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Alzheimer's Research & Therapy Jun 2024Amyloid-β (Aβ) and tau are brain hallmarks of Alzheimer's disease (AD), also present in blood as soluble biomarkers or encapsulated in extracellular vesicles (EVs).... (Comparative Study)
Comparative Study
BACKGROUND
Amyloid-β (Aβ) and tau are brain hallmarks of Alzheimer's disease (AD), also present in blood as soluble biomarkers or encapsulated in extracellular vesicles (EVs). Our goal was to assess how soluble plasma biomarkers of AD pathology correlate with the number and content of EVs.
METHODS
Single-molecule enzyme-linked assays were used to quantify Aβ42/40 and tau in plasma samples and neurally-derived EVs (NDEVs) from a cohort of APOE ε4- (n = 168) and APOE ε4+ (n = 68) cognitively normal individuals and AD patients (n = 55). The ratio of CD56 (Neuronal cell-adhesion molecule) to CD81 signal measured by ELISA-DELFIA was used for the relative quantification of NDEVs in plasma samples.
RESULTS
The soluble plasma Aβ42/40 ratio is decreased in AD patients compared to cognitively normal individuals. The amount and content (Aβ40, Aβ42, tau) of plasma NDEVs were similar between groups. Plasma NDEVs quantity remain consistent with aging and between AD and CN individuals. However, the quantity of soluble biomarkers was negatively correlated to NDEVs number in cognitively normal individuals, while in AD patients, this correlation is lost, suggesting a shift in the mechanism underpinning the production and the release of these biomarkers in pathological conditions.
CONCLUSION
Soluble plasma Aβ42/40 ratio is the most robust biomarker to discriminate between AD patients and CN individuals, as it normalizes for the number of NDEVs. Analysis of NDEVs and their content pointed toward peculiar mechanisms of Aβ release in AD. Further research on independent cohorts can confirm our findings and assess whether plasma Aβ and tau need correction by NDEVs for better AD risk identification in CN populations.
Topics: Humans; Alzheimer Disease; Extracellular Vesicles; Biomarkers; Female; Male; Amyloid beta-Peptides; Aged; tau Proteins; Peptide Fragments; Aged, 80 and over; Middle Aged; Cohort Studies; Apolipoprotein E4
PubMed: 38943196
DOI: 10.1186/s13195-024-01508-6 -
Acta Neuropathologica Communications Jun 2024
PubMed: 38943188
DOI: 10.1186/s40478-024-01819-7 -
Journal of Orthopaedic Surgery and... Jun 2024Tendon stem/progenitor cell (TSPC) senescence contributes to tendon degeneration and impaired tendon repair, resulting in age-related tendon disorders. Ferroptosis, a...
Platelet-derived exosomes alleviate tendon stem/progenitor cell senescence and ferroptosis by regulating AMPK/Nrf2/GPX4 signaling and improve tendon-bone junction regeneration in rats.
BACKGROUND
Tendon stem/progenitor cell (TSPC) senescence contributes to tendon degeneration and impaired tendon repair, resulting in age-related tendon disorders. Ferroptosis, a unique iron-dependent form of programmed cell death, might participate in the process of senescence. However, whether ferroptosis plays a role in TSPC senescence and tendon regeneration remains unclear. Recent studies reported that Platelet-derived exosomes (PL-Exos) might provide significant advantages in musculoskeletal regeneration and inflammation regulation. The effects and mechanism of PL-Exos on TSPC senescence and tendon regeneration are worthy of further study.
METHODS
Herein, we examined the role of ferroptosis in the pathogenesis of TSPC senescence. PL-Exos were isolated and determined by TEM, particle size analysis, western blot and mass spectrometry identification. We investigated the function and underlying mechanisms of PL-Exos in TSPC senescence and ferroptosis via western blot, real-time quantitative polymerase chain reaction, and immunofluorescence analysis in vitro. Tendon regeneration was evaluated by HE staining, Safranin-O staining, and biomechanical tests in a rotator cuff tear model in rats.
