Experimental Biology and Medicine最新文献

{"title":"Induced mesenchymal stem cells generated from periodontal ligament fibroblast for regenerative therapy.","authors":"Hemanathan Vembuli, Sheeja Rajasingh, Patrick Nabholz, Jefferson Guenther, Brian R Morrow, Margaret M Taylor, Marziyeh Aghazadeh, Vinoth Sigamani, Johnson Rajasingh","doi":"10.3389/ebm.2025.10342","DOIUrl":"10.3389/ebm.2025.10342","url":null,"abstract":"<p><p>Bone fractures and bone loss represent significant global health challenges, with their incidence rising due to an aging population. Despite autologous bone grafts remain the gold standard for treatment, challenges such as limited bone availability, immune reactions, and the risk of infectious disease transmission have driven the search for alternative cell-based therapies for bone regeneration. Stem cells derived from oral tissues and umbilical cord mesenchymal stem cells (MSCs) have shown potential in both preclinical and clinical studies for bone tissue regeneration. However, their limited differentiation capacity and wound healing abilities necessitate the exploration of alternative cell sources. In this study, we generated induced pluripotent stem cells (iPSCs) using a safe, nonviral and mRNA-based approach from human periodontal ligament fibroblasts (PDLF), an easily accessible cell source. These iPSCs were subsequently differentiated into MSCs, referred to as induced MSCs (iMSCs). The resulting iMSCs were homogeneous, highly proliferative, and possessed anti-inflammatory properties, suggesting their potential as a superior alternative to traditional MSCs for regenerative therapy. These iMSCs demonstrated trilineage differentiation potential, giving rise to osteocytes, chondrocytes, and adipocytes. The iMSC-derived osteocytes (iOSTs) were homogeneous, patient-specific and showed excellent attachment and growth on commercial collagen-based membranes, highlighting their suitability for bone tissue regeneration applications. Given their promising characteristics compared to traditional MSCs, PDLF-derived iMSCs are strong candidates for future clinical studies in bone regeneration and other regenerative dental therapies.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10342"},"PeriodicalIF":2.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional mass spectrometry indicates anti-protease and complement activity increase with COVID-19 severity.","authors":"Douglas D Fraser, Swapan Roy, Matt Kuruc, Maritza Quintero, Logan R Van Nynatten, Gediminas Cepinskas, Haiyan Zheng, Amenah Soherwardy, Devjit Roy","doi":"10.3389/ebm.2025.10308","DOIUrl":"10.3389/ebm.2025.10308","url":null,"abstract":"<p><p>Investigations on some innate immunity proteins can yield misleading information, as investigators often rely on static measurements and assume a direct correlation to function. As protein function is often not directly proportional to protein abundance, and mechanistic pathways are interconnected and under constant feedback regulatory control, functional analysis is required. In this study, we used functional mass spectrometry to measure anti-protease and complement activity in plasma obtained from coronavirus disease 2019 (COVID-19) patients. Our data suggests that within 48 h of hospital admission, COVID-19 patients undergo a protease storm with significantly elevated neutrophil elastase (p < 0.001) and lymphocyte granzyme B (p < 0.01), while, anti-protease activity is significantly increased, including alpha-1 antitrypsin (AAT; p < 0.001) and alpha-1-antichymotrypsin (ACT; p < 0.001). Concurrently, the ratio of C3a to C3beta activity significantly decreased with increasing COVID-19 severity, suggesting more complement activation (Mild COVID-19 p < 0.05; Severe COVID-19 p < 0.001). Activity levels of AAT, ACT and C3a/C3beta remained unchanged over 10 hospital days. Our data suggests that COVID-19 is associated with both a protease storm and complement activation, with the former somewhat balanced with increased anti-protease activity. Evaluation of the AAT/ACT ratio and C3a/C3beta ratio indicated that COVID-19 severity is associated with both neutrophil elastase neutralization and complement activation.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10308"},"PeriodicalIF":2.