Sanwei DouKou Decoction ameliorate Alzheimer disease by increasing endogenous neural stem cells proliferation through the Wnt/ß-catenin signalling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Sanwei DouKou decoction (SDKD) is a traditional Chinese medicine (TCM) prescription derived from the Tibetan medical book "Si Bu Yi Dian" and is clinically used for the treatment of Alzheimer's disease (AD). However, the potential mechanism of SDKD treatment for AD remains elusive. AIM OF THE STUDY: This study aims to explore the potential mechanism by which SDKD alleviates AD. MATERIALS AND METHODS: Extracts of SDKD were identified with Gas chromatograph-mass spectrometer (GC-MS). 5 × FAD mice were treated with SDKD for 8 weeks. The efficacy of SDKD against AD was evaluated by in-vivo experiments. Morris water maze and contextual fear conditioning tests were used to detect the learning and memory ability of mice. Hematoxylin-eosin staining (H&E) staining was used to observe the pathological changes of brain tissue. Immunohistochemistry was used to detect the positive expression of Nestin in hippocampus. In in-vitro experiments, the Cell Counting Kit 8 (CCK-8) technique was used to detect cell viability, the proliferation of neural stem cells was detected by immunofluorescence staining, the intracellular protein expression was detected by Western Blot. RESULTS: The results of this study suggested that SDKD may ameliorate AD. SDKD significantly shortened the escape latency of mice in the Morris water maze experiment, increased the number of times the mice crossed the target quadrant, and prolonged freezing time in the contextual fear memory experiment. SDKD also improved neuronal pathology in the hippocampus, decreased neuronal loss, and increased Nestin protein levels. Furthermore, in in-vitro experiments, SDKD could significantly increase Neural stem cells (NSCs) viability, promoted NSCs proliferation, and also effectively activated the Wnt/ß-catenin signalling pathway, increased Wnt family member 3A (Wnt3a), ß-catenin and CyclinD1 protein levels, activated the NSCs proliferation pathways in AD model mouse brain tissue. CONCLUSIONS: The present study demonstrated that sanwei doukou decoction can ameliorate AD by increasing endogenous neural stem cells proliferation through the Wnt/ß-catenin signalling pathway. Our observations justify the traditional use of SDKD for a treatment of AD in nervous system.

CXCL12/CXCR7/ß-arrestin1 biased signal promotes epithelial-to-mesenchymal transition of colorectal cancer by repressing miRNAs through YAP1 nuclear translocation.

BACKGROUND: Chemokine CXC motif receptor 7 (CXCR7) is an atypical G protein-coupled receptor (GPCR) that signals in a biased fashion. CXCL12/CXCR7 biased signal has been reported to play crucial roles in multiple stages of colorectal cancer (CRC). However, the mechanism of CXCL12/CXCR7 biased signal in promoting CRC progression and metastasis remains obscure. RESULTS: We demonstrate that CXCR7 activation promotes EMT and upregulates the expression of Vimentin and doublecortin-like kinase 1 (DCLK1) in CRC cells with concurrent repression of miR-124-3p and miR-188-5p through YAP1 nuclear translocation. Cell transfection and luciferase assay prove that these miRNAs regulate EMT by targeting Vimentin and DCLK1. More importantly, CXCL12/CXCR7/ß-arrestin1-mediated biased signal induces YAP1 nuclear translocation, which functions as a transcriptional repressor by interacting with Yin Yang 1 (YY1) and recruiting YY1 to the promoters of miR-124-3p and miR-188-5p. Pharmacological inhibitor of YAP1 suppresses EMT and tumor metastasis upon CXCR7 activation in vivo in tumor xenografts of nude mice and inflammatory colonic adenocarcinoma models. Clinically, the expression of CXCR7 is positively correlated with nuclear YAP1 levels and EMT markers. CONCLUSIONS: Our studies reveal a novel mechanism and clinical significance of CXCL12/CXCR7 biased signal in promoting EMT and invasion in CRC progression. These findings highlight the potential of targeting YAP1 nuclear translocation in hampering CXCL12/CXCR7 biased signal-induced metastasis of colorectal cancer.

Biological nutrients removal performance under starvation stress: Efficacy deterioration and recovery.

Biological nutrients removal performance affected by starvation stress was investigated via the addition of pre-anoxic stage to SBR. COD removal efficiency maintained at around 90% regardless of the starvation stress. Starvation stress presented significant impact on nitrogen and phosphorus removal, with noticeable reduction of TN removal and remarkable deterioration of TP removal as prolonging the pre-anoxic time, which was mainly attributed to the integrative effect of carbon source competition, depression of denitrification and invalid P release as well as the variation of microbial community. It was notable that starvation stress exerted distinct evolution on microbial community. The improvement in relative abundance of the certain genera relating to denitrification was the main reason for the partial recovery of nitrogen removal after eliminating stress starvation. The promotion of P uptake capacity accompanied with the relief of invalid P release and the enriched DPAOs accounted for the complete recovery of phosphorus removal.

Mallotus oblongifolius extracts ameliorate ischemic nerve damage by increasing endogenous neural stem cell proliferation through the Wnt/ß-catenin signaling pathway.

Mallotus oblongifolius (MO), an edible medicinal plant from Hainan in China, shows a wide range of bioactivities. The daily consumption of MO or its extracts has been observed to ameliorate ischemic nerve injury. However the mechanisms remain unclear. In this study, the effects of MO both in vitro and in vivo were investigated. The results indicated that MO improved the motor ability, neurosensory ability, balance and grasping ability of mice with ischemic injuries, induced by bilateral common carotid artery ligation (BCCAL). In addition, MO improved the morphology of neurons, resisted the loss of neurons, and enhanced the content of the nestin protein in the cerebral cortex and subgranular zone (SGZ) area. Furthermore, in the oxygen-glucose deprivation and reperfusion (OGD/R) treated cell model, MO could effectively activate the Wnt/ß-catenin signaling pathway and promote the proliferation of neural stem cells (NSCs) and increase the protein expression levels of ß-catenin and CyclinD1. Our results suggest that Mallotus oblongifolius may be used as nutraceuticals or functional foods to alleviate ischemic nerve damage and promote recovery from ischemic stroke.

Migration and transformation of different phosphorus forms in rainfall runoff in bioretention system.

Artificial bioretention system consisting of Ophiopogon japonicus infiltration medium was used to simulate an infiltration experiment of rainfall runoff. Continuous extraction method was used to detect contents of inorganic phosphorus (P) under exchangeable state (Ex-P) and aluminium phosphate (Al-P) and iron phosphate (Fe-P) at different depths (0, 5, 15 and 35 cm) of soil infiltration medium in bioretention system. Effluent total P (TP) concentration of the system was also monitored. Results indicated that the adsorption of inorganic P, Al-P and Fe-P by soil infiltration medium was implemented layer by layer from top to bottom and gradually weakened. Moreover, Ex-P was gradually transformed into Al-P and Fe-P, whereas Al-P was gradually transformed into Fe-P; thus, Ex-P content reduced layer by layer, whereas Al-P and Fe-P gradually accumulated. The TP removal rate in runoff rainwater by the system was more than 90%, where the TP that was not used by plants was under dynamic equilibrium in water-soil-root system/biological system.