Effect of visual impairment on subjective cognitive decline in older adults: a cross-sectional study in China.

OBJECTIVE: People with visual impairment have more functional limitations associated with subjective cognitive decline (SCD), and those with SCD are extremely susceptible to transitioning to irreversible cognitive impairment. This study aimed to explore if visual impairment is a significant predictor of SCD compared with other socioeconomic and health factors associated with SCD. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: The investigation aimed to assess the factors influencing SCD among 428 participants aged 60 and above in Zhaoyuan, China. PRIMARY OUTCOME MEASURES: The primary outcome variable was SCD, measured by the Chinese version of SCD questionnaire. Multiple logistic regression and propensity score matching (PSM) were used to analyse the influence of visual impairment on the subjective cognition of the elderly.32.2% of the elderly were experiencing SCD. Older adults with SCD showed a higher prevalence of visual impairment (72.5%) than the elderly without SCD (58.6%) (P=0.006). Multivariate logistic regression analysis showed that bad self-reported health status, lack of physical exercise and visual impairment were the risk factors for SCD in older adults, while more than 9 years of education was a protective factor. In addition, PSM model showed that after eliminating the dominant biases caused by the individual observable heterogeneity of older adults with and without visual impairment, the risk of SCD in the elderly with visual impairment was increased by 13.6%-14.5% and the difference was statistically significant (P<0.05). CONCLUSIONS: It was found that older adults experiencing visual impairments are at an elevated risk of developing SCD compared with their counterparts without such impairments. Additionally, visual impairment remains a significant risk factor for SCD in the elderly, even adjusting for potential biases arising from individual observable heterogeneity.

Low life satisfaction status among older people with and without an intimate partner: a nationwide cross-sectional study in China.

BACKGROUND: Focusing on older people with and without an intimate partner, this study aimed to evaluate the prevalence of low life satisfaction in both groups, as well as the potential risk factors. METHODS: The 2017-2018 China Health and Retirement Longitudinal Study (CHARLS) data were used, and 9960 individuals aged 60 years and above were included in the analyses. Factors evaluated in this survey included sociodemographic characteristics, clinical variables, physical and social activities, and economic and social factors. The associations of low life satisfaction with independent variables were analysed using multivariate logistic regression. RESULTS: Compared with those with an intimate partner (n = 2025), elders without an intimate partner (n = 7935) showed a higher prevalence of low life satisfaction (15.1 vs. 9.9%, P < 0.001). Multivariate logistic regression showed that ≥2 physical diseases (P = 0.024), poor self-reported health status (P = 0.012), and lack of community care service (P = 0.014) were risk factors for low life satisfaction among elders without an intimate partner, while poor self-reported health status (P < 0.001), ≥2 physical diseases (P = 0.001), being troubled with bodily pain (P < 0.001), lack of light physical activity >10 mins each time (P = 0.011), lack of moderate physical activity >10 mins each time (P = 0.001), lack of social activities in the previous month (P = 0.039), and lack of community care service (P < 0.001) were risk factors for elders with an intimate partner. Regarding the potential reasons for low life satisfaction in the elderly, dissatisfaction with current health status (28.0%) and air quality (15.6%) were most prevalent. CONCLUSIONS: Older people without an intimate partner have lower life satisfaction. Having ≥2 physical diseases, poor self-reported health status, and lack of community care service were common risk factors for low life satisfaction among older adults with or without an intimate partner.

Assessing intentions for a third child among Chinese adults: A nationwide online survey regarding China's 3-child policy.

