Experimental Biology And Medicine (Maywood, N.J.)[JOURNAL]
Sun
200 papers
Correlation study of CAR, PLR, NLR with the prognosis of cardiogenic cerebral embolism patients.
Du X, Li X, Yue S … +5 more , Sun Y, Zhao M, Zhou L, Wang X, Yang Y
Exp Biol Med (Maywood) · 2025 · PMID 40599820 · Full text
This study explored the association between inflammatory biomarkers-C-reactive protein to albumin ratio (CAR), platelet to lymphocyte ratio (PLR), and neutrophil to lymphocyte ratio (NLR)-and the prognosis of patients wi...
This study explored the association between inflammatory biomarkers-C-reactive protein to albumin ratio (CAR), platelet to lymphocyte ratio (PLR), and neutrophil to lymphocyte ratio (NLR)-and the prognosis of patients with cardiogenic cerebral embolism (CCE). We retrospectively analyzed data from 80 CCE patients diagnosed between June 2020 and June 2024, categorizing them into favorable and unfavorable prognosis groups based on outcomes such as death, recurrence, and disability. The CAR, PLR, and NLR values were calculated from routine blood tests, and statistical analyses, including Spearman correlation, multivariate logistic regression, and ROC curve analysis, were performed to examine their prognostic significance. Results showed that the unfavorable prognosis group had significantly higher CAR, PLR, and NLR values compared to the favorable group (P < 0.05). Spearman correlation analysis revealed positive associations between these biomarkers and prognosis (r = 0.319 for CAR, 0.238 for PLR, 0.251 for NLR, all P < 0.05). Multivariate analysis identified CAR and NLR as independent risk factors for unfavorable prognosis (OR = 1.034 for CAR, OR = 3.887 for NLR). ROC analysis determined optimal cutoff values for CAR (>0.74), PLR (>160.00), and NLR (>3.53) to predict unfavorable prognosis with AUCs of 0.796, 0.694, and 0.705, respectively. The combined biomarker test yielded an AUC of 0.899. Kaplan-Meier survival analysis indicated significantly lower survival rates for patients with higher levels of CAR, PLR, and NLR (P < 0.05). In conclusion, elevated CAR, PLR, and NLR are reliable indicators of a poor prognosis in CCE patients.
The effects of cannabidiol and its main metabolites on human neural stem cells.
Latham LE, Gu Q, Liu S … +2 more , Wang C, Liu F
Exp Biol Med (Maywood) · 2025 · PMID 40584168 · Full text
Cannabidiol (CBD) has been used for different purposes by different populations in recent years. When consumed by pregnant women, CBD can pass through the placenta and enter the fetal blood stream. There is concern over...
Cannabidiol (CBD) has been used for different purposes by different populations in recent years. When consumed by pregnant women, CBD can pass through the placenta and enter the fetal blood stream. There is concern over adverse effects of fetal exposure to CBD and its major metabolites (7-OH-CBD and 7-COOH-CBD). In the present study, human neural stem cells (NSCs) were treated with CBD and its metabolites at different concentrations for various durations to understand how the drug may affect fetal brain development. NSCs were also treated with delta-9 tetrahydrocannabinol (THC) for comparison purposes. CBD, 7-OH-CBD and 7-COOH-CBD dose-dependently reduced NSC viability. CBD and 7-OH-CBD reduced NSC number at the G1 phase. A 24 h exposure did not cause significant change in NSC proliferation. At concentrations comparable to those detected in human blood, longer exposures to CBD, 7-OH-CBD and 7-COOH-CBD caused more obvious cell death. After NSCs differentiation, CBD treatment reduced GFAP and cannabinoid receptor 2 (CB2) expression. THC treatment reduced the GFAP expression, but the change in CB2 expression did not reach statistical significance. The expression of cannabinoid receptor 1 (CB1) and beta-tubulin III were not significantly altered by drug exposures. The study demonstrated that clinically relevant concentrations of CBD, 7-OH-CBD and 7-COOH-CBD affect basic physiological features of human NSCs. After NSC differentiation, the reduced expression of CB2 receptors and GFAP on differentiated cells further indicated the vulnerability of developing central nervous system to CBD and THC. These data will help to contextualize neurodevelopmental studies that may not accurately model human metabolite profiles of CBD.
