Gestational Diabetes Mellitus Remodels the Fetal Brain Fatty Acid Profile Through Placenta-Brain Lipid Axis in C57BL/6J Mice.

BACKGROUND: Polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are critical for proper fetal brain growth and development. Gestational diabetes mellitus (GDM) could affect maternal-fetal fatty acid metabolism. OBJECTIVE: This study aimed to explore the effect of GDM and high-fat (HF) diet on the DHA transport signaling pathway in the placenta-brain axis and fatty acid concentrations in the fetal brain. METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish an animal model of GDM. Eighty female C57BL/6J mice were randomly divided into control (CON), GDM, HF, and HF+GDM groups. The fatty acid profiles of the maternal liver and fetal brain were analyzed by gas chromatography. In addition, we analyzed the protein amounts of maternal liver fatty acid desaturase (FADS1/3), elongase (ELOVL2/5) and the regulatory factor sterol-regulatory element-binding protein (SREBP)-1c, and the DHA transport signaling pathway (Wnt3/ß-catenin/MFSD2a) of the placenta and fetal brain using western blotting. RESULTS: GDM promoted the decrease of maternal liver ELOVL2, ELOVL5, and SREBP-1c. Accordingly, we observed a significant decrease in the amount of maternal liver arachidonic acid (AA), DHA, and total n-3 PUFA and n-6 PUFA induced by GDM. GDM also significantly decreased the amount of DHA and n-3 PUFA in the fetal brain. GDM downregulated the Wnt3/ß-catenin/MFSD2a signaling pathway, which transfers n-3 PUFA in the placenta and fetal brain. The HF diet increased n-6 PUFA amounts in the maternal liver, correspondingly increasing linoleic acid, gamma-linolenic acid, AA, and total n-6 PUFA in the fetal brain, but decreased DHA amount in the fetal brain. However, HF diet only tended to decrease placental ß-catenin and MFSD2a amounts (P = 0.074 and P = 0.098, respectively). CONCLUSIONS: Maternal GDM could affect the fatty acid profile of the fetal brain both by downregulating the Wnt3/ß-catenin/MFSD2a pathway of the placental-fetal barrier and by affecting maternal fatty acid metabolism.

Absorption Characteristics of Combination Medication of Realgar and Indigo Naturalis: In Vitro Transport across MDCK-MDR1 Cells and In Vivo Pharmacokinetics in Mice after Oral Administration.

Realgar and indigo naturalis are clinically combined to treat varieties of leukemia. Exploring the drug-drug interactions might be beneficial to find active substances and develop new targeted drugs. This study aimed at exploring the change of arsenic concentration in mice and across MDCK-MDR1 cells and the cytotoxicity on K562 cells when realgar and indigo naturalis were combined. In the presence or absence of indigo naturalis, pharmacokinetics and cell-based permeability assays were used to evaluate the change of arsenic concentration, and K562 cell line was applied to evaluate the change of cytotoxicity. The drug concentration-time profiles exhibited that the combination medication group generated higher AUC, thalf, and longer MRT for arsenic, compared with the single administration of realgar. The apparent permeability coefficients (Papp) of bidirectional transport in MDCK-MDR1 cell permeability experiments showed that arsenic permeability obviously went up when indigo naturalis was incubated together. The combination medication significantly decreased the cell viability of K562 cells when both the concentration of realgar and the concentration of indigo naturalis were nontoxic. The pharmacokinetic research, the MDCK-MDR1 based permeability study, and the K562 cytotoxicity study were united together to verify the combination medication of realgar and indigo naturalis enhanced the absorption and the permeability across cells for arsenic and effectively inhibited the proliferation of K562 cell line. The molecular binding of As4S4 and indirubin was analyzed by computational study. It is predicted that the formation of the complex [As4S4 …Indirubin] involves noncovalent interaction that changes the concentration of arsenic.

[Current distribution of Schisandra chinensis in China and its predicted responses to climate change].

