Altered Function Research Articles

Alterations in LDL and HDL after an ischemic stroke associated with carotid atherosclerosis are reversed after 1year.

Approximately, 20% of ischemic strokes are attributed to the presence of atherosclerosis. Lipoproteins play a crucial role in the development of atherosclerosis, with LDL promoting atherogenesis and HDL inhibiting it. Therefore, both their concentrations and their biological properties are decisive factors in atherosclerotic processes. In this study, we examined the qualitative properties of lipoproteins in ischemic stroke patients with carotid atherosclerosis. Lipoproteins were isolated from the blood of healthy controls (n=27) and patients with carotid atherosclerosis (n=64) at 7days and 1year postischemic stroke. Compared to controls, patients' LDL 7days poststroke showed increased levels of apoC-III, triacylglycerol, and ceramide, along with decreased cholesterol and phospholipid content. LDL from patients induced more inflammation in macrophages than did LDL from controls. HDL isolated from patients 7days after stroke showed alterations in the apolipoprotein cargo, with reduced levels of apoA-I and increased levels of apoA-II, and apoC-III compared to controls. Patients' HDL also showed a higher electronegative charge than that of controls and partially lost its ability to counteract the modification of LDL and the inflammatory effects of modified LDL. One year after stroke onset, the composition of patients' LDL and HDL resembled those of the controls. In parallel, LDL and HDL gained positive charge, LDL became less prone to oxidation and aggregation, and HDL regained protective properties. In conclusion, LDL and HDL in ischemic stroke patients with carotid atherosclerosis exhibited alterations in composition and function, which were partially reversed 1year after stroke.

Fluconazole induces cardiovascular toxicity in zebrafish by promoting oxidative stress, apoptosis, and disruption of key developmental genes.

This study systematically evaluated the toxic effects of fluconazole on the cardiovascular development of zebrafish. Zebrafish embryos were treated with different concentrations of fluconazole (200, 400, and 800μg/ml) to observe its impact on heart development, reactive oxygen species (ROS) generation, apoptosis, and hemoglobin production. The results showed that as the concentration of fluconazole increased, significant changes in zebrafish heart structure were observed, along with a notable reduction in heart rate. Pericardial edema and cardiac morphological abnormalities were particularly prominent in the high-dose group. In addition, fluconazole treatment significantly increased ROS levels and induced apoptosis in cardiac cells. Enzyme-linked immunosorbent assay (ELISA) results showed that fluconazole treatment significantly increased the malondialdehyde (MDA) content and reduced superoxide dismutase (SOD) and catalase (CAT) activity, suggesting that oxidative stress and cell death may play a key role in its cardiotoxicity. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed that fluconazole treatment significantly affected the expression of several key genes related to heart development and function, particularly cardiac myosin light chain 2 (cmlc2), ventricular myosin heavy chain (vmhc), and myosin heavy chain 6 (myh6), whose expression changes were closely associated with alterations in heart morphology and function. Transcriptomic analysis showed that several signaling pathways related to cardiac development, apoptosis, and metabolism were affected. In summary, this study reveals the multifaceted cardiotoxic mechanisms of fluconazole in zebrafish and provides new insights into drug safety assessment.

Altered local spontaneous activity and functional connectivity density in major depressive disorder patients with anhedonia.

