Study on potential microbial community to the waste water treatment from bauxite desilication process.

Discharging waste water from the bauxite desilication process will bring potential environmental risk from the residual ions and organic compounds, especially hydrolyzed polyacrylamide. Characterization of the microbial community diversity in waste water plays an important role in the biological treatment of waste water. In this study, eight waste water samples from five flotation plants in China were investigated. The microbial community and functional profiles within the waste water were analyzed by a metagenomic sequencing method and associated with geochemical properties. The results revealed that Proteobacteria and Firmicutes were the dominant bacterial phyla. Both phylogenetical and clusters of orthologous groups' analyses indicated that Tepidicella, Paracoccus, Pseudomonas, and Exiguobacterium could be the dominant bacterial genera in the waste water from bauxite desilication process for their abilities to biodegrade complex organic compounds. The results of the microbial community diversity and functional gene compositions analyses provided a beneficial orientation for the biotreatment of waste water, as well as regenerative using of water resources. Besides, this study revealed that waste water from bauxite desilication process was an ideal ecosystem to find novel microorganisms, such as efficient strains for bio-desilication and bio-desulfurization of bauxite.

Shikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathways.

Shikonin is the main component of the traditional Chinese medicine comfrey, which can inhibit the activity of PKM2 by regulating glycolysis and ATP production. Rheumatoid arthritis synovial cells (RA-FLSs) have been reported to increase glycolytic activity and have other similar hallmarks of metabolic activity. In this study, we investigated the effects of shikonin on glycolysis, mitochondrial function, and cell death in RA-FLSs. The results showed that shikonin induced apoptosis and autophagy in RA-FLSs by activating the production of reactive oxygen species (ROS) and inhibiting intracellular ATP levels, glycolysis-related proteins, and the PI3K-AKT-mTOR signaling pathway. Shikonin can significantly reduce the expression of apoptosis-related proteins, paw swelling in rat arthritic tissues, and the levels of inflammatory factors in peripheral blood, such as TNF-α, IL-6, IL-8, IL-10, IL-17A, and IL-1ß while showing less toxicity to the liver and kidney.

Anti-cancer effects of methanol-ethyl acetate partitioned fraction from Magnolia grandiflora in human non-small cell lung cancer H1975 cells.

Non-small cell lung cancer (NSCLC) constitutes nearly 85% of all cases of lung cancer. Drug resistance, dose-limiting toxicity, and metastasis in NSCLC eventually reduce the efficacy of chemotherapeutics. In this study, we have shown that the methanol-ethyl acetate partitioned fraction from Magnolia grandiflora L. seeds (MEM) exhibit potential anti-cancer activities against NSCLC H1975 cells in vivo and in vitro. MEM significantly inhibited the proliferation of H1975 cells in a concentration- and time-dependent manner. Further, MEM exhibited potent anti-tumor efficacy and low toxicity in nude mice bearing H1975 tumors. Our study also showed that MEM could induce cellular apoptosis in H1975 cells by down-regulating the protein expression levels of Akt and p-Akt-473, and by increasing the ratio of Bax/Bcl-2. Also, MEM significantly inhibited metastasis-related cell invasion and migration of H1975 cells, which associated with the down-regulation of HIF-1α, MMP-2, and MMP-9 protein expression levels. Thus, our data shows that MEM may be an effective fraction of M. grandiflora in NSCLC treatment.

Magnolol prevents ovariectomy­induced bone loss by suppressing osteoclastogenesis via inhibition of the nuclear factor­κB and mitogen­activated protein kinase pathways.

