Blueberry extracts antagonize Aß25-35 neurotoxicity and exert a neuroprotective effect through MEK-ERK-BDNF/UCH-L1 signaling pathway in rat and mouse hippocampus.

BACKGROUND: The neuroprotective potential of blueberry (BB) extracts against Alzheimer's disease (AD) has been previously hinted at, while its exact mechanism has remained largely enigmatic. OBJECTIVE: Our study endeavored to unravel the impacts and mechanisms by which BB extracts ameliorated the learning and memory prowess of AD-afflicted mice, with a specific focus on the MEK-ERK pathway. METHODS: We employed 3-month-old APP/PS1 transgenic mice and stratified them into three distinct groups: AD+BB, AD, and control (CT). The Morris Water Maze Test (MWMT) was then administered to gauge their learning and memory faculties. In vitro experiments were executed on Aß25-35-afflicted rat hippocampal neurons, which were subsequently treated with varying concentrations of BB extracts. We then assessed the expression levels of genes and proteins integral to the MEK-ERKBDNF/UCH-L1 pathway. RESULTS: The data showed that the AD mice demonstrated compromised learning and memory faculties in MWMT. However, the AD+BB cohort showcased marked improvements in performance. Furthermore, in the AD subset, significant elevations in the expressions of MEK2 and ERK1/2 were observed, both at the mRNA and protein levels. Conversely, UCH-L1 mRNA expressions exhibited a decline, while BDNF expressions surged significantly. However, post BB extract treatment, the expressions of MEK2 and ERK1/2 were subdued, with UCH-L1 and BDNF mRNA expressions reverting to control levels. CONCLUSIONS: Our findings propounded that BB extracts could offer therapeutic promise for AD by bolstering learning and memory capacities. The unwarranted activation of the MEK-ERK pathway, coupled with the aberrant expressions of BDNF and UCH-L1, might underpin AD's pathogenesis.

Fire needle for recurrent aphthous stomatitis: A protocol for systematic review and network meta-analysis.

BACKGROUND: Recurrent aphthous stomatitis (RAS), are common inflammatory lesions of the oral mucous, usually round or ovoid, circumscribed by erythematous haloes with a yellow-grey floor and mostly painful. The purpose of this study was to evaluate the efficacy and safety of fire needle in the treatment of RAS. METHODS: PubMed, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure, Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database were searched by 2 reviewers from the inception until December 2021. The original study that randomized control trials of fire needle for RAS will be selected and is not limited by country or language. In addition, researches in progress, the reference lists and the citation lists of identified publications will be retrieved similarly. Study selection, data extraction, and assessment of the quality will be performed independently by 2 reviewers who have been trained prior to data extraction. A meta-analysis will be conducted if the quantity and quality of the original studies included are satisfactory; otherwise, a descriptive analysis will be conducted. Review Manager V5.4 software will be using for data synthesis and assessment of the risk of bias according to Cochrane Handbook. RESULTS: This study will provide a comprehensive review of current evidence for the treatment of fire needle on RAS. CONCLUSION: The conclusion of this study will provide a judging basis that whether the treatment of RAS with fire needle is effective. INPLASY REGISTRATION NUMBER: INPLASY2021120118.

Investigation on the Role of BDNF in the Benefits of Blueberry Extracts for the Improvement of Learning and Memory in Alzheimer's Disease Mouse Model.

BACKGROUND: Blueberry (BB) can provide a wide range of antioxidant benefits for AD. There is evidence that BB extracts could improve brain functions. However, the details are still unknown. OBJECTIVE: In the present study, we aimed to investigate the possible mechanism involved in the improvement of learning and memory capacity from BB extracts in AD. METHODS: APP/PS1 transgenic mice were fed BB extracts for 16 weeks. The capacity of learning and memory was assessed by Morris water maze (MWM) test, and long-term potentiation (LTP) was determined to evaluate hippocampal neuronal plasticity at the end of administration. Pathological changes in the brain were observed, and the expressions of brain-derived neurotrophic factor (BDNF) and extracellular signal-related kinase (ERK1/2) were determined to explore the mechanism of BB extract-induced benefits. RESULTS: AD mice exhibited more difficulties to learn and remember the exact position of the platform in the MWM test. The data showed that AD mice lacked effective learning in the platform search. In contrast, AD mice exhibited better performance both in the training phase and probe test of MWM after the BB treatment. Moreover, LTP was enhanced and the neuron loss was alleviated with BB treatment, while we did not find any obvious effect on the elimination of amyloid-ß. In the AD mice, the expression of ERK1/2 was significantly increased (p < 0.05), while the level of BDNF was decreased (p < 0.05). CONCLUSIONS: BB treatment was beneficial for the improvement of learning and memory of AD, and these effects might be related to the regulation of BDNF.

ApoE type 4 allele affects cognitive function of aged population in Tianjin City, China.

Apolipoprotein E type 4 allele (ApoE∊4) is known as a risk gene for the late-onset Alzheimer's disease, and the relationship between ApoE∊4 and cognitive function of the elderly people has drawn the attention of the scientists. In this study, we investigated the relationship between ApoE∊4 and the cognitive function of the old people. A total of 156 old people were investigated, of whom 31 were ApoE∊4 carriers. The ApoE∊4 primarily influenced the global cognitive function, perceptual speed, and work memory. The results indicate that ApoE∊4 has significant negative effect on the cognitive function of the elderly people who are 60 years and older.

Mulberry extracts alleviate aß 25-35-induced injury and change the gene expression profile in PC12 cells.

Mulberry, which contained high amounts of anthocyanins, has been used in traditional Chinese medicine. Mulberry fruit extracts (ME) have demonstrated the antioxidant activity and neuroprotection. The study was to investigate the neuroprotective efficacy of ME against ß-amyloid 25-35- (Aß 25-35-) induced PC12 cells injury. Cells preincubated with or without ME (200 µg/mL) for 24 h were treated with Aß 25-35 (20 µmol/L) for another 24 h. Cell viability was assessed by MTT, gene expression profiles were examined by cDNA microarrays, and RT-PCR were used to confirm the results of microarray assays. ME pretreatment was found to neutralize the cytotoxicity and prevent Aß 25-35-induced cells injury. Analyses of gene expression profile revealed that genes involving cell adhesion, peptidase activity, cytokine activity, ion binding activity, and angiogenesis regulation were significantly modulated by ME pretreatment. Among those genes, Apaf1, Bace2, and Plcb4 were enriched in the "Alzheimer's disease-reference pathway" and downregulated after ME intervention. RT-PCR results showed that ME preincubation could significantly inhibit Aß 25-35 increased mRNA levels of these three genes. Overall, ME pretreatment could substantially alleviate PC12 cells injury and downregulate expression of AD-related genes, such as Apaf1, Bace2, and Plcb4. This study has a great nutrigenomics interest and brings new and important light in the field of AD intervention.