Assessing potential desflurane-induced neurotoxicity using nonhuman primate neural stem cell models.
Wang C, Latham LE, Liu S … +4 more , Talpos J, Patterson TA, Hanig JP, Liu F
Exp Biol Med (Maywood) · 2025 · PMID 40584167 · Full text
Safety concerns about general anesthetics (GA), such as desflurane (a commonly used gaseous anesthetic agent), arose from studies documenting neural cell death and behavioral changes after early-life exposure to anesthet...
Safety concerns about general anesthetics (GA), such as desflurane (a commonly used gaseous anesthetic agent), arose from studies documenting neural cell death and behavioral changes after early-life exposure to anesthetics and compounds with related modes of action. Neural stem cells (NSCs) can recapitulate most critical events during central nervous system (CNS) development and, therefore, represent a valuable model for evaluating potential desflurane-induced developmental neurotoxicity. In this study, NSCs harvested from the hippocampus of a gestational day 80 monkey brain were applied to explore the temporal relationships between desflurane exposures and neural stem cell health, proliferation, differentiation, and viability. At clinically relevant doses (5.7%), desflurane exposure did not result in significant changes in NSC viability [lactate dehydrogenase (LDH) release] and NSC proliferation profile/rate by Cell Cycle Assay, in both short term (3 h) and prolonged (24 h) exposure groups. However, when monkey NSCs were guided to differentiate into neural cells (including neurons, astrocytes, and oligodendrocytes), and then exposed to desflurane (5.7%), no significant changes were detected in LDH release after a 3-h exposure, but a significant elevation in LDH release into the culture medium was observed after a 24-h exposure. Desflurane (24 h)-induced neural damage was further supported by increased expression levels of multiple cytokines, e.g., G-CSF, IL-12, IL-9, IL-10, and TNF-α compared with the controls. Additionally, our immunocytochemistry and flow cytometry data demonstrated a remarkable attenuation of differentiated neurons as evidenced by significantly decreased numbers of polysialic acid neural cell adhesion molecule (PSA-NCAM)-positive cells in the desflurane-exposed (prolonged) cultures. Our data suggests that at the clinically relevant concentration, desflurane did not induce NSC damage/death, but impaired the differentiated neuronal cells after prolonged exposure. Collectively, PSA-NCAM could be essential for neuronal viability. Desflurane-induced neurotoxicity was primarily associated with the loss of differentiated neurons. Changes in the neuronal specific marker, PSA-NCAM, may help understand the underlying mechanisms associated with anesthetic-induced neuronal damage. These findings should be helpful/useful for the understanding of the diverse effects of desflurane exposure on the developing brain and could be used to optimize the usage of these agents in the pediatric setting.
Comparative electrophysiological study of neuroactive steroid-induced hypnosis in mice: sex and drug-specific differences.
Martin A, Coulter I, Cox R … +3 more , Covey DF, Todorovic SM, Timic Stamenic T
Exp Biol Med (Maywood) · 2025 · PMID 40557248 · Full text
Since the discovery of their anesthetic effects, some neuroactive steroids have been used as general anesthetics. However, their effects on thalamocortical oscillations and potential sex differences that are associated w...
