[show abstract][hide abstract] ABSTRACT: As part of a search for antitubercular substances from natural sources, we screened a library of endophytic microbes (50 strains and 300 crude extracts in total) isolated from traditional Chinese medicines (TCMs) for growth inhibitory activity against Bacillus Calmette-Guérin (BCG). The crude extract of Streptomyces sp. strain Y3111, which was associated with the stems of Heracleum souliei, showed good anti-BCG activity with an MIC value of 12.5 μg/mL. Bioassay-guided isolation led to four new pluramycin-type compounds, heraclemycins A-D (1-4). Their structures were determined by different spectroscopic techniques including HRMSESI, 1D NMR, and 2D NMR. This is the first report of pluramycin analogues produced by TCM endophytic microbes as well as the first example of BCG-selective pluramycins. Heraclemycin C (3) showed selective antitubercular activity against BCG with a MIC value of 6.25 μg/mL and a potential new mode of action.
Applied Microbiology and Biotechnology 11/2013; · 3.69 Impact Factor
[show abstract][hide abstract] ABSTRACT: Serial antibacterial furanoditerpenes caesanines A-D (1-4), possessing a cassane-type diterpenoid skeleton with an unusual N bridge between C-19/C-20, were identified from a Chinese herb Caesalpinia sappan Linn. In addition, caesanine D (4) showed the first class of dicassane diterpenoid ethers. Their structures were determined by different spectroscopic methods and ECD calculation. Caesanines A and B exhibited strong activities against MRSA suggesting a promising entry point for the development of anti-infective drugs.
[show abstract][hide abstract] ABSTRACT: Aqueous swelling pretreatment of cellulose was found highly effective for reactive ball milling to prepare surface-esterified cellulose nanofibers. Compared with starting from dry cellulose, water- or 2 % NaOH-pre-swollen materials were esterified and dispersed in significantly shorter milling time. Especially commercial kraft pulp was difficult to disperse even with water pretreatment, but 2 % NaOH treatment gave full surface esterification with a bulk degree of substitution of 0.69 by 12-h ball milling, presumably because of removal of non-cellulosic components.
[show abstract][hide abstract] ABSTRACT: From the deep: The title actinomycete yielded three new abyssomicins J-L. The dimeric thioether J represents a unique example of a masked Michael acceptor with anti-TB properties. Mechanistic insights into the biosynthesis, biomimetic synthesis, stability, and biological mechanism of action of abyssomicins inform our understanding of, and prospects for the development of Michael-acceptor-based drugs.
Angewandte Chemie International Edition 12/2012; · 13.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Got a crush: Native cellulose can be dispersed as nanofibers in organic solvents by ball milling with esterification agents. Milling with hexanoyl chloride/DMF gives hexanoyl-coated nanofibers dispersible in several organic solvents. Milling with succinic anhydride/DMSO results water-dispersible nanofibers. The results open the way to new cellulose mechanochemistries.
[show abstract][hide abstract] ABSTRACT: Multidrug-resistant tuberculosis (MDR-TB) and TB-HIV co-infection have become a great threat to global health. However, the last truly novel drug that was approved for the treatment of TB was discovered 40 years ago. The search for new effective drugs against TB has never been more intensive. Natural products derived from microbes and medicinal plants have been an important source of TB therapeutics. Recent advances have been made to accelerate the discovery rate of novel TB drugs including diversifying strategies for environmental strains, high-throughput screening (HTS) assays, and chemical diversity. This review will discuss the challenges of finding novel natural products with anti-TB activity from marine microbes and plant medicines, including biodiversity- and taxonomy-guided microbial natural products library construction, target- and cell-based HTS, and bioassay-directed isolation of anti-TB substances from traditional medicines.
