Cognitive-exercise dual-task attenuates chronic cerebral ischemia-induced cognitive impairment by activating cAMP/PKA pathway through inhibiting EphrinA3/EphA4.

BACKGROUND: The prevalence of vascular cognitive impairment induced by chronic cerebral ischemia (CCI) is increasing year by year. Cognitive-exercise dual-task intervention has shown beneficial effects on improving cognitive performance in ischemic patients. It is well known that the tyrosine kinase ligand-receptor (Ephrin-Eph) system plays an important role in synaptic transmission and that the cAMP/PKA pathway is associated with cognitive function. However, it is unclear whether they are responsible for the dual-task improving cognitive impairment in CCI. METHODS: Bilateral common carotid artery occlusion (BCCAO) in SD rats was used to establish the CCI model. The effects of dual-task and single-task on cognitive function and the expressions of EphrinA3, EphA4, cAMP, and PKA in rats were detected by the novel object recognition (NOR) test, immunofluorescence staining, quantitative real-time polymerase chain reaction (qPCR), and Western blotting (WB), respectively. Overexpression or knockdown of EphrinA3 in astrocytes or rats were constructed by lentivirus infection to verify the effects of EphrinA3/EphA4 on the cAMP/PKA pathway. RESULTS: After dual-task intervention, the discrimination index of rats increased significantly compared with the rats in the CCI group. The expressions of EphrinA3 and EphA4 were decreased, while the expressions of cAMP and PKA were increased. Furthermore, knockdown of EphrinA3 alleviated the trend of CCI-induced cognitive decline in rats and OGD-stimulated cellular damage. It also increased cAMP/PKA expression in hippocampal neurons. CONCLUSION: Cognitive-exercise dual-task can significantly improve the cognitive impairment induced by CCI, and this effect may be better than that of the cognitive or exercise single-task intervention. The improvement may be related to the inhibition of EphrinA3/EphA4, followed by activation of the cAMP/PKA pathway.

Cognitive-exercise dual-task intervention ameliorates cognitive decline in natural aging rats via inhibiting the promotion of LncRNA NEAT1/miR-124-3p on caveolin-1-PI3K/Akt/GSK3ß Pathway.

Aging-related cognitive impairment (ARCI) is rapidly becoming a healthcare priority. However, there is currently no excellent cure for it. Cognitive-exercise dual-task intervention (CEDI) is a promising method to improve ARCI, while the underlying mechanisms remain unclear. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are involved in the onset, development, and rehabilitation of ARCI. This study aimed to investigate the effects of CEDI and the role of regulation of the lncRNA NEAT1/miR-124-3p on the caveolin-1-PI3K/Akt/GSK3ß pathway in CEDI improving cognitive function. Forty 18-month-old natural aging rats were randomly assigned to four groups: exercise training group, cognitive training group, CEDI group, and aging control group, and underwent 12 weeks of intervention. A novel object recognition test was performed to determine the cognitive function, and the hippocampus was separated three days after the behavioral tests for further molecular detection. In an in vitro study, the mouse hippocampal neuronal cell line HT22 was cultured. MiR-124-3p and lncRNA NEAT1 were over-expressed or down-expressed, respectively. The expressions of related proteins, lncRNA, and miRNA were examined by WB and/or qRT-PCR. The results showed that compared with the aging control group, the CEDI group had a higher discrimination index, and significantly decreased the expressions of lncRNA NEAT1, and the protein expressions of caveolin-1 and p-GSK3ß, while significantly increased the expressions of miR-124-3p, and the protein expressions of p-PI3K and p-Akt. Inhibition of the lncRNA NEAT1 could significantly increase the protein expressions of p-PI3K and p-Akt in HT22 cells. Upregulation of miR-124-3p decreased the protein expressions of caveolin-1 and p-GSK3ß, and increased the protein expressions of p-PI3K and p-Akt significantly. Inhibition of miR-124-3p had the opposite effects. Our study demonstrated that CEDI improved cognitive function in aging rats better than a single intervention. The mechanisms of cognitive improvement could be related to the regulation of the lncRNA NEAT1/miR-124-3p on the caveolin-1-PI3K/Akt/GSK3ß pathway.

Structure Characterization and Immunomodulatory Activity of Misgurnus anguillicaudatus Carbohydrates.

