GRB7 plays a promoting role in the progression of gastric cancer

Abstract Background Gastric cancer is a clinically common tumor, showing an upward trend of both incidence and mortality. GRB7 has been identified as a vital regulator in tumor progression. This study aims to uncover the biological function of GRB7 in gastric cancer process. Methods immunohistochemical (IHC) staining using a tissue microarray (TMA), quantitative reverse transcription PCR (qRT-PCR) and Western blotting were performed to detect the expression of genes. Furthermore, gastric cancer cell lines AGS and MGC-803 were transfected with short hairpin RNAs against GRB7. The biological function of GRB7 in gastric cancer cells were examined by CCK-8, flow cytometry, wound healing and Transwell assays. Then, in vivo tumor formation assay was conducted to explore the effects of GRB7 on tumor growth. Finally, expression levels of proteins related to cell functions were determined by Western blotting. Coimmunoprecipitation (CoIP) assay was performed to assess the protein-protein interaction. Results GRB7 was up-regulated in gastric cancer tissues and cell lines, and its expression was inversely proportional to survival of gastric cancer patients. Moreover, GRB7 knockdown inhibited proliferative, migratory abilities, as well as promoted cell apoptosis in gastric cancer cells. Further study suggested that GRB7 silencing could suppress gastric cancer tumor growth in vivo. Furthermore, our study uncovered an important interaction between GRB7 and MyD88. Silencing MyD88 was observed to alleviate the malignant phenotypes promoted by GRB7 in gastric cancer cells. Conclusions Together, this study provided evidence that GRB7 may be an effective molecular targets for the treatment of gastric cancer

Targeted Delivery of GDNF through the Blood-Brain Barrier by MRI-Guided Focused Ultrasound

Neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), are promising therapeutic agents for neurodegenerative diseases. However, the application of GDNF to treat these diseases effectively is limited because the blood-brain barrier (BBB) prevents the local delivery of macromolecular therapeutic agents from entering the central nervous system (CNS). Focused ultrasound combined with microbubbles (MBs) using appropriate parameters has been previously demonstrated to be able to open the BBB locally and noninvasively. This study investigated the targeted delivery of GDNF MBs through the BBB by magnetic resonance imaging (MRI)-guided focused ultrasound. Evans Blue extravasation and histological examination were used to determine the optimum focused ultrasound parameters. Enzyme-linked immunosorbent assay was performed to verify the effects of GDNF bound on MBs using a biotin-avidin bridging chemistry method to promote GDNF delivery into the brain. The results showed that GDNF can be delivered locally and noninvasively into the CNS through the BBB using MRI-guided focused ultrasound combined with MBs under optimum parameters. MBs that bind GDNF combined with MRI-guided focused ultrasound may be an effective way of delivering neurotrophic factors directly into the CNS. The method described herein provides a potential means of treating patients with CNS diseases

L₁₈ ( 3⁷ ) orthogonal expermiental design.

(#)<p>Ultrasonic irradiation time.</p>(*)<p>The Negative peak value of acoustic pressure measured by hydrophone in water.</p>($)<p>The time from injecting microbubbles into vessels to ultrasonic irradiation.</p

Ultrastructural electron microscopic observation of cell damage.

<p>(A) Control group (unsonicated group). (B) Group 6. (C) Group 11. (D) Group 13. (E) Group 14. Endothelial and nerve cells were severely damaged in Groups D and E, but ultrastructural changes were not observed in Groups A–C. The scale bar represents 150 nm.</p

MRI monitoring of BBB disruption and photographs of harvested brain showing BBB disruption induced by focused ultrasound.

<p>(A) BBB opening was monitored by leakage of the MR contrast agent into the brain parenchyma on axial (AX) and coronal (COR) MR images (arrows). (B) The location of the BBB opening was confirmed by EB staining of the affected area.</p

Evans Blue extravasation under the ultrasonic conditions presented in <b>Table 1</b>.

<p>Evans Blue extravasation (mean ± SEM) was significantly higher in Groups 6, 11, 13, and 14 than in the other groups. *<i>p</i><0.01, compared with the other groups besides groups 6, 11, 13 and 14.</p

Concentration of GDNF in sonicated tissues after focused ultrasound-induced BBB disruption post-injection with GDNF (800 µg/kg) through the tail vein.

<p>(A) Control group (unsonicated group). (B) MB and GDNF group (GDNF group). (C) MB-GDNF group. *<i>p</i><0.01, compared with Group A; ^#<i>p</i><0.05, compared with group B.</p

Bacterial pathogen spectrum of acute diarrheal outpatients in an urbanized rural district in Southwest China

Objectives: To conduct a one-year pathogen surveillance of acute diarrheal disease based on outpatient clinics in township hospitals in rural Hongta District of Yunnan Province, China. Methods: Fecal specimens of acute diarrhea cases and relevant epidemiological information were collected. Salmonella, Shigella, Vibrio, Aeromonas, Plesiomonas shigelloides and diarrheogenic Escherichia coli (DEC) were examined. Results: Among the 797 stool specimens sampled, 198 samples (24.8%) were positive in pathogen isolation, and 223 strains were isolated. The order of isolation rates from high to low were DEC, Aeromonas, P. shigelloides, Salmonella, Shigella and Vibrio. The overall positive rate in middle school students and preschool children was relatively high; while the overall positive rate of less than 1-year-old infants and above 55 years olds was relatively low. The isolates were analyzed by pulsed-field gel electrophoresis (PFGE). Some cases had the same or very close onset time, and the isolates had similar PFGE patterns, suggesting a possible outbreak once occurred but was not detected by the current infectious disease reporting system. Conclusions: Pathogen infection and transmission in rapidly urbanized rural areas is a serious issue. There is a great need for a more sensitive and accurate mode of monitoring, reporting and outbreak identification of diarrheal disease. Keywords: Diarrheal disease, Diarrheogenic pathogen, Molecular typing, Surveillance, Bacterial pathoge