Western blotting confirmed that overexpression of HOXB5 promoted the EMT process. Conversely, knockdown of HOXB5 alleviated EMT. Furthermore, knockdown of HOXB5 suppressed proliferation, migration, and invasion of pancreatic cancer cells via the Glycogen synthase kinase 3β (GSK3β)/β-catenin pathway. Our study demonstrates that HOXB5 is a tumor promoter in pancreatic cancer, and the GSK3β/β-catenin pathway is important in HOXB5-induced proliferation, migration, and invasion in pancreatic cancer cells.Cisplatin is a widely used chemotherapeutic drug in lung cancer treatment. Most cancer patients eventually develop cisplatin resistance, resulting in a poor prognosis. Previously, we identified a novel marker, family with sequence similarity 60A (FAM60A), that was responsible for resistance in cisplatin-resistant human lung adenocarcinoma A549 (A549/DDP) cells. Here, we investigated the biological effects of FAM60A in A549/DDP cells and explored the underlying molecular mechanisms to understand its functional role in cisplatin resistance. compound library inhibitor Real-time quantitative PCR and western blot analysis were used to determine the expression levels of FAM60A in A549/DDP cells. FAM60A and SKP2 were knockdown with small-interfering RNA (siRNA). Cancer cell viability was analyzed with flow cytometry. The mRNA and protein expression levels of FAM60A increased significantly and dose-dependently in A549/DDP cells following cisplatin treatment. FAM60A overexpression up-regulated MDR1 expression, inhibited caspase 3, cleaved-caspase 3, and caspase 8 expression, and prevented cancer cell death. Microarray analysis of cells transfected with siRNA against the FAM60A transcript and control samples showed that SKP2 expression was positively regulated by FAM60A. SKP2 knockdown using a short-hairpin RNA reversed the functions induced by FAM60A. These results suggest that overexpression of FAM60A in A549/DDP cells led to SKP2 upregulation and enhanced cisplatin resistance in cancer cells. These provide new insights into chemoresistance and may contribute to reversing cisplatin resistance during lung cancer treatment.Breast cancer affects women globally; the majority of breast cancer-related mortalities are due to metastasis. Acquisition of a mesenchymal phenotype has been implicated in the progression of breast cancer cells to an invasive, metastatic state. Triple-negative breast cancer (TNBC) subtypes have high rates of metastases, recurrence, and have poorer prognoses compared to other breast cancer types, partially due to lack of commonly targeted receptors. Kinases have diverse and pivotal functions in metastasis in TNBC, and discovery of new kinase targets for TNBC is warranted. We previously used a screening approach to identify intermediate-synthesis nonpotent, nonselective small-molecule inhibitors from the Published Kinase Inhibitor Set that reversed the mesenchymal phenotype in TNBC cells. Two of these inhibitors (GSK346294A and GSK448459A) are structurally similar, but have unique kinase activity profiles and exhibited differential biologic effects on TNBC cells, specifically on epithelial-to-mesenchymal transition (EMT). Here, we further interrogate these effects and compare activity of these inhibitors on transwell migration, gene (qRT-PCR) and protein (western blot) expressions, and cancer stem cell-like behavior. We incorporated translational patient-derived xenograft models in these studies, and we focused on the lead inhibitor hit, GSK346294A, to demonstrate the utility of our comparative analysis as a screening modality to identify novel kinase targets and signaling pathways to pursue in TNBC. This study introduces a new method for discovering novel kinase targets that reverse the EMT phenotype; this screening approach can be applied to all cancer types and is not limited to breast cancer.

This study was designed to assess the efficacy and safety of Saccharomyces cerevisiae variant boulardii CNCM I-3799 (S. boulardii CNCM I-3799) in the management of acute diarrhea in children.

A total of 100 infants and children 3-36 months of age with acute diarrhea received medical care according to the World Health Organization guidelines on the management of acute diarrhea in children and were randomly allocated to the probiotic group (S. boulardii CNCM I-3799 at a daily dose of 5 billion CFU twice daily) or to the placebo group. Infants and children were treated for 5 days and an extended follow-up was planned 1 and 2 months after the end of the treatment period. Primary endpoint was the time of recovery from diarrhea defined as the duration of diarrhea. Other parameters, such as frequency and consistency of stools, associated with the severity of diarrhea episodes were defined as secondary endpoints.

The administration of S. boulardii CNCM I-3799 was associated with beneficial effects on duration and severity of diarrhea. The time of recovery from diarrhea was significantly shorter in the probiotic group compared with the placebo group (65.8 ± 12 hours vs. 95.3 ± 17.6 hours, P = 0.0001). Faster remission in the probiotic group was also demonstrated by a shorter time before the first episode of semisolid stool [-23.5 hours, diff (95% CI) -7.99 (-31.49 to -15.51), P = 0.0001] and the faster normalization of stool consistency. S. boulardii CNCM I-3799 was well tolerated.

S. boulardii CNCM I-3799 supplementation in children with acute diarrhea was shown effective in reducing the duration and severity of diarrhea in infants and children.

S. boulardii CNCM I-3799 supplementation in children with acute diarrhea was shown effective in reducing the duration and severity of diarrhea in infants and children.

Despite the utility of universal screening, most pediatric providers rarely use mental health (MH) screening tools. As such, provider descriptions of their experiences with universal screening are limited. The goal of this study was to describe barriers to, and facilitators of, universal MH screening implementation, the perceived impact of such screening, impressions of a screening-focused quality improvement (QI) Learning Collaborative, and lessons learned.

We invited primary care clinicians participating in a large-scale QI Learning Collaborative on MH screening (n = 107) to complete postproject interviews. Interviews were transcribed and analyzed using constant comparative qualitative analysis, an inductive, iterative process.

Eleven interviews were completed and analyzed. Practice sites included academic health centers, a private practice, and a federally qualified health center. Providers described the positive impact of screening (increased identification of MH concerns) and barriers and facilitators of screening at the practice level (clinic and leadership buy-in and electronic medical record integration), the provider level (provider beliefs about the importance of screening), and the patient level (parent literacy).