The purpose of this study was to investigate the alterations of intrinsic brain function in major depressive disorder (MDD) patients with and without anhedonia based on whole-brain level by using two novel measures, four-dimensional spatial-temporal consistency of local neural activity (FOCA) and local functional connectivity density (lFCD). A total of 26 MDD patients with anhedonia (MDD-WA), 29 MDD patients without anhedonia (MDD-WoA), and 30 healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning and intrinsic brain function was explored by FOCA and lFCD. A two-sample t-test was conducted to explore FOCA and lFCD differences between MDD patients and HCs, then analysis of covariance (ANCOVA) and post hoc tests were performed to obtain brain regions with significant differences among three groups. Finally, the diagnostic performance of FOCA and lFCD values with significant inter-group difference was evaluated using receiver operating characteristic (ROC) curves. Compared to HCs, MDD patients showed decreased FOCA in the right cuneus (CUN) and left postcentral gyrus (PoCG), as well as diminished lFCD in the right CUN and left calcarine fissure and surrounding cortex (CAL). Interestingly, the MDD-WA group was more likely to exhibit decreased FOCA in the left PoCG and reduced lFCD in the left CAL after consideration for the effect of anhedonia in MDD patients. The MDD-WA group further showed increased FOCA in the bilateral caudate (CAU) and right ventral anterior nucleus (VA) when comparing to HCs. Additionally, as compared with MDD-WoA group, the MDD-WA group presented decreased FOCA in the right middle occipital gyrus (MOG), which was also negatively associated with the severity of anhedonia in MDD patients. Finally, FOCA values of the right MOG exhibited excellent discriminant validity in differentiating MDD-WA from MDD-WoA, and the other individual or combined indices of FOCA or lFCD values in the aforementioned distinct brain regions presented significant utility in distinguishing between MDD or MDD-WA and HCs. The present findings suggest that aberrant intrinsic brain function in the left CAL, left PoCG, bilateral CAU, right VA, and, especially the right MOG may be associated with anhedonia in patients with MDD. Altered FOCA in the right MOG may have the potential to be a diagnostic neuroimaging biomarker for MDD patients with anhedonia.

Ligand-receptor interactions: A key to understanding microglia and astrocyte roles in epilepsy.

Epilepsy continues to pose significant social and economic challenges on a global scale. Existing therapeutic approaches predominantly revolve around neurocentric mechanisms, and fail to control seizures in approximately one-third of patients. This underscores the pressing need for novel and complementary treatment approaches to address this gap. An increasing body of literature points to a role for glial cells, including microglia and astrocytes, in the pathogenesis of epilepsy. Notably, microglial cells, which serve as pivotal inflammatory mediators within the epileptic brain, have received increasing attention over recent years. These immune cells react to epileptogenic insults, regulate neuronal processes, and play diverse roles during the process of epilepsy development. Additionally, astrocytes, another integral non-neuronal brain cells, have garnered increasing recognition for their dynamic contributions to the pathophysiology of epilepsy. Their complex interactions with neurons and other glial cells involve modulating synaptic activity and neuronal excitability, thereby influencing the aberrant networks formed during epileptogenesis. This review explores the alterations in microglial and astrocytic function and their mechanisms of communication following an epileptogenic insult, examining their contribution to epilepsy development. By comprehensively studying these mechanisms, potential avenues could emerge for refining therapeutic strategies and ameliorating the impact of this complex neurological disease.

Long-term bowel function following delayed coloanal anastomosis: Analysis of a multicentric cohort study (GRECCAR).

Alteration of bowel function after delayed coloanal anastomosis (DCAA) might be a limitation to its utilization. Our aim was to assess the long-term bowel function of DCAA in a large multicentric cohort. All patients who underwent DCAA interventions at 29 GRECCAR-affiliated hospitals between 2010 and 2021 were retrospectively included. Low anterior resection syndrome (LARS) score or confection of a stoma due to poor bowel function was assessed in eligible patients. Good bowel function was defined by the preservation of bowel continuity with no LARS or a minor LARS. Among the 385 eligible patients to assess long-term bowel continuity, 63% (n = 243) responded to the questionnaire or had a definitive stoma because of poor bowel function. After a median follow-up of 32 months, good bowel function was reported by 60% (n = 146) of patients (with no LARS 36% and minor LARS 24%), whereas 40% of patients (n = 146) had a poor bowel function including major LARS (36%) and definitive stoma due to poor bowel function (4%). No variables tested were predictive of a poor bowel function after DCAA, including a history of pelvic radiotherapy (P = 0.722), salvage DCAA after failure of a previous anastomosis (P = 0.755), presence of a diverting stoma (P = 0.556), occurrence of an anastomotic leakage (P = 0.416) and time interval from the DCAA to the bowel function assessment (P = 0.350). No LARS or minor LARS was reached for 60% of patients after DCAA. Less than 5% of patients received a definitive stoma due to a poor bowel function.

