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Background: The pathophysiological process of amyloid-β, tau deposition, and neurodegeneration of Alzheimer's disease (AD) begin in a preclinical phase, while anxiety is associated with an increased risk of AD in preclinical phase.Objective: To examine the relationships between anxiety and amyloid-β, tau deposition, and neurodegeneration. To test the hypothesis that anxiety could predict clinical progression in the elderly without dementia.Methods: 1,400 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included in the study and were studied over a median period of 3 years. In multivariable models, the cross-sectional and longitudinal associations between anxiety and amyloid-β PET, tau PET, and FDG PET SUVRs in participants without dementia were explored using Spearman rank correlation, logistic regression model, multiple linear regression model, Kaplan-Meier survival curves, and Cox proportional hazards model. The association between baseline anxiety and clinical progression was also explored.Results: There was a positive correlation between anxiety and amyloid-β deposition (r = 0.11, p = 0.0017) and a negative correlation between anxiety and neurodegeneration (r = -0.13, p = 0.00022). MCI participants with anxiety showed a faster clinical progression of dementia (HR = 1.56, p = 0.04). Non-anxious participants with more amyloid-β deposition or more severe neurodegeneration displayed accelerated development into anxiety (HR = 2.352, p < 0.0001; HR = 2.254, p < 0.0001).Conclusion: Anxiety was associated with amyloid-β deposition and neurodegeneration in non-dementia elderly. Anxiety in MCI predicted conversion to dementia. Anxiety may play a selective role and prediction of disease progression in the early phase of AD. [ABSTRACT FROM AUTHOR]

White matter hyperintensities (WMHs), mainly caused by cerebrovascular injury, may lead to cognitive impairment. In order to identify whether the volume of WMHs is associated with cognitive decline over years, this longitudinal study involved 818 individuals from the ADNI-2 dataset from August 2010 to May 2017. Cross-sectional and longitudinal associations of WMHs with 8 cognitive domains were explored, using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating Sum of Boxes (CDRSB), Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog13), Rey Auditory Verbal Learning Test (RAVLT), Functional Assessment Questionnaire (FAQ), executive function (ADNI-EF), and memory function (ADNI-Mem). The association analyses were performed using multiple linear regression models, linear mixed models, Spearman rank correlation, and Kaplan-Meier survival curves. The volumes of WMHs were greater in patients with Alzheimer's disease (AD) dementia compared with controls (p < 0.001) and mild cognitive impairment (p = 0.006) patients at baseline. The bigger volumes of WMHs correlated with worse performances on ADAS-Cog13 and ADNI-EF (p = 0.029; p = 0.003) at baseline and MMSE, MoCA, CDRSB, ADAS-Cog13, FAQ, and ADNI-Mem (overall p < 0.05) longitudinally, after adjusting for age, sex, educational level, apolipoprotein E ɛ4 genotype, hypertension, hyperlipidemia, diabetes, smoking, infarction, and diagnosis. Additionally, the correlations between the change rate of WMHs and change rates of MMSE, MoCA, CDRSB, FAQ, ADNI-EF, and ADNI-Mem were statistically significant. Furthermore, patients with high WMH volumes showed an increased likelihood of dementia. The results of the study suggest that WMH volume is associated with cognitive decline, and it contributes to the conversion to AD. [ABSTRACT FROM AUTHOR]

