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Ageing Research Reviews Jun 2024Dementia, a prevalent condition in the United States, affecting millions of individuals and their families, underscores the importance of healthy cognitive ageing, which... (Review)
Review
Dementia, a prevalent condition in the United States, affecting millions of individuals and their families, underscores the importance of healthy cognitive ageing, which involves maintaining cognitive function and mental wellness as individuals grow older, promoting overall well-being and quality of life. Our original research study investigates the correlation between lifestyle factors and brain atrophy in individuals with mild cognitive impairment (MCI) or Alzheimer's disease (AD), as well as healthy older adults. Conducted over six months in West Texas, the research involved 20 participants aged 62-87. Findings reveal that sleep deprivation in MCI subjects and AD patients correlate with posterior cingulate cortex, hippocampal atrophy and total brain volume, while both groups exhibit age-related hippocampal volume reduction. Notably, fruit/vegetable intake negatively correlates with certain brain regions' volume, emphasizing the importance of diet. Lack of exercise is associated with reduced brain volume and hippocampal atrophy, underlining the cognitive benefits of physical activity. The study underscores lifestyle's significant impact on cognitive health, advocating interventions to promote brain health and disease prevention, particularly in MCI/AD cases. While blood profile data showed no significant results regarding cognitive decline, the study underscores the importance of lifestyle modifications in preserving cognitive function.
PubMed: 38942198
DOI: 10.1016/j.arr.2024.102397 -
The Journal of Heart and Lung... Jun 2024Right ventricular (RV) imaging has not a definite role in risk stratification of pulmonary arterial hypertension (PAH) patients. We tested the hypothesis that...
BACKGROUND
Right ventricular (RV) imaging has not a definite role in risk stratification of pulmonary arterial hypertension (PAH) patients. We tested the hypothesis that echocardiography-derived phenotypes, depicting different degrees of RV remodeling and dysfunction, may provide additional prognostic information to current risk stratification tools.
METHODS
Consecutive incident PAH patients aged ≥ 18 years, diagnosed between January 2005 and December 2021, underwent clinical assessment, right heart catheterization, standard echocardiography. Simple echocardiographic variables were combined in order to define a priori four phenotypes representing different degrees of RV dilatation and RV-pulmonary arterial (PA) coupling: Phenotype 1 with mildy dilated right ventricle and preserved RV-PA coupling (n=152 patients); phenotype 2 with mildly dilated right ventricle and poor RV-PA coupling (n=143 patients); phenotype 3 with severely dilated right ventricle and preserved RV-PA coupling (n=201 patients); phenotype 4 with severely dilated right ventricle and poor RV-PA coupling, with or without severe tricuspid regurgitation (n=519 patients). Risk stratification was based on on the ESC/ERS 3-strata model and REVEAL 2.0 score.
RESULTS
These phenotypes were present in all risk groups. Notably, regardless of the ESC/ERS risk stratum assigned to the patient, phenotype 4 was associated with a 2-fold increase of the odds of death (HR 2.1, 95% C.I. 1.6-2.8, p<0.001), while phenotype 1 was associated with a 71% reduction in the odds of dying (HR 0.29, 95% C.I. 0.18-0.47, p<0.001).
CONCLUSIONS
Echocardiography-derived phenotypes describing RV remodeling and dysfunction may provide prognostic information which is independent of and additional to the clinically defined risk in incident PAH patients.
PubMed: 38942159
DOI: 10.1016/j.healun.2024.06.003 -
Journal of Ethnopharmacology Jun 2024The traditional medicinal formulation, Qifu-yin (QFY), has been widely prescribed for Alzheimer's disease (AD) treatment in China, yet the comprehensive mechanisms...
ETHNOPHARMACOLOGICAL RELEVANCE
The traditional medicinal formulation, Qifu-yin (QFY), has been widely prescribed for Alzheimer's disease (AD) treatment in China, yet the comprehensive mechanisms through which QFY mitigates AD pathology remain to be fully delineated.
AIM OF THE STUDY
This study aimed to explore the therapeutic implications of QFY on the synaptic injury and oxidative stress in the hippocampus of APPswe/PS1dE9 (APP/PS1) mice, with a concerted effort to elucidate the molecular mechanisms related to synaptic preservation and memory improvement.
