Silibinin inhibits cell invasion through inactivation of both PI3K-Akt and MAPK signaling pathways

Silibinin, isolated from Silybum marianum, has been known for its hepatoprotective properties and recent studies have revealed its antiproliferative and apoptotic effects on several cancer cells. An inhibitory effect of silibinin on tumor invasion and matrix metalloproteinase-2 (MMP-2) and urokinasetype plasminogen activator (u-PA) activities in culture medium has been observed in our previous study and the impacts of silibinin on enzyme activities of MMPs, u-PA, mitogen-activated protein kinase (MAPK) and Akt in A549 cells were continued to explore in this study. Our results showed that silibinin exerted an inhibitory effect on the phosphorylation of Akt, as well as extracellular signal-regulated kinases 1 and 2 (ERK1/2), which are the members of the MAPK family involved in the up-regulation of MMPs or u-PA, while no effects on the activities of p38(MAPK) and stress-activated protein kinase/c-Jun N-terminal kinase were observed. A treatment with silibinin to A549 cells also led to a dose-dependent inhibition on the activation of NF-kappaB, c-Jun and c-Fos. Additionally, the treatment of inhibitors specific for MEK (U0126) or PI3K (LY294002) to A549 cells could result in a reduced expression of MMP-2 and u-PA concomitantly with a marked inhibition on cell invasion. These findings suggested that the inhibition on MMP-2 and u-PA expression by silibinin may be through a suppression on ERK1/2 or Akt phosphorylation, which in turn led to the reduced invasiness of the cancer cells.     

Abnormal Organization of White Matter Network in Patients with No Dementia after Ischemic Stroke

Structural changes after ischemic stroke could affect information communication extensively in the brain network. It is likely that the defects in the white matter (WM) network play a key role in information interchange. In this study, we used graph theoretical analysis to examine potential organization alteration in the WM network architecture derived from diffusion tensor images from subjects with no dementia and experienced stroke in the past 5.4–14.8 months (N = 47, Mini-Mental Screening Examination, MMSE range 18–30), compared with a normal control group with 44 age and gender-matched healthy volunteers (MMSE range 26–30). Region-wise connectivity was derived from fiber connection density of 90 different cortical and subcortical parcellations across the whole brain. Both normal controls and patients with chronic stroke exhibited efficient small-world properties in their WM structural networks. Compared with normal controls, topological efficiency was basically unaltered in the patients with chronic stroke, as reflected by unchanged local and global clustering coefficient, characteristic path length, and regional efficiency. No significant difference in hub distribution was found between normal control and patient groups. Patients with chronic stroke, however, were found to have reduced betweenness centrality and predominantly located in the orbitofrontal cortex, whereas increased betweenness centrality and vulnerability were observed in parietal-occipital cortex. The National Institutes of Health Stroke Scale (NIHSS) score of patient is correlated with the betweenness centrality of right pallidum and local clustering coefficient of left superior occipital gyrus. Our findings suggest that patients with chronic stroke still exhibit efficient small-world organization and unaltered topological efficiency, with altered topology at orbitofrontal cortex and parietal-occipital cortex in the overall structural network. Findings from this study could help in understanding the mechanism of cognitive impairment and functional compensation occurred in patients with chronic stroke.     

肺部微生物组通过炎症反应介导慢性阻塞性肺疾病转化为肺癌的研究进展

肺部微生物组存在于呼吸道和实质组织中,通过菌群紊乱、代谢产物、炎症反应、免疫反应、基因毒性等方面介导肺部损伤。随着肺部微生物组的深入研究,发现肺部微生物组的相关活动与慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)和肺癌息息相关,能够促使COPD向肺癌的转变。本文主要介绍了肺部微生物组稳态及其通过炎症反应导致COPD和肺癌,重点探讨了肺部微生物组如何通过炎症反应介导COPD转化为肺癌,以期为COPD和肺癌的临床预防、优化治疗以及新型药物设计提供新的理论依据。     

油菜饼的黄酮成分研究

从油茶饼正丁醇提取物中分离到两个黄酮甙,经UV、~1H NMR、~(13)C NMR、EI-MS、FAB-MS等仪器分析,鉴定为山奈酚-3-O-葡萄吡喃糖基(6→1)鼠李吡喃糖甙(1)和山奈酚-3-O-葡萄吡喃糖基-[(2→1)葡萄吡喃糖基](6→1)鼠李吡喃糖甙(2)。正丁醇提取物以酸水解亦分离到山奈酚(4)。油茶饼正丁醇提取物中还分离到蔗糖,得率达2.3％。     

Screening and production of erythritol by newly isolated osmophilic yeast-like fungi

Twenty-eight erythritol-producing strains were isolated from pollen, honey and high sugar food samples collected in Taiwan. Amongst these, six strains (166-2, 262-1, 278-3, 440, 441 and 442) were high erythritol-producers with a yield higher than 30% for 30% glucose. The erythritol productivity of these strains ranged from 90.9 to 116.4 g l⁻¹. ¹H- and ¹³C-NMR analyses confirmed that the fermentation product was erythritol. The results of morphological and physiological studies indicate that strains 166-2, 262-1, 278-3, 440, and 442 may be members of the genus Moniliella. More studies are required to determine the taxonomic position of strain 441. The use of a medium containing 30% glucose and 1% yeast extract gave the highest erythritol productivity. On batch fermentation in a 5-l fermentor using strain 166-2, a maximal erythritol productivity of 111.0 g l⁻¹ was obtained after cultivation for 144 h.     

