Non-alcoholic fatty liver disease (NAFLD) has emerged as a public health issue with a prevalence of 15-30% in Western populations and 6-25% in Asian populations. Certain studies have revealed the alteration of microRNA (miRNA or miR) profiles in NAFLD and it has been suggested that miR-21 is associated with NAFLD. In the present study, we measured the serum levels of miR-21 in patients with NAFLD and also performed in vitro experiments using a cellular model of NAFLD to further investigate the effects of miR-21 on triglyceride and cholesterol metabolism. Furthermore, a novel target through which miR-21 exerts its effects on NAFLD was identified. The results revealed that the serum levels of miR-21 were lower in patients with NAFLD compared with the healthy controls. In addition, 3-hydroxy-3-methylglutaryl-co-enzyme A reductase (HMGCR) expression was increased in the serum of patients with NAFLD both at the mRNA and protein level. To mimic the NAFLD condition in vitro, HepG2 cells were treated with palmitic acid (PA) and oleic acid (OA). Consistent with the results obtained in the in vivo experiments, the expression levels of miR-21 were decreased and those of HMGCR were increased in the in vitro model of NAFLD. Luciferase reporter assay revealed that HMGCR was a direct target of miR-21 and that miR-21 exerted an effect on both HMGCR transcript degradation and protein translation. Furthermore, the results from the in vitro experiments revealed that miR-21 decreased the levels of triglycerides (TG), free cholesterol (FC) and total cholesterol (TC) in the PA/OA-treated HepG2 cells and that this effect was attenuated by HMGCR overexpression. Taken together, to the best of our knowledge, the present study is the first to report that miR-21 regulates triglyceride and cholesterol metabolism in an in vitro model of NAFLD, and that this effect is achieved by the inhibition of HMGCR expression. We speculate that miR-21 may be a useful biomarker for the diagnosis and treatment of NAFLD.

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Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder poising burgeoning health problem to humans. Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases. Since the roles of lncRNA in NAFLD remain unknown, they were investigated in the study. Microarray expression profiling of mRNAs and lncRNAs was conducted using RNA extracted from patients with and without NAFLD. One thousand seven hundred thirty-five lncRNAs and 1485 mRNA were found differentially expressed in NAFLD samples compared with those in control samples. Among them 535 and 1,200 lncRNAs were upregulated and downregulated in NAFLD, respectively; 760 and 725 mRNAs were upregulated and downregulated in NAFLD, respectively. Moreover, seven lncRNAs and seven mRNAs that were highly up- or downregulated in NAFLD samples were validated by quantitative real-time polymer chain reactions. Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology analysis for the differentially expressed mRNAs showed that these RNAs are involved in various metabolic processes, cellular components, and molecular functions. Our findings indicate that the expression profiles of lncRNAs have changed in NAFLD as compared with normal liver, and the identified regulated RNAs may provide novel insight into the molecular mechanisms underlying the disease and potential novel diagnostic or therapeutic targets for NAFLD.

BackgroundAnaplastic thyroid carcinoma (ATC), a highly aggressive malignancy, has a poor prognosis, and the consensus on the most effective treatment is needed.MethodsClinical data from all ATC patients treated in our institution over a 30-year period (between May 1980 and May 2010) were analyzed retrospectively with regard to mortality and survival rates (Kaplan–Meier). Multivariate analysis was performed using a Cox proportional hazards model.ResultsSixty cases were analyzed. The overall 1- and 3-year survival rates were 35.0% and 22.9%, respectively. Univariate analysis showed that the best prognosis was seen in patients younger than 55 years, those without distant metastases, those with white blood cell (WBC) counts < 10.0 × 109/L or blood platelet (PLT) counts < 300.0 × 109/L at presentation, those who did not receive chemotherapy, and those who received radiotherapy doses ≥ 40 Gy or underwent surgery plus postoperative radiotherapy. According to multivariate analysis, the WBC count at first presentation and the type of therapeutic regimen independently influenced survival.ConclusionsWe found that the elevated peripheral PLT count may be an adverse prognostic factor of ATC patients. The prognosis for ATC is especially poor for patients with distant metastasis, a WBC count ≥ 10.0×109/L, a PLT count ≥ 300.0 × 109/L, or age ≥ 55 years. WBC count at presentation and surgery with or without postoperative radiotherapy independently influenced the prognosis. Intensive treatment combining surgery with postoperative radiotherapy is recommended for ATC patients with stage IVA/B disease.

