Previous studies have revealed that the probiotic Clostridium butyricum (C. butyricum) can attenuate cirrhosis in chronic non-alcoholic liver disease. However, the effects of C. butyricum on acute liver injury (ALI) remain unclear. Therefore, the present study aims to examine the hepatoprotective effects and the underlying mechanisms employed by C. butyricum in a carbon tetrachloride (CCl)-induced ALI murine model. Here, we evaluated the survival rate and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), anti-oxidants, cytokines and the gut microbiota to elucidate the potential mechanisms by which C. butyricum is hepatoprotective. Our results show that five days of prophylactic C. butyricum treatment significantly reduced mortality by 40% and decreased the CCl-induced levels of ALT and AST in the serum of these mice. Additionally, prophylactic treatment with C. butyricum increased the activity of both superoxide dismutase (SOD) and catalase (CAT), and substantially reduced malondialdehyde (MDA) levels, which were deteriorated in the untreated ALI mice compared to normal control mice. Furthermore, C. butyricum up-regulated the nuclear factor (erythroid-derived 2)-like 2 (NRF2) content. CCl-induced mice also exhibited considerable increases of phosphorylation of nuclear factor-kappa B (NF-κB) p65 and pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). However, the inflammatory responses of the liver induced by CCl were significantly alleviated by C. butyricum pretreatment. Additionally, we found that interleukin-10 (IL-10), an anti-inflammatory mediator, was increased in the C. butyricum-pretreated group. Microbiota analysis in these mice revealed crosstalk between the gut microbial metabolites and ALI. The intestinal flora was changed by CCl administration and was shifted by the probiotic C. butyricum toward more beneficial bacteria, particularly the Clostridia orders, which are the known producers of the anti-inflammatory and anti-oxidative metabolite butyrate. In conclusion, we found that the intestinal flora changes after the intraperitoneal injection of CCl. We also offer novel insights into the mechanism by which probiotic C. butyricum pretreatment alleviates the CCl-induced inflammation and oxidative stress of the liver via the modulation of NRF2, NF-κB p65, IL-10 and the intestinal microbiota in mice.

Circular RNAs (circRNAs) have been demonstrated to be involved in various biological processes. Nevertheless, the function of circRNAs in medulloblastoma (MB) is still unknown. The present study aimed to investigate the expression profiles of circRNAs and related mechanisms for regulating the proliferation and growth of tumor cells in MB. The expression profiles of circRNAs were screened from four normal cerebellum and four MB samples using a HiSeq Sequencer. Bioinformatic analysis was employed to predict the interaction between circRNAs and mRNAs in MB. Subsequently, the expression levels of eight differential circRNAs [circ‐SKA3 (hsa_circ_0029696), circ‐DTL (hsa_circ_0000179), circ‐CRTAM, circ‐MAP3K5 (hsa_circ_0006856), circ‐RIMS1‐1 (hsa_circ_0132250), circ‐RIMS1‐2 (hsa_circ_0076967), circ‐FLT3‐1 (hsa_circ_0100165), and circ‐FLT3‐2 (hsa_circ_0100168)] were validated using quantitative reverse transcription−polymerase chain reaction. Moreover, circ‐SKA3 and circ‐DTL were silenced using small interfering RNAs and their host genes were overexpressed to investigate their role in the pathogenesis of MB. A total of 33 circRNAs were found to be differentially expressed in MB tissues (fold change ≥ 2.0, FDR <0.05), of which three were upregulated and 30 were downregulated; six circRNAs were experimentally validated successfully. Upregulated circ‐SKA3 and circ‐DTL promoted the proliferation migration and invasion in vitro by regulating the expression of host genes. This novel study exploited the profiling of circRNAs in MB and demonstrated that circ‐SKA3 and circ‐DTL were crucial in the tumorigenesis and development of MB and might be considered as novel and potential biomarkers for the diagnosis and new targets for the intervention of MB.

Chronic pain is a major public health problem. Mitochondria play important roles in a myriad of cellular processes and mitochondrial dysfunction has been implicated in multiple neurological disorders. This review aims to provide an insight into advances in understanding of the role of mitochondrial dysfunction in the pathogenesis of chronic pain. The results show that the five major mitochondrial functions (the mitochondrial energy generating system, reactive oxygen species generation, mitochondrial permeability transition pore, apoptotic pathways and intracellular calcium mobilisation) may play critical roles in neuropathic and inflammatory pain. Therefore, protecting mitochondrial function would be a promising strategy to alleviate or prevent chronic pain states. Related chronic inflammatory and neuropathic pain models, as well as the spectral characteristics of current fluorescent probes to detect mitochondria in pain studies, are also discussed.

BackgroundGlioblastoma multiform (GBM) is a devastating brain tumor with maximum surgical resection, radiotherapy plus concomitant and adjuvant temozolomide (TMZ) as the standard treatment. Diverse clinicopathological and molecular features are major obstacles to accurate predict survival and evaluate the efficacy of chemotherapy or radiotherapy. Reliable prognostic biomarkers are urgently needed for postoperative GBM patients.MethodsThe protein coding genes (PCGs) and long non-coding RNA (lncRNA) gene expression profiles of 233 GBM postoperative patients were obtained from The Cancer Genome Atlas (TCGA), TANRIC and Gene Expression Omnibus (GEO) database. We randomly divided the TCGA set into a training (n = 76) and a test set (n = 77) and used GSE7696 (n = 80) as an independent validation set. Survival analysis and the random survival forest algorithm were performed to screen survival associated signature.ResultsSix PCGs (EIF2AK3, EPRS, GALE, GUCY2C, MTHFD2, RNF212) and five lncRNAs (CTD-2140B24.6, LINC02015, AC068888.1, CERNA1, LINC00618) were screened out by a risk score model and formed a PCG-lncRNA signature for its predictive power was strongest (AUC = 0.78 in the training dataset). The PCG-lncRNA signature could divide patients into high- risk or low-risk group with significantly different survival (median 7.47 vs. 18.27 months, log-rank test P < 0.001) in the training dataset. Similar result was observed in the test dataset (median 11.40 vs. 16.80 months, log-rank test P = 0.001) and the independent set (median 8.93 vs. 16.22 months, log-rank test P = 0.007). Multivariable Cox regression analysis verified that it was an independent prognostic factor for the postsurgical patients with GBM. Compared with IDH mutation status, O-(6)-methylguanine DNA methyltransferase promoter methylation status and age, the signature was proved to have a superior predictive power. And stratified analysis found that the signature could further separated postoperative GBM patients who received TMZ-chemoradiation into high- and low-risk groups in TCGA and GEO dataset.ConclusionsThe PCG-lncRNA signature was a novel prognostic marker to predict survival and TMZ-chemoradiation response in GBM patients after surgery.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1744-8) contains supplementary material, which is available to authorized users.