Abstract TP336: Neuropathological changes in the chronic phase of ischemic stroke are marked by persistent alteration of microglial function and neurodegenerative phenotypes

Improvements in acute stroke treatment, including EVT and critical care management, have increased survival rates post-stroke. However, many stroke survivors have significant post-stroke disability and cognitive impairment. Despite this, the chronic progression and long-term sequelae of ischemic stroke pathology remains understudied. Methods: We examined the chronicity of neurobehavioral recovery and progressive neuropathology in young male (3 month) and middle-aged male and female (14 month) C57Bl/6 mice at 3 and 6 months after a 60-minute transient middle cerebral artery occlusion (tMCAO) or sham surgery ( n = 10-20/group ). Behavioral testing included NORT, fear conditioning (FC), and tail suspension. Immunohistochemistry (IHC) was performed on mouse brains, as well as post-mortem human brain samples from patients with a chronic infarct ( n = 6/group ), to assess demyelination (MBP), neuronal apoptosis (TUNEL/NeuN), and amyloid burden (Aβ-42). Flow cytometry was performed on the ipsilateral mouse brain hemisphere. RNA isolated from the ipsilateral hemisphere was sent for gene profiling. Results: In both young and middle-aged mice, depressive-like behavior persisted for 6 months post-stroke (PS) (p= <0.0001), while cognitive function progressively worsened from 3 to 6 months, as seen by a reduction in the NORT (p=.0063) and FC (p=.0084). MRI imaging and IHC revealed cerebral atrophy, significant demyelination (mouse, p=.0361; human, p =.0001), and increased microglial density (p=.0059) in the hippocampus of both human and mice. TUNEL/NeuN staining showed ongoing neuronal degeneration in the human hippocampus, distal to the chronic infarct. Human chronic stroke hippocampus had increased amyloid burden compared to age-matched controls (p=.0677). Cytometric anyalses revealed disease-associated microglial (DAM) phenotypes were marked by increased senescence, cytokine production, and an altered redox state. Transcriptomic data showed significant chronic upregulation of DAM genes. Conclusion: Our findings demonstrate that ischemic stroke accelerates inflamm-aging and premature senescence within the chronic infarct microenvironment. Cellular senescence and chronic disease signatures may contribute to progressive cognitive impairment post-stroke. Identification of secondary injury processes, and late pathological events post-stroke, allude to a neurodegenerative etiology and may offer viable targets for delayed treatment to prevent further neurological decline.

Time-Frequency functional connectivity alterations in Alzheimer's disease and frontotemporal dementia: An EEG analysis using machine learning.

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are prevalent neurodegenerative diseases characterized by altered brain functional connectivity (FC), affecting over 100 million people worldwide. This study aims to identify distinct FC patterns as potential biomarkers for differential diagnosis. Resting-state EEG data from 36 AD patients, 23 FTD patients, and 29 healthy controls were analyzed using time-frequency and bandpass filtering FC metrics. These metrics were estimated through Pearson's correlations, mutual information, and phase lag index, and served as input features in a support vector machine (SVM) with Leave-One-Out Cross-Validation for group classification. Both AD and FTD exhibited significantly decreased FC in the theta band within the frontal lobe and increased FC in the beta band in the posterior regions. Additionally, a decreased FC in central regions at theta band was observed uniquely in AD, but not in FTD. SVM classification accuracies reached 95% for AD and 86% for FTD. High classification accuracies underscore the potential of these FC alterations as reliable biomarkers for AD and FTD. This is the first study to integrate time-frequency and bandpass filtering FC metrics to reveal brain network alterations in AD and FTD, providing new insights for diagnostics and neurodegenerative pathologies.

Mapping alterations in the local synchrony of the cerebral cortex in Prader Willi syndrome.