Magnolol is the active component of the traditional Chinese medicine Magnolia officinalis, and has antioxidant, anti­inflammatory and anticancer activities, as well as an effect on bone metabolism in vitro. In the present study, it is reported that magnolol suppresses osteoclastogenesis in vivo and in vitro. Magnolol prevented ovariectomy­induced bone loss and osteoclastogenesis in vivo, and decreased the serum levels of C­terminal telopeptide of type 1 collagen, interleukin­6, tumor necrosis factor (TNF)­α and tartrate­resistant acid phosphatase 5B. In vitro, magnolol inhibited the osteoclastogenesis induced by the receptor activator for nuclear factor­κB ligand, and impaired the osteoclast function in bone marrow monocytes and RAW264.7 cells in a dose­dependent manner. Furthermore, magnolol suppressed the expression levels of the osteoclastogenesis markers cathepsin K, calcitonin receptor, matrix metalloproteinase 9, TNF receptor­associated factor 6 and tartrate­resistant acid phosphatase by inhibiting the nuclear factor­κB and mitogen­activated protein kinase pathways. Therefore, magnolol is a promising agent for the treatment of osteoporosis and associated disorders.

Enzymatic biosynthesis of novel neobavaisoflavone glucosides via Bacillus UDP-glycosyltransferase.

The present study was designed to perform structural modifications of of neobavaisoflavone (NBIF), using an in vitro enzymatic glycosylation reaction, in order to improve its water-solubility. Two novel glucosides of NBIF were obtained from an enzymatic glycosylation by UDP-glycosyltransferase. The glycosylated products were elucidated by LC-MS, HR-ESI-MS, and NMR analysis. The HPLC peaks were integrated and the concentrations in sample solutions were calculated. The MTT assay was used to detect the cytotoxic activity of compounds in cancer cell lines. Based on the spectroscopic analyses, the two novel glucosides were identified as neobavaisoflavone-4'-O-ß-D-glucopyranoside (1) and neobavaisoflavone-4', 7-di-O-ß-D-glucopyranoside (2). Additionally, the water-solubilities of compounds 1 and 2 were approximately 175.1- and 4 031.9-fold higher than that of the substrate, respectively. Among the test compounds, only NBIF exhibited weak cytotoxicity against four human cancer cell lines, with IC50 values ranging from 63.47 to 72.81 µmol·L-1. These results suggest that in vitro enzymatic glycosylation is a powerful approach to structural modification, improving water-solubility.

Effect of Polygonatum odoratum extract on human breast cancer MDA-MB-231 cell proliferation and apoptosis.

Traditional Chinese medicine (TCM) is important in the provision of anti-tumor drugs. Recently, studies have shown that certain types of TCM agents are able to control the growth of tumors, enhance the body's immune function and enhance the therapeutic effect of chemotherapeutic drugs. In women, breast carcinoma is the most common tumor type and the second most common cause of death from cancer. Polygonatum odoratum (P. odoratum) is commonly used in TCM. The aim of the present study was to investigate the effects of P. odoratum extract on the proliferation and apoptosis of MDA-MB-231 breast cancer cells. Cell proliferation was assessed using MTT and colony formation assays. In addition, propidium iodide (PI)/Annexin V-FITC staining was used to investigate the apoptosis of MDA-MB-231 cells following treatment with P. odoratum extract. The protein expression levels of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) were also detected using western blot analysis, while a JC-1 staining assay was used to assess the mitochondrial membrane potential (ΔΨm). The results of the MTT assay showed that the proliferation and colony formation of MDA-MB-231 cells were inhibited following treatment with the extract. Furthermore, the PI/Annexin-V staining showed that the apoptosis of MDA-MB-231 cells was enhanced by the extract, in a concentration-dependent manner. The extract also lowered the ΔΨm of MDA-MB-231 cells, upregulated the expression of Bax and inhibited the expression of Bcl-2. In conclusion, these results showed that the P. odoratum extract inhibited the proliferation and induced apoptosis of breast cancer MDA-MB-231 cells.

Scutellaria baicalensis Georgi extract protects against alcohol­induced acute liver injury in mice and affects the mechanism of ER stress.