Misgurnus anguillicaudatus, also known as oriental weather loach, is widely consumed and favored in East Asia due to its superior nutritional values and excellent flavor. In this study, a crude Misgurnus anguillicaudatus carbohydrates (MAC) was isolated from Misgurnus anguillicaudatus. Subsequently, two parts, which were named MAO and MAP, respectively, were separated from MAC, and their primary structures and immunomodulatory activity were investigated. The results showed that MAO had a molecular weight of 2854 Da, and principally consisted of arabinose (77.11%) and rhamnose (21.97%), together with minor levels of fucose (0.92%); MAP, with a molecular weight of 3873 Da, was mainly composed of fucose (87.55%) and a small amount of rhamnose (8.86%) and galactose (3.59%). The in vitro assay showed that MAC could significantly enhance the proliferation of macrophages without cytotoxicity and increase the production of immune substances (TNF-α, IL-6). Together with Western blot results, we speculated that MAC could stimulate RAW264.7 murine macrophage cells to secrete TNF-α and IL-6 through up-regulating TLR4-MAPK-p38 signaling pathways. The results indicated that MAC could be a potential immune agent and might provide meaningful information for further chain conformation and immune mechanism research.

Effects of different aerobic exercises on the global cognitive function of the elderly with mild cognitive impairment: a meta-analysis.

OBJECTIVES: To summarise the effects of various types of aerobic exercise on the global cognitive function of the elderly with mild cognitive impairment (MCI). DESIGN: A meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: PubMed, EMBASE and the Cochrane Library were searched for clinical RCTs from the earliest available records to March 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included RCTs of subjects older than 60 years with MCI. The outcome indicators of cognitive function of interest were the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). DATA EXTRACTION AND SYNTHESIS: Two researchers independently screened the literature, extracted data and evaluated the quality of the included studies, with disagreements resolved by a third researcher. The Cochrane Handbook for Systematic Reviews of Interventions was used to assess the risk of bias. Meta-analysis was performed by Review Manager V.5.3 software. Random-effect models were used for meta-analysis. RESULTS: A total of 1680 patients who participated in 20 RCTs were included in this study. Based on outcomes of MMSE analysis, the aerobic exercise, which was beneficial for global cognitive function in MCI patients, included multicomponent aerobic exercise (MD=1.79, 95% CI (1.41 to 2.17), p<0.01) and mind-body exercise (MD=1.28, 95% CI (0.83 to 1.74), p<0.01). The results of the meta-analysis of conventional aerobic exercise (MD=0.51, 95% CI (0.09 to 0.93), p=0.02) turned out to be statistically insignificant after sensitivity analysis (MD=0.14, 95% CI (-0.47 to 0.75), p=0.65). With the evaluation of MoCA, multicomponent aerobic exercise (MD=5.74, 95% CI (5.02 to 6.46), p<0.01), mind-body exercise (MD=1.29, 95% CI (0.67 to 1.90), p<0.01) and conventional aerobic exercise (MD=2.06, 95% CI (1.46 to 2.65), p<0.01) were showed significant beneficial effects for the patient. However, there was a high degree of heterogeneity between the results of multicomponent aerobic exercise (MMSE) and conventional aerobic exercise (MoCA), which was analysed and explored. CONCLUSIONS: In general, multicomponent aerobic exercise and mind-body exercise were beneficial in improving global cognitive function in the elderly with MCI. Nevertheless, the improvement effect of mind-body exercise is more reliable compared with multicomponent aerobic exercise and conventional aerobic exercise. PROSPERO REGISTRATION NUMBER: CRD42022327386.

Photoluminescence properties of a novel red emitting Ba10F2(PO 4)6:Eu³âº phosphor.

A novel red-emitting phosphor Ba10F2(PO4)6:Eu(3+) is synthesized by a high-temperature solid-state reaction. X-ray powder diffraction (XRD) analysis confirms the phase formation of Ba10F2(PO4)6:Eu(3+) materials. The photoluminescence excitation (PLE) and emission (PL) spectra, the concentration dependence of the emission intensity, decay curves and Commission International de I'Eclairage (CIE) of the phosphors are investigated. It is observed that Ba10F2(PO4)6:Eu(3+) phosphors exhibit two dominating bands situated at 591 and 616 nm, originating from the (5)D0→(7)F1 and (5)D0→(7)F2 transition of the Eu(3+) ion, respectively. The decay time is also determined for various concentrations of Eu(3+) in Ba10F2(PO4)6:Eu(3+). Crystal lattice, PL spectra and decay time analysis indicate there exist two isolated Eu(3+) crystallography sites in Ba10F2(PO4)6. The calculated color coordinates lie in the red region. Therefore, Ba10F2(PO4)6:Eu(3+) phosphors may be good candidates for red components in near-UV (NUV) white LEDs.