Interleukin-23 (IL-23) is a conventional proinflammatory IL related to colorectal carcinoma (CRC). The signal transducer and activator of transcription (STAT) and suppressors of cytokine signaling (Socs) molecules, respectively, serve as agonists and antagonists of IL-23-associated inflammation. However, it remains unknown whether IL-23 directly affects CRC metastasis. In this study, we measured the metastasis of several human CRC cell lines stimulated by IL-23 in vitro and in vivo. Interestingly, the prometastasis effect of IL-23 was observed only in SW-620 cells. IL-23-associated migration and invasion was mediated by the phosphorylation of STAT5. The expression of Socs3 in SW-620 was impaired by IL-23 via DNA methylation and DNA methyltransferase-1 (DNMT-1)-dependent way. The DNMT-1-associated regulation was not observed in the other three cells. Socs3 was further confirmed to inhibit the prometastatic function of IL-23 both in vitro and in vivo. We analyzed the clinical correlation between the level of IL-23 in tumors and the metastasis of CRC and found that higher IL-23 levels along with lower Socs3 in CRC tissues accounted for more metastatic cases. In conclusion, it was demonstrated that IL-23, assisted by STAT5, might only promote the metastasis of CRC with deficient Socs3 expression in which IL-23-induced DNMT-1 was involved. It was elucidated that Socs3 seemed to be one of the important factors that mediate the selectivity of IL-23. Taken together, these discoveries give rise to new insights into the role of IL-23 in cancer biology and provide additional preclinical data regarding IL-23-associated therapy for CRC.

Astragaloside IV (AS-IV), one of the major active constituents of Astragalus membranaceus in Traditional Chinese Medicine, has been widely used to treat ischemic diseases. However, the potential mechanism is this action is unclear. In this study, we tested the hypothesis that AS-IV might promote angiogenesis through multiple signaling pathways. Our data indicate that AS-IV treatment promotes umbilical vein endothelial cells (HUVEC) proliferation, migration, and tube formation. AS-IV treatment also activates JAK2/STAT3 and ERK1/2 signaling pathways, and up-regulates endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) production. AS-IV-induced angiogenesis in HUVECs is significantly blocked by specific kinase inhibitors. Our study indicated that AS-IV is a key regulator of NO and angiogenesis through the JAK2/STAT3 and ERK1/2 pathways, which provides a mechanistic basis for the potential use of this compound in the treatment of clinical ischemic diseases.

This meta-analysis demonstrates that tonsillectomy is associated with an increased risk of developing CD. We found no evidence to suggest that tonsillectomy exerts a protective effect on the development of UC, as is the case with appendectomy. Further prospective studies are required to confirm the validity of these observations.

Long non‐coding RNA (lncRNA) is one of the important regulators of many malignancies. However, the biological function and clinical significance of a large number of lncRNAs in gastric cancer remain unclear. Therefore, we analysed the TCGA data to find that LINC01303 is significantly up‐regulated in gastric cancer tissues. However, the biological function of LINC01303 in GC remains unknown. In our study, we found that the expression of LINC01303 was significantly higher in GC tissues than in adjacent tissues by real‐time quantitative PCR. We can significantly inhibit the malignant proliferation, migration and invasion of GC cells by silencing LINC01303 expression. In addition, LINC01303 knockdown can also inhibit GC growth in vivo. After the bioinformatics analysis, we found that LINC01303 can be used as a miR‐101‐3p sponge to competitively adsorb miR‐101‐3p with EZH2. Therefore, our results indicate that LINC01303 promotes the expression of EZH2 by inhibiting miR‐101‐3p activity and promotes GC progression. In summary, in this study, we demonstrated for the first time that the LINC01303/miR‐101‐3p/EZH2 axis promotes GC progression.

BackgroundPrevious articles have reported that expression levels of microRNAs (miRNAs) are associated with survival time of patients with gastric cancer (GC). A systematic review and meta-analysis was performed to study the outcome of it.DesignMeta-analysis.MethodsEnglish studies estimating expression levels of miRNAs with any of survival curves in GC were identified up till March 19, 2017 through performing online searches in PubMed, EMBASE, Web of Science and Cochrane Database of Systematic Reviews by two authors independently. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate the correlation between miRNA expression and overall survival (OS).ResultsSixty-nine relevant articles about 26 miRNAs with 6148 patients were ultimately included. GC patients with high expression of miR-20b (HR=2.38, 95%CI=1.16-4.87), 21 (HR=1.77, 95%CI=1.01-3.08), 106b (HR=1.84, 95%CI=1.15-2.94), 196a (HR=2.66, 95%CI=1.94-3.63), 196b (HR=1.67, 95%CI=1.38-2.02), 214 (HR=1.84, 95%CI=1.27-2.67) or low expression of miR-125a (HR=2.06, 95%CI=1.26-3.37), 137 (HR=3.21, 95%CI=1.68-6.13), 141 (HR=2.47, 95%CI=1.34-4.56), 145 (HR=1.62, 95%CI=1.07-2.46), 146a (HR=2.60, 95%CI=1.63-4.13), 206 (HR=2.85, 95%CI=1.73-4.70), 218 (HR=2.61, 95%CI=1.74-3.92), 451 (HR=1.73, 95%CI=1.19-2.52), 486-5p (HR=2.45, 95%CI=1.65-3.65), 506 (HR=2.07, 95%CI=1.33-3.23) have significantly poor OS (P<0.05).ConclusionsIn summary, miR-20b, 21, 106b, 125a, 137, 141, 145, 146a, 196a, 196b, 206, 214, 218, 451, 486-5p and 506 demonstrate significantly prognostic value. Among them, miR-20b, 125a, 137, 141, 146a, 196a, 206, 218, 486-5p and 506 are strong biomarkers of prognosis in GC.