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired fracture healing is associated with callus chondro-osseous junction abnormalities in periostin-null and osteopontin-null mice.","authors":"Marc Teitelbaum, Maya D Culbertson, Charlene Wetterstrand, J Patrick O'Connor","doi":"10.3389/ebm.2024.10066","DOIUrl":"10.3389/ebm.2024.10066","url":null,"abstract":"<p><p>Periostin and osteopontin are matricellular proteins abundantly expressed in bone fracture callus. Null mutation of either the periostin (<i>Postn</i>) gene or the osteopontin (<i>Spp1</i>) gene can impair bone fracture healing. However, the cell and molecular pathways affected by loss of POSTN or SPP1 which lead to impaired fracture healing are not well understood. To identify potential pathways, a detailed radiological, histological, and immunohistochemical analysis of femur fracture healing in <i>Postn</i>-null (<i>Postn</i>KO), <i>Spp1</i>-null (<i>Spp1</i>KO), and normal (WT) mice was performed. Apparent changes in specific protein levels identified by immunohistochemistry were confirmed by mRNA quantitation. Comparisons between the <i>Postn</i>KO and <i>Spp1</i>KO fracture calluses were confounded by interactions between the two genes; loss of <i>Postn</i> reduced <i>Spp1</i> expression and loss of <i>Spp1</i> reduced <i>Postn</i> expression. Consequently, alterations in fracture healing between mice heterozygous for the <i>Postn</i>-null allele (<i>Postn</i>HET) as well as the <i>Postn</i>KO and <i>Spp1</i>KO mice were similar. Calluses from <i>Postn</i>HET, <i>Postn</i>KO, and <i>Spp1</i>KO mice all had dysmorphic chondro-osseous junctions and reduced numbers of osteoclasts. The dysmorphic chondro-osseous junctions in the <i>Postn</i>HET, <i>Postn</i>KO, and <i>Spp1</i>KO calluses were associated with reduced numbers of MMP-13 expressing hypertrophic chondrocytes, consistent with delayed cartilage resolution. Unlike collagen X expressing callus chondrocytes, chondrocytes only expressed MMP-13 when localized to the chondro-osseous junction or after traversing the chondro-osseous junction. Cyclooxygenase-2 (COX-2) expression also appeared to be reduced in osteoclasts from the <i>Postn</i>HET, <i>Postn</i>KO, and <i>Spp1</i>KO calluses, including in those osteoclasts localized at the chondro-osseous junction. The results indicate that POSTN and SPP1 are necessary for normal chondro-osseous junction formation and that signaling from the chondro-osseous junction, possibly from COX-2 expressing osteoclasts, regulates callus vasculogenesis and chondrocyte hypertrophy necessary for endochondral ossification during fracture healing.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"249 ","pages":"10066"},"PeriodicalIF":2.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Function of formyl peptide receptor 2 in adriamycin resistance of breast cancer.","authors":"Landi Su, Jingjing Li, Li Qin, Yang Feng, Dingwen Xu","doi":"10.3389/ebm.2024.10281","DOIUrl":"https://doi.org/10.3389/ebm.2024.10281","url":null,"abstract":"<p><p>FPRL2 has been shown to be associated with a variety of tumours but has not been well studied in breast cancer. In this study, We combine molecular biology techniques with bioinformatics to analyze the role of FPRL2 in breast cancer and adriamycin resistance. By utilizing bioinformatics, we mine TCGA and GEO public databases to assess FPRL2 expression in breast cancer patients and its correlation with patient prognosis. Additionally, we employ the DepMap tool to probe the CCLE database, examining the relationship between FPRL2 gene effects and adriamycin sensitivity. Chemosensitivity of Adriamycin in breast cancer cells was tested by CCK-8 method. The apoptosis of breast cancer cells was determined by flow cytometry assay. Expression of p-ERK5 and p-AKT was determined by Western blot assay. Our results indicate that the expression level of FPRL2 in tumor tissues of breast cancer patients is significantly higher than that in normal tissues, and it correlates with poor prognosis in patients. Furthermore, the expression level of FPRL2 in tumor tissues of adriamycin-resistant breast cancer patients is also significantly higher than that in adriamycin-sensitive patients. The IC₅₀ (Inhibitory Concentration 50). Of Adriamycin was significantly lower in FPRL2 silenced cells than those control cells. The apoptosis was markedly increased in FPRL2-silenced cells. p-ERK5 and p-AKT in breast cancer cells was significantly reduced after FPRL2 knocked down. In Conclusion, FPRL2 mediates Adriamycin resistance in breast cancer cells, and knockdown of FPRL2 increased apoptosis and decreased Adriamycin resistance in breast cancer cells.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"249 ","pages":"10281"},"PeriodicalIF":2.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: Pyridoxal 5' phosphate protects islets against streptozotocin-induced beta-cell dysfunction - <i>in vitro</i> and <i>in vivo</i>.","authors":"","doi":"10.3389/ebm.2024.10441","DOIUrl":"https://doi.org/10.3389/ebm.2024.10441","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.1258/ebm.2011.010361.].