MicroRNA expression profiling after recurrent febrile seizures in rat and emerging role of miR-148a-3p/SYNJ1 axis.

Febrile seizures (FSs) are common neurological disorders in both infants and children, although the precise underlying mechanism remains to be explored, especially in the expression pattern and function of microRNAs (miRNAs). In this report, we aimed to screen new potential miRNAs and examine the role of miR-148a-3p in hippocampal neurons in FS rats via Synaptojanin-1 (SYNJ1). Thirty rats were randomly divided into the normal and FS model groups, which were investigated by miRNA array. This process identified 31 differentially expressed (20 upregulated and 11 downregulated) miRNAs and potential miRNA target genes. In addition, hippocampal neurons were assigned into five groups for different transfections. Apoptosis was detected by TUNEL and flow cytometry. SYNJ1 was identified as a target gene of miR-148-3p. In vitro experiments revealed that inhibition of miR-148a-3p decreased neuronal cell apoptosis. Moreover, overexpression of miR-148a-3p resulted in activation of PI3K/Akt signaling pathway and the apoptosis of hippocampal neurons. MiR-148a-3p inhibitor could reverse the above events. Taken together, our data demonstrated that the hippocampal miRNA expression profiles of a rat model of FS provide a large database of candidate miRNAs and neuron-related target genes. Furthermore, miR-148a-3p acted as a apoptosis enhcaner via the activation of the SYNJ1/PI3K/Akt signaling pathway, highlighting a potential therapeutic target in the treatment of infants with hyperthermia-induced brain injury.

Identification of Hub Genes of Mesio Temporal Lobe Epilepsy and Prognostic Biomarkers of Brain Low-grade Gliomas Based on Bioinformatics Analysis.

Mesio temporal lobe epilepsy (MTLE) syndrome is the most common form of intractable epilepsies. Meanwhile, seizures are common in patients with cancer as a consequence of brain tumors, including brain low-grade gliomas (LGG). However, the underlying molecular mechanisms of MTLE remain poorly understood. Also, the relationship between MTLE and LGG needs our attention. In this study, we aimed to investigate the hub genes and potential mechanism in MTLE, and the relationship between MTLE and LGG, the gene expression profiles (GSE88992) were downloaded from the Gene Expression Omnibus (GEO) database. Difference analysis for MTLE versus control groups under the three time points was conducted to select the differentially expressed genes (DEGs). Time series clustering analysis was used to select the trend genes. Then a series of bioinformatics analyses including functional enrichment analysis, protein-protein interaction (PPI) network and module analyses, and transcription factor (TF) and miRNA prediction were performed. Also, the overall survival analysis and expression of hub genes in LGG were performed using UALCAN from TCGA database. At 6 h, there were 351 upregulated and 80 downregulated DEGs. At 12 h, there were 499 upregulated and 231 downregulated DEGs. Additionally, 532 upregulated and 402 downregulated DEGs were obtained at 24 h. After time series clustering analysis of the DEGs, we obtained 323 uptrend and 248 downtrend genes. We identified 10 key genes with higher degrees, including C3, TIMP1, PENK, CKAP4, etc. Five PPI modules were identified by MCODE. TF analysis predicted four TFs: JUN, STAT3, NR4A2, and Myc. A total of 26,834 miRNA-mRNA pairs were predicted. Moreover, survival analysis of UALCAN suggested that C3, TIMP1, PENK, GNG2, CKAP4, TNC, JUN, STAT3, NR4A2, and Myc can be potential biomarkers for the prognosis of LGG. In summary, DEGs and hub genes were identified in the present study, which provides novel insight into the development of MTLE.

Single-Agent Versus Double-Agent Chemotherapy in Concurrent Chemoradiotherapy for Esophageal Squamous Cell Carcinoma: Prospective, Randomized, Multicenter Phase II Clinical Trial.

