Frontiers in Cell and Developmental Biology最新文献

{"title":"(Multi-) omics studies of ILC2s in inflammation and metabolic diseases.","authors":"Maria Kral, Emiel P C van der Vorst, Christian Weber, Yvonne Döring","doi":"10.3389/fcell.2024.1473616","DOIUrl":"https://doi.org/10.3389/fcell.2024.1473616","url":null,"abstract":"<p><p>Type 2 innate lymphoid cells (ILC2s) have emerged as pivotal regulators in the pathogenesis of diseases, with their roles in inflammation, metabolism, and tissue homeostasis becoming increasingly recognized. This review provides an overview of the current understanding of ILC2s in inflammation and metabolic disorders, including their functional contributions. Moreover, we will discuss how these cells adapt their metabolic processes to support their function and survival and how their metabolic requirements change under different physiological and pathological conditions. Lastly, we will review recent omics studies that have provided insights into the molecular and cellular characteristics of ILC2s. This includes transcriptomic, proteomic, and metabolomic analyses that have elucidated the gene expression profiles, protein interactions, and metabolic networks, respectively, associated with ILC2s. These studies have advanced our understanding of the functional diversity of ILC2s and their involvement in metabolic disease.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1473616"},"PeriodicalIF":4.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An update on ox-LDL-inducing vascular smooth muscle cell-derived foam cells in atherosclerosis.","authors":"Jingjing Guo, Laijing Du","doi":"10.3389/fcell.2024.1481505","DOIUrl":"https://doi.org/10.3389/fcell.2024.1481505","url":null,"abstract":"<p><p>Excess cholesterol accumulation induces the accumulation of foam cells, eventually accelerating atherosclerosis progress. Historically, the mechanisms of macrophage-derived foam cells have attracted attention because of their central role in plaque development, which was challenged by lineage tracing in union with single-cell sequencing (sc-seq). Accumulated studies have uncovered how vascular smooth muscle cells (VSMCs) proliferate and migrate to the vascular intima and accumulate, then transform into foam cells induced by surplus lipids, finally accounting for 30% to 70% of the total foam cells within the plaque of both mice and humans. Therefore, the mechanisms of VSMC-derived foam cells have received increasing attention. The review intends to summarize the transformation mechanism of VSMCs into foam cells induced by oxidized low-density lipoproteins (ox-LDL) in atherosclerosis.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1481505"},"PeriodicalIF":4.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing adipocytokine-related signatures for prognosis prediction in prostate cancer.","authors":"Shicheng Fan, Haolin Liu, Jian Hou, Guiying Zheng, Peng Gu, Xiaodong Liu","doi":"10.3389/fcell.2024.1475980","DOIUrl":"https://doi.org/10.3389/fcell.2024.1475980","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PCa) is a prevalent malignant tumor in males, with a significant incidence of biochemical recurrence (BCR) despite advancements in treatment. Adipose tissue surrounding the prostate, known as periprostatic adipose tissue (PPAT), contributes to PCa invasion through adipocytokine production. However, the relationship between adipocytokine-related genes and PCa prognosis remains understudied. This study was conducted to provide a theoretical basis and serve as a reference for the use of adipocytokine-related genes as prognostic markers in PCa.</p><p><strong>Methods: </strong>Transcriptome and survival data of PCa patients from The Cancer Genome Atlas (TCGA) database were analyzed. Differential gene expression analysis was conducted using the DESeq2 and limma packages. Prognostic genes were identified through univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression. A prognostic model was developed and validated utilizing receiver operating characteristic (ROC) and Kaplan-Meier (K-M) curves. Assessments of immune cell infiltration and drug sensitivity were also carried out. Subsequently, the function of BNIP3L gene in PCa was verified.