MATERIALS AND METHODS
The components of QFY were identified by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The neuroprotective effects of QFY was evaluated using six-month-old male APP/PS1 mice. Subsequent to a 15 days of QFY regimen, spatial memory was assessed utilizing the Morris water maze (MWM) test. Amyloid-beta (Aβ) aggregation was detected via immunostaining, while the quantification of Aβ and Aβ was achieved through enzyme-linked immunosorbent assay (ELISA). Transmission electron microscopy (TEM) was used to investigate the synaptic structure and mitochondrial morphology. Golgi staining was applied to examine dendritic spine density. Reactive oxygen species (ROS), 3-nitrotyrosine (3-NT) and 4-hydroxy-nonenal (4-HNE) assays were employed to assess oxidative stress. The expression profiles of Aβ metabolism-associated enzymes and the Keap1/Nrf2/ARE signaling pathway were determined by Western blot.
RESULTS
A total of 20 principal compounds in QFY were identified. QFY mitigated memory deficits of APP/PS1 mice, including reducing escape latency and search distance and increasing the time and distance spent in the target quadrant. In addition, QFY increased platform crossings of APP/PS1 mice in the probe trial of MWM tests. TEM analysis showed that QFY increased synapse number in the CA1 region of APP/PS1 mice. Further studies indicated that QFY elevated the expression levels of Post synaptic density protein 95 (PSD95) and synaptophysin, and mitigated the loss of dendritic spine density in the hippocampus of APP/PS1 mice. QFY has been shown to ameliorated the structural abnormalities of mitochondria, including mitochondrial dissolution and degradation, up-regulate ATP synthesis and membrane potential in the hippocampus of APP/PS1 mice. Moreover, QFY activated the Keap1/Nrf2/ARE signaling pathway in the hippocampus of APP/PS1 mice, which might contribute to the neuroprotective effects of QFY.
CONCLUSION
QFY activates the Keap1/Nrf2/ARE signaling, and protects against synaptic and mitochondrial dysfunction in APP/PS1 mice, proposing a potential alternative therapeutic strategy for AD management.
PubMed: 38942156
DOI: 10.1016/j.jep.2024.118497 -
Neurochemistry International Jun 2024K+ channels exist in all living systems. They allow a selective transition to the K+ ion, which enables the activity of various vital tissues such as muscle cells,...
K+ channels exist in all living systems. They allow a selective transition to the K+ ion, which enables the activity of various vital tissues such as muscle cells, neurons, and even bacteria and plants. Despite the mechanism variation in the gating process of K+ channels in different tissues, the selectivity for the K+ ion is preserved and the electrochemical cascade is maintained in these tissues. The electrochemical gradient of the K+ ion is very close to the diffusion rate of K+ ions in bulk water. On the molecular level, how does a K+ ion move across the ion conduction pathway? There are many molecular models that describe and answer this question, however, this is rarely described on the macro level. Here, a physical model can serve as a very good basis for enabling a deeper understanding of the K+ ion for ion transport. Classical physical energy and linear and angular momentum laws can provide a good explanation as to how and what happens to K+ ions when they pass through an ion conduction pathway. This model describes the passage of the ion even before it enters the ion conduction path until the last ion at the end exits. The simulation described here is fascinating and depicts the state of the ion at the farthest end released at almost the same speed as the first ion initially, while all the other ions remain almost at rest. How does this occur? What happens if we change the size or mass of the ion? In this work, I describe this principle and the related problems that could be studied.
PubMed: 38942118
DOI: 10.1016/j.neuint.2024.105797 -
Behavioural Brain Research Jun 2024Stressful life event is closely associated with depression, thus strategies that blunt or prevent the negative effect stress on the brain might benefits for the...
