Experimental Biology And Medicine (Maywood, N.J.)[JOURNAL]
Sun
200 papers
silencing of the thalamic Ca3.1 voltage-gated calcium channels demonstrates their region-specific role in anesthetic mediated hypnosis.
Timic Stamenic T, Feseha S, Fine-Raquet B … +2 more , Tadic VP, Todorovic SM
Exp Biol Med (Maywood) · 2025 · PMID 40453358 · Full text
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...
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 gene that encodes the low-threshold-activated Ca3.1 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 . 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) after administration of a traditional volatile GA isoflurane. Effective Ca3.1 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 Ca3.1 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 Ca3.1 channel in the VB thalamus did not affect any of the measured anesthetic endpoints. Hence, we concluded that Ca3.1 channels in nonspecific MIT thalamus have a preferential role in anesthetic hypnosis when compared to the sensory VB thalamus.
α-linolenic acid-induced facilitation of GABAergic synaptic transmission is mediated via acid-sensing ion channel (ASIC1a) activity in the basolateral amygdala.
Pidoplichko VI, Figueiredo TH, Braga MFM … +1 more , Marini AM
Exp Biol Med (Maywood) · 2025 · PMID 40444142 · Full text
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 pharmacore...
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.
Involvement of EGFR-AKT signaling in hemin-induced neurotoxicity.
Huang HJ, Tseng YJ, Lee IJ … +2 more , Lo YL, Lin AM
Exp Biol Med (Maywood) · 2025 · PMID 40444141 · Full text
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 fa...
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.
Vaccination with synthetic long peptide and CpG 2395 in AddaVax induces potent anti-tumor effects.
Jiang S, Zhao S, Zhao Q … +4 more , Wang Y, Zhang W, Feng Y, Zhang L
Exp Biol Med (Maywood) · 2025 · PMID 40395227 · Full text
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 pe...
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 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 T cell and CD8 T cell responses could be elicited by HCA587 SLP in combination with AddaVax and CpG 2395, and CD8 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 T cells may require more time than direct presentation to CD4 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.
A refined set of RxNorm drug names for enhancing unstructured data analysis in drug safety surveillance.
Guo W, Dong F, Liu J … +3 more , Aslam A, Patterson TA, Hong H
Exp Biol Med (Maywood) · 2025 · PMID 40386037 · Full text
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 surveillanc...
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.
Detection of respiratory syncytial virus based on RT-RPA and CRISPR-Cas12a.
Khamwut A, Nimnual J, Chomta N … +6 more , Nimsamer P, Mayuramart O, Kaewsapsak P, Pasittungkul S, Poovorawan Y, Payungporn S
Exp Biol Med (Maywood) · 2025 · PMID 40375877 · Full text
Human respiratory syncytial virus (hRSV) is one of the most prevalent viruses infecting children globally. In this study, we employed the RT-RPA with CRISPR/Cas12a detection methodology to detect and differentiate RSV-A...
Human respiratory syncytial virus (hRSV) is one of the most prevalent viruses infecting children globally. In this study, we employed the RT-RPA with CRISPR/Cas12a detection methodology to detect and differentiate RSV-A and RSV-B, particularly in resource-limited settings. The detection limit for RSV-A and RSV-B was approximately 10 and 10 copies/reaction, respectively. The assay revealed 100% specificity in detecting both RSV-A and RSV-B. Diagnostic accuracy was 90.32 and 93.55% for RSV-A and RSV-B, respectively, compared to RT-qPCR. These data indicate a proficient strategy for RSV screening, demonstrating promise for prospective applications in detecting diverse viral infections.
Pan-immune-inflammation value predicts survival in inflammatory breast cancer patients.
Hu Y, Li J, Wang M … +4 more , Wang X, Li J, Ji H, Niu X
Exp Biol Med (Maywood) · 2025 · PMID 40375876 · Full text
Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer subtype with poor survival. Identifying novel biomarkers is needed to predict survival for this highly progressive form of breast cancer. In this re...
Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer subtype with poor survival. Identifying novel biomarkers is needed to predict survival for this highly progressive form of breast cancer. In this retrospective study, we investigated pan-immune-inflammation value (PIV), a novel immune-inflammation-based biomarker which combined the peripheral blood parameters (lymphocytes, monocytes, neutrophils, and platelets) in a retrospective cohort of 143 IBC patients. Then we explored the difference of PIV levels in IBC and non-IBC cohorts and the relationship between PIV and clinical characteristics in IBC patients. The survival rates of disease-free survival (DFS) and overall survival (OS) in IBC patients were analyzed and univariate and multivariate statistics were used to evaluate the prognostic value. PIV had the most significantly predictive value in IBC patients compared with other peripheral blood parameters. The mean PIV value in IBC patients was significantly higher than non-IBC patients, and the significant difference between the IBC and non-IBC was also observed in subgroups with different clinical stages and pathologic types. Furthermore, PIV performed an extensive systemic immune prognostic factor on both DFS and OS in IBC patients, and PIV was identified an independent prognostic indicator for survival outcome in IBC patients in univariate and multivariate models. Our retrospective study demonstrated the prognostic value of PIV in IBC patients, suggesting the potential application of PIV in IBC treatment outcomes. PIV would also provide some insights into the mechanisms underlying the role of immune and inflammation in IBC development and progression.
Critical role of alpha spectrin in DNA repair: the importance of μ-calpain and Fanconi anemia proteins.
Lambert MW
Exp Biol Med (Maywood) · 2025 · PMID 40375875 · Full text
Nonerythroid spectrins are proteins important in maintaining the structural integrity and flexibility of the cell and nuclear membranes and are essential for a number of functionally important cellular processes. One of...
Nonerythroid spectrins are proteins important in maintaining the structural integrity and flexibility of the cell and nuclear membranes and are essential for a number of functionally important cellular processes. One of these proteins, nonerythroid α spectrin (αSpII), plays a critical role in DNA repair, specifically repair of DNA interstrand crosslinks (ICLs), where it acts as a scaffold, recruiting repair proteins to sites of damage. Loss or breakdown of αSpII is an important factor in a number of disorders. One of these is Fanconi anemia (FA), a genetic disorder characterized by bone marrow failure, chromosome instability, cancer predisposition, congenital abnormalities and a defect in DNA ICL repair. Significantly, breakdown of αSpII occurs in cells from a number of FA complementation groups, due to excessive cleavage by the protease, μ-calpain, leading to defective repair of DNA ICLs in telomeric and non-telomeric DNA. Knockdown of μ-calpain in FA cells by μ-calpain siRNA results in restoration of αSpII levels to normal and repair of DNA ICLs in telomeric and non-telomeric DNA, demonstrating the importance of αSpII stability in the repair process. It is hypothesized that there is a mechanistic link between excessive cleavage of αSpII by μ-calpain and defective DNA ICL repair in FA and that FA proteins, which are deficient in FA, play a key role in maintaining the stability of αSpII and preventing its cleavage by μ-calpain. All of these events are proposed to be important key factors involved in the pathophysiology of FA and suggest new avenues for potential therapeutic intervention.
Aberrant DNMT1-mediated DACH1 methylation is associated with colorectal adenoma-to-carcinoma progression.
Zhang Y, Liu H
Exp Biol Med (Maywood) · 2025 · PMID 40370966 · Full text
Colorectal cancer (CRC) remains a major contributor to cancer-related morbidity and mortality. While Dachshund homolog 1 (DACH1) was recognized as a critical regulator in cancer progression, its role in promoting or supp...
Colorectal cancer (CRC) remains a major contributor to cancer-related morbidity and mortality. While Dachshund homolog 1 (DACH1) was recognized as a critical regulator in cancer progression, its role in promoting or suppressing tumor development remains a subject of ongoing debate. This study aimed to elucidate the role of DACH1 in CRC progression and its underlying regulation mechanisms. The expression levels of Methyltransferase 1 (DNMT1) and DACH1, as well as its methylation status were assessed through a combination of TCGA data analysis and experimental validation using immunohistochemistry, PCR, methylation-specific PCR, and bisulfite sequencing RCR on 120 clinical samples, comprising normal mucosa, adenomas, and adenocarcinomas. The relationships among them were evaluated using Pearson or Spearman correlation analysis. The associations between the DACH1 and DNMT1 levels and clinicopathological parameters were examined to determine their clinical relevance. A progressive decrease in DACH1 expression and a concomitant increase in DACH1 promoter methylation and DNMT1 expression were observed from normal mucosa to adenoma and adenocarcinoma tissues. Higher DNMT1 expression and lower DACH1 expression were associated with poorer clinical outcomes, including worse tumor differentiation, lymphatic metastasis, and advanced tumor stages. Paired analysis of tissues from the same patient further validated their inverse expression patterns during CRC progression. DNMT1-mediated DACH1 epigenetic silencing plays a critical role in CRC progression, suggesting that the DNMT1-DACH1 regulatory axis may serve as a potential biomarker and therapeutic target in CRC.