LESSONS LEARNED: The efficacy of single-agent chemotherapy was not significantly different from that of double-agent chemotherapy in concurrent chemoradiotherapy for inoperable esophageal squamous cell carcinoma. Single-agent concurrent chemoradiotherapy had lower gastrointestinal and hematologic toxicity. Overall survival and progression-free survival were not significantly different between single- and double-agent concurrent chemoradiotherapy. BACKGROUND: This multicenter, randomized, phase II trial aimed to compare the efficacy and safety of single-agent concurrent chemoradiotherapy using the oral fluoropyrimidine S-1 with those of double-agent concurrent chemoradiotherapy using S-1 and cisplatin in patients with inoperable esophageal squamous cell carcinoma. METHODS: Patients with inoperable esophageal squamous cell carcinoma (clinical stages I to III) were randomly allocated to the single-agent group (S-1) or the double-agent group (S-1/cisplatin). The concurrent intensity-modulated radiation therapy plan was similar for both groups: planning target volume 1.8 Gy/f*30-33f and planning gross target volume of 2 Gy/f*30-33f. The primary outcome measure was the endoscopic complete response rate. RESULTS: Of the 105 patients randomized, 89 were assessable. The endoscopic complete response rate was 46.9% (23/49) in the single-agent group and 52.5% (21/40) in double-agent group. The median progression-free survival within a median follow-up of 23 months was 20 and 21 months, respectively. The median overall survival was 26 months and not reached, respectively. Grade 3 hematological toxicities occurred in 4.1% and 27.5% of the patients in the single- and the double-agent group, respectively. CONCLUSION: Single-agent chemotherapy in concurrent chemoradiotherapy for inoperable esophageal squamous cell carcinoma has good efficacy and safety, thus warranting a phase III trial.

Therapeutic effect of the natural compounds baicalein and baicalin on autoimmune diseases.

A series of natural compounds have been implicated to be useful in regulating the pathogenesis of various autoimmune diseases. The present study demonstrated that the Scutellariae radix compounds baicalein and baicalin may serve as drugs for the treatment of autoimmune diseases, including rheumatoid arthritis and inflammatory bowel disease. Following the administration of baicalein and baicalin in vivo, T cell­mediated autoimmune diseases in the mouse model were profoundly ameliorated: In the collagen­induced arthritis model (CIA), the severity of the disease was reduced by baicalein and, consistently, baicalein was demonstrated to suppress T cell proliferation in CIA mice. In the dextran sodium sulfate (DSS)­induced colitis model, the disease was attenuated by baicalin, and baicalin promoted colon epithelial cell (CEC) proliferation in vitro. The present study further revealed that the mRNA expression of signal transducer and activator of transcription (STAT)3 and STAT4 in the tyrosine­protein kinase JAK­STAT signaling pathway in T cells was downregulated by baicalein, contributing to its regulation of T cell proliferation. However, in the DSS model, the STAT4 transcription in CECs, which are the target cells of activated T cells in the gut, was downregulated by baicalin, suggesting that baicalein and baicalin mediated similar STAT expression in different cell types in autoimmune diseases. In conclusion, the similarly structured compounds baicalein and baicalin selectively exhibited therapeutic effects on autoimmune diseases by regulating cell proliferation and STAT gene expression, albeit in different cell types.

S-1 versus S-1 plus cisplatin concurrent intensity modulated radiation therapy in the treatment of esophageal squamous cell carcinoma: Study protocol for a randomized controlled phase II trial.

INTRODUCTION: Chemotherapy regimens are often a 2-drug regimen in concurrent chemotherapy and radiotherapy for esophageal cancer (EC). However, some retrospective studies have suggested that for patients with EC receiving radiotherapy combined with 2-drug chemotherapy have the severe toxicity. And S-1 alone with the combination of radiotherapy treatment effect is good, and achieved good clinical remission rate. The purpose of this trial is compare the efficacy and toxicity of combining S-1 or S-1 plus cisplatin with radiotherapy for esophageal squamous cell carcinoma. METHODS/DESIGN: The study is a randomized, controlled, multicenter trial, comparing S-1 versus S-1 plus cisplatin concurrent radiotherapy for patients with esophageal squamous cell carcinoma. Eighty-eight patients with unresectable or medically unfit for surgery esophageal squamous cell carcinoma (clinical stage I to III), will randomly assigned to receive four cycles (2 concomitant and 2 postradiotherapy) S-1 or S-1 plus cisplatin along with radiotherapy 60-66 Gy/30 to 33 fractions. The primary outcome is complete response rate of primary tumor which will be measured by endoscopy and computer screen at 3 months after the completion of treatment. Secondary outcomes include survival and toxicity. DISCUSSION: To our knowledge, this study protocol is the first to test the effect between S-1 versus S-1 plus cisplatin concurrent intensity modulated radiation therapy in the treatment of esophageal squamous cell carcinoma. If the result will be the same effect and fewer side effects and less costly in S-1 plus radiotherapy. It will supply more treatment selection for esophageal squamous cell carcinoma.