the putative homologs of SNF1 kinase in <i>L. major</i> and knock out strains were prepared using the CRISPR-Cas9 knock-out strategy. The developed strains were evaluated for their growth, characteristics, protein expression and ultra structural changes <i>in vitro</i> and virulence in a mouse model.</p><p><strong>Results: </strong>One of the strain named N2, was found to be completely avirulent and showed limited growth, lack of glycosomes and had a fewer mitochondria with deformed cristae. The N2 strain failed to produce infection in mice when compared to WT mice. Proteome analysis revealed an increase in ribosomal proteins in the N2 strain, highlighting the role of ribosomes in stress adaptation.</p><p><strong>Conclusion: </strong>The essentiality of this gene for developing infections in mice underscores its potential in the development of future antileishmanial therapies and live attenuated strains.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1567703"},"PeriodicalIF":3.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802932","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}
Yi Zhu, Zhuoliang Zhang, Liangliang Gao, Yue Tian, Xinyu Lu, Yinhong Jiang, Huibin Su, Chengyong Gu, Chenghuan Shi, Lei Wei
{"title":"Mesoporous silica loaded with calcitonin gene-related peptide antagonist and <i>curcumin</i> alleviate oxidative stress and inflammation in the sciatic nerve.","authors":"Yi Zhu, Zhuoliang Zhang, Liangliang Gao, Yue Tian, Xinyu Lu, Yinhong Jiang, Huibin Su, Chengyong Gu, Chenghuan Shi, Lei Wei","doi":"10.3389/fmolb.2025.1510141","DOIUrl":"10.3389/fmolb.2025.1510141","url":null,"abstract":"<p><strong>Background: </strong>Neuropathic pain (NP) is a kind of chronic pain that can lead to neurasthenia. The effectiveness of current drug treatment for NP is still unsatisfactory due to its side effects, addiction and withdrawal. In recent years, researchers have begun to develop nano-drug delivery systems for the diagnosis and treatment of NP diseases.</p><p><strong>Methods: </strong>We developed a disulfide-bonded magnetic mesoporous silica dual-drug delivery system consisting of <i>curcumin</i> (<i>Cur</i>) and a calcitonin gene-related peptide (CGRP) antagonist (CGRPi), and characterized by electron microscopy, Dynamic Light Scattering (DLS), Zeta, specific surface area and pore size detection. At the cellular level, the biocompatibility of CGRPi@<i>Cur</i>@Fe<sub>3</sub>O<sub>4</sub>@mSiO<sub>2</sub>-PEG (FMCC) nanoparticles were tested by CCK-8 and dead/alive staining kit in BV2 cells; Inflammation levels and oxidative stress were measured by enzyme linked immunosorbent assay (ELISA) in lipopolysaccharide (LPS)-induced BV2 neuroinflammation model. <i>In vivo</i>, chronic constriction injury (CCI) model was constructed, and the effect of FMCC on pain behavior of CCI mice was detected by von Frey filaments test and thermal hyperalgesia; The effects of FMCC on the anti-inflammatory and oxidative stress of CCI were determined by pathological tests (HE and ROS staining), RT-PCR and ELISA.</p><p><strong>Results: </strong>FMCC had good biocompatibility and could be taken up by BV2 cells. At the cellular level, FMCC could effectively reverse oxidative stress, inflammation and CGRP expression in LPS-induced neuroinflammation model <i>in vitro</i>. At the animal level, the mice with CCI were administered with FMCC, which effectively reduced oxidative stress and inflammation and sustained relief of neuropathic pain.</p><p><strong>Conclusion: </strong>This study provides a new approach for the treatment of neuropathic pain.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1510141"},"PeriodicalIF":3.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802865","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":"Network pharmacology analysis of Lanatoside C: molecular targets and mechanisms in the treatment of ulcerative colitis.","authors":"Wenjing Zhu, Zhengjie Zhang, Xinyuan Wang","doi":"10.3389/fmolb.2025.1552360","DOIUrl":"10.3389/fmolb.2025.1552360","url":null,"abstract":"<p><strong>Introduction: </strong>Ulcerative colitis (UC) is a chronic and progressive inflammatory disease of the intestines, marked by recurrent inflammation along the digestive tract, leading to symptoms such as bloody diarrhea and weight loss, severely impacting patients' quality of life. Despite extensive research, current therapeutic treatment for UC still faces challenges in long-term efficacy and safety. Lanatoside C (LanC), as a type of cardiac glycosides, has shown promising anti-inflammatory effects. This study employs network pharmacology to investigate the effects and mechanisms of LanC in the treatment of UC.</p><p><strong>Method: </strong>LanC- and UC-associated target genes datasets were retrieved from the Genecards, DisGeNET, and Gene Expression Omnibus database. Integration analysis identified a common set of potential LanC targets for UC treatment. Analyses of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on these target genes. Additionally, a protein-protein interaction (PPI) network was constructed to identify the top targets with the highest connectivity. Molecular docking and cellular experiments were subsequently carried out to further validated these findings.</p><p><strong>Results: </strong>23 intersecting genes were identified as potential targets of LanC in UC. Among these, KDR, STAT3, ABCB1, CYP3A5, and CYP2B6 emerged as the top 5 targets with high therapeutic potential. Pathway analysis indicated the involvement of fatty acid and lipid metabolism, as well as xenobiotic metabolism pathways, which could be crucial for LanC's efficacy in treating UC. Molecular docking simulations revealed favorable binding interaction between LanC and KDR, STAT3, ABCB1, CYP3A5, and CYP2B6. Furthermore, <i>In vitro</i> experiments demonstrated that LanC significantly inhibits LPS-induced pro-inflammatory cytokines expression in RAW264.7 cells.