不同病理分期肺腺癌患者血清代谢组学研究

肺癌是当今世界最常见的恶性肿瘤之一,其新发率和死亡率多年来都居于各类癌症之首,其中85%的肺癌都是非小细胞癌,而腺癌又是最常见的非小细胞癌。肺癌的高隐匿性是造成其高死亡率的最主要原因,因此为肺癌的早期诊断和病理分期寻求高效可靠的方法是十分必要的。代谢组学揭示了小分子代谢物的一系列变化,反映了生命活动的最终状态,因此也能直接反映疾病不同发展阶段的病理生理变化。本研究利用核磁共振氢谱(1H-NMR),对在我院就诊的27例不同病理分期的肺腺癌患者和13例健康志愿者进行了血清代谢物分析,运用正交偏最小二乘判别分析(OPLS-DA)对1H-NMR数据进行建模,单变量统计分析对模型进行评价。结果表明肺腺癌患者组的血清中有14种代谢物出现明显差异,其中丙酮酸、丙氨酸、NAC1、乳酸、GPC和甘氨酸比起对照组来有显著上升,而葡萄糖、谷氨酰胺、亮氨酸、异亮氨酸、缬氨酸、丙酮、乙酰乙酸和苏氨酸则显著下降。而在不同分期肺腺癌患者间进行比较后发现,异亮氨酸、乙酰乙酸、NAC1和乳酸的变化与肺腺癌的发展有相关性,可能是肺腺癌早期诊断和分期的潜在生物标志物。     

The use of SARS-CoV-2-related coronaviruses from bats and pangolins to polarize mutations in SARS-Cov-2

正Dear Editor,The coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 coronavirus has become a global pandemic.The SARS-CoV-2 genome has a similarity of 96.2%to that of RaTG13, a bat SARS-CoV-2-related coronavirus detected in Rhinolophus affinis (Paraskevis et al., 2020; Zhou et al.,2020). The SARS-CoV-2 genome also has 85.5%-92.4%     

Rice stripe virus coat protein induces the accumulation of jasmonic acid,activating plant defence against the virus while also attracting its vector to feed

The jasmonic acid (JA) pathway plays crucial roles in plant defence against pathogens and herbivores. Rice stripe virus (RSV) is the type member of the genus Tenuivirus. It is transmitted by the small brown planthopper (SBPH) and causes damaging epidemics in East Asia. The role(s) that JA may play in the tripartite interaction against RSV, its host, and vector are poorly understood. Here, we found that the JA pathway was induced by RSV infection and played a defence role against RSV. The coat protein (CP) was the major viral component responsible for inducing the JA pathway. Methyl jasmonate treatment attracted SBPHs to feed on rice plants while a JA-deficient mutant was less attractive than wild-type rice. SBPHs showed an obvious preference for feeding on transgenic rice lines expressing RSV CP. Our results demonstrate that CP is an inducer of the JA pathway that activates plant defence against RSV while also attracting SBPHs to feed and benefitting viral transmission. This is the first report of the function of JA in the tripartite interaction between RSV, its host, and its vector.     

Streptococcus pneumoniae aminopeptidase N contributes to bacterial virulence and elicits a strong innate immune response through MAPK and PI3K/AKT signaling

Streptococcus pneumoniae is a Gram-positive pathogen with high morbidity and mortality globally but some of its pathogenesis remains unknown. Previous research has provided evidence that aminopeptidase N (PepN) is most likely a virulence factor of S. pneumoniae. However, its role in S. pneumoniae virulence and its interaction with the host remains to be confirmed. We generated a pepN gene deficient mutant strain and found that its virulence for mice was significantly attenuated as were in vitro adhesion and invasion of host cells. The PepN protein could induce a strong innate immune response in vivo and in vitro and induced secretion of IL-6 and TNF-α by primary peritoneal macrophages via the rapid phosphorylation of MAPK and PI3K/AKT signaling pathways and this was confirmed using specific pathway inhibitors. In conclusion, PepN is a novel virulence factor that is essential for the virulence of S. pneumoniae and induces host innate immunity via MAPK and PI3K/AKT signaling.

     

Global Profiling of Alternative Splicing in Callus Induction of Immature Maize Embryo

In Vitro Cellular & Developmental Biology - Plant - Callus induction in plants is similar to pluripotent stem cell induction in animals and can incite global changes in gene expression....     

Platelet‐rich plasma inhibits osteoblast apoptosis and actin cytoskeleton disruption induced by gingipains through upregulating integrin β1

The aim of this study was to explore the effects of platelet‐rich plasma on gingipain‐caused changes in cell morphology and apoptosis of osteoblasts. Mouse osteoblasts MC3T3‐E1 cells were treated with gingipain extracts from Porphyromonas gingivalis in the presence or absence of platelet‐rich plasma. Apoptosis was detected with terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling staining. F‐actin was determined by phalloidin‐fluorescent staining and observed under confocal microscopy. Western blot analysis was used to detect integrin β1, F‐actin, and G‐actin protein expressions. A knocking down approach was used to determine the role of integrin β1. The platelet‐rich plasma protected osteoblasts from gingipain‐induced apoptosis in a dose‐dependent manner, accompanied by upregulation of integrin β1. Platelet‐rich plasma reversed the loss of F‐actin integrity and decrease of F‐actin/G‐actin ratio in osteoblasts in the presence of gingipains. By contrast, the effects of platelet‐rich plasma were abrogated by knockdown of integrin β1. The platelet‐rich plasma failed to reduce cell apoptosis and reorganize the cytoskeleton after knockdown of integrin β1. In conclusion, platelet‐rich plasma inhibits gingipain‐induced osteoblast apoptosis and actin cytoskeleton disruption by upregulating integrin β1 expression.     

Substrate binding to Src: A new perspective on tyrosine kinase substrate recognition from NMR and molecular dynamics

Most signal transduction pathways in humans are regulated by protein kinases through phosphorylation of their protein substrates. Typical eukaryotic protein kinases are of two major types: those that phosphorylate‐specific sequences containing tyrosine (~90 kinases) and those that phosphorylate either serine or threonine (~395 kinases). The highly conserved catalytic domain of protein kinases comprises a smaller N lobe and a larger C lobe separated by a cleft region lined by the activation loop. Prior studies find that protein tyrosine kinases recognize peptide substrates by binding the polypeptide chain along the C‐lobe on one side of the activation loop, while serine/threonine kinases bind their substrates in the cleft and on the side of the activation loop opposite to that of the tyrosine kinases. Substrate binding structural studies have been limited to four families of the tyrosine kinase group, and did not include Src tyrosine kinases. We examined peptide‐substrate binding to Src using paramagnetic‐relaxation‐enhancement NMR combined with molecular dynamics simulations. The results suggest Src tyrosine kinase can bind substrate positioning residues C‐terminal to the phosphoacceptor residue in an orientation similar to serine/threonine kinases, and unlike other tyrosine kinases. Mutagenesis corroborates this new perspective on tyrosine kinase substrate recognition. Rather than an evolutionary split between tyrosine and serine/threonine kinases, a change in substrate recognition may have occurred within the TK group of the human kinome. Protein tyrosine kinases have long been therapeutic targets, but many marketed drugs have deleterious off‐target effects. More accurate knowledge of substrate interactions of tyrosine kinases has the potential for improving drug selectivity.