The aim of this study was to determine whether Saccharomyces boulardii prevents and treats diarrhoea and antibiotic-associated diarrhoea (AAD) in children. A total of 333 hospitalised children with acute lower respiratory tract infection were enrolled in a 2-phase open randomised controlled trial. During the 1st phase, all children received intravenous antibiotics (AB). They were randomly allocated to group A (S. boulardii 500 mg/day + AB, n=167) or group B (AB alone, n=166) and followed for 2 weeks. Diarrhoea was defined as ≥3 loose/watery stools/day during at least 2 days, occurring during treatment and/or up to 2 weeks after AB therapy had stopped. AAD was considered when diarrhoea was caused by Clostridium difficile or when stool cultures remained negative. In the 2nd phase of the study, group B patients who developed diarrhoea were randomly allocated to two sub-groups: group B1 (S. boulardii + oral rehydration solution (ORS)) and group B2 (ORS alone). Data from 283 patients were available for analysis. Diarrhoea prevalence was lower in group A than in group B (11/139 (7.9%) vs. 42/144 (29.2%); relative risk (RR): 0.27, 95% confidence interval (CI): 0.1-0.5). S. boulardii reduced the risk of AAD (6/139 (4.3%) vs. 28/144 (19.4%); RR: 0.22; 95% CI: 0.1-0.5). When group B patients developed diarrhoea (n=42), S. boulardii treatment during 5 days (group B1) resulted in lower stool frequency (P<0.05) and higher recovery rate (91.3% in group B1 vs. 21.1% in B2; P<0.001). The mean duration of diarrhoea in group B1 was shorter (2.31±0.95 vs. 8.97±1.07 days; P<0.001). No adverse effects related to S. boulardii were observed. S. boulardii appeared to be effective in the prevention and treatment of diarrhoea and AAD in children treated with intravenous antibiotics.

Background and purpose: Stimulation of astrocytes by the a 2 -adrenoceptor agonist dexmedetomidine, a neuroprotective drug, transactivates epidermal growth factor (EGF) receptors. The present study investigates signal pathways leading to release of an EGF receptor ligand and those activated during EGF receptor stimulation, and the response of neurons to dexmedetomidine and to astrocyte-conditioned medium. Experimental approach: Phosphorylation of ERK 1/2 was determined by western blotting and immunocytochemistry, and phosphorylation of EGF receptors by immunoprecipitation and western blotting. mRNA expression of fos family was measured by RT-PCR. Key results: Pertussis toxin (0.2 mg ml À1 ) an inhibitor of bg subunit dissociation from Ga i protein, and GF 109203X (500 nM), a protein kinase C inhibitor, abolished ERK 1/2 phosphorylation. PP1 (10 mM), inhibiting Src kinase and GM 6001 (10 mM), an inhibitor of Zn-dependent metalloproteinase, abolished ERK 1/2 phosphorylation by dexmedetomidine (50 nM), but not that by EGF (10 ng ml À1 ), showing Src kinase and metalloproteinase activation during the first stage only; AG 1478 (1 mM), an inhibitor of the EGF receptor tyrosine kinase, abolished ERK 1/2 phosphorylation. Dexmedetomidine-induced EGF receptor phosphorylation was prevented by AG 1478, GM 6001, PP1 and GF 109203X and its induction of cfos and fosB by AG 1478 and by U0126 (10 mM), an inhibitor of ERK phosphorylation, indicating downstream effects of ERK 1/2 phosphorylation. EGF and conditioned medium from dexmedetomidine-treated astrocytes, but not dexmedetomidine itself, induced ERK phosphorylation in primary cultures of cerebellar neurons. Conclusions and implications: Dexmedetomidine-induced transactivation pathways were delineated. Its paracrine effect on neurons may account for its neuroprotective effects.