</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"249 ","pages":"10441"},"PeriodicalIF":2.8,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole blood transcriptome profile identifies motor neurone disease RNA biomarker signatures.","authors":"Sulev Kõks, Karin Rallmann, Mari Muldmaa, Jack Price, Abigail L Pfaff, Pille Taba","doi":"10.3389/ebm.2024.10401","DOIUrl":"10.3389/ebm.2024.10401","url":null,"abstract":"<p><p>Blood-based biomarkers for motor neuron disease are needed for better diagnosis, progression prediction, and clinical trial monitoring. We used whole blood-derived total RNA and performed whole transcriptome analysis to compare the gene expression profiles in (motor neurone disease) MND patients to the control subjects. We compared 42 MND patients to 42 aged and sex-matched healthy controls and described the whole transcriptome profile characteristic for MND. In addition to the formal differential analysis, we performed functional annotation of the genomics data and identified the molecular pathways that are differentially regulated in MND patients. We identified 12,972 genes differentially expressed in the blood of MND patients compared to age and sex-matched controls. Functional genomic annotation identified activation of the pathways related to neurodegeneration, RNA transcription, RNA splicing and extracellular matrix reorganisation. Blood-based whole transcriptomic analysis can reliably differentiate MND patients from controls and can provide useful information for the clinical management of the disease and clinical trials.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"249 ","pages":"10401"},"PeriodicalIF":2.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging AI to improve disease screening among American Indians: insights from the Strong Heart Study.","authors":"Paul Rogers, Thomas McCall, Ying Zhang, Jessica Reese, Dong Wang, Weida Tong","doi":"10.3389/ebm.2024.10341","DOIUrl":"10.3389/ebm.2024.10341","url":null,"abstract":"<p><p>Screening tests for disease have their performance measured through sensitivity and specificity, which inform how well the test can discriminate between those with and without the condition. Typically, high values for sensitivity and specificity are desired. These two measures of performance are unaffected by the outcome prevalence of the disease in the population. Research projects into the health of the American Indian frequently develop Machine learning algorithms as predictors of conditions in this population. In essence, these models serve as <i>in silico</i> screening tests for disease. A screening test's sensitivity and specificity values, typically determined during the development of the test, inform on the performance at the population level and are not affected by the prevalence of disease. A screening test's positive predictive value (PPV) is susceptible to the prevalence of the outcome. As the number of artificial intelligence and machine learning models flourish to predict disease outcomes, it is crucial to understand if the PPV values for these <i>in silico</i> methods suffer as traditional screening tests in a low prevalence outcome environment. The Strong Heart Study (SHS) is an epidemiological study of the American Indian and has been utilized in predictive models for health outcomes. We used data from the SHS focusing on the samples taken during Phases V and VI. Logistic Regression, Artificial Neural Network, and Random Forest were utilized as <i>in silico</i> screening tests within the SHS group. Their sensitivity, specificity, and PPV performance were assessed with health outcomes of varying prevalence within the SHS subjects. Although sensitivity and specificity remained high in these <i>in silico</i> screening tests, the PPVs' values declined as the outcome's prevalence became rare. Machine learning models used as <i>in silico</i> screening tests are subject to the same drawbacks as traditional screening tests when the outcome to be predicted is of low prevalence.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"249 ","pages":"10341"},"PeriodicalIF":2.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"scRNA-seq reveals elevated interferon responses and TNF-α signaling via NFkB in monocytes in children with uncomplicated malaria.","authors":"Collins M Morang'a, Riley S Drake, Vincent N Miao, Nancy K Nyakoe, Dominic S Y Amuzu, Vincent Appiah, Yaw Aniweh, Yaw Bediako, Saikou Y Bah, Alex K Shalek, Gordon A Awandare, Thomas D Otto, Lucas Amenga-Etego","doi":"10.3389/ebm.2024.10233","DOIUrl":"10.3389/ebm.2024.10233","url":null,"abstract":"<p><p>Malaria causes significant morbidity and mortality worldwide, disproportionately impacting sub-Saharan Africa. Disease phenotypes associated with <i>Plasmodium falciparum</i> infection can vary widely, from asymptomatic to life-threatening. To date, prevention efforts, particularly those related to vaccine development, have been hindered by an incomplete understanding of which factors impact host immune responses resulting in these divergent outcomes. Here, we conducted a field study of 224 individuals to determine host-parasite factors associated with symptomatic malaria \"patients\" compared to asymptomatic malaria-positive \"controls\" at both