Explorating the mechanism of Huangqin Tang against skin lipid accumulation through network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Tang (HQT), a famous prescription with the effect of clearing pathogenic heat and detoxifying, was first recorded in "Treatise on Typhoid and Miscellaneous Diseases". It has proved that HQT has good anti-inflammatory and antioxidant effects and can improve acne symptoms clinically. However, the study on the regulation of HQT on sebum secretion which is one of the inducements of acne is not enough. AIM OF THE STUDY: This paper aimed to investigate the mechanisms of HQT in the treatment of skin lipid accumulation by network pharmacology and validating the results via in vitro experiments. MATERIALS AND METHODS: Network pharmacology was employed to predict the potential targets of HQT against sebum accumulation. Then, the palmitic acid (PA)-induced SZ95 cell model was established to evaluate the effect of HQT on lipid accumulation and anti-inflammation, and the core pathways predicted by network pharmacology were verified in cell studies. RESULTS: 336 chemical compounds and 368 targets in HQT were obtained by network pharmacology, of which 65 targets were related to sebum synthesis. 12 core genes were revealed by protein-protein interaction (PPI) network analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results suggested that AMP-activated protein kinase (AMPK) signaling pathway might play a crucial role in regulating lipogenesis. In vitro experiments, HQT suppressed lipid accumulation, downregulated the expressions of sterol-regulatory element binding protein-1 (SREBP-1) and fatty acid synthase (FAS), and upregulated AMPK phosphorylation. Furthermore, AMPK inhibitor reversed HQT-mediated sebosuppressive effect. CONCLUSION: The results disclosed that HQT ameliorates lipogenesis in PA-induced SZ95 sebocytes partially through the AMPK signaling pathway.

Hydrolyzed Conchiolin Protein (HCP) Extracted from Pearls Antagonizes both ET-1 and α-MSH for Skin Whitening.

Pearl powder is a famous traditional Chinese medicine that has a long history in treating palpitations, insomnia, convulsions, epilepsy, ulcers, and skin lightining. Recently, several studies have demonstrated the effects of pearl extracts on protection of ultraviolet A (UVA) induced irritation on human skin fibroblasts and inhibition of melanin genesis on B16F10 mouse melanoma cells. To further explore the effect we focused on the whitening efficacy of pearl hydrolyzed conchiolin protein (HCP) on human melanoma MNT-1 cells under the irritation of alpha-melanocyte-stimulating hormone (α-MSH) or endothelin 1 (ET-1) to evaluate the intracellular tyrosinase and melanin contents, as well as the expression levels of tyrosinase (TYR), tyrosinase related protein 1 (TRP-1), and dopachrome tautomerase (DCT) genes and related proteins. We found that HCP could decrease the intracellular melanin content by reducing the activity of intracellular tyrosinase and inhibiting the expression of TYR, TRP-1, DCT genes and proteins. At the same time, the effect of HCP on melanosome transfer effect was also investigated in the co-culture system of immortalized human keratinocyte HaCaT cells with MNT-1. The result indicated that HCP could promote the transfer of melanosomes in MNT-1 melanocytes to HaCaT cells, which might accelerate the skin whitening process by quickly transferring and metabolizing melanosomes during keratinocyte differentiation. Further study is needed to explore the mechanism of melanosome transfer with depigmentation.

Effect of acupuncture at Xinwu acupoint combined with loratadine and fluticasone propionate on symptom alleviation, nasal function, and serum histamine level in patients with allergic rhinitis.

