[Pathogenesis of Secondary Pulmonary Tuberculosis and Role of Cord Factor in Secondary Infection].

The primary and secondary tuberculosis features two completely different pathogenesis.At present,the pathogenesis of primary tuberculosis has been clear,whereas that of secondary tuberculosis remains unclear.In order to decipher the mechanism of secondary infection of Mycobacterium tuberculosis and provide insights into vaccine research and drug development,this paper reviews the problems of the widely accepted mechanism of secondary infection,the new findings of the research on the mechanism,as well as the role of cord factors.

CEBPD is a master transcriptional factor for hypoxia regulated proteins in glioblastoma and augments hypoxia induced invasion through extracellular matrix-integrin mediated EGFR/PI3K pathway.

Hypoxia contributes to the initiation and progression of glioblastoma by regulating a cohort of genes called hypoxia-regulated genes (HRGs) which form a complex molecular interacting network (HRG-MINW). Transcription factors (TFs) often play central roles for MINW. The key TFs for hypoxia induced reactions were explored using proteomic analysis to identify a set of hypoxia-regulated proteins (HRPs) in GBM cells. Next, systematic TF analysis identified CEBPD as a top TF that regulates the greatest number of HRPs and HRGs. Clinical sample and public database analysis revealed that CEBPD is significantly up-regulated in GBM, high levels of CEBPD predict poor prognosis. In addition, CEBPD is highly expressed in hypoxic condition both in GBM tissue and cell lines. For molecular mechanisms, HIF1α and HIF2α can activate the CEBPD promotor. In vitro and in vivo experiments demonstrated that CEBPD knockdown impaired the invasion and growth capacity of GBM cells, especially in hypoxia condition. Next, proteomic analysis identified that CEBPD target proteins are mainly involved in the EGFR/PI3K pathway and extracellular matrix (ECM) functions. WB assays revealed that CEBPD significantly positively regulated EGFR/PI3K pathway. Chromatin immunoprecipitation (ChIP) qPCR/Seq analysis and Luciferase reporter assay demonstrated that CEBPD binds and activates the promotor of a key ECM protein FN1 (fibronectin). In addition, the interactions of FN1 and its integrin receptors are necessary for CEBPD-induced EGFR/PI3K activation by promoting EGFR phosphorylation. Furthermore, GBM sample analysis in the database corroborated that CEBPD is positively correlated with the pathway activities of EGFR/PI3K and HIF1α, especially in highly hypoxic samples. At last, HRPs are also enriched in ECM proteins, indicating that ECM activities are important components of hypoxia induced responses in GBM. In conclusion, CEPBD plays important regulatory roles in the GBM HRG-MINW as a key TF, which activates the EGFR/PI3K pathway through ECM, especially FN1, mediated EGFR phosphorylation.

[Regulatory mechanism underlying pathogen biofilm formation and potential drug targets].

Bacterial communities usually develop biofilms abound in nature niche. The development of biofilm is a highly dynamic and complex process coordinated by multiple mechanisms, of which two-component system and quorum sensing are two well-defined systems. Biofilm is involved in the virulence of many pathogens. Therefore, targeting the key factors involved in the biofilm formation represents a novel and promising avenue for developing better antibiotics.

[Progress in polyphosphate and related metabolizing enzymes].

Inorganic polyphosphate (Poly P) is a polymer consisting of ten to hundreds of phosphate residues linked by "high-energy" phosphoanhydride bonds, which is abundantly found in all organisms and nature. Here the basic facts of PolyP are summarized: genes regulated by polyP, role in DNA uptake, motility of microorganism, function in stress response, the virulence of pathogens, as well as the proliferation of mammary cancer cells, blood coagulation, cell calcification and the modulation of mitochondrial activity. Enzymes with activities requiring polyP, such as endopolyphosphatase, glucokinase, NAD kinase, AMP phosphotransferase are outlined too. The structure and activity of enzymes regulating polyP level such as polyphosphate kinase and exopolyphosphatase are noted. A thorough analysis of the mycobacterium tuberculosis PPX protein homologs and their biochemical activity is presented.

Essential oil from Fructus Alpinia zerumbet (fruit of Alpinia zerumbet (Pers.) Burtt.et Smith) protected against aortic endothelial cell injury and inflammation in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Alpinia zerumbet (FAZ), a dry and ripe fruit of Alpinia zerumbet (Pers.) Burtt. et Smith, is widely used as a spice to treat cardiovascular diseases in clinic as a miao folk medicine in Guizhou Province of China. Essential oil extracted from FAZ (EOFAZ) is the key bioactive ingredients. AIM OF THE STUDY: This study aimed to examine the effects and mechanisms of EOFAZ on lipopolysaccharide (LPS)-induced endothelial cell injury, inflammation and apoptosis in vitro and in vivo. MATERIALS AND METHODS: For the in vitro study, LPS-treated human aortic endothelial cells were used to perform PCR, western blot analysis and immunofluorescence. For the in vivo study, male mouse were divided into four groups, vehicle control group and LPS group received 0.5% Tween-80 in saline; and two EOFAZ groups receive different dose of EOFAZ (90 mg kg -1·day-1, 180 mg kg -1·day-1) respectively. Each group was fed for 7 days by intragastrical administration at daily base. Then, except vehicle control group received saline, mice in other three groups were administered with LPS (1 mg kg -1, dissolved in saline) by intraperitoneal injection. 24 h later, Aorta tissue was collected and frozen immediately in liquid N2, stored at -80 °C for western blot analysis. RESULTS: We found that EOFAZ completely prevented LPS-induced HAEC activation and inflammation in vitro and in vivo, as assessed by expression of endothelial adhesion molecules, ICAM-1 and VCAM-1. Similarly, EOFAZ significantly blunted LPS-induced endothelial injury, as tested by MTT assay, LDH release and caspase-3 activation. We further demonstrated that TLR4-dependent NF-κB signaling may be involved in the process. CONCLUSION: EOFAZ protected against LPS-induced endothelial cell injury and inflammation likely via inhibition of TLR4-dependent NF-κB signaling.