Aging populations, along with low fertility rates, have become a pervasive world-wide problem. To address this challenge, China issued a universal 3-child policy on May 31, 2021. However, little is known regarding the intentions of childbearing-aged Chinese for a third child. The purpose of this study was to assess the fertility intentions of the Chinese as related to this third-child policy and identify risk factors for third-child refusal. In this cross-sectional study, a total of 2129 Chinese childbearing-aged participants were recruited nationwide from June 15 to July 22, 2021. Each participant was interviewed using questionnaires to establish their sociodemographic variables, psychosocial factors as related to third-child intentions, and reasons for third-child refusal. Finally, 2115 responses (866 men and 1249 women) were analyzed. IBM SPSS Statistical Software (version 19) was used for the statistical analyses. Multivariate logistic regression analyses were used to assess independent influences for third-child refusal. Approximately 30% of these participants reported an intention for having a third child. In those expressing a refusal for a third child, women showed a higher prevalence rate (74.1 vs 63.2%, P < .001). Results from multivariate logistic regression analyses revealed that age (P = .033), unemployment (P = .045), and currently raising 2 children (P = .017) were risk factors for third-child refusal among men, while age (P < .001), >15 years of education (P = .017), current smokers (P = .005) and residing in Northern China (P = .035) were risk factors for women. Overall, increased demands upon time and energy (41.5%), as well as economic burdens (41.4%), were the most prevalent reasons for the refusal of a third child, while achieving mutual care among siblings (52.5%) and reducing child educational costs (33.3%) were the most effective persuasions. In response to the 3-child policy, Chinese childbearing-aged adults showed low rates of intention for a third child, with women showing a higher prevalence of third-child refusal. The identification of risk factors and the reasons for third-child refusal as revealed from the results of this study provide a foundation for the development of programs needed to aid in the implementation of this 3-child policy.

Impact prediction of translocation of the mitochondrial outer membrane 70 as biomarker in Alzheimer's disease.

Mitochondrial dysfunction plays a key role in the pathogenesis of Alzheimer's disease (AD). The translocase of the outer membrane (TOM) complex controls the input of mitochondrial precursor proteins to maintain mitochondrial function under pathophysiological conditions. However, its role in AD development remains unclear. TOM70 is an important translocase present in the TOM complex. In the current study, we found that TOM70 levels were reduced in the peripheral blood and hippocampus of the APP/PS1 mice. In addition, we examined the whole-blood mRNA levels of TOM70 in patients with AD, dementia with Lewy bodies (DLB), and post-stroke dementia (PSD). Our study revealed that the mRNA level of TOM70 was decreased in the blood samples of patients with AD, which was also correlated with the progression of clinical stages. Therefore, we proposed that the expression of TOM70 could be a promising biomarker for AD diagnosis and monitoring of disease progression.

Integrated investigation of DNA methylation, gene expression and immune cell population revealed immune cell infiltration associated with atherosclerotic plaque formation.

BACKGROUND: The clinical consequences of atherosclerosis are significant source of morbidity and mortality throughout the world, while the molecular mechanisms of the pathogenesis of atherosclerosis are largely unknown. METHODS: In this study, we integrated the DNA methylation and gene expression data in atherosclerotic plaque samples to decipher the underlying association between epigenetic and transcriptional regulation. Immune cell classification was performed on the basis of the expression pattern of detected genes. Finally, we selected ten genes with dysregulated methylation and expression levels for RT-qPCR validation. RESULTS: Global DNA methylation profile showed obvious changes between normal aortic and atherosclerotic lesion tissues. We found that differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were highly associated with atherosclerosis by being enriched in atherosclerotic plaque formation-related pathways, including cell adhesion and extracellular matrix organization. Immune cell fraction analysis revealed that a large number of immune cells, especially macrophages, activated mast cells, NK cells, and Tfh cells, were specifically enriched in the plaque. DEGs associated with immune cell fraction change showed that they were mainly related to the level of macrophages, monocytes, resting NK cells, activated CD4 memory T cells, and gamma delta T cells. These genes were highly enriched in multiple pathways of atherosclerotic plaque formation, including blood vessel remodeling, collagen fiber organization, cell adhesion, collagen catalogic process, extractable matrix assembly, and platelet activation. We also validated the expression alteration of ten genes associated with infiltrating immune cells in atherosclerosis. CONCLUSIONS: In conclusion, these findings provide new evidence for understanding the mechanisms of atherosclerotic plaque formation, and provide a new and valuable research direction based on immune cell infiltration.

[Design of Detection Module in Coagulometers Based on Dual-magnetic Circuit Beads Method].

Coagulometer, known as blood coagulation analyzer, is a product that can provide accurate test results for medical diagnosis and treatment analysis by detecting a series of items closely related to thrombosis and hemostasis in coagulation reaction. On the basis of previous traditional methods, and with our deep understanding about the principles of hemagglutination detection, we propose a hemagglutination detection method by using the dual-magnetic circuit beads method. Then, the corresponding hemagglutination detection module is designed. The coagulation time of plasma can be measured by detecting the movement of the magnetic beads when the magnetic field intensity is appropriate. The activated partial thromboplastin time(APTT) of plasma is tested when the most suitable magnetic field intensity is found. The results preliminarily show that this blood coagulation test method is valid and the corresponding test module has a potential value in business.