OBJECTIVE: To determine the influence of acupuncture at the Xinwu acupoint combined with western medicine (loratadine and fluticasone propionate) on symptom alleviation, nasal mucociliary clearance velocity (MCV), and serum histamine level of patients with allergic rhinitis (AR). METHODS: A total of 122 patients with AR treated in Gansu province hospital of TCM and The Third People's Hospital of Gansu Province from April 2019 to April 2021 were retrospectively analyzed. Among them, 54 patients treated with loratadine and fluticasone propionate were assigned to the control group, and 68 patients treated with additional acupuncture at the Xinwu acupoint based on treatment of the control group were assigned to the observation group. The treatment efficacy of the two groups was compared, and the scores of main symptoms and nasal function were also compared before and after therapy. Additionally, the two groups were compared in the levels of histamine, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and immunoglobulin E (IgE) before and after therapy. RESULTS: After therapy, the observation group yielded a higher total effective rate than the control group (P=0.006) and had lower symptom scores than the control group (P<0.001). Additionally, the MCV of the two groups increased (P<0.001), and the nasal mucociliary transit time (MTT) and nasal resistance (NR) of both groups decreased (P<0.001) after therapy. The observation group showed a greatly better improvement of nasal function than the control group (P<0.001). Moreover, after therapy, the observation group showed lower histamine and IgE levels than the control group (P<0.01) and the observation group presented significantly lower levels than the control group, and had lower rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores than the control group (P<0.001). The two groups were not different in the incidence of adverse reactions (P=0.886). CONCLUSION: Acupuncture at Xinwu acupoint combined with loratadine and fluticasone propionate can deliver a powerful efficacy on AR and alleviate the clinical symptoms, without increasing adverse reactions.

The effect of folic acid deficiency on Mest/Peg1 in neural tube defects.

OBJECTIVE: Neural tube defects (NTDs) are one of the most common and serious birth defects in human beings caused by genetic and environmental factors. Folate insufficiency is involved in the occurrence of NTDs and folic acid supplementation can prevent NTDs occurrence, however, the underlying mechanism remains poorly understood. METHODS: We established cell and animal models of folic acid deficiency to detect the methylation modification and expression levels of genes by MassARRAY and real-time PCR, respectively. Results and conclusion: In the present study, we found firstly that in human folic acid-insufficient NTDs, the methylation level of imprinted gene Mest/Peg1 was decreased. By using a folic acid-deficient cell model, we demonstrated that Mest/Peg1 methylation was descended. Meanwhile, the mRNA level of Mest/Peg1 was up-regulated via hypomethylation modification under low folic acid conditions. Consistent with the results in cell models, Mest/Peg1 expression was elevated through hypomethylation regulation in folate-deficient animal models. Furthermore, the up-regulation of Mest/Peg1 inhibited the expression of Lrp6 gene, a crucial component of Wnt pathway. Similar results with Lrp6 down-regulation of fetal brain were verified in animal models under folic acid-deficient condition. Taken together, our findings indicated folic acid increased the expression of Mest/Peg1 via hypomethylation modification, and then inhibited Lrp6 expression, which may ultimately impact on the development of nervous system through the inactivation of Wnt pathway.

OsMYB80 Regulates Anther Development and Pollen Fertility by Targeting Multiple Biological Pathways.

Pollen development is critical to the reproductive success of flowering plants, but how it is regulated is not well understood. Here, we isolated two allelic male-sterile mutants of OsMYB80 and investigated how OsMYB80 regulates male fertility in rice. OsMYB80 was barely expressed in tissues other than anthers, where it initiated the expression during meiosis, reached the peak at the tetrad-releasing stage and then quickly declined afterward. The osmyb80 mutants exhibited premature tapetum cell death, lack of Ubisch bodies, no exine and microspore degeneration. To understand how OsMYB80 regulates anther development, RNA-seq analysis was conducted to identify genes differentially regulated by OsMYB80 in rice anthers. In addition, DNA affinity purification sequencing (DAP-seq) analysis was performed to identify DNA fragments interacting with OsMYB80 in vitro. Overlap of the genes identified by RNA-seq and DAP-seq revealed 188 genes that were differentially regulated by OsMYB80 and also carried an OsMYB80-interacting DNA element in the promoter. Ten of these promoter elements were randomly selected for gel shift assay and yeast one-hybrid assay, and all showed OsMYB80 binding. The 10 promoters also showed OsMYB80-dependent induction when co-expressed in rice protoplast. Functional annotation of the 188 genes suggested that OsMYB80 regulates male fertility by directly targeting multiple biological processes. The identification of these genes significantly enriched the gene networks governing anther development and provided much new information for the understanding of pollen development and male fertility.