the community and healthy facility levels. We further performed comprehensive immune profiling to obtain deeper insights into differences in response between the pair. First, we determined the relationship between host age and parasite density in patients (n = 134/224) compared to controls (n = 90/224). Then, we applied single-cell RNA sequencing to compare the immunological phenotypes of 18,176 peripheral blood mononuclear cells isolated from a subset of the participants (n = 11/224), matched on age, sex, and parasite density. Patients had higher parasite densities compared to the controls, although the levels had a negative correlation with age in both groups, suggesting that they are key indicators of disease pathogenesis. On average, patients were characterized by a higher fractional abundance of monocytes and an upregulation of innate immune responses, including those to type I and type II interferons and tumor necrosis factor-alpha signaling via NFκB. Further, in the patients, we identified more putative interactions between antigen-presenting cells and proliferating CD4 T cells, and naïve CD8 T cells driven by MHC-I and MHC-II signaling pathways, respectively. Together, these findings highlight transcriptional differences between immune cell subsets associated with disease phenotypes that may help guide the development of improved malaria vaccines and new therapeutic interventions.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"249 ","pages":"10233"},"PeriodicalIF":2.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline gene expression in BALB/c and C57BL/6 peritoneal macrophages influences but does not dictate their functional phenotypes.","authors":"Carlos M Restrepo, Alejandro Llanes, Lizzi Herrera, Esteban Ellis, Iliana Quintero, Patricia L Fernández","doi":"10.3389/ebm.2024.10377","DOIUrl":"10.3389/ebm.2024.10377","url":null,"abstract":"<p><p>Macrophages are effector cells of the immune system and essential modulators of immune responses. Different functional phenotypes of macrophages with specific roles in the response to stimuli have been described. The C57BL/6 and BALB/c mouse strains tend to selectively display distinct macrophage activation states in response to pathogens, namely, the M1 and M2 phenotypes, respectively. Herein we used RNA-Seq and differential expression analysis to characterize the baseline gene expression pattern of unstimulated resident peritoneal macrophages from C57BL/6 and BALB/c mice. Our aim is to determine if there is a possible predisposition of these mouse strains to any activation phenotype and how this may affect the interpretation of results in studies concerning their interaction with pathogens. We found differences in basal gene expression patterns of BALB/c and C57BL/6 mice, which were further confirmed using RT-PCR for a subset of relevant genes. Despite these differences, our data suggest that baseline gene expression patterns of both mouse strains do not appear to determine by itself a specific macrophage phenotype.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"249 ","pages":"10377"},"PeriodicalIF":2.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating microRNA as promising biomarkers in hypertrophic cardiomyopathy: can advanced cardiac magnetic resonance unlock new insights in research?","authors":"Olga S Chumakova, Elena A Mershina","doi":"10.3389/ebm.2024.10334","DOIUrl":"10.3389/ebm.2024.10334","url":null,"abstract":"<p><p>Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder associated with an increased risk of arrhythmias, heart failure, and sudden cardiac death. Current imaging and clinical markers are not fully sufficient in accurate diagnosis and patient risk stratification. Although known cardiac biomarkers in blood are used, they lack specificity for HCM and primarily stratify for death due to heart failure in overt cases. Non-coding RNAs, particularly microRNAs, have emerged as promising biomarkers due to their role in regulating gene expression in both healthy and pathological hearts. Circulating microRNA signatures may dynamically reflect the progression of HCM, offering potential utility in diagnosis and disease monitoring as well as inform biologic pathways for innovative therapeutic strategies. However, studying microRNAs in cardiovascular diseases is still in its early stages and poses many challenges. This review focuses on emerging research perspectives using advanced cardiac magnetic resonance techniques. We presume, that the search for circulating miR signatures associated with specific adverse myocardial features observed on cardiac magnetic resonance imaging - such as fibrosis, disarray, and microvascular disease - represents a promising direction in HCM research.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"249 ","pages":"10334"},"PeriodicalIF":2.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}