Since the discovery of their anesthetic effects, some neuroactive steroids have been used as general anesthetics. However, their effects on thalamocortical oscillations and potential sex differences that are associated with their hypnotic/sedative effects are not well studied. Here, we investigated spectral characteristics and sex differences in hypnotic effect of two common neuroactive steroids: Allopregnanolone (AlloP) and its synthetic analog Alphaxalone (Alpx) in wild type mice using behavioral testing (loss of righting reflex - LORR) and electrophysiology. Our data revealed sex-differences in LORR duration with 100 mg/kg intraperitoneally injected AlloP and Alpx confirming that females are more sensitive to neuroactive steroid-induced hypnosis. Spectral analysis, thalamocortical and corticocortical phase synchronization showed notable differences between two neuroactive steroids. AlloP induced a profound reduction in local field potential (LFP) and electroencephalogram (EEG) after LORR with higher LFP/EEG suppression in females during first 60 min after injection. Also, we observed a decrease in thalamocortical synchronization in lower (delta, theta, alpha) and increase in higher low gamma frequency in AlloP group; similar effects were observed in Alpx treated animals with no change in delta thalamocortical phase locking values. Synchronization between right and left cortex was reduced in all frequencies except low gamma in AlloP-treated group. Similarly, Alpx induced reduction in corticocortical synchronization for theta, alpha and beta frequencies. We conclude that AlloP and Alpx have distinct electrophysiological signatures in thalamocortical circuitry that may underly their sedative/hypnotic effects.
Cystamine reduces neurodegeneration and epileptogenesis following soman-induced status epilepticus in rats.
Biney AK, Schultz CR, Stone MF … +4 more , Nguyen DA, Wang A, de Araujo Furtado M, Lumley LA
Exp Biol Med (Maywood) · 2025 · PMID 40552019 · Full text
Acute exposure to a seizure-inducing dose of an organophosphorus nerve agent inhibits acetylcholinesterase, leading to pharmacoresistance if benzodiazepine treatment is delayed. Following soman-induced status epilepticus...
Acute exposure to a seizure-inducing dose of an organophosphorus nerve agent inhibits acetylcholinesterase, leading to pharmacoresistance if benzodiazepine treatment is delayed. Following soman-induced status epilepticus (SE) in rats, prolonged seizure is associated with severe and widespread neurodegeneration. We evaluated the aminothiol cystamine, the oxidized form of cysteamine, for neuroprotective potential against soman-induced SE and associated neurodegeneration. Cystamine has a myriad of effects including antioxidant properties, neuroprotective effects, and immunomodulation, among others, which is of interest in evaluating neuroprotective efficacy against cholinergic-induced neurodegeneration. Adult male rats implanted with telemetry transmitters for continuous EEG recording were exposed to soman and treated with the muscarinic antagonist atropine sulfate and the oxime asoxime dimethanesulfonate 1 min after exposure to increase survival. Midazolam was administered 30 min after seizure onset. Cystamine (10 or 50 mg/kg) or vehicle was administered 30 min after seizure onset and again 4 h after soman exposure. The initial seizure duration, the EEG power integral at 6 h after exposure, and the percentage of rats that developed spontaneous recurrent seizure were reduced in rats treated with cystamine, compared to those that received only midazolam. In addition, cystamine reduced neurodegeneration in seizure-sensitive brain regions following soman exposure, compared to midazolam. Our findings highlight the potential for aminothiols to serve as adjunctive therapy to midazolam in treating cholinergic-induced toxicity and suggest broader applications of aminothiols in neuroprotection and neurological disorders.
Deep brain stimulation for dystonia treatment in cerebral palsy: efficacy exploration.
Zheng H, Zhang D, Xiang W … +4 more , Gan Y, Peng Z, Wu Y, Fu P
Exp Biol Med (Maywood) · 2025 · PMID 40552018 · Full text
Dystonia, a challenging movement disorder, poses significant therapeutic challenges due to its resistance to treatment, resulting in both physical impairment and substantial mental distress, ultimately impacting overall...
Dystonia, a challenging movement disorder, poses significant therapeutic challenges due to its resistance to treatment, resulting in both physical impairment and substantial mental distress, ultimately impacting overall quality of life. Cerebral palsy (CP) is a major non-genetic cause of secondary dystonia, characterized by diverse clinical presentations. This study aims to comprehensively evaluate the effectiveness of deep brain stimulation (DBS) as a therapeutic intervention for individuals with dystonic CP. We conducted a systematic analysis of studies assessing the safety and effectiveness of DBS, with a focus on its long-term outcomes [PROSPERO (Unique identifier: CRD42023399285)]. We examined factors that influence treatment response and proposed strategies to enhance patient quality of life. DBS, especially when targeting the basal ganglia or innovative targets, shows promise as a therapeutic approach for dystonic CP. While existing controlled studies confirm its safety and effectiveness, a thorough evaluation of long-term efficacy remains crucial. This research highlights the potential of DBS in improving the lives of individuals with dystonic CP, providing hope for further refinement, innovation, and broader clinical application of this therapeutic approach.