GDSL esterase/lipases OsGELP34 and OsGELP110/OsGELP115 are essential for rice pollen development.

Pollen exine contains complex biopolymers of aliphatic lipids and phenolics. Abnormal development of pollen exine often leads to plant sterility. Molecular mechanisms regulating exine formation have been studied extensively but remain ambiguous. Here we report the analyses of three GDSL esterase/lipase protein genes, OsGELP34, OsGELP110, and OsGELP115, for rice exine formation. OsGELP34 was identified by cloning of a male sterile mutant gene. OsGELP34 encodes an endoplasmic reticulum protein and was mainly expressed in anthers during pollen exine formation. osgelp34 mutant displayed abnormal exine and altered expression of a number of key genes required for pollen development. OsGELP110 was previously identified as a gene differentially expressed in meiotic anthers. OsGELP110 was most homologous to OsGELP115, and the two genes showed similar gene expression patterns. Both OsGELP110 and OsGELP115 proteins were localized in peroxisomes. Individual knockout of OsGELP110 and OsGELP115 did not affect the plant fertility, but double knockout of both genes altered the exine structure and rendered the plant male sterile. OsGELP34 is distant from OsGELP110 and OsGELP115 in sequence, and osgelp34 and osgelp110/osgelp115 mutants were different in anther morphology despite both were male sterile. These results suggested that OsGELP34 and OsGELP110/OsGELP115 catalyze different compounds for pollen exine development.

Identification of late-stage pollen-specific promoters for construction of pollen-inactivation system in rice.

Large-scale production of male sterile seeds can be achieved by introducing a fertility-restoration gene linked with a pollen-killer gene into a recessive male sterile mutant. We attempted to construct this system in rice by using a late-stage pollen-specific (LSP) promoter driving the expression of maize α-amylase gene ZM-AA1. To obtain such promoters in rice, we conducted comparative RNA-seq analysis of mature pollen with meiosis anther, and compared this with the transcriptomic data of various tissues in the Rice Expression Database, resulting in 269 candidate LSP genes. Initial test of nine LSP genes showed that only the most active OsLSP3 promoter could drive ZM-AA1 to disrupt pollen. We then analyzed an additional 22 LSP genes and found 12 genes stronger than OsLSP3 in late-stage anthers. The promoters of OsLSP5 and OsLSP6 showing higher expression than OsLSP3 at stages 11 and 12 could drive ZM-AA1 to inactivate pollen, while the promoter of OsLSP4 showing higher expression at stage 12 only could not drive ZM-AA1 to disrupt pollen, suggesting that strong promoter activity at stage 11 was critical for pollen inactivation. The strong pollen-specific promoters identified in this study provided valuable tools for genetic engineering of rice male sterile system for hybrid rice production.

Lectin receptor kinase OsLecRK-S.7 is required for pollen development and male fertility.

Pollen grains are covered by exine that protects the pollen from stress and facilitates pollination. Here we isolated a male sterile mutant s13283 in rice exhibiting aborted pollen with abnormal exine and defective aperture. The mutant gene encodes a novel plasma membrane-localized legume-lectin receptor kinase that we named OsLecRK-S.7. OsLecRK-S.7 was expressed at different levels in all tested tissues and throughout anther development. In vitro kinase assay showed OsLecRK-S.7 capable of autophosporylation. Mutation in s13283 (E560K) and mutation of the conserved ATP binding site (K418E) both knocked out the kinase activity. Mass spectrometry showed Thr376 , Ser378 , Thr386 , Thr403 , and Thr657 to be the autophosphorylation sites. Mutation of individual autophosphorylation site affected the in vitro kinase activity to different degrees, but did not abolish the gene function in fertility complementation. oslecrk-s.7 mutant plant overexpressing OsLecRK-S.7 recovered male fertility but showed severe growth retardation with reduced number of tillers, and these phenotypes were abolished by E560K or K418E mutation. The results indicated that OsLecRK-S.7 was a key regulator of pollen development.