Individuals with Prader Willi syndrome (PWS) often exhibit behavioral difficulties characterized by deficient impulse regulation and obsessive-compulsive features resembling those observed in obsessive-compulsive disorder. The genetic configuration of PWS aligns with molecular and neurophysiological findings suggesting dysfunction in the inhibitory gamma-aminobutyric acid (GABA) interneuron system may contribute to its clinical manifestation. In the cerebral cortex, this dysfunction is expressed as desynchronization of local neural activity. We used functional connectivity MRI to examine potential alterations in the local synchrony of the cerebral cortex in PWS. Whole-brain functional connectivity maps were generated using iso-distance average correlation (IDAC) measures in 22 patients with PWS and 22 control participants. Patients with PWS showed reduced local connectivity (weaker synchrony) in frontal areas, including the orbitofrontal cortex, ventral medial and lateral frontal regions, the anterior cingulate cortex, and sensory areas. The presence of obsessive-compulsive symptoms was significantly associated with the degree of functional structure alteration in part of the orbitofrontal and sensory cortices. In addition, abnormally heightened functional connectivity (stronger synchrony) was identified in the posterior cingulate cortex and the bilateral angular gyri, core components of the default mode network, with distance-dependent effects. Our findings of cortical synchrony alterations indicate a degree of overlap with the anatomy of the alterations previously observed in primary obsessive-compulsive disorder, while also suggesting the implication of GABAergic dysfunction in the pathophysiology of the disorder. Our observations may support the rational development of more specific therapeutic strategies in the treatment of behavioral disinhibition characteristic of PWS.

Insight into natural attenuation of tributyl phosphate by indigenous anaerobic microbes in soils: Implication by stable carbon isotope fractionation and microbial community structures.

Organophosphate esters (OPEs) are widespread in the environment, with high persistence and toxicity. However, the underlying mechanisms of anaerobic microbial degradation of OPEs remain elusive in the field environment. In this study, the natural attenuation mechanisms of tributyl phosphate (TnBP) by indigenous anaerobic microorganisms in soils were investigated by using compound-specific stable isotope analysis (CSIA) and characterization of microbial communities. The results indicated that dibutyl phosphate (DnBP) was the major degradation product of TnBP. Significant carbon isotope fractionation was observed for TnBP during the anaerobic microbial degradation, and the carbon isotope enrichment factor (εC) was determined to be -2.71±0.13‰. Unlike aerobic degradation with P-O bond cleavage, C-O bond cleavage was verified as the mode to removal a butyl side chain for TnBP to generate DnBP during the anaerobic microbial degradation. Microbial community analysis indicated that Sphingomonans, Nocardioides and Streptomyces were the important contributors to microbial degradation of TnBP in anoxic soils. TnBP altered microbial metabolic functions in anoxic soils, mainly enhancing the biosynthesis of ansamycins, ketone bodies and amino acids, and flagellar assembly, which promoted microbial degradation of TnBP. This study provided a better method to characterize the chemical bond cleavage mode and effect of OPEs on microbial communities, which was a prerequisite for the bioremediation of OPE pollution in soils.

Warming reduces bacterial diversity and stability in Lake Bosten.

Understanding the effects of warming on bacterial communities is essential for predicting microbial responses to climate change in aquatic ecosystems. However, the mechanisms through which warming influences bacterial diversity and stability in lake ecosystems remain poorly understood. To address this gap, we conducted a mesocosm experiment in Lake Bosten, a climate change hotspot, with three temperature scenarios (26°C, 29°C, and 32°C), and investigated bacterial diversity, community composition, potential functions, and stability. Our findings revealed that temperature, time, and their interactions significantly reduced bacterial α-diversity (two-way ANOVA: P<0.05). Warming altered bacterial potential metabolic functions, with decreases in methanotrophy and methylotrophy and increases in phototrophy and photoheterotrophy. Warming also increased species replacement within bacterial communities, indicating a dynamic shift in community composition. Network analysis indicated heightened complexity under higher temperatures but also a decrease in bacterial stability, evidenced by higher average variation degree (AVD), increased vulnerability, and reduced robustness. Overall, our study highlights the profound effects of warming on the ecological dynamics of lake bacterial communities, underscoring the need for further research to understand and mitigate the impacts of global climate change on aquatic ecosystems.

Uneven-aged and even-aged forest management shape the soil fungal community composition in a boreal Norway spruce (Picea abies Karst) forest.