Biofilm and surface-motility profiles under polymyxin B stress in multidrug-resistant KAPE pathogens isolated from Ghanaian hospital ICUs.
Abban MK, Ayerakwa EA, Isawumi A
Exp Biol Med (Maywood) · 2025 · PMID 40546280 · Full text
The threat of antimicrobial resistance in Ghana is increasing with the recent emergence of KAPE pathogens (, , and species) from the hospital environment. As opportunistic pathogens, KAPE leverage the formation of biof...
The threat of antimicrobial resistance in Ghana is increasing with the recent emergence of KAPE pathogens (, , and species) from the hospital environment. As opportunistic pathogens, KAPE leverage the formation of biofilms and swarms to survive stringent environmental conditions. As research continues to investigate approaches that bacteria employ to exacerbate infection, this study explored biofilm and swarm formation in MDR KAPE pathogens under polymyxin B stress emerging from Ghanaian hospitals. The antimicrobial susceptibility profile of KAPE pathogens to conventional antibiotics and polymyxin B was investigated via antibiotic disk diffusion and broth microdilution assays. Biofilm inhibition and eradication assays, swarm motility and a resazurin-based metabolic assay were used to profile bacterial phenotypic characteristics under polymyxin B stress. The strains exhibited resistance to the tested antibiotics with a high level of resistance to polymyxin B (PMB) (≥512 μg/mL). Additionally, the strains formed biofilms and bacterial swarms at 37°C. In the presence of PMB (≥512 μg/mL), KAPE pathogens formed swarms with no significant reduction in bacterial swarms at 1,048 μg/mL. Biofilm was observed for all strains with PMB neither inhibiting nor eradicating at high PMB (2048 μg/mL). Additionally, there were no significant differences in the phenotypic and antimicrobial susceptibility profiles of clinical and environmental KAPE pathogens from Ghanaian ICUs. Overall, the study established that clinical and environmental KAPE pathogens from Ghanaian ICUs exhibit adaptive phenotypic and resistance characteristics that could potentially enhance bacterial survival during host colonization and infection. This could undermine treatment strategies and pose public health challenges in Ghana.
Retrotransposition-competent L1s are increased in the genomes of individuals with amyotrophic lateral sclerosis.
Pfaff AL, Kõks S
Exp Biol Med (Maywood) · 2025 · PMID 40529392 · Full text
An individual's genetics contributes to their risk of developing amyotrophic lateral sclerosis (ALS); however, there is still a large proportion of the heritability of ALS to be understood. Part of this missing heritabil...
An individual's genetics contributes to their risk of developing amyotrophic lateral sclerosis (ALS); however, there is still a large proportion of the heritability of ALS to be understood. Part of this missing heritability may lie in complex variants, such as the long interspersed element 1 (L1) retrotransposon, which have yet to be evaluated. The majority of L1 insertions in the human genome are no longer able to retrotranspose, but to date 279 retrotransposition-competent (RC) L1s have been reported. Many RC-L1s are polymorphic for their presence/absence; therefore, each individual will have a different number and complement of RC-L1s. These elements have been hypothesized to be involved in disease processes by multiple mechanisms such as somatic mutation by retrotransposition, the triggering of neuroinflammation and DNA damage. We hypothesize that L1s may influence disease development either through their effects on endogenous genes or through the properties that enable them to retrotranspose. Whole genome sequencing data from the New York Genome Center ALS consortium were used to characterize L1 variation identifying 2,803 polymorphic L1 elements and association analysis was performed in European individuals (ALS/ALS with other neurological disorder (ALSND) n = 2,653, controls n = 320). There were no individual L1 elements associated with disease, but we did identify a significant increase in the number of RC-L1s in ALS/ALSND genomes (p = 0.01) and the presence of ≥46 RC-L1s showed the most significant association (OR = 1.09 (1.02-1.16), p = 0.01) with disease. Analysis of individual L1s and their association with age at onset and survival identified one L1 whose presence was significantly associated with a lower age at onset (52.7 years) compared to homozygous absent individuals (59.2 years) (padj = 0.009). Our study has identified novel genetic factors for both disease risk and age at onset in ALS providing further evidence for the role of L1 retrotransposons in neurodegenerative diseases.