Stressful life event is closely associated with depression, thus strategies that blunt or prevent the negative effect stress on the brain might benefits for the treatment of depression. Although previous study showed the role of protein kinase R (PKR)-like ER kinase (PERK) in inflammation related depression, its involvement in the neuropathology of chronic stress induced depression is still unknown. We tried to explore whether block the PERK pathway would alleviate the animals' depression-like behavior induced by chronic restraint stress (CRS) and investigate the underlying mechanism. The CRS-exposed mice exhibited depression-like behavior, including anhedonia in the sucrose preference test (SPT), and increased immobility time in tail suspension test (TST) and forced swim test (FST). ISRIB administration for 2 weeks significantly improved the depression-like behavior in male mice exposed to CRS,which was manifested by markedly increasing the sucrose preference and reducing the immobility time in the FST and TST. However, we observed that exposure to the same dose of ISRIB in CRS female mice only showed improved anhedonia-like deficits,leaving un-altered improvement in the FST and TST. Mechanically, we found thatISRIB reversed the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, indicatingby decreased levels of serum corticosterone, reduced hippocampal glucocorticoidreceptor (GR) expression and expression of FosB in hypothalamic paraventricularnucleus (PVN), which was accompanied by preserved hippocampal neurogenesis. Thepresent findings further expand the potential role of ER stress in depression andprovide important details for a therapeutic path forward for PERK inhibitors in mood disorders.
PubMed: 38942086
DOI: 10.1016/j.bbr.2024.115122 -
Cryobiology Jun 2024The cryopreservation of teleost eggs and embryos remains challenging, and there are no previous reports that demonstrate successful cryopreservation in medaka (Oryzias...
The cryopreservation of teleost eggs and embryos remains challenging, and there are no previous reports that demonstrate successful cryopreservation in medaka (Oryzias latipes). We have reported egg and sperm production, followed by the generation of donor-derived offspring by transplanting vitrified whole testes-derived testicular cells into surrogate fish. The vitrification solutions contained ethylene glycol, sucrose, and ficoll. In this study, we replaced sucrose with trehalose in the vitrification solution and medaka whole testis was vitrified with the solution. The post-vitrification survival (72.8±3.5%) was markedly improved compared with that achieved using the sucrose-containing solution (44.7±4.2%). Moreover, we demonstrated the production of eggs, sperm, and donor-derived offspring from testicular cells transplanted into surrogate recipients. The phenotype of donor-derived offspring was identical to that of transplanted testicular cells. These findings suggest that trehalose is effective for the vitrification of medaka whole testis and can be considered an effective and reliable method for the long-term preservation of their genetic resources.
PubMed: 38942069
DOI: 10.1016/j.cryobiol.2024.104936 -
Cryobiology Jun 2024Growing concerns over declining male semen quality and rising infertility have shifted attention to male fertility. Sperm cryopreservation emerges as a crucial tool in...
Growing concerns over declining male semen quality and rising infertility have shifted attention to male fertility. Sperm cryopreservation emerges as a crucial tool in preserving male fertility, especially for patients who need proactive preservation, such as cancer patients before undergoing radiation or chemotherapy. Although cryopreservation does not directly address infertility, effective preservation can support future fertility. However, the process may compromise sperm DNA integrity. Despite their impairment, damaged sperm often retain vitality and may still have the potential to fertilize an egg. Nonetheless, if damaged sperm fertilize an egg, excessive DNA damage could impede embryo implantation and development, despite the egg's repair capabilities. Consequently, precise detection of sperm DNA damage is crucial and urgent. To better address the issue of sperm DNA damage detection, we have introduced a novel fluorescence biosensor technology known as the TDT/SD Probe. This technology utilizes terminal deoxynucleotidyl transferase (TdT) and strand displacement probes to accurately detect the number of sperm DNA breakage points during the cryopreservation process. Experimental results reveal that the number of sperm DNA breakpoints significantly increases after both sperm vitrification (8.17×10) and conventional slow freezing (10.80×10), compared to the DNA breakpoints of fresh semen samples (5.19×10). However, sperm vitrification has the least impact on sperm breakage points. This research provides innovative means for further optimizing sperm preservation techniques by offering a novel DNA damage detection method, enabling more precise assessment of sperm DNA damage during the freezing process.
PubMed: 38942068
DOI: 10.1016/j.cryobiol.2024.104937 -
Developmental Cell Jun 2024Recent advances in human genetics have shed light on the genetic factors contributing to inflammatory diseases, particularly Crohn's disease (CD), a prominent form of...