</p><p><strong>Results: </strong>A total of 47 adipocytokine-related differentially expressed genes (DEGs) were identified. Five genes (PPARGC1A, APOE, BNIP3L, STEAP4, and C1QTNF3) were selected as prognostic markers. The prognostic model demonstrated significant predictive accuracy in both training and validation cohorts. Patients with higher risk scores exhibited poorer survival outcomes. Immune cell infiltration analysis revealed that the high-risk group had increased immune and ESTIMATE scores, while the low-risk group had higher tumor purity. <i>In vitro</i> experiments confirmed the suppressive effects of BNIP3L on PCa cell proliferation, migration, and invasion.</p><p><strong>Conclusion: </strong>The prognostic model independently predicts the survival of patients with PCa, aiding in prognostic prediction and therapeutic efficacy. It expands the study of adipocytokine-related genes in PCa, presenting novel targets for treatment.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1475980"},"PeriodicalIF":4.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protamine 2 deficiency results in Septin 12 abnormalities.","authors":"Ondrej Sanovec, Michaela Frolikova, Veronika Kraus, Jana Vondrakova, Maryam Qasemi, Daniela Spevakova, Ondrej Simonik, Lindsay Moritz, Drew Lewis Caswell, Frantisek Liska, Lukas Ded, Jiri Cerny, Tomer Avidor-Reiss, Saher Sue Hammoud, Hubert Schorle, Pavla Postlerova, Klaus Steger, Katerina Komrskova","doi":"10.3389/fcell.2024.1447630","DOIUrl":"10.3389/fcell.2024.1447630","url":null,"abstract":"<p><p>There is a well-established link between abnormal sperm chromatin states and poor motility, however, how these two processes are interdependent is unknown. Here, we identified a possible mechanistic insight by showing that Protamine 2, a nuclear DNA packaging protein in sperm, directly interacts with cytoskeletal protein Septin 12, which is associated with sperm motility. Septin 12 has several isoforms, and we show, that in the <i>Prm2</i> ^<i>-/-</i> sperm, the short one (Mw 36 kDa) is mis-localized, while two long isoforms (Mw 40 and 41 kDa) are unexpectedly lost in <i>Prm2</i> ^<i>-/-</i> sperm chromatin-bound protein fractions. Septin 12 co-immunoprecipitated with Protamine 2 in the testicular cell lysate of WT mice and with Lamin B1/2/3 in co-transfected HEK cells despite we did not observe changes in Lamin B2/B3 proteins or SUN4 expression in <i>Prm2</i> ^<i>-/-</i> testes. Furthermore, the <i>Prm2</i> ^<i>-/-</i> sperm have on average a smaller sperm nucleus and aberrant acrosome biogenesis. In humans, patients with low sperm motility (asthenozoospermia) have imbalanced histone-protamine 1/2 ratio, modified levels of cytoskeletal proteins and we detected retained Septin 12 isoforms (Mw 40 and 41 kDa) in the sperm membrane, chromatin-bound and tubulin/mitochondria protein fractions. In conclusion, our findings present potential interaction between Septin 12 and Protamine 2 or Lamin B2/3 and describe a new connection between their expression and localization, contributing likely to low sperm motility and morphological abnormalities.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1447630"},"PeriodicalIF":4.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The application of artificial intelligence in diabetic retinopathy: progress and prospects.","authors":"Xinjia Xu, Mingchen Zhang, Sihong Huang, Xiaoying Li, Xiaoyan Kui, Jun Liu","doi":"10.3389/fcell.2024.1473176","DOIUrl":"https://doi.org/10.3389/fcell.2024.1473176","url":null,"abstract":"<p><p>In recent years, artificial intelligence (AI), especially deep learning models, has increasingly been integrated into diagnosing and treating diabetic retinopathy (DR). From delving into the singular realm of ocular fundus photography to the gradual development of proteomics and other molecular approaches, from machine learning (ML) to deep learning (DL), the journey has seen a transition from a binary diagnosis of \"presence or absence\" to the capability of discerning the progression and severity of DR based on images from various stages of the disease course. Since the FDA approval of IDx-DR in 2018, a plethora of AI models has mushroomed, gradually gaining recognition through a myriad of clinical trials and validations. AI has greatly improved early DR detection, and we're nearing the use of AI in telemedicine to tackle medical resource shortages and health inequities in various areas. This comprehensive review meticulously analyzes the literature and clinical trials of recent years, highlighting key AI models for DR diagnosis and treatment, including their theoretical bases, features, applicability, and addressing current challenges like bias, transparency, and ethics. It also presents a prospective outlook on the future development in this domain.