Three New Highly Oxygenated Germacranolides from Carpesium Divaricatum and Their Cytotoxic Activity.

Three new highly oxygenated (2⁻4), and two known (1 and 5) germacranolides, were isolated from the whole plant of Carpesium divaricatum. The planar structures and relative configurations of the new compounds were determined by detailed spectroscopic analysis. The absolute configuration of 1 was established using the circular dichroism (CD) method and X-ray diffraction, and the stereochemistry of the new compounds 2⁻4 were determined using similar CD spectra with 1. The new compound 2 and the known compound 5 exhibited potent cytotoxicity against hepatocellular cancer (Hep G2) and human cervical cancer (HeLa) cells, superior to those of the positive control cis-platin.

Two new unsaturated fatty acids from the whole plant of Pothos chinensis.

Two new unsaturated fatty acids, (Z)-octadec-13-en-11-ynoic acid (1) and (Z)-octadec-16-en-12,14-diynoic acid (2), along with six known compounds were isolated from the whole plant of Pothos chinensis. The structures of these compounds were elucidated by detailed spectroscopic analysis, including 1D and 2D NMR data. Compound 2 showed moderate antibacterial activity against Staphylococcus aureus.

Bmi1 combines with oncogenic KRAS to induce malignant transformation of human pancreatic duct cells in vitro.

It is critical to understand the pathogenesis of preinvasive stages of pancreatic duct adenocarcinoma (PDAC) for developing novel potential diagnostic and therapeutic targets. The polycomb group family member B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi1) is overexpressed and involved in cancer progression in PDAC; however, its role in the multistep malignant transformation of human pancreatic duct cells has not been directly demonstrated. In this study, we stably expressed Bmi1 in a model of telomerase-immortalized human pancreatic duct-derived cells (HPNE) and showed that Bmi1 promoted HPNE cell proliferation, migration, and invasion but not malignant transformation. We then used mutant KRASG12D as a second oncogene to transform HPNE cells and showed that it further enhanced Bmi1-induced malignant potential. More importantly, coexpression of KRASG12D and Bmi1 caused anchorage-independent growth transformation in vitro but still failed to produce tumors in nude mice. Finally, we found that mutant KRASG12D induced HPNE-Bmi1 cells to undergo partial epithelial-mesenchymal transition (EMT) likely via upregulation of snail. Knockdown of KRASG12D significantly reduced the expression of snail and vimentin at both the messenger RNA (mRNA) and protein level and further impaired the anchorage-independent growth capability of invasive cells. In summary, our findings demonstrate that coexpression of Bmi1 and KRASG12D could lead to transformation of HPNE cells in vitro and suggest potential new targets for diagnosis and treatment of PDAC.

[Chemical investigation of triterpenoids from Dichrocephala benthamii].

The triterpenoids of Dichrocephala benthamii were investigated by means of silica gel, Sephadex LH-20 and semi-preparative HPLC. Nine triterpenoids were isolated from D. benthamii. By analysis of the EI-MS, NMR spectra and comparison to the data reported in literatures, the structures of these compounds were determined as ß-amyrin formiate (1), ß-amyrin acetate (2), ß-amyrenol (3), ß-amyrone (4), 3ß-hydroxy-olean-11, 13 (18)-diene (5) , Δ12-oleanene (6) , friedelin (7), dammaradienyl acetate (8), epi-friedeband (9), respectively. Compounds 1-8 were isolated for the first time form this genus, compound 9 was isolated for the first time from this plant, whereas ß-amyrin formiate (1) was a new natural product.

A new acylated flavonol glycoside from the aerial parts of Cardamine tangutorum.

A new acylated flavonol glycoside, kaempferol-3-O-ß-D-(2-feruloylglucopyranosyl) (1 → 6)-[ß-D-glucopyranosyl(1 → 2)]-ß-D-glucopyranoside, named tangutorumoside A (1), together with 12 known compounds, was isolated from 50% acetone extract of Cardamine tangutorum. Their structures were elucidated by NMR and MS experiments. In addition, compound 1 could promote the proliferation of splenic lymphocytes and thymic lymphocytes with ConA in vitro.

New antiproliferative germacranolides from Carpesium divaricatum.

