Yang Jie Tseng, Hui-Ju Huang, Chien-Hui Lin, Anya Maan-Yuh Lin
{"title":"A double-edged effect of hypoxia on astrocyte-derived exosome releases.","authors":"Yang Jie Tseng, Hui-Ju Huang, Chien-Hui Lin, Anya Maan-Yuh Lin","doi":"10.3389/ebm.2025.10559","DOIUrl":"https://doi.org/10.3389/ebm.2025.10559","url":null,"abstract":"<p><p>Exosomes are the smallest extracellular vesicles secreted from cells, carrying different cargos, including nucleic acids, proteins and others which transfer from cells to cells. The properties of exosomes depend on the donor cells. Hypoxia, referring to a sublethal and insufficient oxygen supply, reportedly influences exosome secretion of hypoxic cells. In the present study, we focused on the effects of hypoxia on exosomes obtained from CTX-TNA2 astrocyte cells exposed to different durations of hypoxia followed by normoxia as a model of hypoxic preconditioning. To evaluate the functions of exosomes, primary cultured cortical neurons were treated with hemin, a potent neurotoxin. Our sulforhodamine B assay showed that incubation of hemin (30 μM) consistently induced neuronal death. Co-incubation of exosomes from CTX-TNA2 cells subjected to 2 hr-hypoxia plus 6 hr-renormoxia (2H/6R exosomes), but not 12 hr-hypoxia plus 24 hr-renormoxia (12H/24R exosomes), attenuated hemin-induced cell death and reduction in growth associated protein 43 level (a biomarker of neurite outgrowth). Western blot assay demonstrated that 2H/6R exosomes attenuated hemin-induced elevations in inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) levels (two proinflammatory biomarkers) as well as heme oxygenase-1 (HO-1). In contrast, 12H/24R exosomes did not alter hemin-induced elevation in HO-1 but further augmented hemin-induced increases in iNOS and COX-2. Moreover, 2H/6R exosomes attenuated hemin-induced reduction in glutathione hydroperoxidase 4 (a biomarker of ferroptosis) and elevation in active caspase 3 (a biomarker of apoptosis) while 12H/24R exosomes did not effectively alter hemin-induced programed cell death. In conclusion, our study showed that 2H/6R exosomes possessed neuroprotective activities while 12H/24R exosomes had mild pro-inflammatory activities, suggesting that different hypoxic preconditionings influenced CTX-TNA2 cells which then secreted exosomes with differential biological activities. These findings highlight a double-edged role of hypoxia on exosome functions.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10559"},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224869","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":"Optimal transport reveals immune perturbation and fingerprints over time in COVID-19 vaccination.","authors":"Zexuan Wang, Jiong Chen, Matei Ionita, Qipeng Zhan, Zhuoping Zhou, Li Shen","doi":"10.3389/ebm.2025.10445","DOIUrl":"https://doi.org/10.3389/ebm.2025.10445","url":null,"abstract":"<p><p>Mass cytometry enables high-throughput characterization of heterogeneous cell populations at single-cell resolution, using metal isotopes to capture cellular signals and avoiding the spectral overlap common in flow cytometry. Despite advancements, conventional data analysis often focuses on manual gating or clustering within specific samples, overlooking disparities across subjects or biological samples. To address this gap, we propose a novel framework that treats the cell-by-protein matrix as a high-dimensional distribution, using Quantized Optimal Transport (QOT) to quantify distances between samples based on their cellular protein expression profiles. This approach allows for a direct comparison of distributions without relying on predefined gating strategies, capturing subtle variations in the data. We validated our method through two experiments using real-world time-series Coronavirus Disease 2019 (COVID-19) cytometry data. First, we conducted a leave-one-out analysis to identify immunologically unstable proteins over time, revealing CD3 and CD45 as the proteins changing the most during the vaccine response. Second, we aimed to capture individual immune fingerprints over time by calculating pairwise Wasserstein distances between samples and applying hierarchical clustering. Using silhouette scores to evaluate clustering effectiveness, we identified optimal combinations of immunological markers that effectively grouped samples from the same participant across different time points. Our findings demonstrate that the QOT framework provides a robust and flexible tool for cohort-level analysis of mass cytometry data, enabling the identification of unstable immunological markers and capturing immune response heterogeneity among vaccinated cohorts.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10445"},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224871","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}