RESULTS
We discovered that ferroptosis was involved in senescent TSPCs. Furthermore, PL-Exos mitigated the aging phenotypes and ferroptosis of TSPCs induced by t-BHP and preserved their proliferation and tenogenic capacity. The in vivo animal results indicated that PL-Exos improved tendon-bone healing properties and mechanical strength. Mechanistically, PL-Exos activated AMPK phosphorylation and the downstream nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway, leading to the suppression of lipid peroxidation. AMPK inhibition or GPX4 inhibition blocked the protective effect of PL-Exos against t-BHP-induced ferroptosis and senescence.
CONCLUSION
In conclusion, ferroptosis might play a crucial role in TSPC aging. AMPK/Nrf2/GPX4 activation by PL-Exos was found to inhibit ferroptosis, consequently leading to the suppression of senescence in TSPCs. Our results provided new theoretical evidence for the potential application of PL-Exos to restrain tendon degeneration and promote tendon regeneration.
Topics: Animals; Ferroptosis; Exosomes; NF-E2-Related Factor 2; Cellular Senescence; Rats; Signal Transduction; Phospholipid Hydroperoxide Glutathione Peroxidase; Regeneration; AMP-Activated Protein Kinases; Stem Cells; Tendons; Male; Blood Platelets; Rats, Sprague-Dawley; Rotator Cuff Injuries; Disease Models, Animal
PubMed: 38943181
DOI: 10.1186/s13018-024-04869-8 -
Trials Jun 2024Social isolation and loneliness (SIL) worsens mortality and other outcomes among older adults as much as smoking. We previously tested the impact of the HOW R U?...
Impact of an intergenerational program to improve loneliness and social isolation in older adults initiated at the time of emergency department discharge: study protocol for a three-arm randomized clinical trial.
BACKGROUND
Social isolation and loneliness (SIL) worsens mortality and other outcomes among older adults as much as smoking. We previously tested the impact of the HOW R U? intervention using peer support from similar-aged volunteers and demonstrated reduced SIL among older adults discharged from the emergency department (ED). Generativity, defined as "the interest in establishing and guiding the next generation," can provide an alternative theoretical basis for reducing SIL via intergenerational programs between members of younger and older generations. The current protocol will examine the impact of younger intergenerational volunteers providing the HOW RU?
METHODS
In this randomized clinical trial, we will compare the following three arms: (1) the standard same-generation peer support HOW R U? intervention, (2) HOW R U? intervention delivered by intergenerational volunteers, and (3) a common wait-list control group. Outcome assessors will be blinded to the intervention. Trained volunteers will deliver 12 weekly telephone support calls. We will recruit participants ≥ 70 years of age with baseline loneliness (six-item De Jong loneliness score of 2 or greater) from two EDs. Research staff will assess SIL, depression, quality of life, functional status, generativity, and perceived benefit at baseline, at 12 weeks, and 24 weeks post-intervention.
DISCUSSION
We hypothesize participants receiving the intergenerational intervention will show improved outcomes compared to the control group and peer support HOW R U?
INTERVENTION
We also hypothesize that participants with higher perceptions of generativity will have greater reductions in SIL than their lower generativity counterparts. Aging is experienced diversely, and social interventions combatting associated SIL should reflect that diversity. As part of a program of research following the Obesity-Related Behavioral Intervention Trials (ORBIT) model, the findings of this RCT will be used to define which intervention characteristics are most effective in reducing SIL.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05998343 Protocol ID:21-0074E. Registered on 24 July 2023.
Topics: Humans; Loneliness; Social Isolation; Aged; Emergency Service, Hospital; Randomized Controlled Trials as Topic; Patient Discharge; Intergenerational Relations; Female; Quality of Life; Male; Peer Group; Social Support; Age Factors; Time Factors; Treatment Outcome; Volunteers
PubMed: 38943176
DOI: 10.1186/s13063-024-08250-2 -
Construction and validation of a brain magnetic resonance imaging template for normal older Koreans.BMC Neurology Jun 2024Spatial normalization to a standardized brain template is a crucial step in magnetic resonance imaging (MRI) studies. Brain templates made from sufficient sample size...
