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Alzheimer disease (AD) is the most common neurodegenerative brain disease that causes cognitive impairment in the elderly. Behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms, represent a heterogeneous group of non-cognitive symptoms and behaviors for AD patients. Sleep disorder is one closely-related psychiatric symptom of AD. In this cross-section study, we aimed to investigate the characteristics of sleep status and BPSD among AD patients in Eastern China and to assess the relationship among sleep disorder, BPSD, and cognition.A total of 176 participants were enrolled in the study, including 84 AD patients and 92 healthy individuals as controls. Mini-mental state examination (MMSE), cooperative study-activities of daily living (ADCS-ADL) and clinical dementia rating (CDR) were used to measure cognition, the competence in basic and instrumental activities of daily living, and severity of dementia, respectively. BPSD were evaluated by neuropsychiatric inventory (NPI). Pittsburgh sleep quality index (PSQI) and Epworth sleepiness scale were designed to assess the sleep status and daytime naps. Spearman correlation analyses were performed to determine the relations between PSQI, MMSE, ADCS-ADL, and NPI scores and CDR.Sleep disorders occurred in 55.9% of AD patients versus only 15.2% of controls. 89.2% of AD patients had BPSD while only 22.9% of controls did, with apathy (64.

BackgroundThe role of stress signals in regulating gastric cancer initiation and progression is not quite clear. It is known that stress signals modulate multiple processes such as immune function, cell migration and angiogenesis. However, few studies have investigated the mechanisms of how stress signals contribute to gastric cancer angiogenesis.MethodsHere, we used β2-adrenergic receptor (β2-AR) agonist isoprenaline to imitate a stress signal and demonstrated the molecular mechanism underlying stress’s influence on tumor angiogenesis.ResultsWe found that isoprenaline stimulated vascular endothelial growth factor (VEGF) secretion in gastric cancer cells and plexin-A1 expression was induced by human recombinant VEGF165 in both gastric cancer cells and vascular endothelial cells. Furthermore, interfere with plexin-A1 expression in gastric cancer cells influence HUVEC tube formation, migration and tumor growth in vivo.ConclusionsThese findings suggest that isoprenaline stimulate VGEF secretion and subsequently up-regulate the expression of plexin-A1 and VEGFR2 in gastric cancer cells, which form a positive impetus to promote tumor angiogenesis. This study reveals a novel molecular mechanism that a stress signal like isoprenaline may enhance angiogenesis via activating plexin-A1/VEGFR2 signaling pathway in gastric cancer, which may be a potential target in development of an anti-angiogenic therapy for gastric cancer.

The emerging role of stress-related signaling in regulating cancer development and progression has been recognized. However, whether stress serves as a mechanism to promote gastric cancer metastasis is not clear. Here, we show that the β2-AR agonist, isoprenaline, upregulates expression levels of CD44 and CD44v8-10 in gastric cancer cells. CD44, a cancer stem cell-related marker, is expressed at high levels in gastric cancer tissues, which strongly correlates with the occurrence of epithelial-mesenchymal transition (EMT)-associated phenotypes both in vivo and in vitro. Combined with experimental observations in two human gastric cancer cell lines, we found that β2-AR signaling can initiate EMT. It led to an increased expression of mesenchymal markers, such as α-SMA, vimentin, and snail at mRNA and protein levels, and conversely a decrease in epithelial markers, E-cadherin and β-catenin. Isoprenaline stimulation of β2-AR receptors activates the downstream target STAT3, which functions as a positive regulator and mediated the phenotypic switch toward a mesenchymal cell type in gastric cancer cells. Our data provide a mechanistic understanding of the complex signaling cascades involving stress-related hormones and their effects on EMT. In light of our observations, pharmacological interventions targeting β2-AR-STAT3 signaling can potentially be used to ameliorate stress-associated influences on gastric cancer development and progression.