Brazilin Inhibits the Invasion and Metastasis of Breast Cancer.

This study aimed to determine the effect of brazilin on the invasion and metastasis of breast cancer. The breast cancer MDA-MB-231 and 4T1 cells were treated with brazilin to investigate proliferation and invasion using cell proliferation assay, wound healing assay, transwell assay. BALB/C mice were randomized into normal, model, positive control, and Sappan L. extract groups (n = 6/group). The mice were injected with 4T1 cells via caudal veins to establish a lung metastasis model and via subcutaneous injection to establish a xenograft model. Metastatic nodules on the lung surface, survival rates and visceral indices were evaluated. Subcutaneous tumor volumes and weights were measured. Brazilin inhibited the proliferation of breast cancer cells and significantly inhibited the wound healing, migration, and invasion of MDA-MB-231 and 4T1 cells. Compared with the normal group, the average survival days and spleen index in the model group were significantly decreased, but the lung index and number of pulmonary metastatic nodules were significantly increased. Compared with the model group, the average survival and spleen index of dose groups were significantly increased, and the lung index, the number of pulmonary metastatic nodules, and tumor volume and weight were significantly decreased. Brazilin significantly inhibits the proliferation and metastasis of breast cancer. This study might suggest a new therapeutic agent for breast cancer.

Elaeagnus mollis Oil Attenuates Non-alcoholic Fatty Disease in High-fat Diet Induced Obese Mice via Modifying the Expression of Lipid Metabolismrelated Genes.

Elaeagnus mollis oil (EMO), which is a type of plant oil, was extracted from the nuts of Elaeagnus mollis Diels that is known as a precious woodyoilcrop in China. The present study investigated the ameliorative effects of EMO on high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) and explored relative regulation mechanism. The analysis of EMO fatty acids showed that EMO rich in unsaturated fatty acids (92.07%), such as linoleic acid (48.24%), oleic acid (34.20%) and linolenic acid (7.57%). In addition, supplementation of EMO could ameliorate the increase in body weight, fat weight, and abnormal serum lipids induced by high-fat diet. A further important implication is that the levels of serum ALT, serum AST, hepatic TG, TC, SOD, GSH/GSSG ration and MDA were improved after supplementing with EMO. All these changes may be due to the ability of EMO to inhibit fatty acid synthesis via reducing the mRNA expression of SREBP-1c, PPARγ and FAS, and elevate fatty acid oxidation by increasing the mRNA expression of PPARα and CPT-1. Meanwhile, our results also showed that endogenously synthesized n-3 PUFAs could significantly increase after treating with EMO. In conclusion, the results suggested that EMO could be regarded as a healthy food for preventing NAFLD.

Effects of solid-state fermentation with three higher fungi on the total phenol contents and antioxidant properties of diverse cereal grains.

Three culinary-medicinal fungi and mushrooms (Agaricus bisporus AS2796, Helvella lacunosa X1 and Fomitiporia yanbeiensis S. Guo & L. Zhou) were individually inoculated into different cereal grains (wheat, rice, oat, corn, millet, quinoa, buckwheat, soybean, pea and sorghum) and the antioxidant properties of fungus-fermented products after solid-state fermentation (SSF) (0, 7, 14, 21, 28 and 35 days; 25°C) were studied. The results showed that the total phenol contents (TPCs) of the fermented cereals varied with fermentation time and the starter organisms. According to the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging capacity, reducing power, ferrous ion chelating ability and superoxide anion radical scavenging ability of ethanolic extracts from the fungus-fermented products (35 days), it was shown that the antioxidant properties of all the products were significantly stronger than uninoculated grains. It revealed that SSF on cereal grains by dietary fungi is a biotechnological strategy, which may enhance the antioxidant properties of the substrate. The three medicinal mushroom and fungi-fermented products were relatively effective in the antioxidant properties assayed and might be potential antioxidants for application in food products.

Lidocaine enhances the effects of chemotherapeutic drugs against bladder cancer.