Alcohol consumption may not be a risk factor for sarcopenia in the older adults.
Mao EH, Bu YL, Liu QL … +5 more , Xu JS, Lu X, Yang XL, Gao W, Shen ZK
Exp Biol Med (Maywood) · 2025 · PMID 40510244 · Full text
The relationship between drinking and sarcopenia remains controversial. The aim of the present study was to investigate the association of alcohol drinking with sarcopenia in the older adults. A prospective study with 52...
The relationship between drinking and sarcopenia remains controversial. The aim of the present study was to investigate the association of alcohol drinking with sarcopenia in the older adults. A prospective study with 5244 Chinese community-dwelling older adults aged ≥65 years was performed. Sarcopenia was assessed by appendicular skeletal muscle mass index, grip strength, and gait speed. A quantitative questionnaire was used to obtain the information of alcohol drinking. After 4-year follow-up, our study showed that drinkers had lower incidence of sarcopenia than those non-drinkers (19.4% vs. 30.4%, < 0.001 in males and 9.5% vs. 20.4%, = 0.004 in females, respectively). Moreover, male drinkers had higher levels of muscle mass [median (IQR): 7.3 (6.7-7.9) kg/m vs. 7.1 (6.5-7.7) kg/m, < 0.001] grip strength [median (IQR): 31.1 (26.5-35.0) kg vs. 29.6 (24.8-38.8) kg, < 0.001], and gait speed [median (IQR): 1.08 (0.98-1.17) m/s vs. 1.05 (0.94-1.15) m/s, < 0.001] than those non-drinkers, while female drinkers had higher gait speed [median (IQR): 1.02 (0.94-1.11) m/s vs. 0.99 (0.89-1.09) m/s, = 0.031] than those non-drinkers. Multivariate logistic regression showed that in older adults younger than 85 years, both interim drinking (RR = 0.60; 95%CI = 0.39-0.93; = 0.021 for males; RR = 0.36; 95%CI = 0.13-0.90; = 0.035 for females) and daily drinking (RR = 0.78; 95%CI = 0.61-0.99; = 0.045 for males; RR = 0.34; 95%CI = 0.12-0.96; = 0.041 for females) were correlated with decreased risk of sarcopenia even after adjustment for confounding factors. However, our dose-response analysis did not show any significant relationship between daily alcohol intake and the risk of sarcopenia as well as the components of sarcopenia. In conclusion, our results indicated that alcohol drinking may not be a risk factor for sarcopenia in the older adults. Further research will help to understand the underlying mechanism of the observed causal relationship.
Potential supplementary tumor markers for liquid biopsy in non-small cell lung cancer.
Xiang J, Peng J, Xing Z … +6 more , Ren G, Zhang H, Song X, Zhang B, Guan M, Cao G
Exp Biol Med (Maywood) · 2025 · PMID 40510243 · Full text
The identification of epidermal growth factor receptor (EGFR) tyrosine kinase (TK) domain mutations in non-small cell lung cancer (NSCLC) patients is crucial for therapeutic decision-making and monitoring EGFR-tyrosine k...
