Experimental Biology and Medicine最新文献

Open burn/open detonation (OB/OD) disposes of explosive waste via uncontrolled combustion, releasing harmful pollutants like toxic gases and particulate matter. Colfax, Louisiana, houses the nation's only commercially OB/OD thermal treatment (TT) facility, raising concerns about environmental and public health impacts due to its emissions. In this exploratory pilot study, we investigated metabolic alterations indicative of potential health impacts from exposure to emissions from a TT facility through an untargeted metabolomics analysis of urine samples obtained from local residents. Urine samples were collected from 51 residents living within a 30-km radius of the facility, with proximity, race, and sex as key variables. Samples were analyzed using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) to identify metabolic alterations and potential biomarkers of exposure. A total of 217 metabolites were identified, with significant differences in abundance based on proximity to the facility. Key metabolic pathways affected included energy metabolism, amino acid metabolism, and oxidative stress-related pathways. Metabolites associated with oxidative stress, such as glutathione sulfonamide (GSA), were elevated in individuals residing closer to the facility, indicating increased oxidative stress. Alterations in the glutathione/glutathione disulfide (GSH/GSSG) ratio further highlighted redox imbalances. Pathway enrichment analyses revealed perturbations in glycolysis, citric acid cycle, sulfur metabolism, and nucleotide metabolism, which are linked to critical biological functions like energy production and DNA repair. Notable differences in metabolite profiles were also observed between sexes and racial groups, pointing to the interplay of intrinsic biological and environmental factors. These findings demonstrate that exposure to emissions from the TT facility may have significant impacts on human health, including disruptions in cellular metabolism and increased oxidative stress. Further research is crucial to understand the long-term health implications of these metabolic alterations and to develop strategies to mitigate the environmental and health risks associated with this facility.

Natural Killer (NK) cells are integral components of the innate immune system, recognizing and eliminating virus-infected cells. They may play a crucial role in the immune response and contribute to the complications associated with Single Ventricle/Hypoplastic Left Heart Syndrome (SV/HLHS). Utilizing single-cell RNA sequencing (scRNA-seq), NK cells from peripheral blood mononuclear cells (PBMCs) were analyzed in three de-identified SV/HLHS cases and three healthy controls. This study identified two novel NK cell subpopulations that could not be detected by conventional scRNA-seq pipelines or traditional flow cytometry. These subpopulations exhibit distinct gene expression profiles linked to the heterogeneity of immune responsiveness and stress adaptation in NK cells. In SV/HLHS patients, one cluster showed a significant upregulation of androgen response and downregulation of heme metabolism compared to healthy controls. Our study offers new insights into the fine-tuning of immune modulation that could help mitigate complications in SV/HLHS. It suggests that while NK cells in SV/HLHS adapt to support survival in a challenging physiological environment, these adaptations may compromise their ability to effectively respond to additional stresses, such as infections and inflammation.

The antiretroviral (ARV) drug combination of abacavir sulfate, dolutegravir, and lamivudine [ABC/DTG/3TC; Tri combination Anti-retroviral therapy (TC-ART)] has revolutionized HIV treatment by effectively targeting different stages of viral replication. Despite its therapeutic efficiency for maintaining low viremia in the mother during pregnancy, there are concerns for long-term liabilities in offspring that are indirectly exposed during vulnerable periods of development. The commensal microbiota plays a crucial role in maintaining overall gut health, and disruption of the microbiome is often linked to various extraintestinal effects such as immune dysregulation and inflammation. We recently reported the effects of this drug combination in altering fecal microbiome composition of aged rats perinatally exposed to ABC/DTG/3TC-ART. The fecal microbiome can provide only a snapshot of the composition of microbial community at the end of the digestive tract, which may not reflect the microbial population interacting with ileal mucosa. Thus, the current work reports the effects of this drug combination in the gut mucosa-associated microbiome of the same animals, which showed significant microbial diversity and species richness in high dose exposed female adult offspring, along with dose-dependent changes in Firmicutes/Bacteroidetes ratio. The high dose exposure also showed an increase in opportunistic bacterial species in male animals. Overall, we found that, similar to the fecal microbiome, perinatal exposure to TC-ART led to sex- and dose-dependent alterations in the gut mucosa-associated microbial population in aged rats, suggesting that early life exposure to these drugs may influence gut mucosa-associated immune responses and intestinal permeability.

Advanced glycation end products (AGEs) have been associated with vascular pathologies including abdominal aortic aneurysms (AAAs), although their causal role remains unclear. In this study, we observed significant accumulation of AGEs in human AAAs, particularly in cases associated with intraluminal thrombus (ILT). In vitro, AGE exposure induced vascular smooth muscle cell (VSMC) migration and suppressed contractility, accompanied by reduced expression of contractile markers (α-SMA and MYH11) and elevated MMP-2. This phenotypic transformation was linked to the activation of the NLRP3 inflammasome and RAGE/RhoA/ROCK signaling, and was reversible upon inhibition of RAGE, RhoA, or ROCK. In macrophages, AGE pretreatment had minimal effects on basal cytokine secretion but attenuated LPS-induced IL-6 and IL-1β release and NF-κB activation. Co-culture experiments further revealed that AGE-pretreated macrophages reduced LPS-driven pro-migratory effects on VSMCs. Spatial transcriptomics demonstrated enriched AGE-RAGE signaling in αSMA+ VSMCs and CD68+αSMA+ macrophage-like VSMCs in ILT-containing AAAs. Overall, these associative findings implicate AGE-RAGE signaling in AAA pathogenesis and warrant further investigation to establish causality.