Forest management alters stand density, microclimate, and litter accrual, which all affect soil fungi. Mycorrhizal fungi play a key role in soil organic carbon (C) accumulation in boreal forests. We aimed to compare how uneven-aged continuous cover forestry (CCF) and even-aged rotation forest management (RFM) affect the soil fungal community, to draw conclusions on possible effects for long-term soil C storage. We compared uncut boreal Norway spruce forests to mature uneven-aged (CCF), even-aged and clear-cut forests (the latter two representing late and early stage in RFM). We compared their fungal community composition, species richness and diversity based on metabarcoding of bulk soil samples using sequences of the fungal ITS2 regions, and analysed the response of saprotrophic, ecto- and ericoid mycorrhizal fungal guilds to management practice. We found that fungal communities differed between all treatments, but species richness and diversity were not impacted. Clear-cuts were most dissimilar to the other treatments and the organic layer was more affected than the mineral soil. Abundance, diversity and richness of ectomycorrhizal fungi was declined in clear-cuts, leading to dominance of saprotrophic fungi. The abundance of functional guilds in even-aged and uneven-aged stands were similar to those in uncut stands. Ericoid mycorrhizae were more abundant in both stages of RFM, but their community composition was not affected by the forest management type. Despite the altered potential functionality, we found similar C stocks and cellulose decomposition rates in all treatments. This highlights the functional redundancy in the fungal community. Therefore, we conclude that CCF is unlikely to change the long-term soil C storage compared to unmanaged forests. The long-term effects of multiple clear-cutting cycles in RFM on the ecological functionality and possible effects on soil C storage should be further studied for example with sites that have been clear-cut more than once.

The ecology of poverty and children's brain development: A systematic review and quantitative meta-analysis of brain imaging studies.

A growing number of studies have demonstrated associations between poverty and brain structure and function. However, the strength of this association and the effects of poverty level (e.g., family or neighborhood poverty), age and sex on the association are strikingly inconsistent across studies. We aimed to synthesize findings on gray matter volume and task-based brain activation associated with poverty in youth samples and disentangle the effects of poverty level, age, and sex. In general, poverty was associated with alterations in volume and activation in the frontal, temporal, and subcortical regions. Among 14,188 participants and 14,057 participants, poverty was associated with smaller gray matter volumes in the amygdala and hippocampus, respectively. Moderator testing revealed that family poverty had a stronger association than neighborhood poverty and that poverty was related to slower development of amygdala volume. Among 2696 participants, convergent functional alterations associated with poverty were observed in the left middle temporal gyrus (MTG) and left middle frontal gyrus across all task domains, with the percentage of girls positively associated with increased activation in the precuneus. Subgroup analyses revealed that greater poverty was associated with deactivation in the left MTG for top-down control and hyperactivity in the right superior temporal gyrus, left superior frontal gyrus, left insula, cerebellum/left fusiform gyrus, and left amygdala/hippocampus for bottom-up processing. These findings provide insights into the neuroscience of poverty, suggesting implications for targeted interventions to support the cognitive and mental health of children living in poverty.

Regional brain structural alterations in reward and salience networks in asthma.

Chronic systemic inflammation is highly prevalent and has deleterious effects on the brain, impacting both function and structure, and manifesting in elevations in psychological symptoms transdiagnostically. Asthma is a chronic inflammatory disease of the airway that affects more than 300 million people worldwide and is known to be highly comorbid with psychological and cognitive dysfunction. Though a growing corpus of work has identified functional brain abnormalities associated with asthma, limited research has investigated structural differences which may partially underlie functional changes. Identifying and characterizing asthma-related structural brain changes will shed light on the neurobiology through which asthma impacts mental function and has the potential to inform prophylaxis and treatment. We examined differences in regional brain volume, cortical thickness, and surface area, in 128 individuals with asthma compared to 134 non-asthma healthy controls. Five regions of interest were examined a priori, based on their previous implication in inflammation-related functional consequences (dorsal and ventral striatum, pallidum, and insula), or previous evidence of asthma-related structural impact (hippocampus and thalamus). We supplemented our region of interest approach with a voxel-wise whole-brain analysis. Additionally, we examined the association of brain structure with depression symptoms, asthma severity, degree of inflammation, and plasma biomarkers of neuroinflammation, neurodegeneration, and Alzheimer's disease specific pathology. Compared to non-asthma control participants, those with asthma had smaller nucleus accumbens volumes, thicker orbitofrontal cortices, larger middle frontal cortex surface areas, and greater diencephalon volumes. Those with more severe asthma had smaller nucleus accumbens and dorsal striatal volumes, reduced anterior cingulate cortex surface area, and greater amygdala volume compared to those with mild asthma. In untreated asthma patients, greater depressive symptoms were associated with smaller striatal volume, suggesting a potential CNS-protective effect of medications that reduce airway inflammation in asthma. In addition, a plasma marker of astrogliosis was associated with larger diencephalon, cerebellum, brainstem, and thalamus volumes, but reduced insula thickness and surface area. Patterns of structural brain changes in participants with asthma encompass key regions of reward and salience networks, which may in part give rise to the functional alterations in these networks characteristic of chronic systemic inflammation.