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1473176"},"PeriodicalIF":4.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Tle6</i> deficiency in male mice led to abnormal sperm morphology and reduced sperm motility.","authors":"Kousuke Kazama, Yuki Miyagoshi, Hirofumi Nishizono","doi":"10.3389/fcell.2024.1481659","DOIUrl":"https://doi.org/10.3389/fcell.2024.1481659","url":null,"abstract":"<p><p>Infertility affects over 15% of the global population, and genetic mutations are a substantial cause of infertility. Recent studies have focused on the subcortical maternal complex and its role in early embryonic development. TLE6, a core protein in the subcortical maternal complex, is crucial for female fertility; however, its role in male germ cells remains poorly understood. In this study, we generated a novel <i>Tle6</i> knockout mouse model using CRISPR-Cas9 to examine the impact of <i>Tle6</i> mutations on male fertility. <i>Tle6</i> knockout males exhibited a reduced total sperm count compared to wild-type mice, with a marked decrease in highly motile sperm. Histological observation of <i>Tle6</i> ^+/- mouse testes showed no apparent structural changes, though impaired sperm maturation was observed. Immunofluorescence staining showed that TLE6 localizes to the midpiece of sperm. It was also confirmed that the expression of <i>Tle6</i> is reduced in <i>Tle6</i> ^+/- male mice. In addition, <i>Tle6</i> ^+/- mice exhibited a significant increase in serum testosterone levels compared to wild-type mice. Changes in the expression of genes related to sperm function were also observed in the testes of <i>Tle6</i> knockout mice. These findings suggest that TLE6 is involved in sperm production and function, and that mutations in TLE6 may impair the production of functional sperm in humans, potentially leading to infertility.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1481659"},"PeriodicalIF":4.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment with novel topoisomerase inhibitors in Ewing sarcoma models reveals heterogeneity of tumor response.","authors":"Unsun Lee, Ludmila Szabova, Victor J Collins, Melanie Gordon, Kristine Johnson, Deborah Householder, Stephanie Jorgensen, Lucy Lu, Laura Bassel, Fathi Elloumi, Cody J Peer, Ariana E Nelson, Sophia Varriano, Sudhir Varma, Ryan D Roberts, Zoe Weaver Ohler, William D Figg, Shyam K Sharan, Yves Pommier, Christine M Heske","doi":"10.3389/fcell.2024.1462840","DOIUrl":"https://doi.org/10.3389/fcell.2024.1462840","url":null,"abstract":"<p><strong>Introduction: </strong>The topoisomerase 1 (TOP1) inhibitor irinotecan is a standard-of-care agent for relapsed Ewing sarcoma (EWS), but its efficacy is limited by chemical instability, rapid clearance and reversibility, and dose-limiting toxicities, such as diarrhea. Indenoisoquinolines (IIQs) represent a new class of clinical TOP1 inhibitors designed to address these limitations.</p><p><strong>Methods: </strong>In this study, we evaluated the preclinical efficacy of three IIQs (LMP400, LMP744, and LMP776) in relevant models of EWS. We characterized the pharmacokinetics of IIQs in orthotopic xenograft models of EWS, optimized the dosing regimen through tolerability studies, and tested the efficacy of IIQs in a panel of six molecularly heterogeneous EWS patient-derived xenograft (PDX) models. For each PDX, we conducted whole genome and RNA sequencing, and methylation analysis.</p><p><strong>Results: </strong>We show that IIQs potently inhibit the proliferation of EWS cells in vitro, inducing complete cell growth inhibition at nanomolar concentrations via induction of DNA damage and apoptotic cell death. LMP400 treatment induced ≥30% tumor regression in two of six PDX models, with more durable regression compared to irinotecan treatment in one of these models. RNA sequencing of PDX models identified a candidate predictive biomarker gene signature for LMP400 response. These data, along with pharmacogenomic data on IIQs in sarcoma cell lines, are available at a new interactive public website: https://discover.nci.nih.gov/rsconnect/EwingSarcomaMinerCDB/.</p><p><strong>Discussion: </strong>Our findings suggest that IIQs may be promising new agents for a subset of EWS patients.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1462840"},"PeriodicalIF":4.