</p><p><strong>Conclusion: </strong>This study demonstrates a comprehensive overview of the therapeutic potential of LanC in UC and elucidates its mechanisms of action. These findings offer a theoretical basis for further optimizing UC clinical therapy and underscore the potential of LanC as a novel therapeutic option for UC.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1552360"},"PeriodicalIF":3.9,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795007","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":"Empowering limited-resource countries: collaborating with expert centers for diagnosis of primary ciliary dyskinesia.","authors":"Mine Yuksel Kalyoncu, Rim Hjeij, Muruvvet Yanaz, Aynur Gulieva, Merve Selcuk Balcı, Şeyda Karabulut, Neval Metin Cakar, Almala Pınar Ergenekon, Ela Erdem Eralp, Yasemin Gokdemir, Heymut Omran, Bülent Taner Karadag","doi":"10.3389/fmolb.2025.1547152","DOIUrl":"10.3389/fmolb.2025.1547152","url":null,"abstract":"<p><strong>Introduction: </strong>Primary ciliary dyskinesia (PCD) is an autosomal recessive rare disease caused by alterations in ciliary structure and function. Without a unique gold standard diagnostic test, the European Respiratory Society and the American Thoracic Society recommend using various diagnostic techniques to improve accuracy. This study aimed to demonstrate the effectiveness of immunofluorescence (IF) analysis in the diagnosis of PCD cases with uncertain genetic results and to demonstrate the importance of international collaboration in the diagnosis of PCD.</p><p><strong>Methods: </strong>In collaboration with IF specialists at the University of Münster, individuals with inconclusive results in the Marmara University PCD panel consisting of the 22 most common genes and clinically suggestive of PCD were included in the study. IF imaging determined the subcellular localization of DNAH5 and GAS8 in respiratory epithelial cells. Nasal nitric oxide measurements, high-speed video microscopy (HSVM) analysis, and genetic analyses were performed.</p><p><strong>Results: </strong>19 patients were evaluated. The median age (25-75p) was 15 years (10-20 years) with 12 (63.2%) males. Three cases (15.7%) showed an absence of DNAH5, and one (5.3%) had a proximal distribution of DNAH5 in the ciliary axoneme. One case (5.3%) had cells without cilia, indicating a possible ciliogenesis defect. All individuals with abnormal IF analysis had a PICADAR score of 6 or above, and their cilia were immotile in HSVM.</p><p><strong>Discussion: </strong>Consistent with the IF finding suggesting a ciliogenesis defect, further genetic analysis revealed biallelic pathogenic variants in CCNO in the affected individual. The absence of DNAH5 in the respiratory epithelial cells of an individual carrying heterozygous pathogenic splice variants in DNAH5 suggests the need for further genetic analysis. This study underscores the importance of international collaboration in diagnosing rare diseases like PCD.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1547152"},"PeriodicalIF":3.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779453","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}
Gabriel Santos Arini, Tiago Cabral Borelli, Elthon Góis Ferreira, Rafael de Felício, Paula Rezende-Teixeira, Matheus Pedrino, Franciene Rabiço, Guilherme Marcelino Viana de Siqueira, Luiz Gabriel Mencucini, Henrique Tsuji, Lucas Sousa Neves Andrade, Leandro Maza Garrido, Gabriel Padilla, Alberto Gil-de-la-Fuente, Mingxun Wang, Norberto Peporine Lopes, Daniela Barretto Barbosa Trivella, Letícia Veras Costa-Lotufo, María-Eugenia Guazzaroni, Ricardo Roberto da Silva
{"title":"A multi-omics reciprocal analysis for characterization of bacterial metabolism.","authors":"Gabriel Santos Arini, Tiago Cabral Borelli, Elthon Góis Ferreira, Rafael de Felício, Paula Rezende-Teixeira, Matheus Pedrino, Franciene Rabiço, Guilherme Marcelino Viana de Siqueira, Luiz Gabriel Mencucini, Henrique Tsuji, Lucas Sousa Neves Andrade, Leandro Maza Garrido, Gabriel Padilla, Alberto Gil-de-la-Fuente, Mingxun Wang, Norberto Peporine Lopes, Daniela Barretto Barbosa Trivella, Letícia Veras Costa-Lotufo, María-Eugenia Guazzaroni, Ricardo Roberto da Silva","doi":"10.3389/fmolb.2025.1515276","DOIUrl":"10.3389/fmolb.2025.1515276","url":null,"abstract":"<p><strong>Introduction: </strong>Exploiting microbial natural products is a key pursuit of the bioactive compound discovery field. Recent advances in modern analytical techniques have increased the volume of microbial genomes and their encoded biosynthetic products measured by mass spectrometry-based metabolomics. However, connecting multi-omics data to uncover metabolic processes of interest is still challenging. This results in a large portion of genes and metabolites remaining unannotated. Further exacerbating the annotation challenge, databases and tools for annotation and omics integration are scattered, requiring complex computations to annotate and integrate omics datasets.</p><p><strong>Methods: </strong>Here we performed a two-way integrative analysis combining genomics and metabolomics data to describe a new approach to characterize the marine bacterial isolate BRA006 and to explore its biosynthetic gene cluster (BGC) content as well as the bioactive compounds detected by metabolomics.</p><p><strong>Results and discussion: </strong>We described BRA006 genomic content and structure by comparing Illumina and Oxford Nanopore MinION sequencing approaches. Digital DNA:DNA hybridization (dDDH) taxonomically assigned BRA006 as a potential new species of the Micromonospora genus. Starting from LC-ESI(+)-HRMS/MS data, and mapping the annotated enzymes and metabolites belonging to the same pathways, our integrative analysis allowed us to correlate the compound Brevianamide F to a new BGC, previously assigned to other function.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1515276"},"PeriodicalIF":3.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779208","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}