Effect of orexin-A on mitochondrial biogenesis, mitophagy and structure in HEK293-APPSWE cell model of Alzheimer's disease.

Mitochondrial dysfunction plays a key role in the pathogenesis and progression of Alzheimer's Disease (AD). Our previous studies showed that over expression of AD-associated mutant ß-amyloid precursor protein (APP) led to abnormalities of mitochondrial biogenesis and mitophagy, leading to mitochondrial dysfunction. However, the mechanism remains unclear. In this study, we investigated the effect of orexin-A on mitochondrial biogenesis, mitophagy and mitochondrial structure in overexpression of AD-associated mutant APP cells. We used 20E2 cells as the AD cell model. 20E2 cells were treated with orexin-A (50, 100 nmol/L). The effect of different concentrations of orexin-A on cell activity was detected by MTT. As compared with the non-treated 20E2 cells, orexin-A-treated 20E2 cells showed increased expression of APP, decreased cell viability and decreased adenosine triphosphate (ATP) level, decreased levels of regulatory proteins of mitochondrial biogenesis (peroxisome proliferator-activated receptor gamma coactivator 1-alpha [PGC-1α], nuclear respiratory factor 1/2 [NRF1/2], mitochondrial transcription factor A [TFAM]), increased levels of regulatory proteins of mitophagy (Parkin, PTEN-induced putative kinase 1 [PINK1], microtubule-associated protein light chain 3 II/I [LC3-II/LC3-I]) and decreased p62 level, with damaged mitochondrial structure. Orexin-A may reduce mitochondrial biogenesis, enhance mitophagy and damage mitochondrial structure in AD.

Automated detection of dynamical change in EEG signals based on a new rhythm measure.

Automated detection of dynamical change in EEG signals has been a long-standing problem in a wide range of clinic applications. It is essential to extract an effective and accurate EEG rhythm indicator that can reflect the dynamical behavior of a given EEG signal. Time-frequency analysis is a promising method to achieve this end, but existing methods still have limitations in real implementation making this kind of methods still progressive until the present day. In this paper, along the line of ongoing research on time-frequency methods, we present a new method based on graph-based modeling. By virtue of this method, an effective and accurate EEG rhythm indicator can be extracted to characterize the dynamical EEG time series. Together with the extracted EEG rhythm indicator, an automatic analysis of continuous monitoring of EEG signal, is developed by means of a null hypothesis testing to inspect whether an EEG change occurs or not during a monitoring period. The proposed framework is applied to both simulated data and real signals respectively to validate its effectiveness. Experimental results, together with theoretical interpretation and discussions, suggest its promising potentials in practice.

Anomaly Detection in EEG Signals: A Case Study on Similarity Measure.

Motivation. Anomaly EEG detection is a long-standing problem in analysis of EEG signals. The basic premise of this problem is consideration of the similarity between two nonstationary EEG recordings. A well-established scheme is based on sequence matching, typically including three steps: feature extraction, similarity measure, and decision-making. Current approaches mainly focus on EEG feature extraction and decision-making, and few of them involve the similarity measure/quantification. Generally, to design an appropriate similarity metric, that is compatible with the considered problem/data, is also an important issue in the design of such detection systems. It is however impossible to directly apply those existing metrics to anomaly EEG detection without any consideration of domain specificity. Methodology. The main objective of this work is to investigate the impacts of different similarity metrics on anomaly EEG detection. A few metrics that are potentially available for the EEG analysis have been collected from other areas by a careful review of related works. The so-called power spectrum is extracted as features of EEG signals, and a null hypothesis testing is employed to make the final decision. Two indicators have been used to evaluate the detection performance. One is to reflect the level of measured similarity between two compared EEG signals, and the other is to quantify the detection accuracy. Results. Experiments were conducted on two data sets, respectively. The results demonstrate the positive impacts of different similarity metrics on anomaly EEG detection. The Hellinger distance (HD) and Bhattacharyya distance (BD) metrics show excellent performances: an accuracy of 0.9167 for our data set and an accuracy of 0.9667 for the Bern-Barcelona EEG data set. Both of HD and BD metrics are constructed based on the Bhattacharyya coefficient, implying the priority of the Bhattacharyya coefficient when dealing with the highly noisy EEG signals. In future work, we will exploit an integrated metric that combines HD and BD for the similarity measure of EEG signals.