Folate deficiency induced H2A ubiquitination to lead to downregulated expression of genes involved in neural tube defects.

BACKGROUND: Neural tube defects (NTDs) are common congenital malformations resulting in failure of the neural tube closure during early embryonic development. Although it is known that maternal folate deficiency increases the risk of NTDs, the mechanism remains elusive. RESULTS: Herein, we report that histone H2A monoubiquitination (H2AK119ub1) plays a role in neural tube closure. We found that the folate antagonist methotrexate induced H2AK119ub1 in mouse embryonic stem cells. We demonstrated that an increase in H2AK119ub1 downregulated expression of the neural tube closure-related genes Cdx2, Nes, Pax6, and Gata4 in mouse embryonic stem cells under folate deficiency conditions. We also determined that the E3 ligase Mdm2 was responsible for the methotrexate-induced increase in H2AK119ub1 and downregulation of neural tube closure-related genes. Surprisingly, we found that Mdm2 is required for MTX-induced H2A ubiquitination and is recruited to the sites of DSB, which is dependent on DNA damage signaling kinase ATM. Furthermore, folic acid supplementation restored H2AK119ub1 binding to neural tube closure-related genes. Downregulation of these genes was also observed in both brain tissue of mouse and human NTD cases, and high levels of H2AK119ub1 were found in the corresponding NTDs samples with their maternal serum folate under low levels. Pearson correlation analysis showed a significant negative correlation between expression of the neural precursor genes and H2AK119ub1. CONCLUSION: Our results indicate that folate deficiency contributes to the onset of NTDs by altering H2AK119ub1 and subsequently affecting expression of neural tube closure-related genes. This may be a potential risk factor for NTDs in response to folate deficiency.

The effect of folic acid deficiency on FGF pathway via Brachyury regulation in neural tube defects.

Folate deficiency in early development leads to disturbance in multiple processes, including neurogenesis during which fibroblast growth factor (FGF) pathway is one of the crucial pathways. Whether folic acid (FA) directly affects FGF pathways to influence neurodevelopment and the possible mechanism remains unclear. In this study, we presented evidence that in human FA-insufficient encephalocele, the FGF pathway was interfered. Furthermore, in Brachyury knockout mice devoid of such T-box transcription factors regulating embryonic neuromesodermal bipotency and a key component of FGF pathway, change in expression of Brachyury downstream targets, activator Fgf8 and suppressor dual specificity phosphatase 6 was detected, along with the reduction in expression of other key FGF pathway genes. By using a FA-deficient cell model, we further demonstrated that decrease in Brachyury expression was through alteration in hypermethylation at the Brachyury promoter region under FA deficiency conditions, and suppression of Brachyury promoted the inactivation of the FGF pathway. Correspondingly, FA supplementation partially reverses the effects seen in FA-deficient embryoid bodies. Lastly, in mice with maternal folate-deficient diets, aberrant FGF pathway activity was found in fetal brain dysplasia. Taken together, our findings highlight the effect of FA on FGF pathways during neurogenesis, and the mechanism may be due to the low expression of Brachyury gene via hypermethylation under FA-insufficient conditions.-Chang, S., Lu, X., Wang, S., Wang, Z., Huo, J., Huang, J., Shangguan, S., Li, S., Zou, J., Bao, Y., Guo, J., Wang, F., Niu, B., Zhang, T., Qiu, Z., Wu, J., Wang, L. The effect of folic acid deficiency on FGF pathway via Brachyury regulation in neural tube defects.

Folic acid supplementation alters the DNA methylation profile and improves insulin resistance in high-fat-diet-fed mice.

