Ginkgolide K potentiates the protective effect of ketamine against intestinal ischemia/reperfusion injury by modulating NF-κB/ERK/JNK signaling pathway

Purpose: To investigate the effect of ginkgolide K and ketamine treatments, alone and in combination, on intestinal  ischemia/reperfusion injury (I/R)-induced injury in rats, as well as the mechanism involved. Methods: Rats were treated with ginkgolide K (GK, 15 mg/kg i.v) and ketamine (KTM, 100 mg/kg i.p.), either alone or in combination 30 min before the induction of intestinal I/R. The effects of GK and KTM were determined by assessing the levels of cytokines in serum, and parameters of oxidative stress and ROS production in the intestinal tissues of I/R rats. Moreover, intestinal mRNA expressions of JNK, ERK, p38 and NF-kB were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: GK and KTM treatments, alone and in combination, reduced cytokine levels in serum and oxidative stress parameters in intestinal tissues, when compared to I/R group of rats. Treatments with GK and KTM, alone and in combination, mitigated the altered mRNA expressions of JNK, ERK, p38 and NF-kB in intestinal tissues of I/R-injured rats. Conclusion: These results reveal that GK potentiates the protective effect of KTM100 on I/R-induced intestinal injury in rats by regulating the NF-kB/ERK/JNK signaling pathway. Therefore, GK and KTM may find use in the management of I/R Keywords: Ginkgolide K, Ketamine, Intestinal injury, Ischemia/Reperfusion, Inflammatio

The Bcl-2/xL inhibitor ABT-263 increases the stability of Mcl-1 mRNA and protein in hepatocellular carcinoma cells

Background Hepatocellular carcinoma (HCC) is one of the major causes of mortality. ABT-263 is a newly synthesized, orally available Bcl-2/xL inhibitor that shows promising efficacy in HCC therapy. ABT-263 inhibits the anti-apoptotic activity of Bcl-2 and Bcl-xL, but not Mcl-1. Previous reports have shown that ABT-263 upregulates Mcl-1 in various cancer cells, which contributes to ABT-263 resistance in cancer therapy. However, the associated mechanisms are not well known. Methods Western blot, RNAi and CCK-8 assays were used to investigate the relationship between Mcl-1 upregulation and ABT-263 sensitivity in HCC cells. Real-time PCR and Western blot were used to detect Mcl-1 mRNA and protein levels. Luciferase reporter assay and RNA synthesis inhibition assay were adopted to analyze the mechanism of Mcl-1 mRNA upregulation. Western blot and the inhibition assays for protein synthesis and proteasome were used to explore the mechanisms of ABT-263-enhanced Mcl-1 protein stability. Trypan blue exclusion assay and flow cytometry were used to examine cell death and apoptosis. Results ABT-263 upregulated Mcl-1 mRNA and protein levels in HCC cells, which contributes to ABT-263 resistance. ABT-263 increased the mRNA level of Mcl-1 in HCC cells by enhancing the mRNA stability without influencing its transcription. Furthermore, ABT-263 increased the protein stability of Mcl-1 through promoting ERK- and JNK-induced phosphorylation of Mcl-1Thr163 and increasing the Akt-mediated inactivation of GSK-3β. Additionally, the inhibitors of ERK, JNK or Akt sensitized ABT-263-induced apoptosis in HCC cells. Conclusions ABT-263 increases Mcl-1 stability at both mRNA and protein levels in HCC cells. Inhibition of ERK, JNK or Akt activity sensitizes ABT-263-induced apoptosis. This study may provide novel insights into the Bcl-2-targeted cancer therapeutics.This study was supported in part by Chongqing Natural Science Foundation (cstc2011BB5030 and 2013jjB10015), the National Natural Science Foundation of China (31201068, 81273226 and 81228005) and the Scientific Funds of Third Military Medical University (2011XHG02 and 2012XZH01)

Perception and the potential of traditional chinese medicine.