Recent advances in human genetics have shed light on the genetic factors contributing to inflammatory diseases, particularly Crohn's disease (CD), a prominent form of inflammatory bowel disease. Certain risk genes associated with CD directly influence cytokine biology and cell-specific communication networks. Current CD therapies primarily rely on anti-inflammatory drugs, which are inconsistently effective and lack strategies for promoting epithelial restoration and mucosal balance. To understand CD's underlying mechanisms, we investigated the link between CD and the FGFR1OP gene, which encodes a centrosome protein. FGFR1OP deletion in mouse intestinal epithelial cells disrupted crypt architecture, resulting in crypt loss, inflammation, and fatality. FGFR1OP insufficiency hindered epithelial resilience during colitis. FGFR1OP was crucial for preserving non-muscle myosin II activity, ensuring the integrity of the actomyosin cytoskeleton and crypt cell adhesion. This role of FGFR1OP suggests that its deficiency in genetically predisposed individuals may reduce epithelial renewal capacity, heightening susceptibility to inflammation and disease.
PubMed: 38942017
DOI: 10.1016/j.devcel.2024.06.001 -
Physics in Medicine and Biology Jun 2024Conventional image quality metrics assume independence between images which is not preserved within spectral CT datasets, limiting their utility for characterizing...
Conventional image quality metrics assume independence between images which is not preserved within spectral CT datasets, limiting their utility for characterizing energy selective images. In this work, we developed a metrology to characterize energy selective images by incorporating the shared information between images within a spectral CT dataset. Approach: Signal-to-noise ratio was extended into a multivariate space where each image was treated as a separate information channel. The general definition was applied to contrast to define a multivariate contrast-to-noise ratio (CNR). The matrix contained two types of terms: a conventional CNR term, characterizing image quality within each image, and covariance weighted CNR (Covar-CNR), characterizing contrast relative to covariance between images. The metrology was demonstrated using experimental data from an investigational photon-counting CT scanner. A cylindrical water phantom containing vials of iodine and gadolinium (2, 4, 8 mg/mL) was imaged with variable tube current, tube voltage, and energy threshold. Two image series (threshold and bin images) containing two images each were defined based upon the contribution of photons to reconstructed images. Analysis of variance was calculated between CNR terms and image acquisition variables. A multivariate regression was fit to experimental data. Main Results: Bin images had a slightly higher mean and wider standard deviation (Covar-CNRlo: 3.38 ±17.25, Covar-CNRhi: 5.77±30.64) than threshold images (Covar-CNRlo: 2.08 ±1.89, Covar-CNRhi: 3.45±2.49) across all conditions. Analysis of variance found each acquisition variable had a significant relationship with both Covar-CNR terms. The multivariate regression model suggested that material concentration had the largest impact on all CNR terms. Significance: In this work, we described a theoretical framework to extend the signal-to-noise ratio to a multivariate form to characterize images independently and provide insight regarding the relationship between images. Experimental data was used to demonstrate the insight that this metrology provides about image formation factors in spectral CT. .
PubMed: 38942009
DOI: 10.1088/1361-6560/ad5d4a -
Physics in Medicine and Biology Jun 2024Reducing the radiation dose leads to the X-ray computed tomography (CT) images suffering from heavy noise and artifacts, which inevitably interferes with the subsequent...
Reducing the radiation dose leads to the X-ray computed tomography (CT) images suffering from heavy noise and artifacts, which inevitably interferes with the subsequent clinic diagnostic and analysis. Leading works have explored diffusion models for low-dose CT imaging to avoid the structure degeneration and blurring effects of previous deep denoising models. However, most of them always begin their generative processes with Gaussian noise, which has little or no structure priors of the clean data distribution, thereby leading to long-time inference and unpleasant reconstruction quality. To alleviate these problems, this paper presents a Structure-Aware Diffusion model (SAD), an end-to-end self-guided learning framework for high-fidelity CT image reconstruction. First, SAD builds a nonlinear diffusion bridge between clean and degraded data distributions, which could directly learn the implicit physical degradation prior from observed measurements. Second, SAD integrates the prompt learning mechanism and implicit neural representation into the diffusion process, where rich and diverse structure representations extracted by degraded inputs are exploited as prompts, which provides global and local structure priors, to guide CT image reconstruction. Finally, we devise an efficient self-guided diffusion architecture using an iterative updated strategy, which further refines structural prompts during each generative step to drive finer image reconstruction. Extensive experiments on AAPM-Mayo and LoDoPaB-CT datasets demonstrate that our SAD could achieve superior performance in terms of noise removal, structure preservation, and blind-dose generalization, with few generative steps, even one step only.
PubMed: 38942004
DOI: 10.1088/1361-6560/ad5d47