Folic acid (FA) supplementation may protect from obesity and insulin resistance, the effects and mechanism of FA on chronic high-fat-diet-induced obesity-related metabolic disorders are not well elucidated. We adopted a genome-wide approach to directly examine whether FA supplementation affects the DNA methylation profile of mouse adipose tissue and identify the functional consequences of these changes. Mice were fed a high-fat diet (HFD), normal diet (ND) or an HFD supplemented with folic acid (20 µg/ml in drinking water) for 10 weeks, epididymal fat was harvested, and genome-wide DNA methylation analyses were performed using methylated DNA immunoprecipitation sequencing (MeDIP-seq). Mice exposed to the HFD expanded their adipose mass, which was accompanied by a significant increase in circulating glucose and insulin levels. FA supplementation reduced the fat mass and serum glucose levels and improved insulin resistance in HFD-fed mice. MeDIP-seq revealed distribution of differentially methylated regions (DMRs) throughout the adipocyte genome, with more hypermethylated regions in HFD mice. Methylome profiling identified DMRs associated with 3787 annotated genes from HFD mice in response to FA supplementation. Pathway analyses showed novel DNA methylation changes in adipose genes associated with insulin secretion, pancreatic secretion and type 2 diabetes. The differential DNA methylation corresponded to changes in the adipose tissue gene expression of Adcy3 and Rapgef4 in mice exposed to a diet containing FA. FA supplementation improved insulin resistance, decreased the fat mass, and induced DNA methylation and gene expression changes in genes associated with obesity and insulin secretion in obese mice fed a HFD.

Folic acid prevents cardiac dysfunction and reduces myocardial fibrosis in a mouse model of high-fat diet-induced obesity.

BACKGROUND: Folic acid (FA) is an antioxidant that can reduce reactive oxygen species generation and can blunt cardiac dysfunction during ischemia. We hypothesized that FA supplementation prevents cardiac fibrosis and cardiac dysfunction induced by obesity. METHODS: Six-week-old C57BL6/J mice were fed a high-fat diet (HFD), normal diet (ND), or an HFD supplemented with folic acid (FAD) for 14 weeks. Cardiac function was measured using a transthoracic echocardiographic exam. Phenotypic analysis included measurements of body and heart weight, blood glucose and tissue homocysteine (Hcy) content, and heart oxidative stress status. RESULTS: HFD consumption elevated fasting blood glucose levels and caused obesity and heart enlargement. FA supplementation in HFD-fed mice resulted in reduced fasting blood glucose, heart weight, and heart tissue Hcy content. We also observed a significant cardiac systolic dysfunction when mice were subjected to HFD feeding as indicated by a reduction in the left ventricular ejection fraction and fractional shortening. However, FAD treatment improved cardiac function. FA supplementation protected against cardiac fibrosis induced by HFD. In addition, HFD increased malondialdehyde concentration of the heart tissue and reduced the levels of antioxidant enzyme, glutathione, and catalase. HFD consumption induced myocardial oxidant stress with amelioration by FA treatment. CONCLUSION: FA supplementation significantly lowers blood glucose levels and heart tissue Hcy content and reverses cardiac dysfunction induced by HFD in mice. These functional improvements of the heart may be mediated by the alleviation of oxidative stress and myocardial fibrosis.

Long Non-Coding RNA Expression Profiling in Obesity Mice with Folic Acid Supplement.

BACKGROUND/AIMS: Obesity is a major contributor to the growing prevalence of metabolic and cardiovascular diseases. This study was designed to investigate the effect of folic acid (FA) on obese mice by detecting the genome-wide expression profile of lncRNAs and mRNAs in the heart. METHODS: Heart samples were collected from mice fed with standard diet (SD), high-fat diet (HFD) and high-fat diet with FA intake (HFDF). LncRNAs and mRNAs between HFD and HFDF group were analyzed by lncRNA microarray. Nine lncRNAs and mRNAs were validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bioinformatics prediction was used to investigate the potential function of these differentially expressed lncRNAs. Co-expresson analysis was used to determine the transcriptional regulatory relationship of differentially expressed lncRNAs and mRNAs between two groups. RESULTS: The expression of 58,952 lncRNAs and 20,145 mRNAs in HFD and HFDF groups was profiled by using microarrays. Gene Ontology and pathway analyses indicated that the biological functions of differentially expressed mRNAs were related to inflammation, energy metabolism, and cell differentiation. Co-expression networks composed of lncRNAs and mRNAs were also constructed to investigate the potential regulatory roles of differentially expressed lncRNAs on mRNAs. LncRNAs, namely, NONMMUT033847, NONMMUT070811, and NONMMUT015327, were validated through qRT-PCR, and these lncRNAs may be important factors regulating inflammation, energy metabolism, and cell differentiation. The expression levels of Dnajb1, Egr2, Hba-a1, Il1ß, Cxcl2, and Tnfsf9 were significantly different between HFD and HFDF. CONCLUSIONS: Results suggested that FA may improve the cardiovascular function of obesity and contribute to those lncRNAs associated with inflammation and cell differentiation. In a nutshell, the present study identified a panel of lncRNAs and mRNAs that may be potential biomarkers or drug targets relevant to the high-fat diet related obesity.

