p-Cymene Modulates In Vitro and In Vivo Cytokine Production by Inhibiting MAPK and NF-κB Activation

The present study was designed to investigate the effects of p-cymene on lipopolysaccharide (LPS)-induced inflammatory cytokine production both in vitro and in vivo. The production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) in LPS-stimulated RAW 264.7 cells and C57BL/6 mice was evaluated by sandwich ELISA. Meanwhile, the mRNA levels of cytokine genes were examined in vitro by semiquantitative RT-PCR. In a further study, we analyzed the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by western blotting. We found that p-cymene significantly regulated TNF-α, IL-1β, and IL-6 production in LPS-stimulated RAW 264.7 cells. Furthermore, the levels of relative mRNAs were also found to be downregulated. In in vivo trail, p-cymene markedly suppressed the production of TNF-α and IL-1β and increased IL-10 secretion. We also found that p-cymene inhibited LPS-induced activation of extracellular signal receptor-activated kinase 1/2, p38, c-Jun N-terminal kinase, and IκBα. These results suggest that p-cymene may have a potential anti-inflammatory action on cytokine production by blocking NF-κB and MAPK signaling pathways.     

Microbial transformation of asiatic acid by Alternaria longipes

Asiatic acid is a major pentacyclic triterpene isolated from Centella asiatica. It shows a variety of bioactivities. In order to obtain its derivatives, potentially useful for detailed pharmacological studies, the substrate was subjected to incubations with selected micro-organisms. In this work, asiatic acid was converted into three new compounds: 2α,3β,23,30-tetrahydroxyurs-12-ene-28-oic acid (1), 2α,3β,22β,23-tetrahydroxyurs-12-ene-28-oic acid (2), and 2α,3β,22β,23,30-pentahydroxyurs-12-ene-28-oic acid (3) by the fungus Alternaria longipes AS 3.2875. The structures of the three metabolites were determined by 1D and 2D NMR spectral data.     

G3BP1 interacts with YWHAZ to regulate chemoresistance and predict adjuvant chemotherapy benefit in gastric cancer

BACKGROUND A large proportion of gastric cancer patients are susceptible to chemoresistance, while the underlying mechanism remains obscure. Stress granules (SGs) play a self-defence role for tumour cells in inhibiting chemotherapy-induced apoptosis. As an SG assembly effector, G3BP1 (Ras-GTPase-activating protein SH3 domain-binding protein) has been reported to be overexpressed in gastric cancer; thus, here we aim to explore its potent roles in gastric cancer chemoresistance.METHODS Kaplan–Meier analysis was used to compare survival rates in gastric cancer patients with different G3BP1 expression. The influence of G3BP1 on gastric cancer cell chemoresistance and apoptosis were evaluated by in vitro and in vivo approaches. The interaction between G3BP1 and YWHAZ was assessed by immunohistochemistry, immunoprecipitation and immunofluorescence.RESULTS G3BP1 was associated with the poor outcome of gastric cancer patients who received adjuvant chemotherapy. G3BP1 knockdown significantly increased the sensitivity of gastric cancer cells to chemotherapy drugs. Mechanically, cell apoptosis and pro-apoptotic-associated molecules were significantly elevated upon G3BP1 depletion. Gene co-expression network analyses identified YWHAZ as the critical interlayer of G3BP1; as a result, G3BP1 interacted with YWHAZ to sequester Bax into the cytoplasm. Clinically, G3BP1^highYWHAZ^high gastric cancer patients displayed the worst outcome compared with other patients after chemotherapy.CONCLUSIONS The expression of G3BP1 and YWHAZ could predict the adjuvant chemotherapy benefit in gastric cancer patients.Subject terms: Gastric cancer, Cell death     

ACLTOP全自动血凝仪纤维蛋白原两种测定方法的应用比较

目的：比较ACL TOP全自动血凝分析仪上Von Clauss法与PT衍生法（PT-der法）测定纤维蛋白原（FIB）的精密性及其临床应用价值。方法：用Von Clauss法与PT衍生法分别对新鲜混合血浆400例临床样本进行检测。结果：两种方法测定FIB的重复性良好;对临床样本按PT-der法检测结果分阶段做分析,FIB在1.50 g/L~3.50 g/L时,两种方法测定结果相近,差异无统计学意义（P〉0.05）,FIB〈1.50 g/L或FIB〉3.50 g/L时,PT-der法结果偏高,差异有统计学意义（P〈0.05）。结论在ACL TOP全自动血凝分析仪上,当PT-der法测出的FIB值在1.50 g/L~3.50 g/L时,直接报告结果,当PT-der法测出的FIB〈1.50 g/L或FIB值〉3.50 g/L时,以Von Clauss法复查的结果发出报告,两者结合应用可确保工作质量,提高实际工作效益。     

