Xenopus Reduced Folate Carrier Regulates Neural Crest Development Epigenetically

Folic acid deficiency during pregnancy causes birth neurocristopathic malformations resulting from aberrant development of neural crest cells. The Reduced folate carrier (RFC) is a membrane-bound receptor for facilitating transfer of reduced folate into the cells. RFC knockout mice are embryonic lethal and develop multiple malformations, including neurocristopathies. Here we show that XRFC is specifically expressed in neural crest tissues in Xenopus embryos and knockdown of XRFC by specific morpholino results in severe neurocristopathies. Inhibition of RFC blocked the expression of a series of neural crest marker genes while overexpression of RFC or injection of 5-methyltetrahydrofolate expanded the neural crest territories. In animal cap assays, knockdown of RFC dramatically reduced the mono- and trimethyl-Histone3-K4 levels and co-injection of the lysine methyltransferase hMLL1 largely rescued the XRFC morpholino phenotype. Our data revealed that the RFC mediated folate metabolic pathway likely potentiates neural crest gene expression through epigenetic modifications

Capillary hemangiomas with hemorrhage in cervicothoracic intramedullary, a case report

A 48-year-old male patient had presented with worsening pain at extremities and body. The MRI showed an inhomogeneously enhancing lesion at C5-T1. During the surgical evacuation through a midline myelotomy, a frozen section could not find any tumor cells or vascular malformations. Immunohistochemically, the diagnosis of capillary hemangiomas was confirmed. Keywords: Capillary hemangiomas, Intramedullary hemorrhage, Intramedullary tumor, Vascular malformatio

Pharmacokinetics, Tissue Distribution, and Metabolism Study of Icariin in Rat

Icariin is one of the predominant flavonoids contained in Herba Epimedii (Yin-yang-huo in Chinese), a well-known Chinese medicine for the treatment of cancers and immune system diseases. Although Herba Epimedii has been widely used in China and there are so many and various research reports on the herbal drug and its main flavones, very limited data is available on the tissue distribution and biotransformation of icariin. In the present study, a liquid chromatographic method combined with electrospray ionization tandem mass spectrometry was developed to quantify the concentration of icariin in rat plasma and various tissues collected at different time points after oral administration of the total flavonoid extract of Herba Epimedii at a dose of 0.69 g/kg (corresponding to 42 mg/g icariin). Biological samples were processed by simple protein precipitation. Genistein was chosen as internal standard. The method was successfully applied to plasma pharmacokinetic and tissue distribution studies of icariin in rat. As a result, it was worth noting that the tissue distribution characteristics of icariin exhibited a significant gender difference. Moreover, in vivo metabolism of icariin was also investigated. A total of 11 potential metabolites were found in rat feces collected in different time periods after oral and intramuscular administration of icariin. In vivo metabolic pathways were involved in hydrolysis, demethylation, oxidation, and conjugation. The preclinical data would be useful for fully understanding in vivo disposition of this compound and interpreting the mechanism of its biological response

Assembly of heteropoly acid into localized porous structures for in situ preparation of silver and polypyrrole nanoparticles

A simple and facile method to fabricate porous films which were locally patterned by heteropoly acid was developed in this study. The mixture of poly(methyl methacrylate) and stabilizer dichloromethane solution which contains heteropoly acid aqueous solution, prepared through shaking, was applied to fabricate a reversed microemulsion. After spreading and evaporating the solvent of microemulsion on a glass slide, an ordered honeycomb film was produced by incorporation of heteropoly acid in the cavities. The locally anchored heteropoly acid could be readily applied for the selective modification of the porous films through the in situ chemical reactions in the cavities with the additive agents. The silver nanoparticles were in situ prepared via the reduction of silver ions by reduced state H3PW12O40, and the polypyrrole spheres were locally obtained through the oxidative polymerization of pyrrole catalyzed by H3PMo12O40 in the cavities. Considering that water-soluble molecules and nanoparticles were universally suitable for the present strategy, the reported approach opened up an efficient way for patterning organically incompatible components on porous polymer films via the assembly of microemulsion droplet carriers to fabricate multi-functional hybrid surface structures

Xenopus Nkx6.3 is a neural plate border specifier required for neural crest development.

In vertebrates, the neural plate border (NPB) is established by a group of transcription factors including Dlx3, Msx1 and Zic1. The crosstalk between these NPB specifiers governs the separation of the NPB region into placode and neural crest (NC) territories and also their further differentiation. Understanding the mechanisms of NPB formation and NC development is critical for our knowledge of related human diseases. Here we identified Nkx6.3, a transcription factor of the Nkx family, as a new NPB specifier required for neural crest development in Xenopus embryos. XNkx6.3 is expressed in the ectoderm of the neural plate border region at neurula stages, covering the epidermis, placode and neural crest territories, but not the neural plate. Inhibition of Nkx6.3 by dominant negative construct or specific morpholino leads to neural crest defects, while overexpression of Nkx6.3 induces ectopic neural crest in the anterior neural fold. In animal caps, Nkx6.3 alone is able to initiate the whole neural crest regulatory network and induces neural crest fate robustly. We showed that overexpression of Nkx6.3 affects multiple signaling pathways, creating a high-Wnt, low-BMP environment required for neural crest development. Gain- and loss-of-function of Nkx6.3 have compound effects on the expression of known NPB genes, which is largely opposite to that of Dlx3. Overexpression of Dlx3 blocks the NC inducing activity of Nkx6.3. The crosstalk between Nkx6.3, Dlx3 and Msx1 is likely crucial for proper NPB formation and neural crest development in Xenopus

Association between high BMI and high homocysteine levels in Chinese patients with bipolar disorder