The aims of the present study were to examine the hepatoprotective effect of Scutellaria baicalensis Georgi extract (Scutellariae Radix extract; SRE) against acute alcohol­induced liver injury in mice, and investigate the mechanism of endoplasmic reticulum (ER) stress. High performance liquid chromatography was used for the phytochemical analysis of SRE. Animals were administered orally with 50% alcohol (12 ml/kg) 4 h following administration of doses of SRE every day for 14 days, with the exception of normal control group. The protective effect was investigated by measuring the levels of aspartate transaminase (AST), alanine transferase (ALT) and triglyceride (TG) in the serum, and the levels of glutathione (GSH) and malondialdehyde (MDA) in liver tissues. The levels of glucose­related protein 78 (GRP78) were detected using immunohistochemical localization and an enzyme­linked immunosorbent assay. Hepatocyte apoptosis was assessed using terminal­deoxynucleoitidyl transferase mediated nick end labeling. The SRE contained 31.2% baicalin. Pretreatment with SRE had a marked protective effect by reversing the levels of biochemical markers and levels of GRP78 in a dose­dependent manner. The results of the present study demonstrated that pretreatment with SRE exerted a marked hepatoprotective effect by downregulating the expression of GRP78, which is a marker of ER stress.

Enzymatic synthesis of novel isobavachalcone glucosides via a UDP-glycosyltransferase.

Glycosylation is often used to improve a natural product's properties such as water solubility, chemical stability, pharmacological potency, and structure diversification. In this study, we studied the enzymatic synthesis of novel isobavachalcone glucosides using a UDP-glycosyltransferase (YjiC) from Bacillus licheniformis DSM-13. The chemical structures of compounds 1 and 2 were elucidated by spectroscopic techniques, including LC-MS, MS, and NMR. Meanwhile, the parameters of glycosylation reaction such as incubation time, UDP-glucose concentration, and pH of buffer were also optimized during this study. Furthermore, the compounds 1 and 2 exhibited weak anti-proliferative activities against five human cancer cell lines, with IC50 values ranging from 58.6 to 86.6 µM.

A new dimeric neolignan from Magnolia grandiflora L. seeds.

Bioassay-guided fractionation of the MeOH extract of Magnolia grandiflora seeds resulted in the isolation of a new dimeric neolignan, named bishonokiol A (1), as well as two known neolignans magnolol (2) and honokiol (3). The structures of the compounds were determined on the basis of data obtained using NMR and MS. Bishonokiol A (1) showed potent anti-proliferative activities in four human cancer cell lines, with IC50 values ranging from 5.1 to 7.5 µM. Additionally, bishonokiol A (1) induced apoptosis, as well as down-regulated the expression of the anti-apoptotic protein Bcl-2 and caspase-3 cleavage in HepG2 cell line.

Huaier aqueous extract inhibits stem-like characteristics of MCF7 breast cancer cells via inactivation of hedgehog pathway.

The theory of targeting cancer stem-like cells (CSCs) provides novel strategy for cancer treatment. In the present study, we examined the inhibitory effect of Huaier aqueous extract on eradicating breast cancer stem cells and explored the underlying mechanisms. Our data demonstrated that various concentrations of Huaier extract significantly decreased the viabilities, numbers, and sizes of mammospheres. After incubation with Huaier extract for 24 h, the clonogenicity of MCF7 cell line was obviously impaired, along with less holoclones. In addition, Huaier extract reduced the number of cells expressing CD44+/CD24- and decreased the level of stem cell markers (OCT-4, NESTIN, and NANOG). The hedgehog (Hh), notch, and Wnt/ß-catenin pathways were essential stem cell signaling pathways involved in regulating CSC renewal and maintenance. We reported that the inhibitory effect of Huaier extract was partly depended on the inactivation of Hh pathway. These findings provided experimental evidence that Huaier extract was a promising therapeutic drug for eliminating the breast cancer stem cells.

Huaier aqueous extract suppresses human breast cancer cell proliferation through inhibition of estrogen receptor α signaling.