Chandra Mohan Reddy Muthumula, Yaswanthi Yanamadala, Kuppan Gokulan, Kumari Karn, Helen Cunny, Vicki Sutherland, Janine H Santos, Sangeeta Khare
{"title":"Effect of in utero and lactational exposure to antiretroviral therapy on the gut microbial composition and metabolic function in aged rat offspring.","authors":"Chandra Mohan Reddy Muthumula, Yaswanthi Yanamadala, Kuppan Gokulan, Kumari Karn, Helen Cunny, Vicki Sutherland, Janine H Santos, Sangeeta Khare","doi":"10.3389/ebm.2025.10468","DOIUrl":"https://doi.org/10.3389/ebm.2025.10468","url":null,"abstract":"<p><p>Despite the highly effective impact of antiretroviral therapy (ART) in reducing mother-to-child transmission of human immunodeficiency virus (HIV), there are concerns of long-term impacts of ART on the health of the offspring. The implications of perinatal exposure to antiviral drugs on the gut bacterial population and metabolic function in the offspring is unclear but may influence health outcomes given the various reported effects of the microbiome in human health. This study aims to gain insight into the potential effect of <i>in utero</i> and lactational exposure to ART on gut microbiota populations and short-chain fatty acids (SCFAs) production in aged rat offspring. Pregnant rats were administered a combination of antiretroviral drugs (abacavir/dolutegravir/lamivudine) at two different dose levels during gestation and throughout lactation, and the fecal bacterial abundance and SCFA levels of the offspring were analyzed when they reached 12 months of age. Our results showed dose-dependent and sex-based differences in fecal microbial abundance at various taxonomic levels. Specifically, we found a decline in <i>Firmicutes</i> in males, and an increase in <i>Actinobacteria</i> among males and females. Furthermore, a sex-specific distribution reorganization of <i>Lactobacillus</i>, <i>Bifidobacterium</i>, and <i>Akkermansia</i> was identified. No significant difference in the concentration of prominent SCFAs and IgA levels were identified. These findings provide preliminary information indicating the need to evaluate perinatal effects of ART more comprehensively on the gut bacterial and metabolic function in future studies, and their potential role in offspring health outcomes.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10468"},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224870","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}
Kim B Pedersen, Tomislav Jelesijevic, Tamara M Morris, Sarah M Melton, Ashley S Henderson, John F Glenn, Gregory J Davenport, Martin J J Ronis, Peter J Winsauer
{"title":"Chronic administration of a cannabis-derived mixture at an antihyperalgesic dose does not significantly enhance hepatotoxicity or the development of metabolic dysfunction-associated steatohepatitis in male mice.","authors":"Kim B Pedersen, Tomislav Jelesijevic, Tamara M Morris, Sarah M Melton, Ashley S Henderson, John F Glenn, Gregory J Davenport, Martin J J Ronis, Peter J Winsauer","doi":"10.3389/ebm.2025.10356","DOIUrl":"10.3389/ebm.2025.10356","url":null,"abstract":"<p><p>Cannabis and cannabinoid mixtures have been linked to a variety of health benefits including pain mitigation, suppression of nausea produced by chemotherapeutic agents, anti-inflammatory effects, and effects on energy homeostasis, glucose, and lipid metabolism. The latter properties have led to the suggestion that these products could have therapeutic effects on the development of metabolic dysfunction-associated steatohepatitis (MASH) - a severe type of liver pathology in obese and diabetic patients. However, varying agonist and antagonistic properties of different cannabinoids on the endogenous cannabinoid system make prediction regarding hepatic effects and diet interactions difficult. The current study was designed to examine hepatic pathology following chronic administration of a cannabinoid mixture (NEPE14) at a dose equivalent to one previously demonstrating antihyperalgesic effects in rats. The effects of NEPE14 were investigated in a mouse model of MASH produced by feeding a Western diet rich in fat and simple sugars. After 24 weeks of NEPE14 administration, there was no hepatotoxicity in mice receiving the control diet and no significant exacerbation of MASH in mice receiving the Western diet. In conclusion, no chronic liver toxicity was observed, but there was also no evidence for protection against MASH by this product.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10356"},"PeriodicalIF":2.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208117","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}
Nemanja Useinovic, Adre Newson, Michelle Near, Stefan Maksimovic, Benjamin Volvovitz, Nidia Quillinan, Vesna Jevtovic-Todorovic