This study aimed to investigate whether lidocaine, alone or in combination with other chemotherapeutic agents, inhibits the growth of human bladder cancer cells in vitro and orthotopically transplanted bladder tumors in vivo. The effects of lidocaine (1.25, 2.5 or 5 mg/mL), mitomycin C (MMC, 0.66 mg/mL), pirarubicin (0.75 mg/mL) and Su Fu'ning lotion (SFN, 0.0625 mg/mL) on the proliferation of human bladder cancer (BIU-87) cells were studied using the MTT assay. A Balb/c nude mouse model of bladder cancer was developed by orthotopic transplantation of BIU-87 cells, and the effects of intravesical instillation of lidocaine and MMC on bladder wet weight (a measure of tumor size) and survival (over 60 days) were studied. Lidocaine inhibited proliferation of BIU-87 cells in a concentration-dependent manner and (when given in combination) enhanced the actions of each of the other antiproliferative agents. In tumor-bearing mice, MMC alone had no effect on mean survival or bladder wet weight. However, the combination of 0.66 mg/mL MMC and 5 mg/mL lidocaine prolonged survival (from 34.62 ± 6.49 to 49.30 ± 6.72 days; n = 8, P < 0.05) and reduced bladder wet weight (from 68.94 ± 53.61 to 20.26 ± 6.07; n = 8, P < 0.05). Intravesical instillation of lidocaine combined with other chemotherapeutic agents potentially could be an effective therapy for bladder cancer.

Antitumor Effects of Purified Protosappanin B Extracted From Lignum Sappan.

HYPOTHESIS: To assess the antitumor effects of protosappanin B extracted from Lignum Sappan. STUDY DESIGN: Lignum Sappan was sequentially extracted by boiling water and ethyl acetate. The resulting extract was separated by column chromatography, to yield protosappanin B. The compound was then identified by thin-layer chromatography, high-performance liquid chromatography, elemental analysis, and spectrometry (infrared and ultraviolet). The effects on tumor cell viability and growth of purified protosappanin B were evaluated in vitro by trypan blue exclusion and MTT assays, respectively. And the effects of protosappanin B were assessed in vivo, on H22 mouse liver cancer cell invasion and the survival of tumor-bearing mice. RESULTS: Protosappanin B (2 mg/mL) reduced the viability of human bladder cancer T24 cells and mouse bladder cancer BTT cells in a time-dependent manner (P < .05) and significantly inhibited the growth of the human colon cancer cell lines HCT-116 and SW-480. IC50 values of 21.32, 26.73, and 76.53 µg/mL were obtained for SW-480, HCT-116, and BTT cells, respectively, after 48 hours of treatment with protosappanin B. In addition, pretreatment of H22 cells with protosappanin B (final concentration = 6.25 mg/mL) resulted in complete inhibition of tumor formation in KM mice. Furthermore, protosappanin B (200 and 300 mg/kg) significantly increased the survival of BTT tumor-bearing T739 mice, at a rate comparable to that of 1 mg/kg mitomycin. CONCLUSION: Protosappanin B extracted from Lignum Sappan exerts marked antitumor effects both in vitro and in vivo.

c-Fos is involved in inhibition of human bladder carcinoma T24 cells by brazilin.

Crude brazilin extract from Sappan wood has demonstrated strong anti tumor activity in the mouse model of human bladder carcinoma and clinical trial for intravesical therapy. Purified brazilin was confirmed the most active molecule in inhibition of bladder carcinoma T24 cells. Brazilin decreased proliferation and viability of T24 cells in a dose- and time-dependent manner, with a calculated LC50 of 32 µg/mL. More than 1,000 of genes were found upregulated and down regulated by brazilin treatment in digital gene expression profiling. Gene ontology analysis indicated that stress response, apoptosis, and cell cycle regulatory pathways were highly enriched. Among the regulated genes, c-Fos was the most and specifically upregulated. Overexpression of c-Fos in T24 cells resulted in tumor cell specific changes in cell morphology and viability. Over expression of stress-responsive gene, HSP70, and other highly upregulated genes did not have any effect on cell growth. Brazilin may inhibit T24 cell growth and trigger cell death through a c-Fos-mediated and tumor cell specific signaling pathway. Further studies of its down stream mediators may help to identify better tumor cell type specific drug targets.

Nephroprotective effects of Isaria felina in rats with adenine-induced chronic renal failure.