Six new highly oxygenated (2-7) and one known (1) germacranolides were isolated from the whole plant of Carpesium divaricatum. The planar structures and relative configurations of the new compounds were determined by detailed spectroscopic analysis. The absolute configurations of 1 and 3 were established by circular dichroism (CD) and X-ray crystallographic analyses, and the stereochemistry of the new compounds 2 and 4-6 were determined by similar CD data to 1 and 3, respectively. All isolates were evaluated for their antiproliferative activities against three human tumor cell lines, and compounds 3 and 6 show antiproliferative activities against HeLa and Hep G2 cells with IC50 values of 4.13-8.37 µM. Intensive mechanism study showed that 3 caused cell-cycle arrest at the S/G2 phase and induced apoptosis in Hep G2 cells through a mitochondria-related pathway.

Revealing of the Activation Pathway and Cathode Electrolyte Interphase Evolution of Li-Rich 0.5Li2MnO3·0.5LiNi0.3Co0.3Mn0.4O2 Cathode by in Situ Electrochemical Quartz Crystal Microbalance.

The first-cycle behavior of layered Li-rich oxides, including Li2MnO3 activation and cathode electrolyte interphase (CEI) formation, significantly influences their electrochemical performance. However, the Li2MnO3 activation pathway and the CEI formation process are still controversial. Here, the first-cycle properties of xLi2MnO3·(1- x) LiNi0.3Co0.3Mn0.4O2 ( x = 0, 0.5, 1) cathode materials were studied with an in situ electrochemical quartz crystal microbalance (EQCM). The results demonstrate that a synergistic effect between the layered Li2MnO3 and LiNi0.3Co0.3Mn0.4O2 structures can significantly affect the activation pathway of Li1.2Ni0.12Co0.12Mn0.56O2, leading to an extra-high capacity. It is demonstrated that Li2MnO3 activation in Li-rich materials is dominated by electrochemical decomposition (oxygen redox), which is different from the activation process of pure Li2MnO3 governed by chemical decomposition (Li2O evolution). CEI evolution is closely related to Li+ extraction/insertion. The valence state variation of the metal ions (Ni, Co, Mn) in Li-rich materials can promote CEI formation. This study is of significance for understanding and designing Li-rich cathode-based batteries.

Isolation, Structure Elucidation, and Absolute Configuration of Germacrane Isomers from Carpesium divaricatum.

Five sets of germacrane isomers (1/8/17, 2/7/10/11/13/16/18, 3/4/5/14/20, 6/12/15, and 9/19) with different skeletal types, including seven new ones (1-3, 8-9, and 15-16) were isolated from the whole plant of Carpesium divaricatum. Among them, there are six pairs of stereoisomers (1/8, 2/13, 4/14, 6/12, 7/11 and 10/11). The planar structures and relative configurations of the new compounds were elucidated by detailed spectroscopic analysis. The absolute configurations of 4, 10, 11, and 17 were established by circular dichroism (CD) spectra and X-ray crystallographic analyses, and the stereochemistry of the new compounds 1-3, 8-9, and 15-16 were determined by similar CD spectra with 4, 10, 11, and 17, respectively. The confusion in the literature about subtypes I and II of germacranolides was clarified in this paper. The NMR data of 10-11, and the absolute configurations of the known compounds 4-6, 13-14, and 17-20 were reported for the first time. Compounds 13, 17, and 18 showed cytotoxicity against human cervical (HeLa), colon (LoVo) and stomach cancer (BGC-823) cell lines with IC50 values in the range 4.72-13.68 µM compared with the control cis-platin (7.90-15.34 µM).

Tumor-driven like macrophages induced by conditioned media from pancreatic ductal adenocarcinoma promote tumor metastasis via secreting IL-8.

Tumor-associated macrophages (TAMs) are abundant population of inflammatory cells which play an essential role in remodeling tumor microenvironment and tumor progression. Previously, we found the high density of TAMs was correlated with lymph node metastasis and poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Therefore, this study was designed to investigate the mechanisms of interaction between TAMs and PDAC. THP-1 monocytes were the exposure to conditioned media (CM) produced by PDAC cells; then, monocyte recruitment and macrophage differentiation were assessed. CM from PDAC attracted and polarized THP-1 monocytes to tumor-driven like macrophages. mRNA expression cytokine profiling and ELISA identified the IL-8 secretion was increasing in tumor-driven like macrophages, and STAT3 pathway was involved. Addition of exogenous recombinant human IL-8 promoted PDAC cells motility in vitro and metastasis in vivo via upregulating Twist expression, which mediated epithelial-mesenchymal transition in cancer cells. What is more, IL-8 expression level in tumor stroma by immunohistochemical analysis was related to lymph node metastasis, the number of tumor CD68 but not CD163 positive macrophages and patient outcome. Taken together, these findings shed light on the important interplay between cancer cells and TAMs in tumor microenvironment and suggested that IL-8 signaling might be a potential therapeutic target for PDAC.