The identification of epidermal growth factor receptor (EGFR) tyrosine kinase (TK) domain mutations in non-small cell lung cancer (NSCLC) patients is crucial for therapeutic decision-making and monitoring EGFR-tyrosine kinase inhibitor (TKI) resistance. Liquid biopsy has emerged as a promising alternative for patients ineligible for invasive tissue sampling. This study investigated the clinical utility of a novel chip-based digital PCR (dPCR) platform for detecting two important EGFR mutations - exon 19 deletions (19del) and threonine-methionine amino acid substitution at position 790 (T790M) - in serum samples, while exploring potential serum biomarkers for mutation prediction. The collection of 350 serum samples were conducted on patients diagnosed with NSCLC at Huashan Hospital between August 2023 and February 2024. Cell-free deoxyribonucleic acid (cfDNA) was extracted from serum and was analyzed for EGFR mutations using dPCR. The serum tumor marker levels were quantified. The dPCR assay demonstrated positive predictive values of 73.33% for 19del and 28.57% for T790M. Biomarker analysis revealed a carbohydrate antigen (CA) 199 cutoff of 11.75 U/mL (AUC = 0.707, 95% CI: 0.573-0.841, = 0.005) for 19del detection, while progastrin-releasing peptide (ProGRP) showed a cutoff of 45.15 pg/mL (AUC = 0.628, 95% CI: 0.521-0.735, = 0.028) for T790M identification. Variant rate exhibited significant positive correlations with biomarker concentrations: 19del variant rates significantly associated with CA125 levels (r = 0.624, = 0.010), while T790M correlated with both carcinoembryonic antigen (CEA) (r = 0.531, = 0.004) and ProGRP (r = 0.395, = 0.041) in mutation-positive cohorts. These findings indicate that serum-based dPCR liquid biopsy demonstrates potential clinical utility as a supplementary approach to tissue biopsy for NSCLC genotyping. Notably, elevated serum tumor marker levels correlate with enhanced mutation detection rates in liquid biopsy, implying their potential supplementary value in prioritizing patients for molecular profiling.
The landscape of non-reference SINE-VNTR-Alus in amyotrophic lateral sclerosis.
Pfaff AL, Bubb VJ, Quinn JP … +1 more , Kõks S
Exp Biol Med (Maywood) · 2025 · PMID 40510242 · Full text
The fatal neurodegenerative disease, amyotrophic lateral sclerosis (ALS), leads to the degeneration of motor neurons in the brain and spinal cord. Many different genetic variants are known to increase the risk of develop...
The fatal neurodegenerative disease, amyotrophic lateral sclerosis (ALS), leads to the degeneration of motor neurons in the brain and spinal cord. Many different genetic variants are known to increase the risk of developing ALS, however much of the disease heritability is still to be identified. To identify novel genetic factors, we characterised SINE-VNTR-Alu (SVA) presence/absence variation in 4403 genomes from the New York Genome Center (NYGC) ALS consortium. SVAs are a type of retrotransposon able to mobilise in the human genome generating new insertions that can modulate gene expression and mRNA splicing and to date 33 insertions are known to cause a range of genetic diseases. In the NYGC ALS consortium sequence data 2831 non-reference genome SVAs were identified and 95% of these insertions were rare with an insertion allele frequency of less than 0.01. Association analysis of the common SVAs with ALS risk, age at onset and survival did not identify any SVAs that survived correction for multiple testing. However, there were three different rare SVA insertions in the ALS associated gene identified in four different individuals with ALS. The frequency of these rare insertions in was significantly higher in the individuals with ALS from the NYGC ALS consortium compared to the gnomAD SV non-neuro controls (p = 0.0002). This study was the first to characterise non-reference SVA presence/absence variation in a large cohort of ALS individuals identifying insertions as potential candidates involved in disease development for further investigation.
Pharmacovigilance in the digital age: gaining insight from social media data.
Dong F, Guo W, Liu J … +2 more , Patterson TA, Hong H
Exp Biol Med (Maywood) · 2025 · PMID 40495881 · Full text
Pharmacovigilance is essential for protecting patient health by monitoring and managing medication-related risks. Traditional methods like spontaneous reporting systems and clinical trials are valuable for identifying ad...