Primary cilia and inflammatory response: unveiling new mechanisms in osteoarthritis progression.
Sun Y, Luo Z, Fu Y … +4 more , Ngo T, Wang W, Wang Y, Kong Y
Exp Biol Med (Maywood) · 2025 · PMID 40357414 · Full text
Osteoarthritis (OA) is a common degenerative joint disease that can lead to chronic pain and disability. The pathogenesis of OA involves chronic low-grade inflammation, characterized by the degradation of chondrocytes, i...
Osteoarthritis (OA) is a common degenerative joint disease that can lead to chronic pain and disability. The pathogenesis of OA involves chronic low-grade inflammation, characterized by the degradation of chondrocytes, inflammation of the synovium, and systemic low-grade inflammation. This inflammatory response accelerates the progression of OA and contributes to pain and functional impairment. Primary cilia play a crucial role in cellular signal transduction and the maintenance of cartilage matrix homeostasis, and their dysfunction is closely linked to inflammatory responses. Given these roles, primary cilia may significantly contribute to the pathogenesis of OA. This review explores inflammation-associated signaling pathways in OA, including NF-κB, MAPK, JAK/STAT, and PI3K/AKT/mTOR signaling. In addition, we place particular emphasis on cilia-mediated inflammatory modulation in OA. Primary cilia mediate chondrocyte responses to mechanical loading and inflammatory cytokines via pathways including NF-κB, MAPK, TRPV4, and Hedgehog signaling. Notably, alterations in the length and incidence of primary cilia in chondrocytes during OA further underscore their potential role in disease pathogenesis. The identification of biomarkers and therapeutic targets related to primary cilia and inflammatory pathways offers new potential for the treatment and management of OA.
Research on the online service mechanism of internet hospital in infectious disease prevention and control.
Zhao X, Huang H, Zeng G … +8 more , Shi Q, Zhu P, Zhang L, Li L, Liu L, Huang N, Liu W, Yu K
Exp Biol Med (Maywood) · 2025 · PMID 40351479 · Full text
Infectious diseases can sometimes lead to pandemics, often transmitted through public and social gatherings, including in-person hospital visits. Consequently, there is an urgent need for innovative approaches to prevent...
Infectious diseases can sometimes lead to pandemics, often transmitted through public and social gatherings, including in-person hospital visits. Consequently, there is an urgent need for innovative approaches to prevent their spread. Taking COVID-19 as an example, we have explored a remote, contactless hospital online model that offers the public online medical consultations, professional psychological counseling, and chronic disease management consultations, thereby mitigating the risk of new transmissions resulting from hospital visits. This model was implemented, validated, and practiced at West China Hospital in China from 29 January 2020, to 12 March 2020. It was also applicable to other infectious diseases, such as influenza A. In this research, we utilized the hospital's internet platform, supplemented by telephone services, to offer the following to the public: 1) General medical education and consultation related to epidemics and psychological anxiety; 2) Online screening for at-risk populations; 3) Online prescription and medication delivery services for patients with chronic diseases. Consequently, over a period of more than 1 month, the online epidemic platform completed a total of 32,755 cases, including 8,783 internet consultations and 1,082 telephone consultations for the public, as well as 22,890 internet consultations for chronic disease patients. Among these, 289 high-risk individuals were identified, with 3 cases confirmed as COVID-19 during follow-up diagnoses, while no infections were detected in the remaining individuals. In conclusion, this innovative medical model serves as a significant supplement to existing healthcare systems and has the potential to be expanded to other hospitals and other infectious diseases. It is particularly beneficial in scenarios where medical resources are limited, populations are under quarantine, and there is a large demand for medical services and anxiety management during infectious disease pandemics.
Gender difference in pre-clinical liver-directed gene therapy with lentiviral vectors.
Guzman E, Khoo C, O'Connor D … +5 more , Devarajan G, Iqball S, Souberbielle B, Mitrophanous K, Lad Y
Exp Biol Med (Maywood) · 2025 · PMID 40351478 · Full text
Viral vector-based therapies are effective therapeutics for the correction of several disorders, both in mouse models and in humans. Several pre-clinical studies have demonstrated differences in transduction efficiencies...