This article aimed to investigate changes in the cytoskeleton of airway smooth muscle cells (ASMCs) in juvenile rats with airway remodeling in asthma. We further investigated the involvement of the RhoA/ROCK signaling pathway mechanism. Rat models of airway remodeling in asthma were established by antigen sensitization with ovalbumin for 2, 4, 6, and 8 weeks. The control group was treated with normal saline instead of ovalbumin. In the intervention group, after 8 weeks of culture, ASMCs were treated with the ROCK-specific inhibitor Y-27632. Immunofluorescence, real-time polymerase chain reaction, and Western blot analyses were used to observe changes in the cytoskeleton (F-actin and α-tubulin) of ASMCs and expressions of RhoA and ROCK. The asthmatic groups had significantly higher average gray values of F-actin in ASMCs compared to the control group (P < 0.01), and these values for the intervention group were significantly lower than those of the 8-week asthmatic group (P < 0.05). Expression levels of the α-tubulin protein in the asthmatic groups were all significantly higher than those of the control group (P < 0.01), and the levels in the intervention group were significantly reduced (P < 0.05). Expressions of RhoA and ROCK mRNA and proteins in all asthmatic groups were significantly higher than those of the control group (P < 0.01). Together, these results demonstrate substantial changes of the ASMC cytoskeleton and abnormal expressions of RhoA and ROCK mRNA and proteins in juvenile rats with airway remodeling in asthma.

To explore the universal law of the abnormal gene expression and the structural variation of genes related to lung adenocarcinoma, the gene expression profile of GSE37765 were downloaded from Gene Expression Omnibus database. The differentially expressed genes (DEGs) were analyzed with t-test and NOISeq tool, and the core DEGs were screened out by combining with another RNA-seq data containing totally 77 pairs of samples in 77 patients with lung adenocarcinoma. Moreover, the functional annotation of the core DEGs was performed by using the Database for Annotation Visualization and Integrated Discovery following selection of oncogene and tumor suppressor by combining with tumor suppressor genes and Cancer Genes database, and motif-finding of core DEGs was performed with motif-finding algorithm Seqpos. We also used Tophat-fusion tool to further explore the fusion genes. In total, 850 downregulated DEGs and 206 upregulated DEGs were screened out in lung adenocarcinoma tissues. Next, we selected 543 core DEGs, including 401 downregulated and 142 upregulated genes, and vasculature development (P=1.89E-06) was significantly enriched among downregulated core genes, as well as mitosis (P=6.26E-04) enriched among upregulated core genes. On the basis of the cellular localization analysis of core genes, wnt-1-induced secreted protein 1 (WISP1) and receptor (G protein-coupled) activity modifying protein 1 (RAMP1) identified mainly located in extracellular region and extracellular space. We also screened one oncogene, v-myb avian myeloblastosis viral oncogene homolog-like 2 (MYBL2). Moreover, transcription factor GATA2 was mined by motif-finding analysis. Finally, four fusion genes belonged to the human leukocyte antigen (HLA) family. WISP1, RAMP1, MYBL2 and GATA2 could be potential targets of treatment for lung adenocarcinoma and the fusion of HLA family genes might have important roles in lung adenocarcinoma.

Asthma is a chronic inflammatory disorder of the lung, which is thought to be determined by the balance between the T helper (Th)2 and Th1 responses. This study evaluated whether the balance between Th17 cells and regulatory T cells (T reg ) was impaired in asthma patients. The proportion of peripheral blood Th17 cells of the total CD4 + cell population in asthma patients was significantly higher than in controls (mean ± SD 0.72 ± 0.5% versus 0.31 ± 0.4%, respectively). The proportion of peripheral T reg cells in asthma patients was significantly lower than in controls (mean ± SD 12.1 ± 4.6% versus 27.2 ± 7.5%, respectively). Analysis of mRNA generally confirmed the flow cytometry data, suggesting that the changes in cytokine levels were mediated at the transcription level. In paediatric asthma patients, the CD4 + T-cell phenotype was skewed toward the Th17 phenotype, suggesting that a Th17/T reg functional imbalance plays a role in asthma.