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional evolution and functional biodiversity: 150 years of <i>déjà vu</i> or new physiology of evolution?","authors":"Leonid L Moroz, Daria Y Romanova","doi":"10.3389/fcell.2024.1485089","DOIUrl":"https://doi.org/10.3389/fcell.2024.1485089","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1485089"},"PeriodicalIF":4.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of the cytoskeleton in fibrotic diseases.","authors":"Caoyuan Niu, Yanan Hu, Kai Xu, Xiaoyue Pan, Lan Wang, Guoying Yu","doi":"10.3389/fcell.2024.1490315","DOIUrl":"https://doi.org/10.3389/fcell.2024.1490315","url":null,"abstract":"<p><p>Fibrosis is the process whereby cells at a damaged site are transformed into fibrotic tissue, comprising fibroblasts and an extracellular matrix rich in collagen and fibronectin, following damage to organs or tissues that exceeds their repair capacity. Depending on the affected organs or tissues, fibrosis can be classified into types such as pulmonary fibrosis, hepatic fibrosis, renal fibrosis, and cardiac fibrosis. The primary pathological features of fibrotic diseases include recurrent damage to normal cells and the abnormal activation of fibroblasts, leading to excessive deposition of extracellular matrix and collagen in the intercellular spaces. However, the etiology of certain specific fibrotic diseases remains unclear. Recent research increasingly suggests that the cytoskeleton plays a significant role in fibrotic diseases, with structural changes in the cytoskeleton potentially influencing the progression of organ fibrosis. This review examines cytoskeletal remodeling and its impact on the transformation or activation of normal tissue cells during fibrosis, potentially offering important insights into the etiology and therapeutic strategies for fibrotic diseases.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1490315"},"PeriodicalIF":4.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of cannabinoid receptor 1 absence on mouse liver mitochondria homeostasis: insight into mitochondrial unfolded protein response.","authors":"Rosalba Senese, Giuseppe Petito, Elena Silvestri, Maria Ventriglia, Nicola Mosca, Nicoletta Potenza, Aniello Russo, Sara Falvo, Francesco Manfrevola, Gilda Cobellis, Teresa Chioccarelli, Veronica Porreca, Vincenza Grazia Mele, Rosanna Chianese, Pieter de Lange, Giulia Ricci, Federica Cioffi, Antonia Lanni","doi":"10.3389/fcell.2024.1464773","DOIUrl":"https://doi.org/10.3389/fcell.2024.1464773","url":null,"abstract":"<p><strong>Introduction: </strong>The contribution of Cannabinoid type 1 receptor (CB1) in mitochondrial energy transduction mechanisms and mitochondrial activities awaits deeper investigations. Our study aims to assess the impact of CB1 absence on the mitochondrial compartment in the liver, focusing on both functional aspects and remodeling processes.</p><p><strong>Methods: </strong>We used CB1^-/- and CB1^+/+ male mice. Cytochrome C Oxidase activity was determined polarographically. The expression and the activities of separated mitochondrial complexes and supercomplexes were performed by using Blue-Native Page, Western blotting and histochemical staining for in-gel activity. Key players of Mitochondrial Quality Control processes were measured using RT-qPCR and Western blotting. Liver fine sub-cellular ultrastructural features were analyzed by TEM analysis.</p><p><strong>Results and discussion: </strong>In the absence of CB1, several changes in the liver occur, including increased oxidative capacity, reduced complex I activity, enhanced complex IV activity, general upregulation of respiratory supercomplexes, as well as higher levels of oxidative stress. The mitochondria and cellular metabolism may be affected by these changes, increasing the risk of ROS-related damage. CB1^-/- mice show upregulation of mitochondrial fusion, fission and biogenesis processes which suggests a dynamic response to the absence of CB1. Furthermore, oxidative stress disturbs mitochondrial proteostasis, initiating the mitochondrial unfolded protein response (UPR^mt). We noted heightened levels of pivotal enzymes responsible for maintaining mitochondrial integrity, along with heightened expression of molecular chaperones and transcription factors associated with cellular stress reactions. Additionally, our discoveries demonstrate a synchronized reaction to cellular stress, involving both UPR^mt and UPR^ER pathways.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1464773"},"PeriodicalIF":4.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}