Viral vector-based therapies are effective therapeutics for the correction of several disorders, both in mouse models and in humans. Several pre-clinical studies have demonstrated differences in transduction efficiencies and therapeutic effect between male and female mice dosed with AAV-based gene therapy product candidates. Here, we report gender-specific transduction and transgene expression differences in mice dosed systemically with lentiviral vectors (LVV). Male mice systemically dosed with LVV carrying the reporter gene luciferase showed at least a 12-fold higher expression of luciferase and a higher vector copy number (VCN) in their livers compared with female mice. Lastly, PAH male mice dosed with a LVV carrying the human phenylalanine hydroxylase (PAH) transgene were observed to have a higher VCN than their female littermates. These findings suggest that sex-based differences initially observed in AAV-mediated therapies also apply to LVV, but the exact mechanism remains to be determined.
Erratum: Retraction: Pyridoxal 5' phosphate protects islets against streptozotocin-induced beta-cell dysfunction - and .
EBM Production Office
Exp Biol Med (Maywood) · 2025 · PMID 40342814 · Full text
[This corrects the article DOI: 10.3389/ebm.2024.10441.].
[This corrects the article DOI: 10.3389/ebm.2024.10441.].
Artificial intelligence for children with attention deficit/hyperactivity disorder: a scoping review.
Sun B, Cai F, Huang H … +2 more , Li B, Wei B
Exp Biol Med (Maywood) · 2025 · PMID 40342813 · Full text
Attention deficit/hyperactivity disorder is a common neuropsychiatric disorder that affects around 5%-7% of children worldwide. Artificial intelligence provides advanced models and algorithms for better diagnosis, predic...
Attention deficit/hyperactivity disorder is a common neuropsychiatric disorder that affects around 5%-7% of children worldwide. Artificial intelligence provides advanced models and algorithms for better diagnosis, prediction and classification of attention deficit/hyperactivity disorder. This study aims to explore artificial intelligence models used for the prediction, early diagnosis and classification of attention deficit/hyperactivity disorder as reported in the literature. A scoping review was conducted and reported in line with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. Out of the 1994 publications, 52 studies were included in the scoping review. The included articles reported the use of artificial intelligence for 3 different purposes. Of these included articles, artificial intelligence techniques were mostly used for the diagnosis of attention deficit/hyperactivity disorder (38/52, 79%). Magnetic resonance imaging (20/52, 38%) were the most frequently used data in the included articles. Most of the included articles used data sets with a size of <1,000 samples (28/52, 54%). Machine learning models were the most prominent branch of artificial intelligence used for attention deficit/hyperactivity disorder in the studies, and the support vector machine was the most used algorithm (34/52, 65%). The most commonly used validation in the studies was k-fold cross-validation (34/52, 65%). A higher level of accuracy (98.23%) was found in studies that used Convolutional Neural Networks algorithm. This review provides an overview of research on artificial intelligence models and algorithms for attention deficit/hyperactivity disorder, providing data for further research to support clinical decision-making in healthcare.
Retraction: Hydrogen-rich saline protects myocardium against ischemia/reperfusion injury in rats.
EBM Editorial Office
Exp Biol Med (Maywood) · 2025 · PMID 40290456 · Full text
[This retracts the article DOI: 10.3181/0812-RM-349.].
[This retracts the article DOI: 10.3181/0812-RM-349.].
Developing predictive models for µ opioid receptor binding using machine learning and deep learning techniques.
Liu J, Li J, Li Z … +5 more , Dong F, Guo W, Ge W, Patterson TA, Hong H
Exp Biol Med (Maywood) · 2025 · PMID 40177220 · Full text
Opioids exert their analgesic effect by binding to the µ opioid receptor (MOR), which initiates a downstream signaling pathway, eventually inhibiting pain transmission in the spinal cord. However, current opioids are add...
Opioids exert their analgesic effect by binding to the µ opioid receptor (MOR), which initiates a downstream signaling pathway, eventually inhibiting pain transmission in the spinal cord. However, current opioids are addictive, often leading to overdose contributing to the opioid crisis in the United States. Therefore, understanding the structure-activity relationship between MOR and its ligands is essential for predicting MOR binding of chemicals, which could assist in the development of non-addictive or less-addictive opioid analgesics. This study aimed to develop machine learning and deep learning models for predicting MOR binding activity of chemicals. Chemicals with MOR binding activity data were first curated from public databases and the literature. Molecular descriptors of the curated chemicals were calculated using software Mold2. The chemicals were then split into training and external validation datasets. Random forest, k-nearest neighbors, support vector machine, multi-layer perceptron, and long short-term memory models were developed and evaluated using 5-fold cross-validations and external validations, resulting in Matthews correlation coefficients of 0.528-0.654 and 0.408, respectively. Furthermore, prediction confidence and applicability domain analyses highlighted their importance to the models' applicability. Our results suggest that the developed models could be useful for identifying MOR binders, potentially aiding in the development of non-addictive or less-addictive drugs targeting MOR.