Background: Bipolar disorder (BD) has been associated with an increased prevalence of weight gain and abnormally elevated plasma homocysteine (Hcy) levels. However, the relationship between BMI and Hcy in BD patients has not been investigated. This study aimed to explore this relationship in Chinese patients with BD. Methods: Plasma Hcy levels, socio-demographic parameters, clinical and anthropometric data were collected from 195 BD inpatients and 84 healthy controls. The level of plasma Hcy was determined by high-performance liquid chromatography. Body mass index (BMI) was calculated by body weight divided by the square of the height. The participants were divided into a high BMI group and a low BMI group using 24 kg/m(2) as a threshold. Results: The prevalence of high BMI was slightly elevated in BD patients in comparison to healthy controls. Patients with elevated BMI had significantly higher Hcy levels than patients with low BMI. Hcy level was an independent contributor of the occurrence of high BMI in BD patients. The level of Hcy was positively correlated with BMI in BD patients. In addition, depressive episodes of BD were positively correlated with the prevalence of high BMI and married BD patients were more likely to have high BMI levels. Conclusions: There is a close relationship between BMI and plasma Hcy levels in patients with BD, suggesting that Hcy may be an important indicator for BD-induced weight gain. This finding provides a new avenue for weight management of BD patients and to help avoid the potential risk of cardiovascular diseases

Bioactive Constituents from the Aerial Parts of Pluchea indica Less

Four new thiophenes, (3′′R)-pluthiophenol (1), (3′′R)-pluthiophenol-4′′-acetate (2), 3′′-ethoxy-(3′′S)-pluthiophenol (3), 3′′-ethoxy-(3′′S)-pluthiophenol-4′′-acetate (4), together with twenty-five known compounds were obtained from the 70% ethanol-water extract of the aerial parts of Pluchea indica Less. Their structures were elucidated by spectroscopic methods. Among the known isolates, compounds 7, 8, 11, 14, 15, 18, 20, 23, 25–27 were isolated from Asteraceae family firstly, while compounds 6, 9, 10, 12, 13, 16, 19, 21, 28 were isolated from Pluchea genus for the first time. Meanwhile, compounds 1, 2, 10, 13, 18, 23 displayed significant inhibitory activities on LPS-induced NO production at 40 µM from RAW 264.7 macrophages, while compounds 3, 4, 26–29 possessed moderate inhibitory effects

Separation and Bioactive Assay of 25R/S-Spirostanol Saponin Diastereomers from Yucca schidigera Roezl (Mojave) Stems

In order to find a simple, generic, efficient separation method for 25R/S-spirostanol saponin diastereomers, the liquid chromatographic retention behaviors of C12 carbonylation and C12 unsubstituted 25R/S-spirostanol saponin diastereomers on different stationary phases (C8, C18, C30 columns) and different mobile phases (MeOH-1% CH3COOH and CH3CN-1% CH3COOH) were investigated. A C30 column was firstly found to offer the highest efficiency for the separation of this kind of diastereomers than C8 and C18 columns. Meanwhile, the analysis results indicated that both CH3CN-1% CH3COOH and MeOH-1% CH3COOH eluate systems were selective for C12 unsubstituted 25R/S-spirostanol saponin diastereomers, while MeOH-1% CH3COOH possessed better selectivity for C12 carbonylation ones. Using the abovementioned analysis method, six pairs of 25R/S-spirostanol saponin diastereomers 1a–6a and 1b–6b from Yucca schidigera Roezl (Mojave) were isolated successfully by using HPLC on C30 column for the first time. Among them, three pairs were new ones, named as (25R)-Yucca spirostanoside E1 (1a), (25S)-Yucca spirostanoside E1 (1b), (25R)-Yucca spirostanoside E2 (2a), (25S)-Yucca spirostanoside E2 (2b), (25R)-Yucca spirostanoside E3 (3a), (25S)-Yucca spirostanoside E3 (3b), respectively. Moreover, 3a, 5a, 6a, 3b–6b showed strong inhibitory activities on the growth of SW620 cell lines with the IC50 values of 12.02–69.17 μM

5-mehtyltetrahydrofolate rescues alcohol-induced neural crest cell migration abnormalities

Background: Alcohol is detrimental to early development. Fetal alcohol spectrum disorders (FASD) due to maternal alcohol abuse results in a series of developmental abnormalities including cranial facial dysmorphology, ocular anomalies, congenital heart defects, microcephaly and intellectual disabilities. Previous studies have been shown that ethanol exposure causes neural crest (NC) apoptosis and perturbation of neural crest migration. However, the underlying mechanism remains elusive. In this report we investigated the fetal effect of alcohol on the process of neural crest development in the Xenopus leavis. Results: Pre-gastrulation exposure of 2-4% alcohol induces apoptosis in Xenopus embryo whereas 1% alcohol specifically impairs neural crest migration without observing discernible apoptosis. Additionally, 1% alcohol treatment considerably increased the phenotype of small head (43.4% ± 4.4%, total embryo n = 234), and 1.5% and 2.0% dramatically augment the deformation to 81.2% ± 6.5% (n = 205) and 91.6% ± 3.0% (n = 235), respectively (P < 0.05). Significant accumulation of Homocysteine was caused by alcohol treatment in embryos and 5-mehtyltetrahydrofolate restores neural crest migration and alleviates homocysteine accumulation, resulting in inhibition of the alcohol-induced neurocristopathies. Conclusions: Our study demonstrates that prenatal alcohol exposure causes neural crest cell migration abnormality and 5-mehtyltetrahydrofolate could be beneficial for treating FASD.Psychiatry, Department ofOther UBCNon UBCMedicine, Faculty ofReviewedFacult