This project examines people's perception of traditional chinese medicine in relation to the recent developments within the chinese medicine industry

A strategy of synergistically using ether oxygen and phenolic hydroxyl groups for Ultra-High selective and fast Cs+ isolation

Hypercrosslinked polymers (HCPs) with synergistic effect of ether oxygen and phenolic hydroxyl groups was designed and fabricated for Cs+ isolation in the salt lake system. The separation factors (S.F.)(Cs+/K+) of the adsorbents were significantly increased through regulating the content of the ether oxygen group in the frameworks. The S.F. of PO-HCPs-6 was increased by nearly 5 times to an ultra-high value (S.F. = 57) compared with the Cs+ adsorbents reported in the literature. Moreover, the mild and sufficient polymerization process endowed PO-HCPs-6 with an extremely fast kinetic adsorption rate. PO-HCPs-6 could quickly reach 90% of the equilibrium adsorption capacity in just 1 min. Finally, after 5 times adsorption-desorption experiments, the remarkable elution rate (> 92%) and reusability adsorption capacity (> 91%) of PO-HCPs-6 proved it has inspiring application potential for the Cs+ isolation in the salt lake brine system

Leaf Senescence, Root Morphology, and Seed Yield of Winter Oilseed Rape (Brassica napus L.) at Varying Plant Densities

In this study, the yield and yield components were studied using a conventional variety Zhongshuang 11 (ZS 11) and a hybrid variety Zhongyouza 12 (ZYZ 12) at varying plant densities. The increase in plant density led to an initial increase in seed yield and pod numbers per unit area, followed by a decrease. The optimal plant density was 58.5 × 104 plants ha−1 in both ZS 11 and ZYZ 12. The further researches on physiological traits showed a rapid decrease in the green leaf area index (GLAI) and chlorophyll content and a remarkable increase in malondialdehyde content in high plant density (HPD) population than did the low plant density (LPD) population, which indicated the rapid leaf senescence. However, HPD had higher values in terms of pod area index (PAI), pod photosynthesis, and radiation use efficiency (RUE) after peak anthesis. A significantly higher level of dry matter accumulation and nitrogen utilization efficiency were observed, which resulted in higher yield. HPD resulted in a rapid decrease in root morphological parameters (root length, root tips, root surface area, and root volume). These results suggested that increasing the plant density within a certain range was a promising option for high seed yield in winter rapeseed in China

Haplotype and genotype distributions in patient and control cohorts.

<p>Ref: used as reference values. OR^C: Crude Odds Ratio; OR^a: Odds Ratio adjusted by logic regression based on age, gender, smoking, and drinking status; 95% CI: 95% confidence interval.</p><p>Haplotype and genotype distributions in patient and control cohorts.</p

Genetic polymorphisms in ZFHX3 are associated with atrial fibrillation in a Chinese Han population.

The gene zinc finger homeobox 3 (ZFHX3) encodes a transcription factor with cardiac expression and its genetic variants are associated with atrial fibrillation (AF). We aimed to explore the associations between single nucleotide polymorphisms (SNPs) of ZFHX3 and the risk of AF in a Chinese Han population.We genotyped eight SNPs, including seven potentially functional SNPs and one previously reported SNP by using the middle-throughput iPLEX Sequenom MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in logistic regression models.We enrolled a total of 1,593 Chinese Han origin individuals in the study, including 597 AF patients and 996 non-AF controls. Logistic regression analyses revealed that potentially functional SNPs rs6499600 and rs16971436 were associated with a decreased risk of AF (adjusted OR  = 0.73, 95% CI: 0.63-0.86, P = 1.07×10-4; adjusted OR  = 0.74, 95% CI: 0.56-0.98, P = 0.039, respectively). In addition, rs2106261 showed a robust association with an increased risk of AF (adjusted OR  = 1.71, 95% CI: 1.46-2.00, P = 1.85×10-11). After multiple comparisons, rs16971436 conferred a borderline significant association with the risk of AF. Stratification analysis indicated that the risks of AF were statistically different among subgroups of age for rs2106261, and the effect for rs16971436 was more evident in subgroups of patients with coronary artery disease.In summary, our study investigated the role of genetic variants of ZFHX3 in AF and two SNPs (rs2106261, rs6499600) showed significant associations while rs16971436 conferred a borderline significant association with AF risk in Chinese Han populations. However, further large and functional studies are warranted to confirm our findings

PCR primer sequences for SNP amplification and extension.

<p>F  =  Forward; R  =  Reverse; E  =  Extension.</p><p>PCR primer sequences for SNP amplification and extension.</p