Multiple Transcriptomic Analyses Explore Potential Synaptic Biomarker Rabphilin-3A for Alzheimer's Disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder afflicting the elderly population worldwide. The identification of potential gene candidates for AD holds promises for diagnostic biomarkers and therapeutic targets. Employing a comprehensive strategy, this study integrated transcriptomic data from diverse data sources, including microarray and single-cell datasets from blood and tissue samples, enabling a detailed exploration of gene expression dynamics. Through this thorough investigation, 19 notable candidate genes were found with consistent expression changes across both blood and tissue datasets, suggesting their potential as biomarkers for AD. In addition, single cell sequencing analysis further highlighted their specific expression in excitatory and inhibitory neurons, the primary functional units in the brain, underscoring their relevance to AD pathology. Moreover, the functional enrichment analysis revealed that three of the candidate genes were downregulated in synaptic signaling pathway. Further validation experiments significantly showed reduced levels of rabphilin-3A (RPH3A) in 3xTg-AD model mice, implying its role in disease pathogenesis. Given its role in neurotransmitter exocytosis and synaptic function, further investigation into RPH3A and its interactions with neurotrophic proteins may provide valuable insights into the complex molecular mechanisms underlying synaptic dysfunction in AD.

Exploring the Potential Role of Oligodendrocyte-Associated PIP4K2A in Alzheimer's Disease Complicated with Type 2 Diabetes Mellitus via Multi-Omic Analysis.

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are two common diseases that affect the elderly population worldwide. The identification of common genes associated with AD and T2DM holds promise for potential biomarkers and intriguing pathogenesis of these two complicated diseases. This study utilized a comprehensive approach by integrating transcriptome data from multiple cohorts, encompassing both AD and T2DM. The analysis incorporated various data types, including blood and tissue samples as well as single-cell datasets, allowing for a detailed assessment of gene expression patterns. From the brain region-specific single-cell analysis, PIP4K2A, which encodes phosphatidylinositol-5-phosphate 4-kinase type 2 alpha, was found to be expressed mainly in oligodendrocytes compared to other cell types. Elevated levels of PIP4K2A in AD and T2DM patients' blood were found to be associated with key cellular processes such as vesicle-mediated transport, negative regulation of autophagosome assembly, and cytosolic transport. The identification of PIP4K2A's potential roles in the cellular processes of AD and T2DM offers valuable insights into the development of biomarkers for diagnosis and therapy, especially in the complication of these two diseases.

A comprehensive bibliometric analysis of global research on the role of acrolein in Alzheimer's disease pathogenesis: involvement of amyloid-beta.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive and behavioral decline. Acrolein, an environmental pollutant and endogenous compound, is implicated in AD development. This research employs bibliometric analysis to assess current trends and key areas concerning acrolein-AD interaction. Methods: The Web of Science was used to extensively review literature on acrolein and AD. Relevant data were systematically gathered and analyzed using VOSviewer, CiteSpace, and an online bibliometric tool. Results: We identified 120 English publications in this specialized field across 19 journals. The Journal of Alzheimer's Disease was the most prominent. The primary contributors, both in terms of scientific output and influence, were the USA, the University of Kentucky, and Ramassamy C, representing countries/regions, institutions, and authors, respectively. In this field, the primary focus was on thoroughly studying acrolein, its roles, and its mechanisms in AD utilizing both in vivo and in vitro approaches. A significant portion of the research was based on proteomics, revealing complex molecular processes. The main focuses in the field were "oxidative stress," "lipid peroxidation," "amyloid-beta," and "cognitive impairment." Anticipated future research trajectories focus on the involvement of the internalization pathway, covering key areas such as synaptic dysfunction, metabolism, mechanisms, associations, neuroinflammation, inhibitors, tau phosphorylation, acrolein toxicity, brain infarction, antioxidants, chemistry, drug delivery, and dementia. Our analysis also supported our previous hypothesis that acrolein can interact with amyloid-beta to form a protein adduct leading to AD-like pathology and altering natural immune responses. Conclusion: This study provides a broad and all-encompassing view of the topic, offering valuable insights and guidance to fellow researchers. These emerging directions underscore the continuous exploration of the complexities associated with AD. The analyses and findings aim to enhance our understanding of the intricate relationship between acrolein and AD for future research.

Relationship between Quality of Nursing Work Life and Uniformed Nurses' Attitudes and Practices Related to COVID-19 in the Philippines: A Cross-Sectional Study.

(1) Background: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide. Uniformed nurses have played a critical role during the COVID-19 pandemic in the Philippines; however, uptake of literature is limited. This study assessed the relationship between quality of nursing work life (QNWL) and nurses' attitudes and practices during the COVID-19 pandemic. (2) Methods: A descriptive cross-sectional design was used. Participants were recruited from four government hospitals in the Manila metropolitan area of the Philippines. Participants completed three questionnaires in an online survey: a demographic questionnaire, a QNWL questionnaire, and the attitude and practices toward COVID-19 questionnaire. Descriptive statistics, an independent t-test, a one-way analysis of variance, the Pearson correlation coefficient, and hierarchical linear regression were applied for data analysis. (3) Results: The mean age of the participants was 29 years. Most of the participants were single women who were not certified in their specialties. A total of QNWL scores were high, indicating that the participants displayed favorable attitudes and practices in relation to COVID-19. A statistically significant relationship was observed between QNWL, specialty certification, and practices related to COVID-19. Practices related to COVID-19 were a significant predictor of QNWL and one of its subscales, work design. (4) Conclusion: Young adult uniformed nurses in the Philippines have assumed numerous responsibilities during the COVID-19 pandemic. Providing these frontline nurses with comprehensive specialized education and training is crucial.

Association of Two Indices of Insulin Resistance Marker with Abnormal Liver Function Tests: A Cross-Sectional Population Study in Taiwanese Adults.

Background and objectives: Insulin resistance (IR) is frequently associated with chronic low-grade inflammation and has an important role as a mediator in the development of liver disease. Thus, this study aimed to explore the relationship between two indexes of IR and abnormal liver function parameters. Materials and Methods: This cross-sectional study obtained data of 41,510 men and 92,357 women aged ≥30 years from a private health screening institute in Taiwan. Two IR indexes namely triglyceride-glucose (TyG) index and triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio were used to examine their relationship to predict abnormal liver function parameters (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP)). Results: Positive trend was shown for the association of TyG index in the highest quintile (Q5) and risk of high AST (OR = 1.45, 95% CI: 1.33-1.57), high ALT (OR = 1.85, 95% CI: 1.73-1.97), high GGT (OR = 2.04, 95% CI: 1.93-2.15), and high ALP (OR = 1.13, 95% CI: 1.07-1.19) compared with the median quintile (Q3) in the fully adjusted model. Similarly, participants in the Q5 of the TG/HDL-C ratio were associated with 1.38 (95% CI: 1.27-1.49), 1.71 (95% CI: 1.61-1.82), 1.75 (95% CI: 1.66-1.84), and 1.21 (1.16-1.27) odds for having high AST, ALT, GGT, and ALP respectively. The AUC (95% CI) value of the TyG index for predicting high AST, high ALT, and high GGT was 0.699 (0.692-0.705), 0.738 (0.734-0.742), and 0.752 (0.749-0.755), respectively. Meanwhile, the AUC (95% CI) of the TG/HDL-C ratio for predicting high AST, high ALT, and high GGT was 0.680 (0.673-0.686), 0.738 (0.734-0.742), 0.734 (0.731-0.738), respectively. Conclusions: Our study supported that the TyG index and TG/HDL-C ratio may be useful as non-invasive methods to predict the existence of impaired liver function in the early stage.