Lnc-NEAT1 induces cell apoptosis and inflammation but inhibits proliferation in a cellular model of hepatic ischemia/reperfusion injury.

OBJECTIVE: We aimed to investigate the effect of long non-coding RNA nuclear-enriched abundant transcript 1 (lnc-NEAT1) on regulating hepatocyte proliferation, apoptosis, and inflammation during hepatic ischemia/reperfusion (I/R) injury. METHODS: Human liver cells (HL-7702) were cultured under glucose-free and oxygen-free conditions to construct the I/R injury model. Expression of lnc-NEAT1 was detected in this model and in normal cells. Plasmids of control overexpression [NC(+)], lnc-NEAT1 overexpression [NEAT1(+)], control short hairpin (sh)RNA [NC(-)], and lnc-NEAT1 shRNA [NEAT1(-)] were transfected into HL-7702 cells and subsequently subjected to I/R treatment. Cell proliferation, apoptosis, apoptosis-related proteins, and inflammatory cytokines were assessed. RESULTS: Lnc-NEAT1 expression was elevated in the I/R group compared with the normal group. Cell proliferation was decreased in the NEAT1(+) group compared with the NC(+) group but increased in NEAT1(-) compared with NC(-). The apoptosis rate increased in the NEAT1(+) group compared with the NC(+) group but decreased in NEAT1(-) compared with NC(-). Western blot assay (detection of apoptosis-related proteins) showed similar results. Expression of interleukin-1ß, interleukin-6, and tumor necrosis factor-α increased in the NEAT1(+) group compared with NC(+) but decreased in NEAT1(-) compared with NC(-). CONCLUSION: Lnc-NEAT1 is overexpressed, induces cell apoptosis and inflammation, and inhibits proliferation during hepatic I/R injury.

Protective activity of asatone against ovalbumin-induced allergic asthma.

Allergic asthma is a chronic lung disease characterized by wheezing, coughing, chest tightness and shortness of breath. Clinically, the treatments against asthma focus on controlling the symptoms rather than inhibiting recurrence radically. Additionally, local and systemic side effects caused by current treatments are worthy of attention. Therefore, a novel therapeutic strategy against asthma is needed. Asatone is a pharmacologically active component from Radix et Rhizoma Asari, which has anti-inflammatory effects in lipopolysaccharide-induced lung injury. In the present study, we showed that asatone could protect mice against OVA-induced asthma, as manifested by attenuating inflammation infiltration, mucus production, and airway hyperreactivity and suppressing the elevation of IL-4, IL-5, and IL-13 in broncho-alveolar lavage fluid. Overall, results of the present study support use of asatone as a potent therapeutic strategy for clinical treatment of allergic asthma.

Correlation of sex-determining region Y-box 30 with tumor characteristics and its prognostic value in breast cancer.

OBJECTIVE: Sex-determining region Y-box 30 (SOX30) suppresses progression of several cancers, whereas its role in breast cancer is unclear. Therefore, we aimed to determine the correlation of SOX30 with tumor characteristics and prognosis in breast cancer patients. METHODS: The tumor samples of 510 breast cancer patients who underwent resection were obtained, and SOX30 expression was analyzed by immunohistochemistry. Clinical characteristics, disease-free survival (DFS), and overall survival (OS) of breast cancer patients were recorded. RESULTS: There were 368 breast cancer patients in SOX30 low-expression group and 142 in SOX30 high-expression group. SOX30 was negatively correlated with tumor size (P = .010), tumor (T) stage (P < .001), node (N) stage (P = .001), and tumor, node, metastasis (TNM) stage (P < .001) in breast cancer patients. For prognosis, patients in SOX30 high-expression group had prolonged DFS (P = .011) and OS (P = .002); moreover, increased SOX30 grade (assessed by semi-quantitative scoring method assessment) was correlated with better DFS (P = .015) and OS (P = .014). Univariate Cox's regression analysis disclosed that SOX30 high expression was correlated with enhanced DFS (P = .012, hazard ratio (HR) = 0.582) and OS (P = .002, HR = 0.389); however, multivariate Cox's regression analysis revealed that SOX30 could not independently predict DFS (P = .224, HR = 0.766) or OS (P = .087, HR = 0.582) in breast cancer patients, indicating it might interact with other independent predictive factors (such as pathological differentiation, T stage, and N stage) to influence DFS and OS in breast cancer patients. CONCLUSION: Sex-determining region Y-box 30 is a potential prognostic biomarker in breast cancer, which might contribute to the better outcome of breast cancer patients.

Correlation of microRNA expression profile with clinical response to tumor necrosis factor inhibitor in treating rheumatoid arthritis patients: A prospective cohort study.