OBJECTIVE: Chronic renal failure (CRF) is a progressive, life-threatening condition with limited treatment options. Cordyceps sinensis is a fungus that has nephroprotective effects, and Isaria felina (IF) is a fungus isolated from C. sinensis fruiting bodies. We evaluated IF efficacy using an adenine-induced CRF animal model. METHODS: Forty male Sprague-Dawley rats were divided into normal control (n = 8) and adenine groups (n = 32; 100 mg/kg for 30 days). The adenine group was subdivided into a model control group (n = 7), a positive control group (200 mg/kg Jinshuibao capsule (JSB; n = 8), and two IF groups (200 mg/kg, n = 8; 100 mg/kg, n = 8). After treatment for 30 days, animals were narcotized and abdominal aortic blood was analysed. Kidney functions were evaluated. KEY FINDINGS: Higher serum creatinine, blood urea nitrogen and uric acid levels, and lower creatinine clearance was observed in the model control group compared with JSB and IF groups (P < 0.05). Red blood cell count, haemoglobin and haematocrit levels in the 200 mg/kg IF group were higher than in the model control group (P < 0.05). Transforming growth factor-ß1 mRNA expression in the model control group was higher than the normal control and 200 mg/kg IF groups (P < 0.05). Epidermal growth factor mRNA in the model control group was lower than in the normal control and both IF-treated groups (P < 0.05). Structural renal damage was observed in all adenine-treated rats, but was less severe in the JSB and IF groups. CONCLUSION: IF may reverse the damaged kidney functions-induced with adenine in rats.

Fluorescence spectroscopic and viscosity studies of hydrogen bonding in Chinese Fenjiu.

The associative behavior of ethanol with water and total hydrogen bonding property in Chinese Fenjiu were examined on the basis of fluorescence and viscosity measurements, respectively. Ethyl esters and acetic acid initially strengthened and then weakened ethanol-water hydrogen-bonding structure, while sodium chloride exhibited its enhanced effect. The fluorescence intensities and viscosities were measured for 12 Fenjiu samples of a distillery, aged for 0-20 years in two different types of containers. The ethanol-water fluorescence intensities and viscosities of Fenjiu samples are proportional to their contents of sodium ion and opposite to their contents of total esters. It can be concluded that the strength of the ethanol-water hydrogen bonding as well as the total hydrogen bonding in aged Fenjiu are directly predominated by total esters lost and sodium ion gained in ceramic containers and not dependent on just the aging time.

Bacterial and fungal diversity in the traditional Chinese liquor fermentation process.

This study endeavored to investigate the variability of bacteria and fungi present during the fermentation process of the light-fragranced distilled liquor known as Fen liquor. To accomplish this, we used a combination of clone libraries of 16S rRNA genes, bar-coded pyrosequencing of the internal transcribed spacer region 1 (ITS1), and quantitative real-time PCR (qPCR). Fifteen families of bacteria and six families of fungi were detected. More than 91% of 16S rRNA gene sequences could be assigned to the family Lactobacillaceae, which were then classified to eight different operational taxonomic units (OTUs), based on a 3% cut-off. The most abundant OTU which contributed to 51% of the total 16S rRNA gene sequences was affiliated with Lactobacillus acetotolerans and had a significantly similar variation trend with the chemical constituents detected. Sixty percent of the fungal ITS1 region sequences were affiliated with the family Saccharomycetaceae. The most abundant OTU was very similar to Issatchenkia orientalis, which displayed notable similarities with respect to the change trends in both ethanol and organic acid contents. The sequences of the second most abundant OTU were closest to Saccharomyces cerevisiae, an important species in the process of ethanol production. Furthermore, about one fourth of the ITS1 region sequences belonged to the family Saccharomycopsidaceae. Conversely, very few sequences could be grouped together with filamentous fungi. The results of qPCR showed that the content of bacteria was increased while that of fungi was more stable in the fermentation process. It is very important to simultaneously investigate bacterial and fungal variations in food-fermentation processes.

[A new SVRDF 3D-descriptor of amino acids and its application to peptide quantitative structure activity relationship].