Evaluation of additional points in the 24-2C visual field test in pre-perimetric glaucoma.

Early detection and prevention of glaucoma progression are critical. However, studies of early visual field (VF) changes, particularly those using the 24-2C VF test, are limited. Evaluation of additional points in 2C may help identify glaucoma at an early stage, enabling timely intervention. Pre-perimetric glaucoma (PPG) is characterised by structural damage without noticeable VF loss in standard tests. Assessments of changes in retinal nerve fibre layer (RNFL) and macular ganglion cell complex (mGCC) thickness are valuable, but exploring how these structural changes are related to functional deficits is crucial. This study focused on the average of the additional points in the 24-2C test to understand their correlation with structural measures in the PPG. This study included 59 patients with PPG and 36 healthy individuals. All the patients underwent peripapillary and macular optical coherence tomography (OCT) (Nidek RS-3000 Advance; Nidek, Japan). RNFL thickness was evaluated using peripapillary OCT, and mGCC thickness was evaluated using the macular OCT glaucoma module. The mean deviation (MD), pattern standard deviation (PSD), visual field index (VFI), and average of additional points in the 2C (AAP-2C) were evaluated using the 24-2C SITA Faster VF Humphrey Field Analyser III Model 850 (HFAIII; Zeiss Meditec, Dublin, CA, USA). The relationship between structural and functional parameters was statistically evaluated. The PPG group showed significantly lower RNFL and mGCC thickness values than the healthy group. The MD, PSD, and VFI did not differ significantly between the groups. For AAP-2C, the PPG group showed significantly lower sensitivity than healthy individuals. A statistically significant positive correlation between was observed between AAP-2C and mGCC thickness (p = 0.003, r = 0.385). However, the RNFL and mGCC thickness values showed no statistically significant correlations with the MD, PSD, and VFI. Although no glaucomatous change was observed in the VF in patients with PPG, these patients showed reduced sensitivity of the additional points. The reduced sensitivity of the additional points in the 24-2C VF test may reflect early macular functional alterations that correlate with structural damage during the pre-perimetric period.

Childhood family environment and μ-opioid receptor availability in vivo in adulthood.

Animal studies have reported associations of early maternal separation with altered μ-opioid receptor function but data on humans are scarce. We now investigated whether childhood family environment is related to μ-opioid receptor availability in the human brain in adulthood. Healthy participants (n = 37-39 in the analyses) were recruited from the prospective population-based Young Finns Study (YFS) that started in 1980. Childhood family environment was evaluated in 1980, including scores for stress-prone life events, disadvantageous emotional family atmosphere, and adverse socioeconomic environment. We used positron emission tomography (PET) with radioligand [11C]carfentanil to measure μ-opioid receptor availability in adulthood. Age- and sex-adjusted analyses showed that exposure to stress-prone life events in childhood was related to lower μ-opioid receptor binding in the orbitofrontal cortex, hippocampus, putamen, amygdala, insula, thalamus, anterior cingulate cortex, and dorsal caudate in adulthood (when compared to participants not exposed to stress-prone life events). Unfavorable socioeconomic family environment or disadvantageous emotional family atmosphere was not associated with μ-opioid receptor availability in adulthood. In conclusion, exposure to environmental instability (i.e., to stress-prone life events below traumatic threshold) during early development is associated with dysregulation of the u-opioid receptor transmission in adulthood. The findings increase understanding of the neurobiological mechanisms involved in the associations between childhood adversities and adulthood mental disorders.