BACKGROUND
Spatial normalization to a standardized brain template is a crucial step in magnetic resonance imaging (MRI) studies. Brain templates made from sufficient sample size have low brain variability, improving the accuracy of spatial normalization. Using population-specific template improves accuracy of spatial normalization because brain morphology varies according to ethnicity and age.
METHODS
We constructed a brain template of normal Korean elderly (KNE200) using MRI scans 100 male and 100 female aged over 60 years old with normal cognition. We compared the deformation after spatial normalization of the KNE200 template to that of the KNE96, constructed from 96 cognitively normal elderly Koreans and to that of the brain template (OCF), constructed from 434 non-demented older Caucasians to examine the effect of sample size and ethnicity on the accuracy of brain template, respectively. We spatially normalized the MRI scans of elderly Koreans and quantified the amount of deformations associated with spatial normalization using the magnitude of displacement and volumetric changes of voxels.
RESULTS
The KNE200 yielded significantly less displacement and volumetric change in the parahippocampal gyrus, medial and posterior orbital gyrus, fusiform gyrus, gyrus rectus, cerebellum and vermis than the KNE96. The KNE200 also yielded much less displacement in the cerebellum, vermis, hippocampus, parahippocampal gyrus and thalamus and much less volumetric change in the cerebellum, vermis, hippocampus and parahippocampal gyrus than the OCF.
CONCLUSION
KNE200 had the better accuracy than the KNE96 due to the larger sample size and was far accurate than the template constructed from elderly Caucasians in elderly Koreans.
Topics: Humans; Female; Magnetic Resonance Imaging; Male; Aged; Brain; Middle Aged; Republic of Korea; Asian People; Aged, 80 and over; Aging; Image Processing, Computer-Assisted; East Asian People
PubMed: 38943101
DOI: 10.1186/s12883-024-03735-8 -
BMC Plant Biology Jun 2024WRKY proteins are important transcription factors (TFs) in plants, involved in growth and development and responses to environmental changes. Although WRKY TFs have been...
BACKGROUND
WRKY proteins are important transcription factors (TFs) in plants, involved in growth and development and responses to environmental changes. Although WRKY TFs have been studied at the genome level in Arachis genus, including oil crop and turfgrass, their regulatory networks in controlling flowering time remain unclear. The aim of this study was to predict the molecular mechanisms of WRKY TFs regulation flowering time in Arachis genus at the genome level using bioinformatics approaches.
RESULTS
The flowering-time genes of Arachis genus were retrieved from the flowering-time gene database. The regulatory networks between WRKY TFs and downstream genes in Arachis genus were predicted using bioinformatics tools. The results showed that WRKY TFs were involved in aging, autonomous, circadian clock, hormone, photoperiod, sugar, temperature, and vernalization pathways to modulate flowering time in Arachis duranensis, Arachis ipaensis, Arachis monticola, and Arachis hypogaea cv. Tifrunner. The WRKY TF binding sites in homologous flowering-time genes exhibited asymmetric evolutionary pattern, indicating that the WRKY TFs interact with other transcription factors to modulate flowering time in the four Arachis species. Protein interaction network analysis showed that WRKY TFs interacted with FRUITFULL and APETALA2 to modulate flowering time in the four Arachis species. WRKY TFs implicated in regulating flowering time had low expression levels, whereas their interaction proteins had varying expression patterns in 22 tissues of A. hypogaea cv. Tifrunner. These results indicate that WRKY TFs exhibit antagonistic or synergistic interactions with the associated proteins.
CONCLUSIONS
This study reveals complex regulatory networks through which WRKY TFs modulate flowering time in the four Arachis species using bioinformatics approaches.