Pharmacovigilance is essential for protecting patient health by monitoring and managing medication-related risks. Traditional methods like spontaneous reporting systems and clinical trials are valuable for identifying adverse drug events, but face delays in data access. Social media platforms, with their real-time data, offer a novel avenue for pharmacovigilance by providing a wealth of user-generated content on medication usage, adverse drug events, and public sentiment. However, the unstructured nature of social media content presents challenges in data analysis, including variability and potential biases. Advanced techniques like natural language processing and machine learning are increasingly being employed to extract meaningful information from social media data, aiding in early adverse drug event detection and real-time medication safety monitoring. Ensuring data reliability and addressing ethical considerations are crucial in this context. This review examines the existing literature on the use of social media data for drug safety analysis, highlighting the platforms involved, methodologies applied, and research questions explored. It also discusses the challenges, limitations, and future directions of this emerging field, emphasizing the need for ethical principles, transparency, and interdisciplinary collaboration to maximize the potential of social media in enhancing pharmacovigilance efforts.
Limitations to clinically restoring meaningful peripheral nerve function across gaps and overcoming them.
Foy CA, Kuffler DP
Exp Biol Med (Maywood) · 2025 · PMID 40495880 · Full text
Clinically, reliably restoring meaningful peripheral sensory and motor nerve function across peripheral nerve gaps is limited. Thus, although autografts are the clinical "gold standard" repair technique for bridging nerv...
Clinically, reliably restoring meaningful peripheral sensory and motor nerve function across peripheral nerve gaps is limited. Thus, although autografts are the clinical "gold standard" repair technique for bridging nerve gaps, even under relatively good conditions, <50% of patients recover meaningful function. Due to this low recovery rate, many patients are not even provided repair surgery and, consequently, suffer permanent loss of function. This paper examines intrinsic and extrinsic changes associated with injured neurons and Schwann cells that reduce the extent of axon regeneration and recovery. It also examines how these changes can be reversed, leading to enhanced regeneration and recovery. It next examines the efficacy of platelet-rich plasma (PRP) in promoting axon regeneration and two novel techniques involving bridging nerve gaps with an autograft within a platelet-rich (PRP) collagen tube or only a PRP-filled collagen tube, which induce meaningful recovery under conditions where autografts alone are not effective. Finally, it looks at potential mechanisms by which platelet-released factors may enhance axon regeneration and recovery. This review shows that although there are many limitations to restoring meaningful function following peripheral nerve trauma, there are a number of ways these can be overcome. Presently, the most promising techniques involve using PRP.
N-acetyl-L-cysteine improves mitochondrial and oxidative defects in the acadian variant of fanconi syndrome.
Al-Younis I, Martín-Jiménez R, Khan M … +4 more , Baussan Y, Jose C, Thibeault Y, Hebert-Chatelain E
Exp Biol Med (Maywood) · 2025 · PMID 40488120 · Full text
The Acadian variant of Fanconi Syndrome (AVFS) is a rare genetic disorder characterized by renal deficiencies. AVFS is caused by a mutation to encoding a complex I assembly factor, and leading to metabolic alterations....
The Acadian variant of Fanconi Syndrome (AVFS) is a rare genetic disorder characterized by renal deficiencies. AVFS is caused by a mutation to encoding a complex I assembly factor, and leading to metabolic alterations. We confirmed that fibroblasts derived from AVFS patients have lower complex I activity, mitochondrial membrane potential and cellular respiration. These mitochondrial defects were accompanied by higher levels of 8-hydroxy-2'deoxyguanosine, malondialdehyde and carbonyl, which are markers of oxidative damage to DNA, lipids and proteins, respectively. Thus, we hypothesized that the antioxidant N-Acetyl-L-cysteine (NAC) would reduce oxidative stress and mitochondrial defects in AVFS fibroblasts. Treatment with NAC during 5 days partially restored complex I activity, mitochondrial membrane potential and cellular respiration in AVFS fibroblasts. NAC also prevented oxidative damage in AVFS fibroblasts. This work shows for the first time that the physiopathology of AVFS includes high oxidative stress. It also reveals that NAC and other antioxidant-based strategies might represent an effective pharmacological treatment for AVFS.
Diagnostic accuracy of HRP2-based malaria rapid diagnostic tests and antigenemia persistence in Kenyan children from a holoendemic region: implications for case management and surveillance.
