MTOR, a central regulator of autophagy, is involved in cancer and cardiovascular and neurological diseases. Modulating the MTOR signaling balance could be of great significance for numerous diseases. No chemical activators of MTOR have been found, and the urgent challenge is to find novel MTOR downstream components. In previous studies, we found a chemical small molecule, 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO), that inhibited autophagy in human umbilical vein endothelial cells (HUVECs) and neuronal cells. Here, we found that 3BDO activated MTOR by targeting FKBP1A (FK506-binding protein 1A, 12 kDa). We next used 3BDO to detect novel factors downstream of the MTOR signaling pathway. Activation of MTOR by 3BDO increased the phosphorylation of TIA1 (TIA1 cytotoxic granule-associated RNA binding protein/T-cell-restricted intracellular antigen-1). Finally, we used gene microarray, RNA interference, RNA-ChIP assay, bioinformatics, luciferase reporter assay, and other assays and found that 3BDO greatly decreased the level of a long noncoding RNA (lncRNA) derived from the 3' untranslated region (3'UTR) of TGFB2, known as FLJ11812. TIA1 was responsible for processing FLJ11812. Further experiments results showed that FLJ11812 could bind with MIR4459 targeting ATG13 (autophagy-related 13), and ATG13 protein level was decreased along with 3BDO-decreased FLJ11812 level. Here, we provide a new activator of MTOR, and our findings highlight the role of the lncRNA in autophagy.

TGFB2-OT1 (TGFB2 overlapping transcript 1) is a newly discovered long noncoding RNA (lncRNA) derived from the 3'UTR of TGFB2. It can regulate autophagy in vascular endothelial cells (VECs). However, the mechanisms of TGFB2-OT1 action are unclear, and whether it is involved in VECs dysfunction needs investigation. Here, the level of TGFB2-OT1 was markedly increased by lipopolysaccharide and oxidized low-density lipoprotein, 2 VECs inflammation triggers. A chemical small molecule, 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO) significantly decreased TGFB2-OT1 levels and inhibited the effect of LPS and oxLDL. The NUPR1 level was upregulated by the 2 inflammation inducers and modulated the TGFB2-OT1 level by promoting the expression of TIA1, responsible for TGFB2-OT1 processing. We focused on how TGFB2-OT1 regulated autophagy and inflammation. Use of miRNA chip assay, TGFB2-OT1 overexpression technology and 3BDO revealed that TGFB2-OT1 regulated the levels of 3 microRNAs, MIR3960, MIR4488 and MIR4459. Further studies confirmed that TGFB2-OT1 acted as a competing endogenous RNA, bound to MIR3960, MIR4488 and MIR4459, then regulated the expression of the miRNA targets CERS1 (ceramide synthase 1), NAT8L (N-acetyltransferase 8-like [GCN5-related, putative]), and LARP1 (La ribonucleoprotein domain family, member 1). CERS1 and NAT8L participate in autophagy by affecting mitochondrial function. TGFB2-OT1 increased the LARP1 level, which promoted SQSTM1 (sequestosome 1) expression, NFKB RELA and CASP1 activation, and then production of IL6, IL8 and IL1B in VECs. Thus, NUPR1 and TIA1 may control the level of TGFB2-OT1, and TGFB2-OT1 bound to MIR3960, MIR4488 and MIR4459, which targeted CERS1, NAT8L, and LARP1, respectively, the key proteins involved in autophagy and inflammation.

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BackgroundChina has a high rate of antibiotic use. The Chinese Ministry of Health (MOH) established the Center for Antibacterial Surveillance (CAS) to monitor the use of antibacterial agents in hospitals in 2005. The purpose of this study was to identify trends, pattern changes and regional differences in antibiotic consumption in 151 public general tertiary hospitals across China from 2011–2014.Materials and methodsValid data for antibiotic use were collected quarterly, and the antibiotic consumption data were expressed as the defined daily dose (DDD) per 100 inpatient days (ID). We compared the patterns of antibiotic use in different classes and geographical clusters.ResultsTotal antibiotic use significantly decreased (P = 0.018) from 75.86 DDD/100 ID in 2011 to 47.03 DDD/100 ID in 2014. The total consumption of flomoxef sodium and cefminox increased from 1.31 DDD/100 BD in 2011 to 8.6 DDD/100 BD in 2014. Cephalosporins were the most frequently used antibiotics in all regions. Third-generation cephalosporins accounted for more than 45% of the cephalosporins used. Carbapenem use substantially increased (P = 0.043). Penicillin combinations with inhibitors accounted for 50% of the penicillin used, and prescribed meropenem accounted for most of the carbapenems used in all regions in 2014. The subclasses in each antibiotic group were used differently between the seven regions, and the total hospital antibiotic use in 2014 differed significantly by region (P = 0.014).ConclusionAlthough the volume and intensity of total antibiotic use decreased, the antibiotic use patterns were not optimal, and broad-spectrum antibiotics were still the main classes. The aggregate data obtained during the study period reveal similar antibiotic consumption patterns in different regions. These findings provide useful information for improving the rational use of antibiotics. More detailed data on antibiotics linked to inpatient diseases need to be collected in future studies.

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Background: Idiopathic granulomatous mastitis (IGM) is a rare, benign breast disease without any definitive therapeutic strategy. It is controversial whether to use conservative or surgical treatment of IGM and high-level evidence-based medicine data are lacking. The purpose of this study was to systemically evaluate the clinical effectiveness of the conservative versus surgical treatment for IGM. Methods: In this meta-analysis, we searched PubMed, EMbase, ScienceDirect, and Web of Science for comparative studies about the conservative versus surgical treatment of IGM. Two researchers independently identified reports and extracted data. We used Stata 11 for data analysis. A meta-analysis was performed to investigate the differences in the recurrence rate of conservative and surgical treatment using a random effects model. Results: A total of 10 studies involving 1,101 patients were included. The results demonstrated that there was no significant difference in the recurrence rate among patients who were treated by nonsurgical therapy and surgical treatment. No publication bias was detected. Conclusion: This meta-analysis demonstrates that both the conservative and surgical treatment approaches have appropriate efficacy in IGM treatment and relapse. Further randomized controlled trials with longer follow-up periods are required to confirm the advantages of each approach.

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