融入“思政元素”的情景教学法在住院医师规范化培训中的应用

目的探讨融入“思政元素”的情景教学法对在肝病科住院医师规范化培训（简称规培）中的应用效果。方法选取进行住院医师规范化培训的学生48人，随机分为两组，试验组采用融入“思政元素”的情景教学法，对照组采用传统教学法，对两组规范化培训学生理论考试、实践技能考核成绩及教学评价满意度进行比较。结果两组学生理论考试成绩无明显差异(P＞0.05）；两组学生临床实践技能得分比较，试验组在接诊患者、临床思维路径分析、医嘱处置、病案书写、医患沟通能力和实践技能总成绩得分均优于对照组(P<0.05)；两组学生教学效果调查问卷比较，试验组在提升学习兴趣、提升自主学习能力、团结协作能力、职业道德素养和总体教学满意度方面得分均明显高于对照组(P<0.05)。结论融入“思政元素”的情景教学法在肝病科住院医师规范化培训中应用，具有良好的效果。     

槲皮素壳聚糖膜对口腔溃疡及创面组织中超氧化物歧化酶和丙二醛含量的影响

背景:以天然可吸收的壳聚糖为膜载体,加入具有抗菌消炎、促进创面愈合的槲皮素制成复合膜,拟通过动物模型对该膜的药理作用进行初步观察。目的:观察槲皮素壳聚糖复合药膜对NaOH所致大鼠口腔溃疡的治疗作用。方法:采用NaOH烧灼法制备SD大鼠口腔溃疡模型80只,随机分为4组,空白对照组不采取任何处理措施,壳聚糖膜组在溃疡处贴壳聚糖膜,复合膜组在溃疡处贴槲皮素与壳聚糖复合药膜,冰硼散组在溃疡处喷洒冰硼散,2次/d,直至溃疡完全愈合为止。另外从上述实验动物中取SD大鼠10只,在大鼠背部脊柱两侧制作全层皮肤缺损模型,创面制作后次日,空白对照组不做任何处理,冰硼散组创面涂抹冰硼散液,壳聚糖组创面涂抹壳聚糖液,复合溶液组创面涂抹槲皮素壳聚糖液,2次/d,连续给药3d。结果与结论:复合膜组各时间点的溃疡面积均小于空白对照组(P<0.01),且给药后第2,4天的溃疡面积也小于冰硼散组(P<0.05)。在溃疡表面感染程度上复合膜组明显好于空白对照组(P<0.01),与冰硼散组之间差异无显著性意义。复合溶液组创面组织中超氧化物歧化酶活力明显高于空白对照组(P<0.01),而丙二醛含量低于空白对照组(P<0.01)。结果可见槲皮素壳聚糖复合药膜可促进溃疡面愈合,这可能与其提高创面组织中超氧化物歧化酶活性,降低丙二醛含量有关。     

KA1表达再分布对神经元兴奋毒性的影响

背景:特异的兴奋性神经递质受体过度活化时便发生细胞的兴奋性中毒,有关NMDA受体和AMPA受体活化致细胞兴奋性中毒死亡通路较为明确,但关于红藻氨酸(Kainate,KA)受体的功能到目前为止仍未明了。目的:探究小鼠海马内注射KA之后KA1受体的再分布状况对中枢神经元兴奋性中毒的影响。方法:成年雄性C57BL6小鼠海马内注射KA或PBS,2h后进行Bederson体征评分、全脑切片免疫组化分析和死亡神经元检测。结果与结论:海马内注射KA2h后,Bederson体征评分表明中枢神经功能出现明显损伤;KA1受体表达的变化主要出现在海马CA1和CA3区,在CA1区的表达上调明显,并开始出现神经元死亡,4~6h后可见大量神经元死亡。结果表明KA促使KA1受体亚单位在海马神经元CA区重新分布,增加神经元对兴奋性氨基酸毒性的敏感性,导致神经细胞死亡,中枢神经功能缺失。     

Analysis of a QX-like avian infectious bronchitis virus genome identified recombination in the region containing the ORF 5a, ORF 5b, and nucleocapsid protein gene sequences

The complete genome of a QX-like infectious bronchitis virus (IBV) strain Sczy3 isolated recently in Sichuan was sequenced. The genome contains 27,695 nucleotides (nt), and possesses a genomic structure similar to other IBV strains. Sequence comparisons demonstrated that the Sczy3 genome had the highest nt sequence identity with QX-like IBVs and was most dissimilar to the Massachusetts type IBV. Differences in the sequences of genes present in the Sczy3 genome and other IBVs gene sequences were also identified. Phylogenic analysis showed that the entire genome and most of the Sczy3 genes were located in the same cluster as LX4. Recombination analysis showed that Sczy3 is a chimeric strain derived from LX4 (major parental sequence) and H120 (minor parental sequence) suggesting that recombination occurred in a region containing the 3′ terminal 5a sequence (83 nt), the 5′ terminal 5b sequence (222 nt), and the 5′ terminal nucleocapsid protein gene sequence (132 nt). Mutations and intergenic recombination may have played an important role in the evolution of IBVs.