{"title":"Anesthesia-induced developmental neurotoxicity in the setting of systemic inflammation: the role of microglia.","authors":"Nemanja Useinovic, Adre Newson, Michelle Near, Stefan Maksimovic, Benjamin Volvovitz, Nidia Quillinan, Vesna Jevtovic-Todorovic","doi":"10.3389/ebm.2025.10549","DOIUrl":"10.3389/ebm.2025.10549","url":null,"abstract":"<p><p>Although it is well documented in animal research that an early exposure to general anesthetics during critical stages of synaptogenesis disturbs normal brain development ultimately leading to cognitive and affective impairments, it is less clear whether and how surgical interventions and/or underlying systemic inflammation impact the detrimental effects of general anesthetics. Some emerging evidence suggests that aseptic systemic inflammation preceding exposure to the commonly used general anesthetics worsens anesthesia-induced neuroapoptosis and activates inflammasome pathways while resulting in impaired cognitive-affective behaviors. To improve our understanding of the underlying mechanisms, here we focused on multicellular interactions between damaged neurons and microglia since microglia is the resident macrophages within the brain that respond to stress. Using infant rats (post-natal day 7) and most commonly used inhaled anesthetic, sevoflurane, we examine microglia role in sevoflurane-induced inflammation-propagated developmental neurotoxicity. We show that sevoflurane exposure leads to a significant neuroapoptosis in young rat pup hippocampal subiculum, a neuroapoptosis that is worsened in the setting of systemic inflammation caused by either lipopolysaccharide (LPS) injection or trauma (tibial fracture). The worsening is not only shown in terms of the intensity of neuroapoptosis but in its duration and onset. We further report that sevoflurane-induced neuroapoptosis triggers activation of microglia, which in turn releases proinflammatory cytokine MCP-1 and upregulates endothelial cell adhesion molecule, ICAM-1. This leads to T-lymphocyte infiltration in the hippocampal subiculum, an event that further perpetuates microglia activation in an attempt to control neuroapoptosis which is suggested by the fact that microglia depletion leads to a significant worsening of sevoflurane-induced developmental neuroapoptosis. Our work gets us a step closer to making our animal work more relevant to the clinical setting and hence more translational. This is vitally important considering that exposure to anesthesia is exceedingly rare in the absence of any kind of a pathological process.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10549"},"PeriodicalIF":2.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198637","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}
Tamara Timic Stamenic, Simon Feseha, Brier Fine-Raquet, Vasilije P Tadic, Slobodan M Todorovic
{"title":"<i>In vivo</i> silencing of the thalamic Ca<sub>V</sub>3.1 voltage-gated calcium channels demonstrates their region-specific role in anesthetic mediated hypnosis.","authors":"Tamara Timic Stamenic, Simon Feseha, Brier Fine-Raquet, Vasilije P Tadic, Slobodan M Todorovic","doi":"10.3389/ebm.2025.10553","DOIUrl":"10.3389/ebm.2025.10553","url":null,"abstract":"<p><p>Although substantial progress has been made in the last three decades towards our understanding of how general anesthetics (GAs) act at the molecular level, much less is known about how GAs cause loss of consciousness at the level of neuronal networks. The role of thalamus as an important brain region in anesthetic-induced hypnosis is relatively well established, but the specific roles of voltage-gated ion channels in different functional regions of the thalamus in anesthetic mechanisms are not well studied. To address this gap in knowledge, we selectively silenced the <i>Cacna1g</i> gene that encodes the low-threshold-activated Ca<sub>V</sub>3.1 T-type voltage-gated calcium channel subunit by injecting short-hairpin RNA (shRNA) into midline and intralaminar - nonspecific thalamus (MIT) and sensory - specific ventrobasal (VB) thalamic nuclei in wild-type (WT) mice. Control animals were injected with scrambled shRNA. To validate our silencing approach, we performed patch-clamp experiments in acute thalamic slices <i>ex vivo</i>. In injected animals we determined anesthetic endpoints such as hypnosis measured with loss of righting reflex (LORR) and immobilization measured with loss of withdrawal reflex (LOWR) <i>in vivo</i> after administration of a traditional volatile GA isoflurane. Effective Ca<sub>V</sub>3.1 channel knock-down was documented by greatly diminished amplitudes of T-currents and absence of rebound burst firing in our patch-clamp recordings from thalamic slices. We found that knocking down Ca<sub>V</sub>3.1 channels in MIT significantly decreased inhaled isoflurane concentration that is required to induce LORR, but it did not affect speed of anesthetic induction and the immobilizing effect of isoflurane. In contrast, knocking down the Ca<sub>V</sub>3.1 channel in the VB thalamus did not affect any of the measured anesthetic endpoints. Hence, we concluded that Ca<sub>V</sub>3.1 channels in nonspecific MIT thalamus have a preferential role in anesthetic hypnosis when compared to the sensory VB thalamus.