Cerebral microbleeds are the presence of a group of pathological processes affecting the small arteries, arterioles, capillaries, and venules of the brain. Previous studies showed that cerebral microbleeds were associated with higher risk of dementia and stroke. We conducted a genome-wide association study of cerebral microbleeds to identify novel loci associated with the presence and progression of cerebral microbleeds. This study included 454 individuals composed by 176 subjects with cerebral microbleeds and 278 subjects without cerebral microbleeds in a non-Hispanic/Latino white population. Association of genetic variants with the presence and progression of cerebral microbleeds was assessed by logistic regression model. Potential genetic risk variants Apolipoprotein E (ApoE) polymorphisms were independently genotyped and checked the association with the presence and progression of cerebral microbleeds. No single-nucleotide polymorphisms (SNPs) associated with the presence or progression of cerebral microbleeds were identified at genome-wide significant level (P < 1 × 10−8). A total of 19 SNPs were associated with the presence of microbleeds at suggestive level (P < 1 × 10−5). One SNP was associated with lower progression risk for cerebral microbleeds with suggestive evidence (P < 1 × 10−5). ApoE ε4ε4 was independently associated with the presence and progression of cerebral microbleeds (odds ratio = 2.54, 95% confidence interval 1.08–6.00 and odds ratio = 5.1, 95% confidence interval 1.36–19.16). We highlighted 19 novel SNPs associated with the presence of cerebral microbleeds and one novel SNP associated with the progression of cerebral microbleeds for the first time. ApoE ε4ε4 was confirmed independently associated with the presence and progression of cerebral microbleeds. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Hydrogen sulfide (H2S) has been reported to be a gasotransmitter which regulates cardiovascular homeostasis. The present study aims to examine the hypothesis that hydrogen sulfide is able to promote angiogenesis. Methods: Angiogenesis was assessed using in vitro parameters (i.e. endothelial cell proliferation, adhesion, transwell migration assay, scratched wound healing and formation of tube-like structure) and in vivo by assessing neovascularization in mice. Phosphorylation of Akt was measured using Western blot analysis. Results: Exogenously administered NaHS (H2S donor) concentration-dependently (10–20 μmol/l) increased cell growth, migration, scratched wound healing and tube-like structure formation in cultured endothelial cells. These effects of NaHS on endothelial wound healing and tube-like structure formation were prevented by either the phosphatidylinositol 3-kinase (PI3K) inhibitor LY 294002 (5 μmol/l) or transfection of a dominant-negative mutant of Akt. NaHS increased Akt phosphorylation and this effect was also blocked by either LY 294002 or wortmannin (25 nmol/l). NaHS did not significantly alter the levels of vascular endothelial growth factor, mRNA expression of fibroblast growth factor and angiopoietin-1, or nitric oxide metabolites. NaHS treatment (10 and 50 μmol kg−1 day−1) significantly promoted neovascularization in vivo in mice. Conclusion: The present study reports a novel proangiogenic role of H2S which is dependent on activation of Akt. [Copyright &y& Elsevier]

Background: Pharmacological treatments are very common to be used for alleviating neuropsychiatric symptoms (NPS) in dementia. However, decision on drug selection is still a matter of controversy., Aims: To summarise the comparative efficacy and acceptability of currently available monotherapy drug regimens for reducing NPS in dementia., Method: We searched PubMed, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials between inception and 26 December 2022 without language restrictions; and reference lists scanned from selected studies and systematic reviews. Double-blind randomised controlled trials were identified from electronic databases for reporting NPS outcomes in people with dementia. Primary outcomes were efficacy and acceptability. Confidence in the evidence was assessed using Confidence in Network Meta-Analysis (CINeMA)., Results: We included 59 trials (15,781 participants; mean age, 76.6 years) and 15 different drugs in quantitative syntheses. Risperidone (standardised mean difference [SMD] -0.20, 95% credible interval [CrI] -0.40 to -0.10) and galantamine (-0.20, -0.39 to -0.02) were more effective than placebo in short-term treatment (median duration: 12 weeks). Galantamine (odds ratio [OR] 1.95, 95% CrI 1.38-2.94) and rivastigmine (1.87, 1.24-2.99) were associated with more dropouts than placebo, and some active drugs. Most of the results were rated as low or very low according to CINeMA., Conclusions: Despite the scarcity of high-quality evidence, risperidone is probably the best pharmacological option to consider for alleviating NPS in people with dementia in short-term treatment when considering the risk-benefit profile of drugs., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Hydrogen sulfide (H2S)has emerged as pivotal signaling molecules since it is recognized as the third gasotransmitter together with nitric oxide and carbon monoxide. The development of detecting technologies contributed to the research in H2S biology.H2S plays significant roles in human body systems, such as the cardiovascular system, nervous system, respiratory system etc.. Alterations of H2S concentrations have been connected with many diseases. Hypertension, atherosclerosis, neurodegenerative disorder, asthma and many other diseases are found to be related with abnormal H2S metabolism. It has become a potential drug for therapeutic purposes. Understanding the mechanism of H2S biology, including a molecular switch contained in its "receptor", has deepened the research on how small molecules regulate big molecules, as well as providing new strategy for the therapeutic approaches for varies of diseases.