To establish a new amino acid structure descriptor that can be applied to polypeptide quantitative structure activity relationship (QSAR) studies, a new descriptor, SVRDF, was derived from a principal components analysis of a matrix of 150 radial distribution function index of amino acids. The scale was then applied in three panels of peptide QSAR that were molded by partial least squares regression. The obtained models with the correlation coefficients (R2(cum)), cross-validation correlation coefficients (Q2(cum)) were 0.766 and 0.724 for 48 bitter tasting dipeptides; 0.941 and 0.811 for 21 oxytocin analogues; 0.996 and 0.919 for 20 thromboplastin inhibitors. Satisfactory results showed that information related to biological activity can be systemically expressed by SVRDF scales, which may be an useful structural expression methodology for the study of peptides QSAR.

Quantitative structure spectroscopy relationships of carbon-13 nuclear magnetic resonance chemical shifts of steroids.

Quantitative structure spectroscopy relationships (QSSRs) are systematically studied for carbon-13 nuclear magnetic resonance ((13)C NMR) spectroscopic simulation of steroid compounds. Both the atomic electronegativity interaction vector (AEIV) and the atomic hybridization state index (AHSI) are used for the expression of local chemical microenvironment and atomic hybridization state of 4434 resonance carbon atoms in 203 steroid molecules. A multiple linear regression (MLR) model is built after screening some insignificant parameters with the stepwise multiple regression (SMR) technique. Correlation coefficients of the developed model are R(cum)(2)=0.9341 and Q(LOO)(2)=0.9336 for classical estimation of molecular modeling and the cross-validation with leave-one-out (LOO) procedures, respectively, primarily indicating that the MLR model has good modeling stability and prediction ability. Furthermore, the superior performance of the MLR model is tested by the leave-33%-out (L33%O) cross-validation method, where the mean correlation coefficients of three test sets are Q(2)=0.9310 and Q(ext)(2)=0.9196 for both internal and external sets. In conclusion, AEIV and AHSI descriptors can be used for estimating and predicting (13)C NMR chemical shifts of steroids.

Prediction of 31P nuclear magnetic resonance chemical shifts for phosphines.

Quantitative relationships of the (31)P NMR chemical shifts of the phosphorus atoms in 291 phosphines with the atomic ionicity index (INI) and stereoscopic effect parameters (epsilon(alpha), epsilon(beta), epsilon(gamma)) were primarily investigated in this paper for modeling some fundamental quantitative structure-spectroscopy relationships (QSSR). The results indicated that the (31)P NMR chemical shifts of phosphines can be described as the quantitative equation by multiple linear regression (MLR): delta(p)(ppm)= -174.0197-2.6724INI+40.4755epsilon(alpha)+15.1141epsilon(beta)-3.1858epsilon(gamma), correlation coefficient R=0.9479, root mean square error (rms)=13.9, and cross-validated predictive correlation coefficient was found by using the leave-one-out procedure to be Q(2)=0.8919. Furthermore, through way of random sampling, the estimative stability and the predictive power of the proposed MLR model were examined by constructing data set randomly into both the internal training set and external test set of 261 and 30 compounds, respectively, and then the chemical shifts were estimated and predicted with the training correlation coefficient R=0.9467 and rms=13.4 and the external predicting correlation coefficient Q(ext)=0.9598 and rms=10.8. A partial least square model was developed that produced R=0.9466, Q=0.9407 and Q(ext)=0.9599, respectively. Those good results provided a new, simple, accurate and efficient methodology for calculating (31)P NMR chemical shifts of phosphines.

[Quantitative structure-activity relationship study of tetrahydroimidazobenzodiazepinone anti-HIV drug using three-dimensional holographic vector of atomic interaction field].

AIM: To study the quantitative structure-activity relationship ( QSAR) of 23 tetrahydroimidazobenzodiazepinone (TIBO) as anti-HIV drug. METHODS: A newly developed three-dimensional holographic vector of atomic interaction field (3D-HoVAIF) was used to describe the chemical structure of anti-HIV drug-23 TIBO, a partial least square regression (PLS) model was built. RESULTS: The obtained model with the cumulative multiple correlation coefficient (Rcum(2)), cumulative cross-validated (Qcum(2)) and standard error of estimation (SD) were Rcum(2) = 0. 824, Qcum(2) = 0.778 and SD = 0.56, respectively. The model had favorable estimation stability and good prediction capabilities. CONCLUSION: Satisfactory results showed that 3D-HoVAIF with definite physic-chemical meanings and easy structural interpretation for structural characterization could preferably express information related to biological activity of TIBO.