Sulforaphane (SFN) extracted from broccoli sprout has previously been investigated for its potential properties in cancers, however, the underlying mechanisms of the anticancer activity of SFN remain not fully understood. In the present study, we investigate the effects of SFN on cell proliferation, cell cycle, cell apoptosis, and also the expression of several cell cycle and apoptosis-related genes by MTT assay, flow cytometry and western blot analysis in gastric cancer (GC) cells. The results showed that SFN could impair the colony-forming ability in BGC-823 and MGC-803 cell lines compared with the control. In addition, SFN significantly suppressed cell proliferation by arresting the cell cycle at the S phase and enhancing cell apoptosis in GC cells in a dose-dependent manner. Western blot results showed that SFN treatment significantly increased the expression levels of p53, p21 and decreased CDK2 expression, which directly regulated the S phase transition. The Bax and cleaved-caspase-3 genes involved in apoptosis executive functions were significantly increased in a dose-dependent manner in BGC-823 and MGC-803 cells. These results suggested that SFN-induced S phase cell cycle arrest and apoptosis through p53-dependent manner in GC cells, which suggested that SFN has a potential therapeutic application in the treatment and prevention of GC.

In nematode Caenorhabditis elegans, some microRNAs (miRNAs) could be dysregulated by multi-walled carbon nanotubes (MWCNTs), suggesting their involvement in regulating the response of nematodes to MWCNTs. Among these dysregulated miRNAs induced by MWCNT exposure, prolonged exposure to MWCNTs increased mir-35 expression. mir-35 further acted in the intestine to regulate the response to MWCNTs. In the intestine, a transcription factor MAB-3 was identified as its target in regulating the response to MWCNTs. Moreover, during the control of response to MWCNTs, MAB-3 acted upstream of DAF-16, a fork head transcriptional factor in insulin signaling pathway. Therefore, MWCNTs exposure potentially dysregulates intestinal mir-35 and its direct target MAB-3, which may activate a protective intestinal response of nematodes against the MWCNTs toxicity.

Nanomaterials have received increasing attentions owing to their potential hazards to the environment and human health; however, the multi-generational toxicity of graphene oxide under consecutive multi-generational exposure scenario still remains unclear. In the present study, Caenorhabditis elegans as an in vivo model organism was employed to explore the multi-generational toxicity effects of graphene oxide and the underlying mechanisms. Endpoints including development and lifespan, locomotion behaviors, defecation cycle, brood sizes, and oxidative response were evaluated in the parental generation and subsequent five filial generations. After continuous exposure for several generations, worms grew smaller and lived shorter. The locomotion behaviors were reduced across the filial generations and these reduced trends were following the impairments of locomotion-related neurons. In addition, the extended defecation cycles from the third filial generation were in consistency with the relative size reduction of the defecation related neuron. Simultaneously, the fertility function of the nematode was impaired under consecutive exposure as reduced brood sizes and oocytes numbers, increased apoptosis of germline, and aberrant expression of reproductive related genes ced-3, ced-4, ced-9, egl-1 and ced-13 were detected in exposed worms. Furthermore, the antioxidant enzyme, SOD-3 was significantly increased in the parent and filial generations. Thus, continuous multi-generational exposure to graphene oxide caused damage to the neuron development and the reproductive system in nematodes. These toxic effects could be reflected by indicators such as growth inhibition, shortened lifespan, and locomotion behavior impairment and induced oxidative response.

CONTEXT: The optimal duration of antibiotic treatment of children with community-acquired pneumonia (CAP) remains unclear. OBJECTIVES: This study aimed to compare the efficacy and safety of shorter versus longer duration of antibiotic treatment of children with CAP. DATA SOURCES: We searched Medline, Embase, CENTRAL, and CINAHL. STUDY SELECTION: Randomized clinical trials comparing shorter (≤5 days) with longer duration antibiotic treatments in children with CAP. DATA EXTRACTION: Paired reviewers independently extracted data and we performed random-effects meta-analyses to summarize the evidence. RESULTS: Sixteen trials with 12 774 patients, treated as outpatients with oral antibiotics, proved eligible. There are probably no substantial differences between shorter-duration and longer-duration antibiotics in clinical cure (odds ratio 1.01, 95% confidence interval [CI] 0.87 to 1.17; risk difference [RD] 0.1%; moderate certainty), treatment failure (relative risk [RR] 1.06, 95% CI 0.93 to 1.21; RD 0.3%; moderate certainty), and relapse (RR 1.12, 95% CI 0.92 to 1.35; RD 0.5%; moderate certainty). Compared with longer-duration antibiotics, shorter-duration antibiotics do not appreciably increase mortality (RD 0.0%, 95% CI −0.2 to 0.1; high certainty), and probably have little or no impact on the need for change in antibiotics (RR 1.03, 95% CI 0.72 to 1.47; RD 0.2%; moderate certainty), need for hospitalization (RD −0.2%, 95% CI −0.9 to 0.5; moderate certainty), and severe adverse events (RD 0.0%, 95% CI −0.2 to 0.2; moderate certainty). LIMITATIONS: For some outcomes, evidence was lacking. CONCLUSIONS: Duration of antibiotic therapy likely makes no important difference in patient-important outcomes. Healthcare workers should prioritize the use of shorter-duration antibiotics for children with CAP treated as outpatients with oral antibiotics.

The transcription factor MYB proto-oncogene like 2 (MYBL2) has been reported to be involved in the occurrence and development of various tumors, however, its role in gastric cancer (GC) remains to be elucidated. In this study, the Kaplan-Meier plotter was used to evaluate the prognostic value of different MYBL2 expression levels in GC patients. The UALCAN database were applied to analyze the relationships between MYBL2 and clinicopathological characteristics of GC. GC cell proliferation, cell cycle and apoptosis were determined by CCK-8 and flow cytometry assays, and proteins were examined by Western blot analysis. Next, signaling pathway enrichment analysis of MYBL2-related genes and protein expression were analyzed by Gene Set Enrichment Analysis (GSEA) and Western blot assays. The results found that MYBL2 expression was significantly upregulated in GC compared with adjacent non-malignant tissues and associated with poor patient survival, tumor, stages and lymph node metastasis. Forced expression of MYBL2 could promote cell proliferation, resulting in an accelerated S phase progression and inhibiting cell apoptosis in GC cells. Conversely, MYBL2 silencing inhibited cell proliferation, induced G2/M phase arrest and promoted cell apoptosis in GC cells. Mechanistically, Western blot analysis showed that MYBL2 silencing decreased the expression of BCL2 and upregulated the expression of Cleaved-caspase-3 and BAX in HGC-27 cells. Conversely, MYBL2 overexpression in AGS cells resulted in the opposite effects. Furthermore, enforced expression of MYBL2 activated the PI3K/AKT signaling pathway, especially AKT phosphorylation. Additionally, the AKT inhibitor MK2206 significantly reversed the proliferation capacity of GC cells induced by MYBL2 overexpression. Therefore, these results suggest that upregulated expression of MYBL2 contributes to GC cell growth and inhibits cell apoptosis by regulating the PI3K/AKT and BCL2/BAX/Cleaved-caspase-3 signaling pathways in GC cells indicating that MYBL2 may be a new therapeutic target and prognostic marker for GC.