BMP/Smad Pathway Is Involved in Lithium Carbonate-Induced Neural-Tube Defects in Mice and Neural Stem Cells.

Neural-tube defects (NTDs) are one type of the most serious birth defects. Studies have shown that inositol deficiency is closely related to the occurrence of NTDs. Bone morphogenetic protein (BMP)-mediated Smad signaling pathways have been implicated in neurogenesis and neural-tube closure. However, the role of the BMP/Smad pathway in inositol-deficiency-induced NTDs remains unclear. Inositol-deficiency models in C57 mice and mouse neural stem cells (mNSCs) were induced with Li2CO3 treatment or inositol withdrawal. The role of the BMP/Smad pathway in the regulation of cell proliferation and the development of NTDs was determined utilizing qRT-PCR, HE staining, Western blot, immunostaining, MTT assay, EdU staining, and flow cytometry. The intraperitoneal injection of Li2CO3 at Embryonic Day 7.5 induced the occurrence of NTDs. The mRNA levels of Bmp2, Bmp4, Smad1, Smad5, Smad8 and Runx2, the phosphorylation of Smad1/5/8, and the nuclear translocation of Runx2 were significantly increased in NTD embryonic brain tissues and mNSCs exposed to Li2CO3 or an inositol-free medium, which were suppressed by BMP receptor selective inhibitor LDN-193189. The Li2CO3-induced phosphorylation of Smad1/5/8 was inhibited by inositol supplementation. Cell proliferation was significantly promoted by Li2CO3 exposure or the absence of inositol in mNSCs, which was reversed by LDN-193189. These results suggest that the activation of the BMP/Smad signaling pathway might play an important role in the development of NTDs induced by maternal Li2CO3 exposure via inositol deficiency.

Combined therapy of Di-Huang-Yi-Zhi with Donepezil in patients with Parkinson's disease dementia.

Here we conducted a randomized and double-blind study attempting to explore the safety and efficacy of combined therapy of Di-Huang-Yi-Zhi (DHYZ) with donepezil in treating Parkinson's disease dementia (PDD). Sixty PDD patients were included and randomly divided into control group and DHYZ group. All patients were given donepezil (5 mg last for a month, then 10 mg for the rest months, once daily), while patients in DHYZ group were additionally administrated with DHYZ (150 ml, twice daily). The measurement subjects included mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), the Barthel Index for activities of daily living (ADL) and Traditional Chinese medical (TCM) symptoms before and after treatment in this study. The whole study lasted for six months. Significant differences were observed on MMSE, MoCA, ADAS-Cog, ADL and TCM in both control and DHYZ group (P<0.05 or P<0.01) before and after drug treatment. Furthermore, there were more obvious changes of MMSE, MoCA, ADAS-Cog, ADL and TCM scores compared the DHYZ group with the control group (P<0.01) which suggested the DHYZ group showed a more effective improvement on cognition, behavior as well global function. In conclusion, the combined therapy of DHYZ with donepezil showed a more effective improvement in PDD and the underlying mechanism may be related to the synergic amelioration of cholinergic system between them.