The herbal medicine combination of notoginseng-safflower has been commonly used clinically for the prevention and treatment of cardiovascular diseases. A reliable liquid chromatography-tandem mass ...spectrometry (LC⁻MS/MS) method was developed for simultaneous determination of six bioactive components (hydroxysafflor yellow A, notoginsenoide R1, ginsenoside Rb1, Re, Rd, and Rg1) in rat urine and feces after oral administration of notoginseng total saponins (NS), safflower total flavonoids (SF), and the combination of NS and SF (CNS). The chromatographic separation was achieved on a Waters HSS T3 column under gradient elution with acetonitrile and water containing formic acid as the mobile phase. The calibration curves were linear, with correlation coefficient (
) > 0.99 for six components. The intra- and interday precision (RSD) and accuracy (RE) of QC samples were within -14.9% and 14.9%, respectively. The method was successfully applied to study of the urinary and fecal excretion of six bioactive constituents following oral administration of NS, SF, and CNS in rats. Compared to the single herb, the cumulative excretion ratios of six constituents were decreased in the herbal combination. The study indicated that the combination of notoginseng and safflower could reduce the renal and fecal excretion of the major bioactive constituents and promote their absorption in rats.
A chemical synthesis of a unique nanosaccharide fragment from Helicobacter pylori lipopolysaccharide was achieved via a convergent glycosylation method. Challenges involved in the synthesis include ...the highly stereoselective construction of β-3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) and two 1,2-cis-glycosidic linkages, as well as the formation of a branched 2,7-disubstituted heptose subunit. Hydrogen-bond mediated aglycone delivery strategy and benzoyl-directing remote participation effect were employed, respectively, for the efficient generation of the desired β-Kdo glycoside and 1,2-cis-α-l-fucoside/d-glucoside. Moreover, the key branched framework was successfully established through a (7 + 1) + 1 assembly approach involving the stepwise glycosylation of the heptasaccharide alcohol with two monosaccharide donors. The synthesized 1 containing a propylamine linker at the reducing end can be covalently bound to a carrier protein for further immunological studies.
An expedient synthesis of the nonreducing hexasaccharide fragment of axinelloside A has been completed via a linear stepwise glycosylation approach. Challenges involved in the synthesis include the ...highly stereoselective construction of five consecutive 1,2-cis-glycosidic linkages and the formation of a sterically crowded 2,3-disubstituted l-fucoside subunit. Protecting group-directing glycosylation strategies such as the remote participation effect of the benzoyl substituent and the stereocontrolling effect of the 4,6-O-benzylidene group were employed for the synthesis of the desired 1,2-cis-glycosidic linkages. Moreover, the 2,3-branched l-fucoside framework was established through a 3-O and then 2-O glycosylation sequence in which the 3-hydroxyl group of the core l-fucose unit was glycosylated first and then the 2-hydroxyl. The synthetic hexasaccharide is properly protected, so it can be employed as a precursor to synthesize its natural form.
The first total synthesis of a major component of marine glycolipid vesparioside B (Scheme , 1, R1 = n-C22H45, R2 = n-C14H29) has been accomplished through a convergent 4 + 3 coupling strategy. Key ...steps included stereoselective installment of a set of challenging 1,2-cis-glycoside bonds. A 2-quinolinecarbonyl-assisted α-galactosylation and a novel β-arabinosylation were developed, respectively, to synthesize the α-galactofuranosidic and the β-arabinopyranosidic linkages. Furthermore, a 4,6-O-benzylidene-controlled α-galactopyranosylation reaction allowed the efficient connection of the left tetrasaccharide donor 2 with the right disaccharide lipid acceptor 3, hence leading to the total synthesis of 1.
Recent evidence indicates that long noncoding RNAs (lncRNAs) play a critical role in the regulation of cellular processes, such as differentiation, proliferation and metastasis. These lncRNAs are ...found to be dysregulated in a variety of cancers. BRAF activated non-coding RNA (BANCR) is a 693-bp transcript on chromosome 9 with a potential functional role in melanoma cell migration. The clinical significance of BANCR, and its' molecular mechanisms controlling cancer cell migration and metastasis are unclear.