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10553"},"PeriodicalIF":2.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198636","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":"Involvement of EGFR-AKT signaling in hemin-induced neurotoxicity.","authors":"Hui-Ju Huang, Yang-Jie Tseng, I-Jung Lee, Yu-Li Lo, Anya Maan-Yuh Lin","doi":"10.3389/ebm.2025.10554","DOIUrl":"10.3389/ebm.2025.10554","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH), as bleeding from ruptured vessels within the brain, is the second leading neuropathological problem following ischemic stroke. In the present study, the involvement of epithelial growth factor receptor (EGFR)-tyrosine kinase (TK) signaling underlying ICH-related neurodegeneration was investigated using afatinib, a clinically available EGFR-tyrosine kinase inhibitor (EGFR-TKI). We employed hemin (a breakdown product of hemoglobin) to mimic the pathophysiology of ICH in primary cultured cortical neurons. Using a lactate dehydrogenase (LDH) assay, incubation of hemin concentration- and time-dependently induced neuronal death. Simultaneous incubation of afatinib (10 nM) significantly inhibited hemin (30 μM)-induced neuronal death. Immunofluorescent data demonstrated that co-treatment of afatinib for 1 h attenuated hemin (30 μM)-induced elevation in phosphorylated-EGFR (p-EGFR) immunoreactivity and neurite impairment. Western blot assay demonstrated that co-incubation of afatinib for 16 h diminished hemin-induced elevation in p-EGFR and p-AKT, tumor necrosis factor-α and cyclooxygenase 2 (two proinflammatory biomarkers) as well as heme oxygenase-1 (HO-1, an enzyme catalyzing heme/hemin), glutathione hydroperoxidase 4 and receptor-interacting protein 3 (two biomarkers of ferroptosis and necroptosis). In addition, co-treatment of afatinib for 24 h inhibited hemin-induced NO production in the culture medium. In conclusion, our study shows that afatinib via blocking EGFR-AKT signaling inhibits hemin-induced EGFR-AKT activation, neuroinflammation, HO-1 expression and programed cell death, suggesting that EGFR-AKT signaling is involved in hemin-induced neurotoxicity and may be a druggable target for ICH.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10554"},"PeriodicalIF":2.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180969","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}
Volodymyr I Pidoplichko, Taiza H Figueiredo, Maria F M Braga, Ann M Marini
{"title":"α-linolenic acid-induced facilitation of GABAergic synaptic transmission is mediated via acid-sensing ion channel (ASIC1a) activity in the basolateral amygdala.","authors":"Volodymyr I Pidoplichko, Taiza H Figueiredo, Maria F M Braga, Ann M Marini","doi":"10.3389/ebm.2025.10545","DOIUrl":"10.3389/ebm.2025.10545","url":null,"abstract":"<p><p>Epilepsy affects more than 70 million people worldwide. A seizure focus that develops in different cortical brain regions can present as either focal or generalized seizures. Temporal lobe epilepsy is a highly pharmacoresistant form of epilepsy that involves the amygdala, hippocampus with or without hippocampal sclerosis as well as other limbic structures. Loss and/or dysfunction of GABAergic inhibitory neurons play a critical role in tipping the balance toward excitation. Synchronous burst firing is a feature of inhibitory neurons that is thought to regulate and rectify large excitatory neuronal networks in the BLA and is thought to underlie higher cognitive function. Acid sensing ion channels (ASIC) activated by decreases in pH, the presence of ammonium ion or a slight lowering of temperature are present on excitatory and inhibitory neurons and can alter excitability. The net effect of the activation of ASIC1a channels in the BLA is inhibition. ASIC1a channels are active in the basal state, enhancing primarily GABAergic inhibition by direct depolarization of interneurons but also by indirect excitation of interneurons via ASIC1a-mediated depolarization of pyramidal neurons. In this study, we examine the contribution of ASIC1a channel activation on alpha-linolenic acid (ALA)-induced GABAergic inhibitory synchronous burst firing in the BLA. Our results show that ALA initiates inhibitory bursts that are dependent, in part, on the activation of ASIC1a channels that may in turn be mediated by mature brain-derived neurotrophic factor.