Estrogen receptor α (ERα) has been reported to play a critical role in promoting the growth of breast tumor cells. In the present study, we explored the effect of Huaier extract on estrogen receptor α signaling in breast cancer cell lines. Our data demonstrated that Huaier extract effectively inhibited the proliferation of the MCF-7, T47D and ZR-75-1 human breast cancer cell lines. For the mechanism analysis, we demonstrated that Huaier extract significantly reduced the mRNA and protein levels of ERα in all three ERα-positive cell lines. The downregulation of ERα protein levels was correlated with activation of the proteasomes. We demonstrated that Huaier extract markedly decreased the expression of both ERα and its downstream genes, inhibited the estrogen-stimulated proliferation and reversed the estrogen-induced activation of the nuclear factor κB (NFκB) pathway. Our study provides evidence that Huaier extract is a novel estrogen receptor modulator and is a promising drug for the prevention and treatment of ERα-positive human breast cancers.

Anti-angiogenic and antitumor activities of Huaier aqueous extract.

Traditional Chinese medicine, a rich source of potent cancer chemopreventive agents, is attracting increasing attention worldwide. Recently, the anticancer activity of Trametes robiniophila Μurr. (Huaier) has been widely investigated. However, the mechanisms are not yet fully understood. This study aimed to elucidate the inhibitory effect of Huaier extract on angiogenesis and tumor growth. Incubation with Huaier extract inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) and mouse mammary tumor cells (4T1). In addition, treatment with Huaier extract decreased the motility and tube formation of HUVECs in a dose-dependent manner in vitro. As determined by western blot analysis, Huaier extract dose-dependently decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK), transcription factor p65, c-Jun N-terminal kinase (JNK), signal transducer and activator of transcription 3 (STAT3) and the expression of vascular endothelial growth factor (VEGF). In ex vivo experiments, new vessel growth was suppressed as shown by chick embryo chorioallantoic membrane (CAM) and rat aortic ring assays in the presence of Huaier extract. To further evaluate the inhibitory effect, 4T1 cells were injected subcutaneously into BALB/c mice. The administration of Huaier extract suppressed tumor volume, decreased microvessel density and induced apoptosis. These data suggest that Huaier extract may serve as a potent anti-angiogenic and antitumor agent.

Cytotoxic sesquiterpenes and lignans from Saussurea deltoidea.

Two new sesquiterpenes deltoiden A (1) and deltoiden B (2), and two new lignans deltoignan A (9) and deltoignan B (10), together with 14 known compounds, including six sesquiterpenes 3-8 and three lignans 11-13, were isolated from the whole plant of Saussurea deltoidea. Compounds 3-8 and 11-17 were isolated for the first time from this plant. Their structures were established by spectroscopic analysis, including 2D-NMR spectroscopic techniques. Cytotoxicities of compounds 1-13 were tested against three cancer cell lines A549, Hela and SMMC-7721. Results showed that 5, 6 and 7 exhibited cytotoxicity against SMMC-7721 with the IC(50) values of 6.49, 9.53, 1.23 µg/ml, 5 and 7 against A549 with the IC(50) values of 4.99 and 5.35 µg/ml, 5, 6, 7, 13 against Hela with the IC(50) values of 1.40, 4.75, 0.93 and 5.42 µg/ml, respectively. The structure-activity relationships of sesquiterpenes 1-8 were discussed on the base of cytotoxic results.

Apoptosis inducement of bigelovin from Inula helianthus-aquatica on human Leukemia U937 cells.

Inula helianthus-aquatica C. Y. Wu is a traditional medicinal plant used to treat some cancers in folk herbal medicine of Yunnan, China. Bigelovin, a sesquiterpene lactone isolated from this herb, potently inhibits the growth of a panel of eight cancer cell lines, especially in human monoblastic leukemia U937 cells with an IC(50) value of 0.47 microM. Characteristic morphological features of apoptosis were observed in U937 cells treated with bigelovin. Annexin V and nuclear DNA content distribution assays showed that the percentage of Annexin V positive cells increased to 8.86% (24 h) with 1 microM bigelovin treatment, and cells treated with bigelovin at this concentration apparently arrested at G(0)/G(1) phase compared with the control. These data suggested that cytotoxic effect of bigelovin on U937 cells involves induction of apoptosis, and the cell cycle is arrested at G(0)/G(1) phase.