Elevated plasma levels of exosomal BACE1­AS combined with the volume and thickness of the right entorhinal cortex may serve as a biomarker for the detection of Alzheimer's disease.

Long non-coding RNA (lncRNA) and exosomes are involved in the pathological process of Alzheimer's disease (AD), the pathological changes of which are usually first observed in the entorhinal cortex and hippocampus. The aim of the present study was to determine whether the measurement of plasma exosomal lncRNA combined with image data of the entorhinal cortex and hippocampus could be used as a biomarker of AD. A total of 72 patients with AD and 62 controls were recruited, and the expression levels of several lncRNAs were assessed. Of the recruited participants, 22 patients and 26 controls received brain 3D­BRAVO sequence magnetic resonance imaging (MRI) scans, which were analyzed using an automated analysis tool. The plasma exosomal ß­site amyloid precursor protein cleaving enzyme­1­antisense transcript (BACE1­AS) levels in patients with AD were significantly higher compared with the controls (P<0.005). Receiver operating characteristic curve analysis revealed that the area under the curve (AUC) was 0.761 for BACE1­AS, the sensitivity was 87.5%, and the specificity was 61.3%. Analysis of MRI images indicated that the right entorhinal cortex volume (P=0.015) and thickness (P=0.022) in patients with AD were significantly smaller. The AUC was 0.688 for the right entorhinal cortex volume, with a sensitivity of 59.1%, and the specificity was 84.6%. The AUC was 0.689 for right entorhinal cortex thickness, with a sensitivity of 80.8%, and the specificity was 59.1%. A series­parallel test which integrated the BACE1­AS with the right entorhinal cortex volume and thickness, raised the specificity and sensitivity to 96.15 and 90.91%, respectively. A logistic regression model demonstrated that combination of the 3 indices provided improved sensitivity and specificity simultaneously, particularly when adjusting for age and sex (AUC, 0.819; sensitivity, 81%; specificity, 73.1%). The results of the present study demonstrated that detection of plasma exosomal BACE1­AS levels combined with the volume and thickness of the right entorhinal cortex may be used as a novel biomarker of AD.

Transplantation of IFN-γ Primed hUCMSCs Significantly Improved Outcomes of Experimental Autoimmune Encephalomyelitis in a Mouse Model.

The aim of this study was to investigate potential therapeutic effects of IFN-γ primed human umbilical cord mesenchymal stem cell (IFN-γ-hUCMSCs) transplantation on experimental autoimmune encephalomyelitis (EAE) in mice. In this study, EAE mouse model was established by MOG35-55 immunization method. Outcomes of the EAE mice in terms of body weight and clinical symptoms were analyzed. Electromyography (EMG) was performed to evaluate nerve conduction. ELISA was applied to quantify inflammatory cytokine levels in serum. Our results showed that IFN-γ could up-regulate protein expression of indoleamine 2, 3-dioxygenease 1 (IDO1), an important molecule released by MSCs to exert their immune suppressive activity (p < 0.01). In this study treatment efficacy for EAE was compared between transplantation of hUCMSCs alone and the IFN-γ-hUCMSCs which were cultured in the presence of IFN-γ for 48 h prior to be harvested for transplantation. Compared with hUCMSCs alone and control (PBS transfusion) group, transplantation of the IFN-γ-hUCMSCs could significantly alleviate the body weight loss and clinical symptoms of EAE mice (p < 0.05). Consistently EMG latency was significantly improved in treatment groups (p < 0.001), and the IFN-γ-hUCMSCs group was even better than the hUCMSCs group (p < 0.05). Moreover, the concentrations of IL-17A and TNF-α in serum of the mice treated by IFN-γ-hUCMSCs were significantly lower than hUCMSCs alone and controls, respectively (p < 0.05). In few of the roles of IL-17A and TNF-α in the pathogenesis of EAE, IFN-γ-hUCMSCs treatment associated-suppression of IL-17A and TNF-α expression may contribute in part to their therapeutic effects on EAE. In sum, our study highlights a great clinical potential of IFN-γ-hUCMSCs for multiple sclerosis (MS) treatment.

Orexin-A aggravates cytotoxicity and mitochondrial impairment in SH-SY5Y cells transfected with APPswe via p38 MAPK pathway.