With integration of literature data, specimens records, and field surveys, the current distribution map of Schisandra chinensis in China was drawn, and, based on this map and considering 21 environmental factors, the future distribution of S. chinensis in China in the 2050s and 2080s under the IPCC A2 and A1B climate change scenarios was predicted by using Maxent software. Currently, the S. chinensis in China occurred in 15 provinces, involving 151 counties, and its distribution area decreased with decreasing latitude and longitude. The main distribution area included Heilongjiang, Liaoning, Inner Mongolia, and Jilin. The potential distribution area of S. chinensis in China was 145.12 x 10(4) km2, 48.6% of which were the favorable habitat area, mainly distributed in Changbai Mountains, Xiaoxing'anling Mountains, Daxing'anling Mountains, and the regions between Hebei and Liaoning provinces. The most favorable habitat area only accounted for 0.3%, and was mainly in the Kuandian Manchu Autonomous County, Benxi Manchu Autonomous County, and Huanren Manchu Autonomous County of Liaoning Province, the Antu County and Helong County of Jilin Province, and the Yakeshi City of Inner Mongolia. Under the two climate change scenarios, the potential future distribution area of S. chinensis in China would have a gradual decrease, and the decrement would be larger under A2 than under A1B scenario. By 2050, the distribution area of the S. chinensis under A1B and A2 scenarios would be moderately decreased to 84.0% and 81.5% of the current distribution area, respectively; by 2080, the distribution of S. chinensis under A2 scenario would be dramatically decreased to only 0.5% of the current range, and that under A1B scenario would be decreased to 1/2 of the current range.

[Studies on the extraction of volatile oil from Thymus marschallianus and preparation of its beta-CD inclusion compounds].

OBJECTIVE: To study the optimum conditions for the extraction of volatile oil from Thymus marschallianus and the preparation of its beta-CD inclusion compounds. METHODS: The study was carried out with single factor and orthogonal design. With the percentages of extracted volatile oil of Thymus marschallianus as the target marker we selected the optimum conditions for extracting the volatile oil. The ration of inclusion and the oiling-bearing from the inclusion as the target marker was to optimize the conditions for including the oils with beta-CD. RESULTS: The optimized extraction conditions were as follows: the water was 12 times of the herbs in weight, Thymus marschallianus should be extracted for 4 hours after soaked 0.5 hours with water. The optimized inclusion conditions were as follows: applying the saturated aqueous solution method, the proportion of oil and beta-CD was 1 mL: 8 g, the temperature and time were 60 degrees C and 60 minutes, respectively. CONCLUSION: The established process can be used for the extraction and the inclusion of volatile oil from Thymus marschallianus with its high ration of oil and the economic cost.

[Effects of kangfengshi granules on expressions of osteoprotegerin, RANKL and M-CSF in bone tissues of rats with collagen-induced arthritis].

OBJECTIVE: To observe the effects of Kangfengshi Granules (KFSG) on expressions of the mRNAs of osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand (RANKL) and macrophage colony stimulating factor (M-CSF) in bone tissues of rats with collagen-induced arthritis. METHODS: Forty SD rats were randomly divided into four groups: normal control group, untreated group, cyclosporine A (CsA)-treated group and KFSG-treated group. Except the rats in the normal control group, all the other rats received subcutaneous injection of collagen II to establish collagen-induced arthritis (CIA) models. Then the rats in each group were fed normal saline or corresponding drugs for four weeks. Total RNA was extracted from carpal and digital bones. The expressions of OPG, RANKL and M-CSF mRNAs were examined by real-time PCR. RESULTS: The total incidence of arthritis induced by collagen II in the rats was approximately 90%. The expression levels of RANKL and M-CSF mRNAs and the RANKL mRNA/OPG mRNA ratio in the untreated group, KFSG-treated group and CsA-treated group were all significantly higher than those in the normal control group, while the expression levels of OPG mRNA in those three groups were significantly lower than that in the normal control group. The expression level of OPG mRNA in the KFSG-treated group was obviously higher while the expression level of M-CSF mRNA and the RANKL mRNA/OPG mRNA ratio in the same group were both lower as compared with those in the untreated group. CONCLUSION: The molecular mechanism of effects of KFSG on bone erosion and destruction induced by rheumatoid arthritis is closely correlated with up-regulating the expression of OPG mRNA, down-regulating the expression of M-CSF mRNA and RANKL mRNA/OPG mRNA ratio.

[Effect of Herba Epimedii flavone on the osteoblasts metabolism in vitro].

OBJECTIVE: To explore the effect of Herba Epimedii flavone (HEF) on the osteoblast metabolism in vitro. METHOD: Osteoblast were obtained from new born rat calvaria by digestive enzymes. MTF, PNPP and RT-PCR were used to observe the proliferation, activity of ALP and mRNA expression of OPG and RANKL of cultured osteoblasts in vitro. RESULT: It was found that HEF had the effect on stimulating cell proliferation, activity of ALP and the mRNA expression of OPG of cultured osteoblasts (P < 0.01, P < 0.05). CONCLUSION: HEF can promote the proliferation, the differentiation and the expression of OPG mRNA of the osteoblasts cultured in vitro.