Survivin is known to be essential for cell division and to inhibit apoptosis during embryonic development and in adult cancerous tissues. However, the cardiovascular role of survivin is unknown. We observed that in cardiomyocytes cultured under conditions of serum and glucose deprivation (DEPV), the levels of survivin, Bcl-2 and extracellular signal-regulated kinase (ERK) were positively correlated with the anti-apoptotic action of a delta-opioid receptor agonist, [D-Ala2, D-Leu5]-enkephalin acetate (DADLE). By contrast, Bax translocation, mitochondrial membrane damage and reactive oxygen species (ROS) production were inversely correlated with the changes of survivin and Bcl-2. The use of RNA interference (RNAi) targeting survivin increased DEPV-induced cardiomyocyte apoptosis, whereas the anti-apoptotic effect of DADLE was blunted by survivin RNAi. Moreover, survivin transfection and overexpression provided protection against DEPV-induced cardiomyocyte apoptosis. Inhibition of ERK prevented the DADLE-induced decrease in apoptosis and Bax translocation, and increase in survivin and Bcl-2. DADLE-induced increase in survivin was also blunted by phosphoinositol 3-kinase (PI 3-kinase) inhibition. In conclusion, the present study provides the first direct evidence of an anti-apoptotic role of survivin mediating the anti-apoptotic effect of delta-opioid receptor activation in cardiomyocytes. ERK and PI 3-kinase were found to be upstream regulators of survivin. Mitochondrial membranes as well as ROS, Bcl-2 and Bax were also involved in this anti-apoptotic action.

To observe the morphological features of endothelial cells and cardiac explants cultured in two- or three-dimensional culture systems, several three-dimensional collagen type I culture systems, such as the in gel, on gel, sandwich model, and the microscope slide model, were used to examine the growth patterns of the cells and explants from heart by using immunofluorescence staining and microscopic observation in the presence or absence of vascular endothelial growth factor (VEGF). In two-dimensional cultures the primary cardiac endothelial cells arrayed into a cobblestone-like structure. When cultured in three-dimensional matrix, the cells were elongated and migrated into the gel, with a phenotype similar to that in the process of angiogenesis and vasculogenesis in vivo. VEGF promoted the process of the endothelial cells transforming into tube-like structure. Cardiac explants grew well in the collagen gel. Adjacent explants were connected to each other by the migrating cells with the occurrence of autorhythmic beating of the explants. Thin-layer collagen gel, microscope slide chamber and aorta-strip model were also tested and proved to be good tools for vasculogenesis or angiogenesis studies. Three-dimensional culture systems enable the endothelial cells to proliferate, migrate, and anchor to three-dimensional vascular structures, showing advantages for observing the feature of angiogenesis. Different three-dimensional culture models may be used for variable research purposes.

Embryonic stem cells are pluripotent cells derived from blastocyst-stage embryos. They are characterized by their capacity for self-renewal and by the ability to differentiate into a variety of cell types. In vitro, ES cells can spontaneously aggregate into the formation of embryoid bodies (EBs) comprised of a range of differentiated cells. When injected into severe combined immunodeficient (SCID) mice, ES cells will induce the generation of teratomas, which include differentiated cells from three embryonic germ layers. We can induce the differentiation of ES cells into cardiocytes by treatment with several growth factors or co-culture with certain other cells. The pure differentiated cardiocytes from ES cells are then selected and implanted into the infarcted hearts. The hearts' function will be improved. ES cells implantation is a novel and potential method to treat infarcted hearts.