Current Issue : October-December Volume : 2024 Issue Number : 4 Articles : 5 Articles
Background Alzheimer’s disease (AD) is a devastating neurodegenerative disorder affecting 44 million people worldwide, leading to cognitive decline, memory loss, and significant impairment in daily functioning. The recent single-cell sequencing technology has revolutionized genetic and genomic resolution by enabling scientists to explore the diversity of gene expression patterns at the finest resolution. Most existing studies have solely focused on molecular perturbations within each cell, but cells live in microenvironments rather than in isolated entities. Here, we leveraged the large-scale and publicly available single-nucleus RNA sequencing in the human prefrontal cortex to investigate cell-to-cell communication in healthy brains and their perturbations in AD. We uniformly processed the snRNA-seq with strict QCs and labeled canonical cell types consistent with the definitions from the BRAIN Initiative Cell Census Network. From ligand and receptor gene expression, we built a high-confidence cell-to-cell communication network to investigate signaling differences between AD and healthy brains. Results Specifically, we first performed broad communication pattern analyses to highlight that biologically related cell types in normal brains rely on largely overlapping signaling networks and that the AD brain exhibits the irregular inter-mixing of cell types and signaling pathways. Secondly, we performed a more focused cell-type-centric analysis and found that excitatory neurons in AD have significantly increased their communications to inhibitory neurons, while inhibitory neurons and other non-neuronal cells globally decreased theirs to all cells. Then, we delved deeper with a signaling-centric view, showing that canonical signaling pathways CSF, TGFβ, and CX3C are significantly dysregulated in their signaling to the cell type microglia/PVM and from endothelial to neuronal cells for the WNT pathway. Finally, after extracting 23 known AD risk genes, our intracellular communication analysis revealed a strong connection of extracellular ligand genes APP, APOE, and PSEN1 to intracellular AD risk genes TREM2, ABCA1, and APP in the communication from astrocytes and microglia to neurons. Conclusions In summary, with the novel advances in single-cell sequencing technologies, we show that cellular signaling is regulated in a cell-type-specific manner and that improper regulation of extracellular signaling genes is linked to intracellular risk genes, giving the mechanistic intra- and inter-cellular picture of AD....
Background While depression is increasing worldwide, some patients are diagnosed as having Major Depressive Disorder (MDD), but others are diagnosed with minor depression, however, the potential neuro mechanism is unknown. Methods Sixty-two patients with minor depression, 44 adolescents with MDD and 54 healthy adolescents participated in this study. Functional near-infrared spectroscopy (fNIRS), both HAMD and HAMA data were collected from all of the participants. Results The result indicates the pervasively decreased activation of BA, 11, 21, 45 and 46 were observed in the MDD group and reduced activation of BA 45 was observed in the minor depression group. However, cortical activation was not observed between the minor depression or MDD groups. Cortical activation was also not correlated with the depressive/anxious score in the minor and MDD groups separately. Conclusions Cortical activation was pervasively decreased in the MDD group and slightly reduced in the minor depression group, which may be a potential neural mechanism. As reduced cortical activation in minor depression, interventions in the early stages of minor depression may help slow or even modify the development of the illness....
T cells play an important role in the acquired immune response, with regulatory T cells (Tregs) serving as key players in immune tolerance. Tregs are found in nonlymphoid and damaged tissues and are referred to as “tissue Tregs”. They have tissue-specific characteristics and contribute to immunomodulation, homeostasis, and tissue repair through interactions with tissue cells. However, important determinants of Treg tissue specificity, such as antigen specificity, tissue environment, and pathology, remain unclear. In this study, we analyzed Tregs in the central nervous system of mice with ischemic stroke and experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. The gene expression pattern of brain Tregs in the EAE model was more similar to that of ischemic stroke Tregs in the brain than to that of spinal cord Tregs. In addition, most T-cell receptors (TCRs) with high clonality were present in both the brain and spinal cord. Furthermore, Gata3+ and Rorc+ Tregs expressed TCRs recognizing MOG in the spinal cord, suggesting a tissue environment conducive to Rorc expression. Tissue-specific chemokine/ chemokine receptor interactions in the spinal cord and brain influenced Treg localization. Finally, spinal cord- or brainderived Tregs had greater anti-inflammatory capacities in EAE mice, respectively. Taken together, these findings suggest that the tissue environment, rather than pathogenesis or antigen specificity, is the primary determinant of the tissue-specific properties of Tregs. These findings may contribute to the development of novel therapies to suppress inflammation through tissue-specific Treg regulation....