BACKGROUND: Alzheimer's disease (AD) is one of the common neurodegenerative diseases and is characterized by the accumulation of amyloid-ß (Aß). Orexin-A is a neuropeptide produced in the hypothalamus and thought to be involved in the pathogenesis of AD. However, its underlying mechanism and signaling pathway remains unclear. The aim of this work was to investigate the effect of Orexin-A on AD, and to explore its potential mechanism and signaling pathway. METHODS: SH-SY5Y cells that were stably transfected with the Swedish mutant amyloid precursor protein (APPswe), a cell model of AD with excessive Aß production, were used in this study. Cells were treated with Orexin-A, and with or without SB203580, an inhibitor of the p38 mitogen-activated protein kinase (MAPK) pathway, one of the key MAPK pathways associated with cell death. Following treatment, cells were collected and analyzed by western blotting, ELISA, electron microscopy, real-time PCR, fluorescence microscopy, and other biochemical assays. RESULTS: Orexin-A increased the level of Aß1-40 and Aß1-42 in the cell medium, and activated the p38 MAPK pathway. As evidenced by the CCK-8 and ELISA BrdU assays, Orexin-A decreased cell viability and cell proliferation. Electron microscopic analysis used to observe the morphology of mitochondria, showed that Orexin-A increased the percentage of abnormal mitochondria. Further, decreased activity of cytochrome c oxidase (CCO), level of ATP, and mitochondrial DNA (mtDNA) copy number following Orexin-A treatment showed that Orexin-A exacerbated mitochondrial dysfunction. The level of intracellular reactive oxygen species (ROS), which is mainly generated in mitochondria and reflects mitochondrial dysfunction, was also increased by Orexin-A. SB203580 blocked the cytotoxicity and mitochondrial impairment aggravated by Orexin-A. CONCLUSIONS: These findings demonstrate that Orexin-A aggravates cytotoxicity and mitochondrial impairment in SH-SY5Y cells transfected with APPswe through the p38 MAPK pathway, and suggest that Orexin-A participates in the pathogenesis of AD, which may provide a new treatment target in the future.

Orexin-A exacerbates Alzheimer's disease by inducing mitochondrial impairment.

Alzheimer's disease (AD) is a progressive neurodegenerative disease which is characterized by the accumulation of amyloid-ß peptide (Aß). Orexin-A is a neuropeptide which has been reported to participate in the pathogenesis of AD. Thus, we aimed to investigate the possible mechanism by which Orexin-A acts in AD. APP/PS1 transgenic mice, an animal model of AD, were intracerebroventricularly injected with Orexin-A. Aß-treated SH-SY5Y cells were used as a cell model of AD and treated with Orexin-A. The Morris water maze test, fluorescence microscopy, enzyme-linked immunosorbent assay (ELISA), electron microscopy, real-time PCR, and other biochemical assays were conducted. The Morris water maze test showed that Orexin-A aggravated cognitive deficit in APP/PS1 mice. Using thioflavine-S staining and ELISA, we found that Orexin-A promoted Aß accumulation in APP/PS1 mice. By evaluating mitochondrial morphology, cytochrome c oxidase activity, ATP level, mitochondrial DNA copy number, and reactive oxygen species, we found that Orexin-A aggravated mitochondrial impairment in APP/PS1 mice and Aß-treated SH-SY5Y cells. Our results indicate that Orexin-A exacerbates AD by inducing mitochondrial impairment. This is a new mechanism that explains how Orexin-A participates in the pathogenesis of AD.

The effect of BACE1-AS on ß-amyloid generation by regulating BACE1 mRNA expression.

BACKGROUND: The BACE1 antisense transcript (BACE1-AS) is a conserved long noncoding RNA (lncRNA). The level of BACE1-AS is significantly increased and the level of the BACE1 mRNA is slightly increased in subjects with AD. BACE1-AS exerts a significant moderating effect on the expression of the BACE1 mRNA and promotes the formation of Aß. After the administration of Aß1-42 to SH-SY5Y cells and C57/BL6J mice, we detected the expression of BACE1-AS, BACE1 mRNA, and BACE1 protein, as well as the concentration of Aß1-40. Then, we silenced the expression of BACE1-AS in SH-SY5Y and 20E2 cells using siRNAs targeting BACE1-AS and detected its effects on the levels of the BACE1 mRNA and BACE1 protein and Aß1-40 generation. RESULTS: The administration of Aß1-42 increased the expression of BACE1-AS, BACE1 mRNA and protein, as well as the concentration of Aß1-40 in SH-SY5Y cells and the brains of C57BL/6J mice. Pretreatment with the BACE1-AS siRNA inhibited the effect of Aß1-42 on increasing the expression of BACE1-AS and BACE1, as well as the generation of Aß. CONCLUSIONS: The mechanism by which exogenous Aß1-42 induces BACE1 expression and Aß generation is mediated by BACE1-AS. BACE1-AS is involved in the mechanism regulating BACE1 expression and Aß generation in APPsw transgenic cells.