Expression of BANCR was analyzed in 113 non-small cell lung cancer (NSCLC) tissues and seven NSCLC cell lines using quantitative polymerase chain reaction (qPCR) assays. Gain and loss of function approaches were used to investigate the biological role of BANCR in NSCLC cells. The effects of BANCR on cell viability were evaluated by MTT and colony formation assays. Apoptosis was evaluated by Hoechst staining and flow cytometry. Nude mice were used to examine the effects of BANCR on tumor cell metastasis in vivo. Protein levels of BANCR targets were determined by western blotting and fluorescent immunohistochemistry.
BANCR expression was significantly decreased in 113 NSCLC tumor tissues compared with normal tissues. Additionally, reduced BANCR expression was associated with larger tumor size, advanced pathological stage, metastasis distance, and shorter overall survival of NSCLC patients. Reduced BANCR expression was found to be an independent prognostic factor for NSCLC. Histone deacetylation was involved in the downregulation of BANCR in NSCLC cells. Ectopic expression of BANCR impaired cell viability and invasion, leading to the inhibition of metastasis in vitro and in vivo. However, knockdown of BANCR expression promoted cell migration and invasion in vitro. Overexpression of BANCR was found to play a key role in epithelial-mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin and Vimentin expression.
We determined that BANCR actively functions as a regulator of EMT during NSCLC metastasis, suggesting that BANCR could be a biomarker for poor prognosis of NSCLC.
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•A approach to the construction of aryl 1,2-cis-furanosidic bonds is developed.•Aryl 1,2-cis-furanosides are synthesized using Quin-substituted thiofuranosides.•The method is ...demonstrated by preparation of the sugar portion of hygromycin A.
An efficient methodology for the synthesis of aryl 1,2-cis-furanosidic linkages has been developed with 2-quinolinecarbonyl (Quin) group substituted furanose ethyl thioglycosides as glycosyl donors. The method permits a wide range of phenol acceptors to be used, thus resulting in the formation of structurally diverse phenol furanosides in good to excellent chemical yields with complete 1,2-cis anomeric selectivity. The synthetic utility of the approach has been demonstrated by concise preparation of the carbohydrate portion of antibiotic hygromycin A.
Bcl-xL is a pro-survival member of the Bcl-2 family that plays indispensable roles in regulating cell survival and apoptosis. It is overexpressed in many malignant tumors including colorectal cancer ...(CRC). However, it is still unclear if Bcl-xL can be used as an independent molecular marker for predicting the prognosis of CRC patients. In this study, reverse transcription-PCR assay was performed to detect the expression of Bcl-xL mRNA in CRC and corresponding non-tumor colon tissues. Immunohistochemistry was performed to detect the immunolocalization of Bcl-xL protein in sixty-eight primary CRC tissue samples. The association between Bcl-xL protein expression and clinicopathological factors of CRC patients was analyzed and the survival was assessed by the Kaplan-Meier method and proportional hazards model. The averaged level of Bcl-xL mRNA expression in CRC tissues (0.85±0.13) was significantly higher than that in non-tumor colon tissues (0.08±0.02). Immunohistochemical staining showed that the Bcl-xL protein was mainly located in the cytoplasm of tumor cells. The level of Bcl-xL protein expression was closely correlated with tumor differentiation (P=0.002), lymph node metastasis (P=0.010), venous permeation (P=0.004), and Duke's classification (P=0.021). Furthermore, patients with high Bcl-xL expression showed poorer overall survival than those with low Bcl-xL expression (P=0.016). Univariate and multivariate analysis indicated that the status of Bcl-xL protein expression might be an independent prognostic marker for CRC patients (P=0.032). Taken together, immunohistochemical assessment of status of Bcl-xL protein may offer a valuable approach for predicting survival after curative surgery for colorectal cancer.