Topics: Transcription Factors; Flowers; Computational Biology; Plant Proteins; Arachis; Gene Expression Regulation, Plant; Gene Regulatory Networks
PubMed: 38943100
DOI: 10.1186/s12870-024-05343-7 -
BMC Geriatrics Jun 2024Research examining the healthy aging trajectory of retired older adults with multimorbidity is limited, leaving uncertainties regarding the optimal physical activity...
BACKGROUND
Research examining the healthy aging trajectory of retired older adults with multimorbidity is limited, leaving uncertainties regarding the optimal physical activity (PA) intensity and frequency necessary to sustain healthy aging during retirement.
METHODS
Our study investigated the moderating effects of PA on the healthy aging trajectories of retired older adults living with multimorbidity in the United States (US). We utilized data from 1,238 retired individuals aged 50 to 102 who contributed 11,142 observations over 16 years from the Health and Retirement Study (HRS). We employed mixed effects modeling to assess the impact of various classes of multimorbidity on this group and examine how different PA, PA intensities, and PA frequencies influence the disability, physical, and cognitive functioning domains of healthy aging.
RESULTS
The results reveal that while outcomes differed significantly, retired older adults in the US attained healthy aging at baseline. However, their ability to maintain healthy aging declined over time, with multimorbidity, especially musculoskeletal and neurological conditions, accelerating this decline. Fortunately, PA, especially light to moderate intensities, is associated with improving healthy aging and moderating the impact of multimorbidity on the disability and cognitive functioning domains of healthy aging. However, the specific moderating effects of PA depend on its frequency, intensity, and chronic conditions.
CONCLUSIONS
The significant variability in healthy aging attainment among retired older adults underlies the need to consider these differences when addressing healthy aging issues in the US. Accounting for these variations would aid in evaluating the potential impact of future interventions and contribute to achieving health equity. Fortunately, our dynamic findings facilitate this objective by identifying specific frequencies and intensities of PA tailored to different aspects of multimorbidity and healthy aging. This highlights PA, especially light-to-moderate intensity, as an essential, cost-effective, and amenable strategy for alleviating the impact of multimorbidity on healthy aging.
Topics: Humans; Aged; Multimorbidity; Male; Female; Healthy Aging; Aged, 80 and over; Exercise; Middle Aged; United States; Retirement; Longitudinal Studies
PubMed: 38943080
DOI: 10.1186/s12877-024-05067-1 -
BMC Pregnancy and Childbirth Jun 2024Educational programs incorporating physical activity (PA) sessions and nutritional workshops have demonstrated potential benefits for overweight and obese pregnant...
BACKGROUND
Educational programs incorporating physical activity (PA) sessions and nutritional workshops have demonstrated potential benefits for overweight and obese pregnant women. However, participation in such programs remains challenging. This prospective study aimed to investigate the factors influencing participation and regular attendance, while examining changes in health behaviors, along with obstetric and neonatal outcomes.
METHODS
Pregnant women with at 12-22 weeks' gestation a BMI ≥ 25 kg/m2 were invited to join an educational program combining three nutritional workshops conducted in groups and 12 weekly PA sessions. They self-selected their participation into the program. Regardless of program uptake and regularity of attendance, the women's PA levels, eating behaviors, and affectivity were assessed using validated questionnaires at 20-24 weeks, 32-34 weeks, and postpartum. A multivariable logistic regression model was used to determine the factors influencing participation.
RESULTS
Of the 187 women enrolled in the study, 61.5% agreed to participate in the program. Of these, only 45% attended six or more sessions (regardless of the nature of sessions, i.e. nutritional workshops and/or PA sessions), while only 8.7% attended six or more PA sessions. Participation was associated with higher rates of problematic eating behaviors and lower PA levels at baseline, while regular attendance was mainly associated with higher household incomes. No significant difference was observed between participants and non-participants in terms of changes in eating behaviors, PA levels, or affectivity. However, at the 32-34 week visit, regular participants displayed a higher change in positive affectivity, but unexpectedly also in cognitive restraint, than non-regular participants, a difference that did not persist at postpartum.