Alzheimer's disease may develop from changes in the immune system, cell cycle, and protein processing following alterations in ribosome function.

The prevalence of Alzheimer's disease (AD) is increasing as society ages. The details of AD pathogenesis have not been fully elucidated, and a comprehensive gene expression analysis of the process leading up to the onset of AD would be helpful for understanding the mechanism. We performed an RNA sequencing analysis on a cohort of 1227 Japanese blood samples, representing 424 AD patients, 543 individuals with mild cognitive impairment (MCI), and 260 cognitively normal (CN) individuals. A total of 883 and 1169 statistically significant differentially expressed genes (DEGs) were identified between CN and MCI (CN-MCI) and between MCI and AD (MCI-AD), respectively. Pathway analyses using these DEGs, followed by protein-protein interaction network analysis, revealed key roles of ribosomal function in MCI progression, whereas immune responses, cell cycle, and protein processing in endoplasmic reticulum were involved in AD progression. Our findings indicate that the onset of AD might be associated with gene expression changes in the immune system, cell cycle, and protein processing following alterations in the expression of ribosomal protein genes during the MCI stage, although validation using brain tissue samples will be necessary in the future. Given the known effectiveness of delaying MCI progression in preventing AD, the genes related to ribosomal function might emerge as biomarkers for early diagnosis.

Physiological impact of secondary nanoplastics on aquatic inhabitants in special reference to immunotoxicity.

Nanoplastic (NP) pollution poses serious health hazards to aquatic ecosystems, impacting various physiological systems of aquatic organisms. This review examines the complex interplay between NPs and different physiological systems. In the digestive system, NPs downregulate the hsp70-like gene in Mytilus galloprovincialis, leading to decreased metabolic processes and impaired digestion. Neural system exposure to NPs induces abnormal expression of genes like neurogenin1, GFAP, FBJ murine osteosarcoma viral oncogene, GAP-43, synapsin IIa, apoptosis regulator a, Bcl2 and Caspase a, and apoptosis-related cysteine peptidase. These genes play a crucial role in neurodevelopment, synaptic function and apoptosis regulation, potentially impacting neurobiology and cancer biology. NPs also affect reproduction, including gametogenesis, spawning, fertilization, embryogenesis and larval survivability. In the respiratory system, treatment with these causes inflammation in the lungs and gills, resulting in respiratory dysfunction. Moreover, this review investigates the complex interaction between NPs and the immune systems of both invertebrates (e.g., molluscs, arthropods, echinoderms) and vertebrates (e.g., zebrafish). NPs-induced alterations in immune cell function heightened the susceptibility to pathogens and disrupted immune signalling pathways. Subcellular inflammatory responses have been characterized by the secretion of inflammation-promoting and chemotactic cytokines such as irg1l, interleukin 1, interferon, interleukin 6, C-C motif chemokine ligand 20a and tumour necrosis factor. The assessment of the combined effects of NPs and other xenobiotics highlighted their possible synergistic impacts on aquatic fauna and the environment. This comprehensive review emphasizes the urgent need for further research to understand the cumulative effects of NPs on organism health and fitness across multiple physiological systems.

Habitual snoring in adolescents and its relationship to inhibitory control and attention.