Fresh water shortages are severally restricting sustainable agriculture development in the North China Plain. The scarcity of fresh water has forced farmers to use brackish water from shallow ...underground sources, which helps to overcome drought and increase crop yields but also increases the risk of soil salinization. To identify safe and effective ways of using brackish water in this region, field experiments were conducted to evaluate the effect of brackish water irrigation and straw mulching on soil salinity and crop yield in a winter wheat–summer maize double cropping system. The experiment was in a split-plot design. Six rates of straw mulching (0, 4.5, 6.0, 7.5, 15.0 and 30.0
Mg/ha) were assigned to the main plots and two irrigation water qualities (i.e. brackish water with salt content of 3.0–5.0
g/L and fresh water with only 1.27
g salt/L) were applied to subplots. The brackish water irrigation significantly increased the salt content at different soil depths in the upper 1
m soil layer during the two growing seasons. Straw mulching affected the vertical distribution of salt in the brackish water irrigation plots and the average salt content of straw mulch treatments (4.5, 6.0, 7.5, 15.0 and 30.0
Mg/ha) within the 0–20, 20–40 and 0–100
cm soil depths was 10.2, 14.0 and 1.8% lower than that without straw mulch (A
0). No salt accumulation occurred to a depth of 1
m in the brackish water irrigation plots and there was no correlation between the value of SAS (salt accumulated in 1
m of soil) and straw mulch rate. In 2000 and 2001, the salt content within the 0–40
cm soil layer in brackish water irrigation plots increased due to high evaporation rates during April–June, and then decreased up to September as salts were leached by rain. For the fresh water irrigation plots, the salt content remained relatively stable. Straw mulching affected the salt content in the 0–40
cm soil layer in brackish water irrigation plots in different periods of 2000 and 2001, but no correlation between salt content and straw mulch rates was observed except in September of 2000. Unlike for wheat, the yield of maize increased as the straw mulch rate increased according to the equation,
y
=
0.1589
x
+
5.3432 (
R
2
=
0.6506). Our results would be helpful in adopting brackish water irrigation and straw mulching in ways that enhance crop yields and reduce the risk of soil salinization. However, long-term effects of brackish water irrigation and straw mulching on soil salinity and crop yield need to be further evaluated for sustainability of the system.
Background The hepatocyte growth factor receptor c-Met and its ligand hepatocyte growth factor (HGF) have been reported to be involved in cellular motility, growth, and invasion by activating ...mitogenic signaling pathways. The overexpression of c-Met gene has been found in many malignant cancers, but the roles of c-Met overexpression in SCLC tumors still remain unclear. The aim of the present study was to explore its roles and potential as a therapeutic target for SCLC. Methods Quantitative real-time RT-PCR and immunohistochemistry assays were performed to detect the expression of c-Met mRNA and protein in SCLC tissue or corresponding non-tumor lung tissue samples. Adenovirus-mediated small interfering RNA (siRNA) was employed to down-regulate the expression of c-Met gene in SCLC cell line (NCI-H446). MTT and colony formation assays were performed to detect in vitro proliferation of NCI-H446 cells. In vitro wound-healing and transwell invasion assays were performed to detect in vitro invasion and metastasis of NCI-H446 cells. Finally, in vivo tumorigenicity and metastasis assays were done to analyze in vivo proliferation and metastasis of NCI-H446 cells in a xenograft model. Results We showed that the levels of c-Met mRNA expression were significantly higher in SCLC tissue samples (0.97 ± 0.08) than those in corresponding non-tumor lung tissue samples (0.21 ± 0.02; P < 0.05). Additionally, the immunostaining of c-Met protein in SCLC tissues was stronger than that in corresponding non-tumor tissues. Adenovirus-mediated siRNA targeting c-Met could significantly down-regulate c-Met expression, and the specific down-regulation of c-Met expression in SCLC cells could strongly inhibit proliferation of SCLC cells both in vitro and in vivo . Moreover, c-Met down-regulation could also reduce invasion capacity in vitro and metastasis capacity in vivo of SCLC cells. Conclusions Taken together, our results indicated that the overexpression of c-Met gene played an important role in the progression and development of SCLC, and adenovirus-mediated siRNA targeting c-Met could potentially be an experimental approach for SCLC gene therapy.
Lipids play roles in membrane structure, energy storage, and signal transduction as well as in human cancers. Here we adopt lipidomics to identify plasma lipid markers for early screening and ...detection of lung cancer.
Using mass spectrometry, we profiled 390 individual lipids using training and validation strategy in a total of 346 plasma samples from 199 early NSCLC patients, including 113 adenocacinoma and 86 squamous cell cancers (SqCC), and from 147 healthy controls.
In the training stage, we found distinct lipid groups that were significantly distributed between NSCLC cases and healthy controls. We further defined a panel of four lipid markers (LPE(18:1), ePE(40:4), C(18:2)CE and SM(22:0)) for prediction of early cancer with a accuracy of 82.3% AUC (Area under ROC curve), sensitivity of 81.9% and specificity of 70.7% at the training stage and yielded the predictive power with accuracy (AUC,80.8%), sensitivity 78.7%, specificity 69.4% and in the validation stage.
Using lipidomics we identified several lipid markers capable of discerning early stage lung carcinoma from healthy individuals, which might be further developed as a quick, safe blood test for early diagnosis of this disease.
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