Background Anxiety disorders can cause serious physical and psychological damage, so many anxiety scales have been developed internationally to measure anxiety disorders, but due to the cultural differences and cultural dependence of quality of life between Chinese and Western cultures, it is difficult to reflect the main characteristics of Chinese patients. Therefore, we developed a scale suitable for Chinese patients with anxiety disorders: the Anxiety Disorders Scale of the Quality of Life Instruments for Chronic Diseases (QLICD-AD), hoping to achieve satisfactory QOL assessments for anxiety disorders. Objectives Items from the Anxiety Disorders Scale of the Quality of Life in Chronic Disease Instrument QLICD-AD system were analyzed using CTT and IRT to lay the groundwork for further refinement of the scale to accurately measure anxiety disorders. Methods 120 patients with anxiety disorder were assessed using the QLICD-AD (V2.0). Descriptive statistics, variability method, correlation coefficient method, factor analysis and Cronbach’s coefficient of CTT, and graded response model (GRM) of item response theory were used to analyze the items of the scale. Result CTT analysis showed that the standard deviation of each item was between 0.928 and 1.466; Pearson correlation coefficients of item-to-domain were generally greater than 0.5 and also greater than that of item-to-other domain; the Cronbach ‘s of the total scale was 0.931, α of each domain was between 0.706 and 0.865. IRT analysis showed that the discrimination was between 1.14 and 1.44. The difficulty parameter of all items increased with the increase of grade. But some items (GPH6,GPH8,GPS3,GSO2-GSO4,AD2,AD5) difficulty parameters were less than 4 or greater than 4. The average of information amount was between 0.022 and 0.910. Conclusion Based on CTT and IRT analysis, most items of the QLICD-AD (V2.0) scale have good performance and good differentiation, but a few items still need further revision. Suggests that the QLICD-AD (V2.0) appears to be a valid measure of anxiety disorders. It may effectively improve the diagnosticity of anxiety disorders, but due to the limitations of the current sample, further validation is needed in a broader population extrapolation trial....
Background Adolescents with depression who engage in non-suicidal self harming behaviors are more likely to adopt negative coping strategies when faced with negative events. Therefore, these patients should be introduced to positive coping strategies. Evidences have showed that mindfulness-based interventions can positively impact the psychology of patients with mental disorders. This study was to explore the impact of a combination of mindfulness therapy and mentalization-based family therapy (MBFT) on suicidal ideation in adolescents with depressive disorder. Methods Eighty adolescent patients with depression and suicidal ideation admitted to our hospital from September 2021 to February 2022 were selected as subjects. They were divided into a control group and a study group using the random number table method, with each group comprising 40 subjects. The control group received MBFT, whereas the study group received both mindfulness therapy and MBFT. The psychological status and suicidal ideations of the two groups were compared before and after the intervention. Results The psychological health scores of both groups of patients were lower after the intervention, with the scores of the study group being lower than those of the control group (P < 0.05). The scores on the suicidal ideation scales for both groups were lower after intervention, and the study group scored lower than the control group (P < 0.05). The absolute values of the differences in psychological health scale scores and suicidal ideation scale scores before and after the intervention were higher in the study group than in the control group (P < 0.05). Conclusion The combination of mindfulness therapy and MBFT can improve the psychological condition of adolescents with depression, reduce their suicidal ideations, and help them develop a healthy and positive outlook toward life, making this method worthy of clinical recommendation....
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