Antonie van Leeuwenhoek 07/2012; 102(3):447-61. · 2.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Advances in the taxonomic characterization of microorganisms have accelerated the rate at which new producers of natural products can be understood in relation to known organisms. Yet for many reasons, chemical efforts to characterize new compounds from new microbes have not kept pace with taxonomic advances. That there exists an ever-widening gap between the biological versus chemical characterization of new microorganisms creates tremendous opportunity for the discovery of novel natural products through the calculated selection and study of organisms from unique, untapped, ecological niches. A systematics-guided bioprospecting, including the construction of high quality libraries of marine microbes and their crude extracts, investigation of bioactive compounds, and increasing the active compounds by precision engineering, has become an efficient approach to drive drug leads discovery. This review outlines the recent advances in these issues and shares our experiences on anti-infectious drug discovery and improvement of avermectins production as well.
Antonie van Leeuwenhoek 11/2011; 101(1):55-66. · 2.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Mitochondria play important roles in the intrinsic pathways that trigger apoptosis. Anticancer chemotherapies eliminate cancer cells mainly through the induction of apoptosis. In the present study, we investigated the mechanism of the cytotoxic effects of tubeimoside I (TBMS1) on the human choriocarcinoma cell line (JEG-3). Choriocarcinoma is one of the most common malignant tumors in the reproductive system. TBMS1, a triterpenoid saponin, isolated from the tubers of Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae), showed potent antitumor effects. However, the potential roles of TBMS1 in the treatment of choriocarcinoma remain unknown. In the present study, we examined the effects of TBMS1 on JEG-3 cells. TBMS1 displayed strong growth inhibitory effects on JEG-3 cell growth. In addition, TBMS1 treatment with TBMS1 led to marked cell apoptosis, significant cell cycle arrest at G2 phase and decrease in mitochondrial transmembrane potential (ΔΨm). Cytochrome c was released from the mitochondria and caspase-3 expression was enhanced. Furthermore, TBMS1 induced the up-regulation of Bcl-2 associated X protein (Bax) expression, down-regulation of Bcl-2 expression, inhibition of nuclear factor-κ-B (NF-κB) function and impacted the phosphorylation of p38 mitogen-activated protein kinase (p38/MAPK), extracellular signal-regulated kinases (ERK)1/2 and protein kinase B (Akt). Taken together, our findings suggest that TBMS1 is an efficient apoptosis-inducing agent for choriocarcinoma cells, which exerts its effects, at least partially, by the induction of mitochondrial dysfunction and regulation of the p38/MAPK, ERK1/2 and PI3K/Akt signaling pathways.
International Journal of Molecular Medicine 06/2011; 28(4):579-87. · 1.96 Impact Factor
[show abstract][hide abstract] ABSTRACT: Magnetic wheat straw (MWS) with different Fe(3)O(4) content was synthesized by using in-situ co-precipitation method. It was characterized by powder X-ray diffraction (XRD) and vibrating sample magnetometer (VSM). This material can be used for arsenic adsorption from water, and can be easily separated by applied magnetic field. The introduction of wheat straw template highly enhanced the arsenic adsorption of Fe(3)O(4). Among three adsorption isotherm models examined, the data fitted Langmuir model better. Fe(3)O(4) content and initial pH value influenced its adsorption behavior. Higher Fe(3)O(4) content corresponded to a higher adsorption capacity. In the pH range of 3-11, As(V) adsorption was decreased with increasing of pH; As(III) adsorption had the highest capacity at pH 7-9. Moreover, by using 0.1 mol L(-1) NaOH aqueous solution, it could be regenerated. This work provided an efficient way for making use of agricultural waste.
Journal of hazardous materials 05/2011; 193:10-6. · 4.14 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate whether and how COS inhibited IL-8 production in LPS-induced human umbilical vein endothelial cells (HUVECs).
RT-PCR, enzyme-linked immunosorbent assays (ELISA) and Western blotting were used to study IL-8 expression and related signaling pathway. Wound healing migration assays and monocytic cell adhesion analysis were used to explore the chemotactic and adhesive activities of HUVECs.