Coenzyme Q10 alleviates neurological deficits in a mouse model of intracerebral hemorrhage by reducing inflammation and apoptosis.
Yang X, Zhao Y, Yu S … +2 more , Chi L, Cai Y
Exp Biol Med (Maywood) · 2025 · PMID 40093659 · Full text
This research study was directed towards to assessing whether coenzyme Q10 (CoQ10) is linked to neuroprotection and induces anti-inflammatory and anti-neuronal death responses in an Intracerebral hemorrhage (ICH) mouse m...
This research study was directed towards to assessing whether coenzyme Q10 (CoQ10) is linked to neuroprotection and induces anti-inflammatory and anti-neuronal death responses in an Intracerebral hemorrhage (ICH) mouse model via right caudate nucleus injection with collagenase VII. Autologous blood was injected into mice to induce ICH. We found that FoxM1 was upregulated in the ICH-injured animals. Moreover, CoQ10 treatment effectively ameliorated neurological deficits, mitigated cerebral edema, and minimized hematoma in model mice, demonstrating dose-dependent efficacy and promoting the functional recovery of the animals. ELISA and real-time PCR assays of pro-inflammatory cytokines indicated that CoQ10 was capable of alleviating neuroinflammation in ICH. In line with the part of CoQ10 in attenuating the inflammatory response, CoQ10 also suppressed cell apoptosis in the ICH-injured brain, which partly accounts for its neuroprotective effect. Furthermore, our analysis of different inflammatory pathways indicated that CoQ10 targeted the nuclear factor-kappa B signaling axis. Our findings suggest that CoQ10 protects against ICH by mitigating neuroinflammatory responses and preventing neuronal apoptosis, with the underlying mechanism possibly being connected with nuclear factor-kappa B pathway regulation. Therefore, CoQ10 holds significant potential as a therapeutic strategy for treating ICH.
AI-powered topic modeling: comparing LDA and BERTopic in analyzing opioid-related cardiovascular risks in women.
Ma L, Chen R, Ge W … +6 more , Rogers P, Lyn-Cook B, Hong H, Tong W, Wu N, Zou W
Exp Biol Med (Maywood) · 2025 · PMID 40093658 · Full text
Topic modeling is a crucial technique in natural language processing (NLP), enabling the extraction of latent themes from large text corpora. Traditional topic modeling, such as Latent Dirichlet Allocation (LDA), faces l...
Topic modeling is a crucial technique in natural language processing (NLP), enabling the extraction of latent themes from large text corpora. Traditional topic modeling, such as Latent Dirichlet Allocation (LDA), faces limitations in capturing the semantic relationships in the text document although it has been widely applied in text mining. BERTopic, created in 2022, leveraged advances in deep learning and can capture the contextual relationships between words. In this work, we integrated Artificial Intelligence (AI) modules to LDA and BERTopic and provided a comprehensive comparison on the analysis of prescription opioid-related cardiovascular risks in women. Opioid use can increase the risk of cardiovascular problems in women such as arrhythmia, hypotension etc. 1,837 abstracts were retrieved and downloaded from PubMed as of April 2024 using three Medical Subject Headings (MeSH) words: "opioid," "cardiovascular," and "women." Machine Learning of Language Toolkit (MALLET) was employed for the implementation of LDA. BioBERT was used for document embedding in BERTopic. Eighteen was selected as the optimal topic number for MALLET and 23 for BERTopic. ChatGPT-4-Turbo was integrated to interpret and compare the results. The short descriptions created by ChatGPT for each topic from LDA and BERTopic were highly correlated, and the performance accuracies of LDA and BERTopic were similar as determined by expert manual reviews of the abstracts grouped by their predominant topics. The results of the t-SNE (t-distributed Stochastic Neighbor Embedding) plots showed that the clusters created from BERTopic were more compact and well-separated, representing improved coherence and distinctiveness between the topics. Our findings indicated that AI algorithms could augment both traditional and contemporary topic modeling techniques. In addition, BERTopic has the connection port for ChatGPT-4-Turbo or other large language models in its algorithm for automatic interpretation, while with LDA interpretation must be manually, and needs special procedures for data pre-processing and stop words exclusion. Therefore, while LDA remains valuable for large-scale text analysis with resource constraints, AI-assisted BERTopic offers significant advantages in providing the enhanced interpretability and the improved semantic coherence for extracting valuable insights from textual data.