BACKGROUND: This study aimed to explore the correlation of circulating microRNA (miRNA) expression profile with clinical response to tumor necrosis factor (TNF) inhibitor in treating rheumatoid arthritis (RA) patients. METHODS: Baseline PBMC samples from eight responders and eight non-responders after 24-week TNF inhibitor (etanercept) treatment were subjected to miRNA microarray. Then, top 10 dysregulated miRNAs were selected and further validated by quantitative polymerase chain reaction (qPCR) in baseline PBMC samples from 92 RA patients treated with 24-week TNF inhibitor (etanercept). Responders and non-responders were divided referring to the decline in disease activity score in 28 joints. RESULTS: In microarray assay, total 59 upregulated and 78 downregulated miRNAs were identified in responders compared to non-responders, which were mainly enriched in regulating immune- and inflammation-related biological processes and pathways. The top 10 dysregulated miRNAs were as follows: miR-192-5p, miR-146a-5p, miR-19b-3p, miR-320c, miR-335-5p, miR-149-3p, miR-766-3p, let-7a-5p, miR-24-3p, and miR-1226-5p. In qPCR validation, miR-146a-5p was increased, while let-7a-5p was decreased in responders compared with non-responders. Multivariate logistic analysis illuminated that miR-146a-5p and CRP independently correlated with higher clinical response, while let-7a-5p and biologics history independently associated with lower clinical response. Subsequently, receiver operating characteristic curve showed that combination of these four independent factors presented with a great predictive value for clinical response with area under curve: 0.863, 95% CI 0.781-0.945. CONCLUSION: miRNA expression profile is closely implicated in the treatment efficacy of TNF inhibitor, and combined measurement of miR-146a-5p, let-7a-5p, CRP, and biologics history disclosed a great predictive value for clinical response to TNF inhibitor in RA patients.

Aloperine Protects Mice against Bleomycin-induced Pulmonary Fibrosis by Attenuating Fibroblast Proliferation and Differentiation.

Aloperine is a quinolizidine alkaloid extracted from Sophora alopecuroides. It has been proven to alleviate oxidative stress and effectively promote tumor cell apoptosis in mice. Herein, we investigated whether aloperine could also mediate its protective effects on bleomycin (BLM)-induced pulmonary fibrosis. Pathological staining, western blot, RT-PCR and flow cytometry were used to evaluate the impact of aloperine on the development of pulmonary fibrosis. The effect of aloperine on fibroblast proliferation, differentiation and related signaling pathways were next investigated to demonstrate the underlying mechanisms. In the present report, we showed that aloperine provided protection for mice against BLM-induced pulmonary fibrosis as manifested by the attenuated lung injury and reduced fibrosis along with alleviated fibroblast proliferation and differentiation. Additionally, we provided in vitro evidence revealing that aloperine inhibited cellular proliferation in PDGF-BB-stimulated mouse lung fibroblasts by repressed PI3K/AKT/mTOR signaling and fibroblast to myofibroblast differentiation by repressed TGF-ß/Smad signaling. Overall, our data showed that aloperine could protect the mice against BLM-induced pulmonary fibrosis by attenuated fibroblast proliferation and differentiation, which indicated that aloperine may be therapeutically beneficial for IPF patients.

MicroRNA­455 is downregulated in gastric cancer and inhibits cell proliferation, migration and invasion via targeting insulin­like growth factor 1 receptor.

Gastric cancer is the fourth most common and the second leading cause of cancer mortality worldwide. The dysregulation of microRNAs has been demonstrated to be significant in gastric cancer carcinogenesis and progression due to changes in expression of their target genes. In the current study, microRNA­455 (miR­455) was identified to be significantly downregulated in gastric cancer tissue samples and cell lines. A low expression level of miR­455 was correlated with the clinical stage, lymph node metastasis and tumor invasion in gastric cancer. Restoration of miR­455 expression inhibited cell proliferation, migration and invasion of gastric cancer cells in vitro. Bioinformatic analysis and luciferase reporter assay revealed that miR­455 directly targeted the 3'­untranslated region of insulin­like growth factor 1 receptor (IGF­1R). In addition, the IGF­1R mRNA expression level was increased in gastric cancer tissue samples and was inversely correlated with miR­455 expression levels. Restoration of miR­455 downregulated IGF­1R mRNA and protein expression levels in gastric cancer cells. Furthermore, silencing of IGF­1R significantly inhibited gastric cancer cell proliferation, migration and invasion, which was similar to the functions induced by miR­455 overexpression. Thus, these results indicate that miR­455 is involved in gastric cancer progression by directly targeting IGF­1R and may serve as a novel therapeutic target for the treatment of gastric cancer.