Introduction. Sleep-disordered breathing (RBD), from habitual snoring to obstructive sleep apnea syndrome (OSAS), can influence brain functioning by affecting executive functions such as attention and inhibitory control. Objective. To analyze the association between snoring and executive functions, specifically attention, impulsivity/inhibitory control in Argentine adolescents. Population and methods. In 2018, a cross-sectional study was conducted on 831 adolescents attending public and private schools in La Pampa. Sleep duration, snoring, and the risk of OSAS were assessed using the pediatric sleep questionnaire (PSQ) and executive functions (attention and inhibitory control) using the Go/No-Go test. The association between SRT and executive functions was performed using a robust regression model adjusted for body mass index, hours of sleep, and physical activity. Results. About 10% of the participants were habitual snorers, and about 7% were at risk of OSA (positive PSQ), with no significant differences between sexes. Errors of commission (No-Go errors) (β= 2.06; -3.20, -0.92) and errors of omission (Go errors) (β= -0.66; -1.31, -0.01) were significantly higher in snorers vs.non-snorers. In addition, individuals at risk for OSAS showed significantly more commission errors (NoGo errors) than those without OSAS risk (β= -1.98; -3.31, -0.66). Conclusions. The associations between snoring and inattention and impulsivity, and between the risk of sleep apnea and lower inhibitory control found in the present study suggest alterations in executive functions due to sleep disorders.

CD8+T cells and monocytes were associated with brain alterations in human immunodeficiency virus-infected individuals with cognitive impairment.

Cognitive impairment (CI) continues to be a concern for people living with HIV-1 (PLWH) in the era of antiretroviral therapy (ART), yet the underlying mechanisms remain unclear. We aimed to elucidate the structural and functional brain alterations and peripheral immune profile of PLWH with CI, as well as the correlation between them. PLWH were divided into CI (n= 30) and cognitive normal (CN, n= 59) groups based on the Montreal Cognitive Assessment, and underwent multi-modal magnetic resonance imaging. Mass cytometry was utilized to profile immune cells, while the liquid chip technique was employed to measure plasma levels of cytokines and chemokines. Spearman correlation analyses were conducted for correlation analysis. Here, we found that the gray matter volume in left supramarginal gyrus was reduced, and the ReHo in the right middle frontal gyrus and the functional connectivity between right middle frontal gyrus and left postcentral gyrus were enhanced in CI group compared to CN group. Additionally, the frequencies of naïve CD8+T cells (Tn) and CD31lowCD8+ Tn were significantly correlated with gray matter volume in the left supramarginal gyrus. The amplitude of low frequency fluctuations in a specific brain region of frontal-middle lobe was negatively correlated with the frequencies of non-classical monocytes (nCM) and their subpopulations (CCR2lownCM, CD57lownCM and CD127+nCM), and positively associated with the plasma interleukin 25 and transforming growth factor-α levels. These findings suggest the association between peripheral immunity and the brain abnormalities in PLWH, highlighting a potential role of the immune-brain-cognition axis in the pathogenesis of CI in Chinese PLWH.

Inhibition of p75NTR/p53 axis by ambrisentan suppresses apoptosis and oxidative stress-mediated renal damage in a cisplatin AKI model.

Cisplatin (CP) is a potent antineoplastic agent that triggers nephrotoxicity as a major adverse effect which can cause treatment interruptions and limitations to its clinical use. Nephrotoxicity associated with CP involves inflammation, oxidative stress and apoptosis in kidney tubules. The objective of this work was to assess the effect of the blockade of endothelin-1 (ET-1) receptor with ambrisentan (Amb) on altered renal function induced by CP. Swiss albino mice were assigned into control, CP, CP/Amb-5 and CP/Amb-10 groups. Ambrisentan improved kidney function (serum creatinine and BUN) and histopathological changes in comparison to CP-treated group. Ambrisentan significantly reduced protein expression of p75NTR and JNK influencing renal apoptosis as evidenced by reducing p53, caspase-3 and Bax level and elevating Bcl-2 level (p<0.05 vs CP group). Moreover, vasodilatory effect of ambrisentan was indicated by significant increase in level of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) (p<0.05 vs CP group). Ambrisentan also significantly restored oxidative balance in renal tissues as evidenced by reduced malondialdehyde and increased total antioxidant capacity and superoxide dismutase activity, in addition to decreasing nitric oxide levels (p<0.05 vs CP group). This protective effect of ambrisentan might be mediated through the downregulation of death receptor, P75NTR that in turn restores renal blood flow and oxidative balance and regulates p53, VEGF/eNOS, NF-κB, and bcl-2/Bax/caspase-3 signaling.