Altered GNAS imprinting due to folic acid deficiency contributes to poor embryo development and may lead to neural tube defects.

Disturbed epigenetic modifications have been linked to the pathogenesis of Neural Tube Defects (NTDs) in those with folate deficiency during pregnancy. However, evidence is lacking to delineate the critical region in epigenome regulated by parental folic acid and mechanisms by which folate deficiency affects normal embryogenesis. Our data from clinical samples revealed the presence of aberrant DNA methylation in GNAS imprinting cluster in NTD samples with low folate concentrations. Results from mouse models indicated that the establishment of GNAS imprinting was influenced by both maternal and paternal folate-deficient diets. Such aberrant GNAS imprinting was present prior to the gametogenesis period. Imprinting in Exon1A/GNAS gDMR was abolished in both spermatozoa and oocytes upon treating with a parental folate-deficient diet (3.6% in spermatozoa, 9.8% in oocytes). Interestingly, loss of imprinting in the GNAS gene cluster altered chromatin structure to an overwhelmingly open structure (58.48% in the folate-free medium group vs. 39.51% in the folate-normal medium group; P < 0.05), and led to a disturbed expression of genes in this region. Furthermore, an elevated cyclic AMP levels was observed in folate acid deficiency group. Our results imply that GNAS imprinting plays major roles in folic acid metabolism regulation during embryogenesis. Aberrant GNAS imprinting is an attribute to NTDs, providing a new perspective for explaining the molecular mechanisms by which folate supplementation in human pregnancy provides protection from NTDs.

Rorippa indica Regeneration via Somatic Embryogenesis Involving Frog Egg-like Bodies Efficiently Induced by the Synergy of Salt and Drought Stresses.

Frog egg-like bodies (FELBs), novel somatic embryogenesis (SE) structures first observed in Solanum nigrum, were induced in Rorippa indica. NaCl-mediated salt and mannitol-mimicked drought stresses induced FELBs in R. indica, which is very different from the induction by plant growth regulators (PGRs) under low light condition that was used in S. nigrum FELB induction. It demonstrated that NaCl or mannitol supplements alone could induce FELBs in R. indica, but with low induction rates, while the synergy of NaCl and mannitol significantly increased the FELB induction rates. For the combination of 5.0 g/L mannitol and 10.0 g/L NaCl the highest FELB induction rate (100%) was achieved. It suggests that the synergy of drought and salt stresses can replace PGRs to induce FELBs in R. indica. On medium supplemented with 1.0 mg/L gibberellic acid all the inoculated in vitro FELBs developed into multiple plantlets. Morphological and histological analyses confirmed the identity of FELBs induced in R. indica and revealed that FELBs originate from root cortex cells.

CENTRIST: A Visual Descriptor for Scene Categorization.

CENsus TRansform hISTogram (CENTRIST), a new visual descriptor for recognizing topological places or scene categories, is introduced in this paper. We show that place and scene recognition, especially for indoor environments, require its visual descriptor to possess properties that are different from other vision domains (e.g., object recognition). CENTRIST satisfies these properties and suits the place and scene recognition task. It is a holistic representation and has strong generalizability for category recognition. CENTRIST mainly encodes the structural properties within an image and suppresses detailed textural information. Our experiments demonstrate that CENTRIST outperforms the current state of the art in several place and scene recognition data sets, compared with other descriptors such as SIFT and Gist. Besides, it is easy to implement and evaluates extremely fast.