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Head and neck cancer is the sixth most common malignancy around the world, and 90% of cases are squamous cell carcinomas. In this study, we performed a systematic investigation of the immunogenomic landscape to identify prognostic biomarkers for head and neck squamous cell carcinoma (HNSCC). We analyzed the expression profiles of immune-related genes (IRGs) and clinical characteristics by interrogating RNA-seq data from 527 HNSCC patients in the cancer genome atlas (TCGA) dataset, including 41 HPV+ and 486 HPV− samples. We found that differentially expressed immune genes were closely associated with patient prognosis in HNSCC by comparing the differences in gene expression between cancer and normal samples and performing survival analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the biological functions of the differentially expressed immunogenomic prognosisrelated genes. Two additional cohorts from the Oncomine database were used for validation. 65, 56 differentially expressed IRGs was associated with clinical prognosis in total and HPVsamples, respectively. Furthermore, we extracted 10, 11 prognosis-related IRGs from 65, 56 differentially expressed IRGs, respectively. They were significantly correlated with clinical prognosis and used to construct the prognosis prediction models. The multivariable ROC curves (specifically, the AUC) were used to measure the accuracy of the prognostic models. these genes were mainly enriched in several gene ontology (GO) terms related to immunocyte migration and receptor and ligand activity. KEGG pathway analysis revealed enrichment of pathways related to cytokine−cytokine receptor interactions, which are primarily involved in biological processes. In addition, we identified 63 differentially expressed transcription factors (TFs) from 4784 differentially expressed genes, and 16 edges involving 18 nodes were formed in the regulatory network between differentially expressed TFs and the high-risk survival-associated IRGs. B cell and CD4 T cell infiltration levels were significantly negatively correlated with the expression of prognosis-related immune genes regardless of HPV status. In conclusion, this comprehensive analysis identified the prognostic IRGs as potential biomarkers, and the model generated in this study may enable an accurate prediction of survival. Head and neck cancer is a common malignancy accounting for 5-10% of cancers worldwide. Head and neck squamous cell carcinoma constitutes 90% of head and neck cancers, which arises from the pharynx, the oral cavity and lip, the ear, the larynx, the nasal cavity, the salivary glands and the paranasal sinuses 1-3. The tobacco, alcohol use and human papillomavirus (HPV) infection are important causes of head and neck squamous cell carcinoma 4. HNSCC represents a biologically complex disease process and a heterogeneous collection of tumors in which multiple pathways are altered, leading to the development of HNSCC, and the mechanisms leading to this disease...

The primary reasons for the treatment failure of patients with oral tongue squamous cell carcinoma (OTSCC) are metastasis and tumor recurrence. Identifying the exact mechanisms underlying metastasis is a key point in improving patient prognosis. It has been reported that a hypoxic microenvironment plays an important role during the metastasis of malignancies. We found that the expression of fibronectin type III domain containing 3B (FNDC3B) is positively correlated with lymph node metastasis and advanced cTNM stage of OTSCC by IHC assay and correlation analysis. Furthermore, we found that knockdown of FNDC3B could suppress the migratory and invasive abilities of OTSCC cells. In addition, treating OTSCC cells with CoCl2 (a hypoxia mimetic agent) upregulated the mRNA and protein expression of FNDC3B via HIF-1α. Moreover, the resultant increase in FNDC3B expression significantly induced epithelial-mesenchymal transition (EMT) in OTSCC cells. The present study elucidated the important role played by FNDC3B in OTSCC metastasis and indicates FNDC3B as a potential target for the treatment of OTSCC metastasis. However, many questions remain to be explored.

BackgroundAcute lung injury (ALI) is a life-threatening lung disease where alveolar macrophages (AMs) play a central role both in the early phase to initiate inflammatory responses and in the late phase to promote tissue repair. In this study, we examined whether BML-111, a lipoxin A4 receptor agonist, could alter the phenotypes of AM and thus present prophylactic benefits for ALI.MethodsIn vitro, isolated AMs were treated with lipopolysaccharide (LPS) to induce ALI. In response to BML-111 pre-treatment, apoptosis and autophagy of AMs were examined by flow cytometry, and by measuring biomarkers for each process. The potential involvement of MAPK1 and mTOR signaling pathway was analyzed. In vivo, an LPS-induced septic ALI model was established in rats and the preventative significance of BML-111 was assessed. On the cellular and molecular levels, the pro-inflammatory cytokines TNF-α and IL-6 from bronchoalveolar lavage were measured by ELISA, and the autophagy in AMs examined using Western blot.ResultsBML-111 inhibited apoptosis and induced autophagy of AMs in response to ALI inducer, LPS. The enhancement of autophagy was mediated through the suppression of MAPK1 and MAPK8 signaling, but independent of mTOR signaling. In vivo, BML-111 pre-treatment significantly alleviated LPS-induced ALI, which was associated with the reduction of apoptosis, the dampened production of pro-inflammatory cytokines in the lung tissue, as well as the increase of autophagy of AMs.ConclusionsThis study reveals the prophylactic significance of BML-111 in ALI and the underlying mechanism: by targeting the MAPK signaling but not mTOR pathway, BML-111 stimulates autophagy in AMs, attenuates the LPS-induced cell apoptosis, and promotes the resolution of ALI.