Neuroprotective Effect of Fructus broussonetiae on APP/PS1 Mice via Upregulation of AKT/ß-Catenin Signaling.

OBJECTIVE: To evaluate the mechanisms underlying the protective effect of Chinese herbal medicine Fructus broussonetiae (FB) in both mouse and cell models of Alzheimer's disease (AD). METHODS: APP/PS1 mice treated with FB for 2 months and vehicle-treated controls were run through the Morris water maze and object recognition test to evaluate learning and memory capacity. RNA-Seq, Western blotting, and immunofluorescence staining were also conducted to evaluate the effects of FB treatment on various signaling pathways altered in APP/PS1 mice. To further explore the mechanisms underlying FB's protective effect, PC-12 cells were treated with Aß25-35 in order to establish an in vitro model of AD. RESULTS: FB-treated mice showed improved learning and memory capacity on both the Morris water maze and object recognition tests. RNA-seq of hippocampal tissue from APP/PS1 mice showed that FB had effects on multiple signaling pathways, specifically decreasing cell apoptotic signaling and increasing AKT and ß-catenin signaling. Similarly, FB up-regulated both AKT and ß-catenin signaling in PC-12 cells pre-treated with Aß25-35, in which AKT positively regulated ß-catenin signaling. Further study showed that AKT promoted ß-catenin signaling via enhancing ß-catenin (Ser552) phosphorylation. Moreover, AKT and ß-catenin signaling inhibition both resulted in the attenuated survival of FB-treated cells, indicating the AKT/ß-catenin signaling is a crucial mediator in FB promoted cell survival. CONCLUSIONS: FB exerted neuroprotective effects on hippocampal cells of APP/PS1 mice, as well as improved cell viability in an in vitro model of AD. The protective actions of FB occurred via the upregulation of AKT/ß-catenin signaling.

Acupuncture for Improving Cognitive Impairment After Stroke: A Meta-Analysis of Randomized Controlled Trials.

Objective: This meta-analysis evaluated the efficacy of acupuncture in improving cognitive impairment of post-stroke patients. Design: Randomized controlled trials (RCTs) investigating the effects of acupuncture compared with no treatment or sham acupuncture on post-stroke cognitive impairment (PSCI) before December 2019 were identified from databases (PubMed, EMBASE, Ovid library, Cochrane Library, Chinese National Knowledge Infrastructure, VIP Chinese Periodical Database, Wanfang Database, and SinoMed). The literature searching and data extracting were independently performed by two investigators. Study quality was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. Meta-analyses were performed for the eligible RCTs with Revman 5.3 software. Results: Thirty-seven RCTs (2,869 patients) were included in this meta-analysis. Merged Random-effects estimates of the gain of MMSE (Mini-Mental State Examination) or MoCA (Montreal Cognitive Assessment) were calculated for the comparison of acupuncture with no acupuncture or sham acupuncture. Following 2-8 weeks of intervention with acupuncture, pooled results demonstrated significant effects of acupuncture in improving PSCI assessed by MMSE (MD [95% CI] = 2.88 [2.09, 3.66], p < 0.00001) or MoCA (MD [95% CI] = 2.66 [1.95, 3.37], p < 0.00001). Conclusion: The results suggest that acupuncture was effective in improving PSCI and supported the needs of more rigorous design with large-scale randomized clinical trials to determine its therapeutic benefits.

High-dose vitamin C suppresses the invasion and metastasis of breast cancer cells via inhibiting epithelial-mesenchymal transition.

PURPOSE: Vitamin C (VC) is a kind of essential nutrient in the body regarded as a canonical antioxidant during the past hundred years. However, the anti-cancer effect of VC is controversial. Our study is trying to clarify the relationship between VC dosage and breast cancer metastasis. METHODS: Human breast cancer cell lines Bcap37 and MDA-MB-453 were treated with VC at three different concentrations (low-dose, 0.01 mM; medium-dose, 0.1 mM; high-dose, 2 mM). Wound healing assays were conducted for migration assay; transwell tests were performed to detect the ability of cell invasion. The protein levels were evaluated by Western blot analysis or immunohistochemistry. Tumor xenografts in nude mice were built to test the effects of VC on breast cancer cell proliferation and metastasis. RESULTS: 0.01 and 0.1 mM VC promoted cell migration and invasion when compared with the control group, but 2 mM VC significantly suppressed cell migration and invasion of breast cancer cell lines. High-dose VC increased E-cadherin and reduced Vimentin, indicating that high-dose VC suppressed epithelial-mesenchymal transition (EMT) in breast cancer cells. Besides, high-dose VC inhibited cell invasion promoted by TGF-ß1 in breast cancer cells. Meanwhile, high-dose VC reversed the suppression of E-cadherin and enhancement of Vimentin induced by TGF-ß1 in breast cancer cells. Furthermore, high-dose VC significantly inhibited breast cancer metastasis in vivo. CONCLUSION: High-dose VC inhibits cell migration and invasion of breast cancer cell lines through suppressing EMT. Thus, it may be considered as an anticancer drug candidate for breast cancer patients.

Cerebral Responses to Acupuncture at GV24 and Bilateral GB13 in Rat Models of Alzheimer's Disease.

Acupuncture has been widely used in China to treat neurological diseases including Alzheimer's disease (AD). However, its mechanism remains unclear. In the present study, eighty healthy Wistar rats were divided into a normal control group (n = 15) and premodel group (n = 65). Forty-five rats that met the criteria for the AD model were then randomly divided into the model group (MG), the nonacupoint group (NG), and the acupoint group (AG). All rats received positron emission tomography (PET) scanning, and the images were analyzed with Statistical Parametric Mapping 8.0. MG exhibited hypometabolism in the olfactory bulb, insular cortex, orbital cortex, prelimbic cortex, striatum, parietal association cortex, visual cortex, cingulate gyrus, and retrosplenial cortex. AG exhibited prominent and extensive hypermetabolism in the thalamus, hypothalamus, bed nucleus of the stria terminalis, cerebral peduncle, midbrain tegmentum, and pontine tegmentum compared to NG. These results demonstrated that acupuncturing at GV24 and bilateral GB13 acupoints may improve the learning and memory abilities of the AD rats, probably via altering cerebral glucose metabolism (CGM) in the hypothalamus, thalamus, and brain stem. The observed effects of acupuncture may be caused by regulating the distribution of certain kinds of neurotransmitters and enhancing synaptic plasticity.