Methylation in the TP53 promoter is associated with ischemic stroke.

Cerebral ischemic stroke (IS) is a disease presenting high morbidity and mortality rates worldwide. Understanding of the pathogenesis underlying IS may facilitate the development of effective clinical therapeutic strategies and improve the prevention of this disease, decreasing its occurrence rate. Epigenetic alterations have recently attracted attention as possible mechanisms underlying IS. Additionally, tumor protein p53 (TP53) was identified to be involved in the pathophysiology of cerebral stroke. In the present study, the methylation status of the TP53 promoter was investigated in patients with IS and in age­matched healthy controls. The methylation status of the promoter of TP53 was significantly increased in patients with IS compared with healthy subjects. Additionally, the methylation level of the TP53 promoter was identified to be associated with carotid intima­media thickness, the degree of carotid atherosclerosis and the circulating levels of homocysteine in peripheral blood. The present findings may improve the understanding of the role of the epigenetic modifications of the TP53 promoter in IS pathogenesis.

Activation of Mitochondrial Unfolded Protein Response in SHSY5Y Expressing APP Cells and APP/PS1 Mice.

Alzheimer disease (AD) is the most common form of dementia. Amyloid ß-peptide (Aß) deposition is a major neuropathologic feature of AD. When unfolded or misfolded proteins accumulate in mitochondria, the unfolded protein responses (UPRmt) is initiated. Numerous lines of evidence show that AD pathogenesis involves mitochondrial dysfunction. However little is known about whether the UPRmt is engaged in the process of AD development. In this study, we investigated the UPRmt in mouse and cell models of AD. We found that UPRmt was activated in the brain of 3 and 9 months old APP/PS1 mice, and in the SHSY5Y cells after exposure to Aß25-35, Aß25-35 triggered UPRmt in SHSY5Y cells could be attenuated upon administration of simvastatin or siRNA for HMGCS-1 to inhibit the mevalonate pathway, and or upon knocking down Serine palmitoyltransferase long chain subunit 1 (SPTLC-1) to lower sphingolipid biosynthesis. We observed that inhibition of UPRmt aggravated cytotoxic effects of Aß25-35 in SHSY5Y cells. Our research suggests that the UPRmt activation and two pathways necessary for this response, and further provides evidence for the cytoprotective effect of UPRmt during the AD process.

Anti-inflammatory effects of bone marrow mesenchymal stem cells on mice with Alzheimer's disease.

Anti-inflammatory effects of bone marrow mesenchymal stem cells (BMSCs) on mice with Alzheimer's disease (AD) were investigated. Twenty amyloid precursor protein (APP)/presenilin-1 (PS1) double transgenic mice were randomly divided into two groups: the AD control group and the stem cell treatment group. The normal control group consisted of 10 non-transgenic mice. The stem cell treatment group was injected with BMSCs, and the two control groups were given the same volume of normal saline. The Morris water maze test was used to compare the memory function of mice, and the relative expression levels of ß-site APP cleaving enzyme 1 (BACE1) and α-2-macroglobulin (A2M) genes were detected by fluorescence quantitative polymerase chain reaction (qPCR). Amyloid ß (Aß)1-42 content in brain tissues of mice and inflammatory cytokines, interleukin (IL)-1, IL-2, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were detected using enzyme-linked immunosorbent assay (ELISA). Compared with that in the AD control group, the escape latency in the water maze in the stem cell treatment group was shortened, the time of crossing the ring for the first time was decreased, but the frequency of crossing the ring was increased (P<0.05). Aß1-42 content in the AD control group was higher than that in the stem cell treatment group and the normal control group (P<0.05). The relative expression level of BACE1 gene in the stem cell treatment group was lower than that in the AD control group (P<0.05), but that of A2M gene was increased (P<0.05). At 14 days after treatment, the contents of IL-1, IL-2, TNF-α and IFN-γ in blood in the stem cell treatment group were lower than those in the AD control group (P<0.05). Human BMSCs can ameliorate the symptoms of AD by decreasing the levels of inflammatory cytokines and regulating the expression of Aß-related genes.