Detection and phylogenetic profiling of nodavirus associated with white tail disease in Malaysian <Emphasis Type="Italic">Macrobrachium rosenbergii</Emphasis> de Man

White tail disease (WTD) is a serious viral disease in the hatcheries and nursery ponds of Macrobrachium rosenbergii in many parts of the world. A new disease similar to WTD was observed in larvae and post larvae of M. rosenbergii cultured in Malaysia. In the present study, RT-PCR assay was used to detect the causative agents of WTD, M. rosenbergii nodavirus (MrNV) and extra small virus (XSV) using specific primers for MrNV RNA2 and XSV. The results showed the presence of MrNV in the samples with or without signs of WTD. However, XSV was only detected in some of the MrNV-positive samples. Phylogenetic analysis showed that the RNA2 of our Malaysian isolates were significantly different from the other isolates. Histopathological studies revealed myofiber degeneration of the tail muscles and liquefactive myopathy in the infected prawns. This was the first report on the occurrence of MrNV in the Malaysian freshwater prawn.     

Tagging SNPs in the ERCC4 gene are associated with gastric cancer risk

ERCC4 plays an essential role in the nucleotide excision repair (NER) pathway, which is involved in the removal of a wide variety of DNA lesions. To determine whether the ERCC4 tagging SNPs (tSNPs) are associated with risk of gastric cancer, we conducted a hospital-based case-control study of 350 cases and 468 cancer-free controls. In the logistic regression (LR) analysis, we found a significantly decreased risk of gastric cancer associated with the rs744154 GC/CC genotypes [adjusted odds ratio (OR) = 0.56, 95% confidence interval (CI) = 0.42–0.75, false discovery rate (FDR) P = 0.003] compared with the wild-type GG genotype. Haplotype-based association study revealed that the CGC haplotype that containing the rs744154 C allele can decrease the risk of gastric cancer compared with the most common haplotype GGT (adjusted OR = 0.61, 95% CI = 0.46–0.81). Using the multifactor dimensionality reduction (MDR) analysis, we identified that the SNP rs744154 and smoking status were the best two predictive factors for gastric cancer with a testing accuracy of 55.76% and a perfect cross-validation consistency (CVC) of 10 (P = 0.001). Furthermore, the smokers with the rs744154 GC/CC genotypes showed a decreased risk of gastric cancer (adjusted OR = 0.55, 95% CI = 0.35–0.85) compared with the smokers with the GG genotype using multivariate LR analysis. The above findings consistently suggested that genetic variants in the ERCC4 gene may play a protective role in the etiology of gastric cancer, even in the smokers.     

Stimulation of smooth muscle cell proliferation by ox-LDL- and acetyl LDL-induced macrophage-derived foam cells.

To test the hypothesis that LDL lacking of initial oxidation may also anticipate an essential role in the progression for atherosclerotic lesions, we studied the in vitro effect of foam cells induced by low density lipoprotein (LDL), oxidized (ox)-LDL or acetyl-LDL on smooth muscle cell (SMC) proliferation. Intraperitoneal macrophages collected from ICR mice were incubated with buffered saline LDL, ox-LDL or acetyl-LDL to induce foam cell formation. Porcine aortas with atherosclerotic lesions were collected from 5 pigs fed high cholesterol diets. The results indicate that foam cells induced by ox-LDL and acetyl-LDL, but not by LDL, promoted SMC proliferation. SMC proliferation was also increased by ruptured, ox-LDL- and acetyl-LDL- induced foam cells. Immunohistochemically, epitopes of the LDL, ox-LDL, and malondialdelyde (MDA)-LDL were present in atherosclerotic lesions, but the acetyl epitope was not. We suggest that foam cells, whether induced by the oxidized or acetyl or acetyl (unoxidized) form, play an essential role in the pathogenesis of atherosclerosis by stimulating SMC proliferation.     

The Effect of Multiple Evolutionary Selections on Synonymous Codon Usage of Genes in the Mycoplasma bovis Genome

Mycoplasma bovis is a major pathogen causing arthritis, respiratory disease and mastitis in cattle. A better understanding of its genetic features and evolution might represent evidences of surviving host environments. In this study, multiple factors influencing synonymous codon usage patterns in M. bovis (three strains’ genomes) were analyzed. The overall nucleotide content of genes in the M. bovis genome is AT-rich. Although the G and C contents at the third codon position of genes in the leading strand differ from those in the lagging strand (p<0.05), the 59 synonymous codon usage patterns of genes in the leading strand are highly similar to those in the lagging strand. The over-represented codons and the under-represented codons were identified. A comparison of the synonymous codon usage pattern of M. bovis and cattle (susceptible host) indicated the independent formation of synonymous codon usage of M. bovis. Principal component analysis revealed that (i) strand-specific mutational bias fails to affect the synonymous codon usage pattern in the leading and lagging strands, (ii) mutation pressure from nucleotide content plays a role in shaping the overall codon usage, and (iii) the major trend of synonymous codon usage has a significant correlation with the gene expression level that is estimated by the codon adaptation index. The plot of the effective number of codons against the G+C content at the third codon position also reveals that mutation pressure undoubtedly contributes to the synonymous codon usage pattern of M. bovis. Additionally, the formation of the overall codon usage is determined by certain evolutionary selections for gene function classification (30S protein, 50S protein, transposase, membrane protein, and lipoprotein) and translation elongation region of genes in M. bovis. The information could be helpful in further investigations of evolutionary mechanisms of the Mycoplasma family and heterologous expression of its functionally important proteins.