Maternal serum vitamin B12, folate and homocysteine and the risk of neural tube defects in the offspring in a high-risk area of China.

OBJECTIVE: To examine the association between the risk of neural tube defects (NTD) and maternal serum vitamin B12, folate and homocysteine in a high-risk area of China. DESIGN: A case-control study was carried out in Luliang mountain area of Shanxi Province. SUBJECTS/SETTING: A total of eighty-four NTD pregnancies and 110 matched controls were included in the study; their serum vitamin B12 and folate concentrations were measured by chemiluminescent immunoenzyme assay and total homocysteine concentrations by fluorescent polarisation immunoassay. RESULTS: Serum vitamin B12 and folate concentrations were lower in NTD-affected pregnant women than in controls (P < 0.01). Serum total homocysteine was higher in the NTD group than in controls at less than 21 weeks of gestation (P < 0.01). Adjusted odds ratios revealed that women with lower vitamin B12 (adjusted OR=4.96; 95 % CI 1.94, 12.67) and folate (adjusted OR=3.23; 95 % CI 1.33, 7.85) concentrations had a higher risk of NTD compared to controls. Based on dietary analysis, less consumption of meat, egg or milk, fresh vegetables and fruit intake would increase the risk of NTD. CONCLUSIONS: Lower serum concentrations of folate and vitamin B12 are related to the increased risk of NTD in high-risk populations. Both folate and vitamin B12 intake insufficiency could contribute to the increased risk of NTD. A dietary supplement, combining folate and vitamin B12, might be an effective measure to decrease the NTD incidence in these areas.

Tetrandrine inhibits activation of rat hepatic stellate cells stimulated by transforming growth factor-beta in vitro via up-regulation of Smad 7.

Tetrandrine is a bisbenzylisoquinoline alkaloid derived from the root of a Chinese herbal medicine Stephania tetrandra S. Moore, which has been used traditionally for the treatment of hepatofibrogenic disease in China for several decades. In the present study, the inhibitory effects of tetrandrine lower concentrations (0.25, 0.5, 1, 2 mg/L) on culture-activation and transforming growth factor-beta(1) (TGF-beta(1))-stimulated activation of quiescent rat hepatic stellate cells (HSCs) in vitro were assessed, and the possible relations between the underlying mechanism of these effects and TGF-beta signaling via its receptors were investigated. As shown by the examination of alpha-SMA using immunocytochemical staining or Western blot, tetrandrine inhibited both culture-activation and TGF-beta(1)-stimulated activation of HSCs. Further investigations revealed that, in this process, TGF-beta(1) mRNA expression was suppressed significantly in contrast to an up-regulation of Smad 7, while the expressions of type I and type II TGF-beta(1) receptors and Smad 3 mRNA were insignificantly changed by tetrandrine. These results suggest that tetrandrine at lower concentrations has a significant inhibiting effect on culture-activation and TGF-beta(1)-stimulated activation of rat HSCs, and that it may be due to an up-regulation of Smad 7 which in turn blocks TGF-beta(1) expression and its downstream signaling.

[Effects of Xinmailong Xiangdan and Shenmai Injection on early kidney damage induced by toxin of grass carp bile].

OBJECTIVE: To observe the effects of Xinmailong (XML), Xiangdan (XD) and Shenmai (SM) Injection on early kidney damage induced by toxin of grass carp bile (GCB) and provide experimental evidence for Chinese medicine in treating toxication of GCB. METHODS: GCB (6ml/kg) was administered orally to adult SD rats to induce the model of GCB intoxication and a single intraperitoneal injection of XML, XD or SM was administered 10 min later. RESULTS: It was found that the levels of blood creatinine and blood urea nitrogen were decreased and the creatinine clearance rate was increased by XML, XD or SM. Degenerated epithelial cells of proximal convoluted tubules and glomeruli containing red blood cells in saccular cavities were decreased as compared with the normal group (P<0.01). CONCLUSION: The Chinese medicine XML, XD and SM Injection have therapeutic effects on early kidney damage induced by toxin of GCB.