Mitochondrial biogenesis mediated by melatonin in an APPswe/PS1dE9 transgenic mice model.

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease, but the pathogenesis is unclear. Damaged mitochondrial biogenesis has been observed in AD. Increasing evidence suggests that mitochondrial biogenesis is involved in the pathogenesis of AD, but the exact mechanism is unclear. In this study, we used the amyloid precursor protein Swedish mutations K594N/M595L (APPswe)/presenilin 1 with the exon-9 deletion (PS1dE9) transgenic mouse model of AD, which was successfully established by the expression of amyloid ß precursor protein and presenilin 1 (PS1). Then, we compared APPswe/PS1dE9 transgenic mice with and without melatonin (MT) in drinking water for 4 months (estimated 0.5 mg/day) and control C57BL/6J mice without MT for expression of mitochondrial biogenesis factors (mitochondrial transcription factor A, nuclear respiratory factor 1 and 2, peroxisome proliferator-activated receptor γ coactivator 1-α), mitochondrial structure, mitochondrial DNA to nuclear DNA ratio, behavioral changes, and amyloid ß (Aß) deposition and soluble Aß levels in the cerebral cortex and hippocampus. Compared with controls, APPswe/PS1dE9 mice with long-term MT intake showed increased levels of mitochondrial biogenesis factors, alleviated mitochondrial impairment, enhanced mitochondrial DNA copy number, improved spatial learning and memory deficits, and reduced Aß deposition and soluble Aß levels. Defective mitochondrial biogenesis may contribute toward the damaged mitochondrial structure and function in AD. MT may alleviate AD by promoting mitochondrial biogenesis.

Exosomes Isolated From Human Umbilical Cord Mesenchymal Stem Cells Alleviate Neuroinflammation and Reduce Amyloid-Beta Deposition by Modulating Microglial Activation in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by excessive accumulation of the amyloid-ß peptide (Aß) in the brain, which has been considered to mediate the neuroinflammation process. Microglial activation is the main component of neuroimmunoregulation. In recent years, exosomes isolated from human umbilical cord mesenchymal stem cells (hucMSC-exosomes) have been demonstrated to mimic the therapeutic effects of hucMSCs in many inflammation-related diseases. In this study, exosomes from the supernatant of hucMSCs were injected into AD mouse models. We observed that hucMSC-exosomes injection could repair cognitive disfunctions and help to clear Aß deposition in these mice. Moreover, we found that hucMSC-exosomes injection could modulate the activation of microglia in brains of the mice to alleviated neuroinflammation. The levels of pro-inflammatory cytokines in peripheral blood and brains of mice were increased and the levels of anti-inflammatory cytokines were decreased. We also treated BV2 cells with hucMSC-exosomes in culture medium. HucMSC-exosomes also had inflammatory regulating effects to alternatively activate microglia and modulate the levels of inflammatory cytokines in vitro.

Automatic Change Detection for Real-Time Monitoring of EEG Signals.

In recent years, automatic change detection for real-time monitoring of electroencephalogram (EEG) signals has attracted widespread interest with a large number of clinical applications. However, it is still a challenging problem. This paper presents a novel framework for this task where joint time-domain features are firstly computed to extract temporal fluctuations of a given EEG data stream; and then, an auto-regressive (AR) linear model is adopted to model the data and temporal anomalies are subsequently calculated from that model to reflect the possibilities that a change occurs; a non-parametric statistical test based on Randomized Power Martingale (RPM) is last performed for making change decision from the resulting anomaly scores. We conducted experiments on the publicly-available Bern-Barcelona EEG database where promising results for terms of detection precision (96.97%), detection recall (97.66%) as well as computational efficiency have been achieved. Meanwhile, we also evaluated the proposed method for real detection of seizures occurrence for a monitoring epilepsy patient. The results of experiments by using both the testing database and real application demonstrated the effectiveness and feasibility of the method for the purpose of change detection in EEG signals. The proposed framework has two additional properties: (1) it uses a pre-defined AR model for modeling of the past observed data so that it can be operated in an unsupervised manner, and (2) it uses an adjustable threshold to achieve a scalable decision making so that a coarse-to-fine detection strategy can be developed for quick detection or further analysis purposes.