The effects of major abdominal surgery on skeletal muscle mitochondrial respiration in relation to systemic redox status and cardiopulmonary fitness.
Stevens JL, McKenna HT, Minnion M … +3 more , Murray AJ, Feelisch M, Martin DS
Exp Biol Med (Maywood) · 2025 · PMID 40061448 · Full text
More complex surgeries are being performed in increasingly sicker patients, resulting in a greater burden of postoperative morbidity. Delineating the metabolic and bioenergetic changes that occur in response to surgical...
More complex surgeries are being performed in increasingly sicker patients, resulting in a greater burden of postoperative morbidity. Delineating the metabolic and bioenergetic changes that occur in response to surgical stress may further our understanding about how humans respond to injury and aid the identification of resilient and frail phenotypes. Skeletal muscle biopsies were taken from patients undergoing hepato-pancreatico-biliary surgery at the beginning and end of the procedure to measure mitochondrial respiration and thiol status. Blood samples were taken at the same timepoints to measure markers of inflammation and systemic redox state. A sub-group of patients underwent cardiopulmonary exercise testing prior to surgery, and were assigned to two groups according to their oxygen consumption at anaerobic threshold (≤10 and >10 mL/kg/min) to determine whether redox phenotype was related to cardiorespiratory fitness. No change in mitochondrial oxidative phosphorylation capacity was detected. However, a 26.7% increase in LEAK (uncoupled) respiration was seen after surgery (P = 0.03). Free skeletal muscle cysteine also increased 27.0% (P = 0.003), while S-glutathionylation and other sulfur and nitrogen-based metabolite concentrations remained unchanged. The increase in LEAK was 200% greater in fit patients (P = 0.004). Baseline plasma inflammatory markers, including TNF-⍺ and IL-6 were greater in unfit patients, 96.6% (P = 0.04) and 111.0% (P = 0.02) respectively, with a 58.7% lower skeletal muscle nitrite compared to fit patients. These data suggest that oxidative phosphorylation is preserved during the acute intraoperative period. Increase in free cysteine may demonstrate the muscle's response to surgical stress to maintain redox balance. The differences in tissue metabolism between fitness groups suggests underlying metabolic phenotypes of frail and resilient patients. For example, increased LEAK in fitter patients may indicate mitochondrial adaptation to stress. Higher baseline measurements of inflammation and lower tissue nitrite in unfit patients, may reflect a state of frailty and susceptibility to postoperative demise.
Artificial intelligence in the diagnosis of uveal melanoma: advances and applications.
Dadzie AK, Iddir SP, Ganesh S … +6 more , Ebrahimi B, Rahimi M, Abtahi M, Son T, Heiferman MJ, Yao X
Exp Biol Med (Maywood) · 2025 · PMID 40046904 · Full text
Advancements in machine learning and deep learning have the potential to revolutionize the diagnosis of melanocytic choroidal tumors, including uveal melanoma, a potentially life-threatening eye cancer. Traditional machi...
Advancements in machine learning and deep learning have the potential to revolutionize the diagnosis of melanocytic choroidal tumors, including uveal melanoma, a potentially life-threatening eye cancer. Traditional machine learning methods rely heavily on manually selected image features, which can limit diagnostic accuracy and lead to variability in results. In contrast, deep learning models, particularly convolutional neural networks (CNNs), are capable of automatically analyzing medical images, identifying complex patterns, and enhancing diagnostic precision. This review evaluates recent studies that apply machine learning and deep learning approaches to classify uveal melanoma using imaging modalities such as fundus photography, optical coherence tomography (OCT), and ultrasound. The review critically examines each study's research design, methodology, and reported performance metrics, discussing strengths as well as limitations. While fundus photography is the predominant imaging modality being used in current research, integrating multiple imaging techniques, such as OCT and ultrasound, may enhance diagnostic accuracy by combining surface and structural information about the tumor. Key limitations across studies include small dataset sizes, limited external validation, and a reliance on single imaging modalities, all of which restrict model generalizability in clinical settings. Metrics such as accuracy, sensitivity, and area under the curve (AUC) indicate that deep learning models have the potential to outperform traditional methods, supporting their further development for integration into clinical workflows. Future research should aim to address current limitations by developing multimodal models that leverage larger, diverse datasets and rigorous validation, thereby paving the way for more comprehensive, reliable diagnostic tools in ocular oncology.
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