New Highly Oxygenated Germacranolides from Carpesium divaricatum and their Cytotoxic Activity.

Eight highly oxygenated germacranolides (1-8) including four new ones (2-5) were isolated from the whole plant of Carpesium divaricatum. The planar structures and relative configurations of the new compounds were determined by NMR experiment and HRESIMS data. The absolute configuration of 1 was established by circular dichroism (CD) method and X-ray diffraction, and the stereochemistry of the new compounds 2-5 were determined by similar CD spectra with 1. Compound 2 is the first hydroperoxyl germacrane from the genus Carpesium. The (13)C NMR data of 1, NMR data of 6-7, and their absolute configurations were reported for the first time. Two new compounds (2 and 4) and two known compounds (6 and 8) exhibited potent cytotoxicity against human cervical cancer (HeLa) cells, superior to that of the positive control doxorubicin.

A combination of models for end-stage liver disease and cirrhosis-related complications to predict the prognosis of liver cirrhosis.

BACKGROUND: The Child-Pugh score, the model for end-stage liver disease (MELD) score, and the occurrence of cirrhosis-related complications are independent prognostic predictors used in the assessment of chronic liver diseases. OBJECTIVES: The objectives of this study were to determine the best prognostic scoring system, and to create a combined method to predict the prognosis of liver cirrhosis more accurately. METHODS: We retrospectively reviewed 435 cirrhotic patients from January 2009 to June 2010 and evaluated their short- and medium-term survival. Child-Pugh, MELD and its advanced scoring systems were computed for each patient. The sensitivity and specificity of these scoring systems were analyzed and their validity was assessed using concordance (c)-statistics in predicting the prognosis of cirrhotic patients. RESULTS: Overall, 107 patients died within 6 months and 150 patients died within 1 year. The clinical and biochemical characteristics, cirrhosis-related complications, and the scores were significantly different among the survivors and patients who died. The largest area under the receiver operating characteristic curve was 0.741 for the integrated MELD (iMELD) at 6 months and 0.713 for iMELD at 12 months, indicating that iMELD was the best scoring system tested. Given this result, we created a new scoring system that combined iMELD and an index of cirrhosis-related complications, called iMELD-C. This novel system had c indexes of 0.758 for the 6-month survival and 0.746 for the 1-year survival. CONCLUSIONS: The iMELD-C score is a better predictor of both short- and medium-term survival in patients with cirrhosis.

Anti-diabetic activity and potential mechanism of total flavonoids of Selaginella tamariscina (Beauv.) Spring in rats induced by high fat diet and low dose STZ.

AIM OF THE STUDY: To evaluate the anti-diabetic effects of the total flavonoids of Selaginella tamariscina (Beauv.) Spring (TFST), and to explore the pertinent mechanism. MATERIALS AND METHODS: High fat diet and STZ (35 mg/kg) induced diabetic rats were administered with TFST at graded oral doses (100, 200 and 400mg/kg/day, ig.) for 8 weeks. A range of parameters, including blood glucose and lipid, serum insulin and glucagon, glucose tolerance, were tested to evaluate its anti-diabetic effects. The determination of protein expression of peroxisome proliferator activated receptor γ (PPAR-γ) in adipose tissue and insulin receptor substrate 1 (IRS-1) in hepatic and skeletal muscle tissues was used to study the mechanism of TFST. Moreover, the preliminary study of TFST on the antioxidant activity was performed. RESULTS: The TFST possessed anti-diabetic activities as shown by the decreased serum levels of fast blood glucose (FBG), glycosylated hemoglobulin A1C (HbA1c), triglyceride (TG), total cholesterol (TC), free fatty acid (FFA), low density lipoprotein-cholesterol (LDL-C) and glucagon, as well as increased serum levels of high density lipoprotein-cholesterol (HDL-C), insulin and C-peptide. TFST also improved the oral glucose tolerance test (OGTT) to a certain degree. Furthermore, TFST increased the protein expression of PPAR-γ in adipose tissue, and increased the protein expressions of IRS-1 in hepatic and skeletal muscle tissues. These benefits were associated with increased superoxide dismutase (SOD) and decreased malondialdehyde (MDA) in serum. CONCLUSIONS: TFST exert beneficial effects on hyperglycosemia and hyperlipoidemia in diabetic rats possibly through regulating the levers of PPAR-γ in adipose tissue and IRS-1 in hepatic and skeletal muscle tissues.