CONCLUSION
The educational program combining nutrition and PA was shown to be safe. Women facing challenges related to health behavior displayed a willingness to sign up for the program, but tailored interventions addressing their individual challenges are needed to improve attendance. Accordingly, four recommendations are proposed for the design of future interventions.
TRIAL REGISTRATION
ClinicalTrials.gov; Identifier: NCT02701426; date of first registration: 08/03/2016.
Topics: Humans; Female; Pregnancy; Adult; Exercise; Prospective Studies; Obesity; Overweight; Pregnancy Complications; Feeding Behavior; Prenatal Care; Health Behavior
PubMed: 38943053
DOI: 10.1186/s12884-024-06648-z -
Nature Communications Jun 2024Compounding functional nanoparticles with highly conductive and porous carbon scaffolds is a basic pathway for engineering many important functional devices. However,...
Compounding functional nanoparticles with highly conductive and porous carbon scaffolds is a basic pathway for engineering many important functional devices. However, enabling uniform spatial distribution of functional particles within a massively conjugated, monolithic and mesoporous structure remains challenging, as the high processing temperature for graphitization can arouse nanoparticle ripening, agglomerations and compositional changes. Herein, we report a unique "popcorn-making-mimic" strategy for preparing a highly conjugated and uniformly compounded graphene@NiFeO composite film through a laser-assisted instantaneous compounding method in ambient condition. It can successfully inhibit the unwanted structural disintegration and mass loss during the laser treatment by avoiding oxidation, bursting, and inhomogeneous heat accumulations, thus achieving a highly integrated composite structure with superior electrical conductivity and high saturated magnetization. Such a single-sided film exhibits an absolute shielding effectiveness of up to 20906 dB cm g with 75% absorption rate, superior mechanical flexibility and excellent temperature/humidity aging reliability. These performance indexes signify a substantial advance in EMI absorption capability, fabrication universality, small form-factor and device reliability toward commercial applications. Our method provides a paradigm for fabricating sophisticated composite materials for versatile applications.
PubMed: 38942779
DOI: 10.1038/s41467-024-49498-1 -
Scientific Reports Jun 2024Older adults (OAs) are typically slower and/or less accurate in forming perceptual choices relative to younger adults. Despite perceptual deficits, OAs gain from...
Older adults (OAs) are typically slower and/or less accurate in forming perceptual choices relative to younger adults. Despite perceptual deficits, OAs gain from integrating information across senses, yielding multisensory benefits. However, the cognitive processes underlying these seemingly discrepant ageing effects remain unclear. To address this knowledge gap, 212 participants (18-90 years old) performed an online object categorisation paradigm, whereby age-related differences in Reaction Times (RTs) and choice accuracy between audiovisual (AV), visual (V), and auditory (A) conditions could be assessed. Whereas OAs were slower and less accurate across sensory conditions, they exhibited greater RT decreases between AV and V conditions, showing a larger multisensory benefit towards decisional speed. Hierarchical Drift Diffusion Modelling (HDDM) was fitted to participants' behaviour to probe age-related impacts on the latent multisensory decision formation processes. For OAs, HDDM demonstrated slower evidence accumulation rates across sensory conditions coupled with increased response caution for AV trials of higher difficulty. Notably, for trials of lower difficulty we found multisensory benefits in evidence accumulation that increased with age, but not for trials of higher difficulty, in which increased response caution was instead evident. Together, our findings reconcile age-related impacts on multisensory decision-making, indicating greater multisensory evidence accumulation benefits with age underlying enhanced decisional speed.
Topics: Humans; Aged; Adult; Middle Aged; Female; Male; Aged, 80 and over; Decision Making; Adolescent; Reaction Time; Young Adult; Auditory Perception; Aging; Visual Perception; Photic Stimulation; Acoustic Stimulation
PubMed: 38942761
DOI: 10.1038/s41598-024-65549-5