COS 50-200 μg/mL exerted a significant inhibitory effect on LPS 100 ng/mL-induced IL-8 expression in HUVECs at both the transcriptional and translational levels. In addition, COS 50-200 μg/mL inhibited LPS-induced HUVEC migration and U937 monocyte adhesion to HUVECs in a concentration-dependent manner. Signal transduction studies suggest that COS blocked LPS-induced activation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) as well as phosphorylation of p38 mitogen-activated protein kinase (MAPK) and phosphokinase Akt. Further, the over-expression of LPS-induced IL-8 mRNA in HUVECs was suppressed by a p38 MAPK inhibitor (SB203580, 25 μmol/L) or a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002, 50 μmol/L).
COS inhibited LPS-induced IL-8 expression in HUVECs through the blockade of the p38 MAPK and PI3K/Akt signaling pathways.
[show abstract][hide abstract] ABSTRACT: This study aimed to investigate the inhibitive effects of chitosan oligosaccharides (COS) on tumor necrosis factor (TNF)-α-induced over-expression of vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs). We found that COS effectively inhibited TNF-α-induced expression of VCAM-1 and ICAM-1 at the level of transcription and translation. Signal transduction studies suggested that COS blocked TNF-α-induced activation of NF-κB, degradation of IκBα, and phosphorylation of p38 MAPK and ERK1/2. A further investigation showed that the NF-κB activation can be partly suppressed by p38 MAPK inhibitor (SB203580) and ERK1/2 inhibitor (PD98059), which also ameliorated the mRNA expression of VCAM-1 and ICAM-1 in TNF-α-induced HUVECs. Additionally, COS decreased U937 monocyte adhesion to HUVECs induced by TNF-α. Our findings suggest that COS inhibit VCAM-1 and ICAM-1 production in activated HUVECs at least partly through the blockade of p38 and ERK1/2 signaling pathways.
[show abstract][hide abstract] ABSTRACT: The mechanisms of neointima formation after synthetic vascular grafting are not clear. The aim of this study was to investigate the intima and perigraft adventitia remodeling process in terms of cell apoptosis versus proliferation after synthetic patch implantation.
Female Merino sheep were randomized equally into two groups and underwent implantion with a patch of gelatin sealed Dacron graft into the left common carotid artery. At 1 and 6 months, grafted vessels were harvested, processed, and assessed. Intimal area and lumen sizes were measured with histologic assessment of eight segments from each animal assisted with image analysis. Immunohistochemical labeling of alpha-actin and D33 desmin was performed on tissue sections of perigraft adventitia, graft matrix, and intima. Cell proliferation and cell phenotype were determined with double immunohistochemical staining with anti-proliferating cell nuclear antigen and anti-alpha-actin or antimacrophage antibodies (HAM 56) in perigraft adventitia, graft matrix, and intima. Apoptosis was detected with in situ terminal deoxynucleiotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-fluorescence nick end labeling (TUNEL) in perigraft adventitia, graft matrix, and intima.
The carotid artery lumen size at 6 months was significantly larger than at 1 month (P <or=.05). The intimal area was significantly reduced at 6 months compared with 1 month (P <.05). At 1 month and 6 months, perigraft adventitia, graft matrix, and intima showed positive alpha-actin expression but negative desmin staining. In the anastomotic area, a small number of intimal cells suggested their muscle origin (expression alpha-actin and desmin). The number of proliferating cells in the intima was significantly greater at 1 month than at 6 months (P =.01). TUNEL-positive cells were significantly greater in the intima at 1 month than at 6 months (P <.05), whereas TUNEL-positive cells were significantly greater at 6 months in the perigraft adventitia (P <.05). HAM 56-positive cells in the intima at 1 month were significantly greater compared with 6 months (P <.05), whereas in graft and perigraft regions, no significant difference was seen between 1 month and 6 months.
The cell proliferation and cell phenotype change in intima and perigraft adventitia are associated with thickening of perigraft adventitia and intima at 1 month. The balance between cell proliferation and apoptosis could account in part for the reduction in intima area and perigraft adventitial cellularity at 6 months.
Journal of Vascular Surgery 08/2002; 36(2):371-8. · 2.88 Impact Factor