Background: Masked hypertension is associated with adverse cardiovascular outcomes. Nonetheless, no randomized controlled trials exist in the treatment of masked hypertension. The aim of this randomized, placebo-controlled trial was to investigate the efficacy and safety of blood pressure (BP) lowering treatment with a Chinese herbal formula, gastrodia-uncaria granules (GUG), in patients with masked hypertension. Methods: Patients with an office BP of <140/90 mmHg and daytime ambulatory BP of 135-150 mmHg systolic and/or 85-95 mmHg diastolic were randomized 1:1 to the treatment of GUG or placebo 5-10 grams twice daily for 4 weeks. The primary efficacy variable was the change in daytime ambulatory BP. Results: At baseline, office and daytime BP of the 251 participants (mean age 50.4 years, 53.4% men, mean body mass index 24.5 kg/m 2 , and 2.8%, 1.6%, and 30.7% with cardiovascular disease, diabetes mellitus, and smoking, respectively) averaged 129/82 and 135/89 mmHg, respectively. In the intention-to-treat analysis, daytime systolic/diastolic BP was reduced by 5.44 /3.39 and 2.91/1.60 mmHg in the GUG and placebo groups, respectively. The between-group difference in BP reductions was significant for the daytime (2.52/1.79 mmHg, P ≤0.025) and 24-h BP (2.33/1.49 mmHg, P ≤0.012), but not for the clinic and nighttime BPs ( P ≥0.162). The per-protocol analysis in 229 patients produced similar results. Only one adverse event (sleepiness during the day) was reported and no serious adverse event occurred. Conclusions: BP lowering treatment with Chinese traditional medicine GUG is efficacious for patients with masked hypertension. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02156024.

BackgroundNumerous articles reported that dysregulated expression levels of miRNAs correlated with survival time of HCC patients. However, there has not been a comprehensive meta-analysis to evaluate the accurate prognostic value of miRNAs in HCC.DesignMeta-analysis.Materials and MethodsStudies, published in English, estimating expression levels of miRNAs with any survival curves in HCC were identified up until 15 April, 2017 by performing online searches in PubMed, EMBASE, Web of Science and Cochrane Database of Systematic Reviews by two independent authors. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate the correlation between miRNA expression and overall survival (OS).Results54 relevant articles about 16 miRNAs, with 6464 patients, were ultimately included. HCC patients with high expression of tissue miR-9 (HR = 2.35, 95% CI = 1.46–3.76), miR-21 (HR = 1.76, 95% CI = 1.29–2.41), miR-34c (HR = 1.64, 95% CI = 1.05–2.57), miR-155 (HR = 2.84, 95% CI = 1.46–5.51), miR-221 (HR = 1.76, 95% CI = 1.02–3.04) or low expression of tissue miR-22 (HR = 2.29, 95% CI = 1.63–3.21), miR-29c (HR = 1.35, 95% CI = 1.10–1.65), miR-34a (HR = 1.84, 95% CI = 1.30–2.59), miR-199a (HR = 2.78, 95% CI = 1.89–4.08), miR-200a (HR = 2.64, 95% CI = 1.86–3.77), miR-203 (HR = 2.20, 95% CI = 1.61–3.00) have significantly poor OS (P < 0.05). Likewise, HCC patients with high expression of blood miR-21 (HR = 1.73, 95% CI = 1.07–2.80), miR-192 (HR = 2.42, 95% CI = 1.15–5.10), miR-224 (HR = 1.56, 95% CI = 1.14–2.12) or low expression of blood miR-148a (HR = 2.26, 95% CI = 1.11–4.59) have significantly short OS (P < 0.05).ConclusionsIn conclusion, tissue miR-9, miR-21, miR-22, miR-29c, miR-34a, miR-34c, miR-155, miR-199a, miR-200a, miR-203, miR-221 and blood miR-21, miR-148a, miR-192, miR-224 demonstrate significantly prognostic value. Among them, tissue miR-9, miR-22, miR-155, miR-199a, miR-200a, miR-203 and blood miR-148a, miR-192 are potential prognostic candidates for predicting OS in HCC.

CircPRTM5 is associated with cell proliferation and migration in many kinds of malignancies. However, the functions and mechanisms of CircPRTM5 in CRC progression remain unclear. We explored the role and the mechanisms of CircPRTM5 in the development of CRC. Tissues of CRC patients and matched adjacent non‐tumour tissues were collected to evaluate the expression of CircPRTM5. The expression of CircPRTM5 in CRC tissues was significantly higher than that in adjacent tissues. The biological functions of CircPRTM5 in CRC were determined by overexpression and down‐regulation of CircPRTM5 in CRC cells in vitro and in vivo. The results indicate that knockdown of CircPRTM5 can significantly inhibit the proliferation of CRC cells. The potential mechanisms of CircPRTM5 in CRC development were identified by RT‐qPCR, Western blotting analysis and luciferase reporter assay. CircPRTM5 competitively regulates the expression of E2F3 by capillary adsorption of miR‐377. CircPRMT5 regulates CRC proliferation by regulating the expression of E2F3, which affects the expression of the cell cycle‐associated proteins cyclinD1 and CDK2. CircPRTM5 exerts critical regulatory role in CRC progression by sponging miR‐377 to induce E2F3 expression.