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10545"},"PeriodicalIF":2.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180912","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":"Vaccination with synthetic long peptide and CpG 2395 in AddaVax induces potent anti-tumor effects.","authors":"Shanshan Jiang, Shuqi Zhao, Qiaojiajie Zhao, Yinfang Wang, Weihua Zhang, Yangmeng Feng, Lijie Zhang","doi":"10.3389/ebm.2025.10509","DOIUrl":"10.3389/ebm.2025.10509","url":null,"abstract":"<p><p>Cancer/testis antigen HCA587, also known as MAGE-C2, highly expressed in a wide range of malignant tumors with unique immunological characteristics, serves as a potential target for tumor immunotherapy. Synthetic long peptides from HCA587 (HCA587 SLP) were proved to be highly immunogenic and promising in the application of cancer vaccine composed of Freud's adjuvant (FA) and CpG 1826, whereas, scarce CD8<sup>+</sup> T cell response may limit their anti-tumor effects during previous research. In this study, notwithstanding the multiple potential of IFN-α in immune modulation, there was no evidence of IFN-α in enhancing the immune response elicited by HCA587 SLP vaccine (HCA587 SLP + FA + CpG 1826). Given the unpleasant side-effects of Freud's adjuvant, then we applied AddaVax as a substitute for Freud's adjuvant, and we demonstrated that HCA587 SLP, formulated with AddaVax and CpG 2395, could induce more robust immune response in comparison with combined use of AddaVax and CpG 1826 through ELISpot assay. Furthermore, both IFN-γ-secreting CD4<sup>+</sup> T cell and CD8<sup>+</sup> T cell responses could be elicited by HCA587 SLP in combination with AddaVax and CpG 2395, and CD8<sup>+</sup> T cell response was most obviously observed under the condition of 10-h inhibition of cytokine secretion by brefeldin A post 10-h stimulation with HCA587 SLP, suggesting that cross presentation of exogenous long peptides to CD8<sup>+</sup> T cells may require more time than direct presentation to CD4<sup>+</sup> T cells. This vaccine formulation also conferred protection against challenge with HCA587-expressing B16 melanoma presented by delayed tumor growth and prolonged survival compared. This formulation of HCA587 SLP vaccine holds promise for the treatment of patients with cancer in future clinical trials.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10509"},"PeriodicalIF":2.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12088984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110198","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}
Wenjing Guo, Fan Dong, Jie Liu, Aasma Aslam, Tucker A Patterson, Huixiao Hong
{"title":"A refined set of RxNorm drug names for enhancing unstructured data analysis in drug safety surveillance.","authors":"Wenjing Guo, Fan Dong, Jie Liu, Aasma Aslam, Tucker A Patterson, Huixiao Hong","doi":"10.3389/ebm.2025.10374","DOIUrl":"10.3389/ebm.2025.10374","url":null,"abstract":"<p><p>Adverse drug events are harms associated with drug use, whether the drug is used correctly or incorrectly. Identifying adverse drug events is vital in pharmacovigilance to safeguard public health. Drug safety surveillance can be performed using unstructured data. A comprehensive and accurate list of drug names is essential for effective identification of adverse drug events. While there are numerous sources for drug names, RxNorm is widely recognized as a leading resource. However, its effectiveness for unstructured data analysis in drug safety surveillance has not been thoroughly assessed. To address this, we evaluated the drug names in RxNorm for their suitability in unstructured data analysis and developed a refined set of drug names. Initially, we removed duplicates, the names exceeding 199 characters, and those that only describe administrative details. Drug names with four or fewer characters were analyzed using 18,000 drug-related PubMed abstracts to remove names which rarely appear in unstructured data. The remaining names, which ranged from five to 199 characters, were further refined to exclude those that could lead to inaccurate drug counts in unstructured data analysis. We compared the efficiency and accuracy of the refined set with the original RxNorm set by testing both on the 18,000 drug-related PubMed abstracts. The results showed a decrease in both computational cost and the number of false drug names identified. Further analysis of the removed names revealed that most originated from only one of the 14 sources. Our findings suggest that the refined set can enhance drug identification in unstructured data analysis, thereby improving pharmacovigilance.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10374"},"PeriodicalIF":2.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093129","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}