Wasena SA, Onyango CO, Osata SW … +8 more , Anyona SB, Raballah E, Hurwitz I, Seidenberg PD, Ouma C, Cheng Q, Schneider KA, Perkins DJ
Exp Biol Med (Maywood) · 2025 · PMID 40476012 · Full text
Malaria remains a significant cause of childhood morbidity and mortality, with Histidine-Rich Protein 2 (HRP2)-based malaria rapid diagnostic tests (mRDTs) widely used in endemic regions where microscopy is sometimes no...
Malaria remains a significant cause of childhood morbidity and mortality, with Histidine-Rich Protein 2 (HRP2)-based malaria rapid diagnostic tests (mRDTs) widely used in endemic regions where microscopy is sometimes not feasible. While these tests offer high sensitivity, persistent HRP2 antigenemia and gene deletions can cause false-positive and false-negative results, compromising their accuracy for malaria case management and surveillance. This study evaluated the diagnostic performance and antigen persistence of HRP2-mRDTs using data from a longitudinal birth cohort of 750 children followed monthly from birth to 36 months in a holoendemic region of Kenya. Malaria diagnosis was performed using both microscopy and mRDTs, with a total of 15,006 clinical events recorded from 573 children between 2017 and 2023. Data from an independent acute febrile cohort of 937 children (<5 years) followed for 14 days was analyzed to validate the findings. The mRDT showed a high sensitivity of 97.27% but a moderate specificity of 65.00% in acute febrile illness, indicating frequent false-positive results. The positive predictive value was low (35.10%), suggesting that confirmatory testing is needed, while the negative predictive value was high (98.89%), reinforcing the reliability of mRDTs in ruling out malaria. Persistent HRP2 antigenemia was observed, with a median antigen clearance time of 51.14 days, respectively. Higher initial parasite densities (>50,000/μL) were associated with a slower antigen decay rate ( = 0.001), highlighting the challenge of interpreting positive mRDT results after treatment. Validation using the acute febrile cohort showed that mRDT specificity exceeded 95% at initial diagnosis and follow-up. Overall, HRP2-based mRDTs remain valuable for frontline malaria diagnosis but are limited by antigen persistence, leading to false positives in follow-up testing. Where feasible, integration of confirmatory diagnostic methods, such as microscopy or molecular assays, could improve the performance of malaria case management and clinical decision making, particularly in high-transmission settings.
A double-edged effect of hypoxia on astrocyte-derived exosome releases.
Tseng YJ, Huang HJ, Lin CH … +1 more , Lin AM
Exp Biol Med (Maywood) · 2025 · PMID 40469772 · Full text
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 d...
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.
Effect of in utero and lactational exposure to antiretroviral therapy on the gut microbial composition and metabolic function in aged rat offspring.
Muthumula CMR, Yanamadala Y, Gokulan K … +5 more , Karn K, Cunny H, Sutherland V, Santos JH, Khare S
Exp Biol Med (Maywood) · 2025 · PMID 40469771 · Full text
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 offs...
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 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 in males, and an increase in among males and females. Furthermore, a sex-specific distribution reorganization of , , and 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.
Optimal transport reveals immune perturbation and fingerprints over time in COVID-19 vaccination.
Wang Z, Chen J, Ionita M … +3 more , Zhan Q, Zhou Z, Shen L
Exp Biol Med (Maywood) · 2025 · PMID 40469770 · Full text
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 cytom...
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.
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.
Pedersen KB, Jelesijevic T, Morris TM … +6 more , Melton SM, Henderson AS, Glenn JF, Davenport GJ, Ronis MJJ, Winsauer PJ
Exp Biol Med (Maywood) · 2025 · PMID 40458821 · Full text
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 ho...
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.
Anesthesia-induced developmental neurotoxicity in the setting of systemic inflammation: the role of microglia.
Useinovic N, Newson A, Near M … +4 more , Maksimovic S, Volvovitz B, Quillinan N, Jevtovic-Todorovic V
Exp Biol Med (Maywood) · 2025 · PMID 40453359 · Full text
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 imp...
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.
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