Cataract is the leading cause of blindness globally, imposing a significant socioeconomic burden. While diet is associated with various eye diseases, the causal relationship between dietary-related characteristics (DRCs) and cataract remains unclear. This study investigates the causal associations between DRCs and cataract using Mendelian randomization (MR) to provide insights into potential dietary interventions for cataract prevention. We conducted a two-sample MR analysis using data from the open GWAS database, focusing on individuals of European descent. Instrumental variables were selected based on stringent criteria, and multiple MR methods were applied to estimate causal effects. Sensitivity analyses assessed the robustness of the findings. Significant causal associations were found between oily fish intake (OR = 0.86) and variation in diet (OR = 1.26) with cataract. Sensitivity analyses supported the robustness of these findings. Mediation effect analysis suggested that the intake of oily fish might indirectly influence cataract risk through metabolites. This study provides evidence for causal relationships between specific DRCs and cataract, highlighting the potential role of dietary interventions in cataract prevention.

The focus of this study was to evaluate motor unit number and size across the upper extremity in older adults (aged 60+ years) versus young healthy adults (aged 20-30 years). We hypothesized that older adults would have: fewer motor units and increased motor unit size as compared to young healthy adults (H1), that motor unit size would differ across the upper extremity muscles as compared to young healthy adults (H2), and higher body mass index (BMI) would be associated with lower motor unit numbers (H3). Compound muscle action potential (CMAP), motor unit number index (MUNIX), and motor unit size index (MUSIX) were evaluated in five muscles of the upper extremity. Group differences in CMAP due to aging were accounted for by increased body mass index (BMI); group differences in MUSIX were not impacted by BMI. No difference in MUNIX was found; however, an influence of BMI was found across groups. While this data provides supporting evidence of age-related motor unit changes, body composition changes with age may confound these conclusions when surface electromyography is utilized as the measurement modality. Adiposity estimation should be considered in future EMG studies, particularly in populations with higher BMI values.

The Oropouche virus (OROV), an arbovirus transmitted primarily by the Culicoides paraensis midge, has caused significant outbreaks in the Americas, especially in the Amazon region. The virus's spread is closely linked to a combination of environmental, climatic, and ecological factors. These include deforestation, urbanization, and changes in rainfall patterns, which influence the proliferation of vectors, and, consequently, increase the chances of mutations and reassortment events to occur. In 2024 and 2025, the number of OROV cases increased significantly, with outbreaks extending beyond the traditionally endemic Amazon region, highlighting the growing geographic expansion of the disease throughout Brazil. Despite its growing dispersion, diagnostic and therapeutic tools for OROV remain limited. Current diagnostic strategies rely almost exclusively on molecular detection methods, and there are no vaccines for effective prevention. Additionally, immunological responses to OROV infection are not fully understood, and further studies are needed. The ecological dynamics influencing OROV transmission, particularly the role of environmental changes in shaping vector populations, highlight the need for more integrated surveillance and control strategies. The ongoing expansion of OROV outside its traditional hotspots may be indicative of broader environmental shifts that facilitate viral spread. Therefore, continuous monitoring of both environmental and epidemiological data is crucial to understanding and mitigating the impact of OROV in the future. Collaborative efforts among researchers, policymakers, and local communities will be essential to prevent further outbreaks and minimize the health burden caused by OROV. This review summarizes important and up-to-date data information to the ongoing epidemic of Oropouche fever, focusing on topics that are particularly important to Public Health.

Our objective was to study the effect of vitamin D₃ (VD) on hepatocellular oxidative-nitrosative stress and pro/anti-inflammatory cytokines in relation to nitric oxide (NO) formation and NO synthase (NOS) levels in type 2 diabetes mellitus (T2DM). After T2DM induction by high-fat diet and a single streptozotocin injection (25 mg/kg b. w.), male Wistar rats were treated with/without VD (1,000 IU/kg b. w., 30 days). Oxidative stress/inflammation and NOS/NO were assessed by flow cytometry, RT-qPCR, western blotting, and ELISA. A 3.3-fold decrease in serum 25(OH)D₃ was established in diabetic rats, suggesting their VD deficient status. T2DM was associated with excess reactive oxygen species (ROS; 2.4-fold) and NO (2.5-fold) production in hepatocytes paralleled by elevated levels of myeloperoxidase (1.7-fold), carbonylated (2.8-fold) and nitrotyrosylated (1.7-fold) proteins in liver tissue vs. control, indicative of oxidative-nitrosative stress. Low-grade inflammation in diabetic liver was confirmed by increased NF-κB transcriptional activity (1.24-fold) and mRNA expression of proinflammatory cytokines TNF-α (3.5-fold) and IL-1β (2.2-fold) with alleviating mRNAs of anti-inflammatory cytokines IL-4 (1.7-fold) and IL-10 (2.6-fold), while TGF-β1 expression raised 1.4-fold vs. control. Higher iNOS and eNOS mRNAs (2.7- and 3.3-fold, respectively) and protein (2.1- and 3.2-fold, respectively) levels, as well as NOS activity (1.6-fold) were found in diabetic liver. VD supplementation restored 25(OH)D₃, partially normalized NF-κB transcriptional activity and pro/anti-inflammatory cytokines, lowered hepatocellular ROS/NO, and oxidative protein modifications. However, VD had no effect on eNOS, IL-10 and TGF-β1 mRNAs. It also led to a further increase in myeloperoxidase, eNOS and iNOS proteins and NOS activity compared to diabetes. In conclusion, abnormal oxidative metabolism in T2DM is associated with enhanced NF-κB/NOS/NO response, which can be partially attenuated by VD treatment via normalization of pro-oxidative/pro-inflammatory processes. The paradoxical sustained increase in NOS expression in the presence of VD antioxidant activity likely improves hepatocellular NO bioavailability, ultimately reducing T2DM-associated liver injury.

[This corrects the article DOI: 10.3389/ebm.2025.10559.].