[Expression and significance of jumonji domain-containing protein 2B and hypoxia inducible factor-1α in non-Hodgkin lymphoma tissues in children]. / 含jumonji结构域的蛋白2Bå’Œç¼ºæ°§è¯±å¯¼å› å­1α在儿童非霍奇金淋巴瘤组织中的表达及意义.

OBJECTIVES: To investigate the expression and significance of jumonji domain-containing protein 2B (JMJD2B) and hypoxia-inducible factor-1α (HIF-1α) in non-Hodgkin's lymphoma (NHL) tissues in children. METHODS: Immunohistochemistry was used to detect the expression of JMJD2B and HIF-1α in lymph node tissue specimens from 46 children with NHL (observation group) and 24 children with reactive hyperplasia (control group). The relationship between JMJD2B and HIF-1α expression with clinicopathological characteristics and prognosis in children with NHL, as well as the correlation between JMJD2B and HIF-1α expression in NHL tissues, were analyzed. RESULTS: The positive expression rates of JMJD2B (87% vs 21%) and HIF-1α (83% vs 42%) in the observation group were higher than those in the control group (P<0.05). The expression of JMJD2B and HIF-1α was correlated with serum lactate dehydrogenase levels and the risk of international prognostic index in children with NHL (P<0.05). The expression of JMJD2B was positively correlated with the HIF-1α expression in children with NHL (rs=0.333, P=0.024). CONCLUSIONS: JMJD2B and HIF-1α are upregulated in children with NHL, and they may play a synergistic role in the development of pediatric NHL. JMJD2B can serve as a novel indicator for auxiliary diagnosis, evaluation of the severity, treatment guidance, and prognosis assessment in pediatric NHL.

Circ_0038467 regulates lipopolysaccharide-mediated cell proliferation, apoptosis, and inflammatory response by miR-195-5p/TLR4 axis through NF-κB pathway in MRC-5 cells.

Infantile pneumonia (IP) is an acute lower respiratory infection and brings a heavy burden to children health. Circular RNAs (circRNAs) participate in the regulation of pneumonia process. In this research, the effects of circ_0038467 in regulating lipopolysaccharide (LPS)-induced cell injury and underlying mechanism were revealed. Results showed that circ_0038467 expression and TLR4 protein level were upregulated, while miR-195-5p expression was downregulated in LPS-induced MRC-5 cells. Circ_0038467 silencing restored LPS-mediated inhibition on cell proliferation and promotion on apoptosis and inflammatory response. Additionally, circ_0038467 acted as a sponge of miR-195-5p, which was further revealed to target TLR4. MiR-195-5p inhibitor reversed circ_0038467 silencing-mediated influences under LPS treatment. Furthermore, LPS-activated NF-κB pathway was partly blocked by circ_0038467 silencing, which was restrained by TLR4 overexpression. Circ_0038467 silencing protected MRC-5 cells from LPS-induced injury by miR-195-5p/TLR4 axis through NF-κB pathway, providing a theoretical basis for circRNA-directed IP therapy.

[Changes of plasma cardiotrophin-1 levels in neonates with myocardial ischemic injury].

OBJECTIVE: To study the changes and significance of plasma cardiotrophin-1 (CT-1) in neonates with hypoxic-ischemic encephalopathy (HIE) complicated by myocardial ischemic injury. METHODS: Forty-five neonates with HIE (15 mild cases, 24 moderate cases and 6 severe cases) were enrolled and divided into two subgroups based on the presence of myocardial injury (n=19) and not (n=26). Twenty healthy neonates were used as the control group. Plasma CT-1 levels were measured using double-antibody sandwich enzyme immunoassay method. Serum creatinine kinase MB (CK-MB) and cardiac troponin I (CTnI ) levels were also measured. RESULTS: Plasma CT-1 levels in the mild HIE (169±20 pg/mL) and moderate/severe HIE subgroups (287±44 pg/mL) were significantly higher than those in the control group (30±8 pg/mL), and plasma CT-1 levels were associated with the severity of HIE (P<0.01). Plasma CT-1 levels were positively correlated with serum CK-MB and CTnI levels in neonates with HIE in the acute phase (r=0.565 and 0.621 respectively; P<0.01). Plasma CT-1 levels in neonates with myocardial injury were significantly higher than those without myocardial injury (249 ±35 pg/mL vs 177±26 pg/mL; P<0.01). Plasma CT-1 levels were significantly reduced in neonates with myocardial injury in the convalescent phase (157±19 pg/mL) compared with those in the acute phase (249±35 pg/mL; P<0.01). CONCLUSIONS: Detection of plasma CT-1 levels may be useful in the diagnosis of myocardial ischemic injury and the severity evaluation of HIE.

[ZO-1 gene methylation status and its clinical significance in children with non-Hodgkin lymphoma].

OBJECTIVE: To investigate the methylation status of zonula occludens-1 (ZO-1) gene promoter and its clinical significance in children with stage IV non-Hodgkin lymphoma (NHL) and to provide a basis for further etiological study and early diagnosis of this disease. METHODS: Fifty-five children with a confirmed diagnosis of stage IV NHL (40 cases of T-NHL and 15 cases of B-NHL) were selected as the case group, and 20 children with diseases other than hematologic malignancies were selected as the control group. Bone marrow samples were collected from these subjects. Methylation-specific PCR (MS-PCR) was applied to evaluate the methylation status of ZO-1 gene promoter, and the integrated optical density (IOD) was determined. RT-PCR was used to measure the mRNA expression of ZO-1. RESULTS: MS-PCR showed that the methylated bands of ZO-1 gene promoter were found in 39 (70.9%) of 55 patients in the case group before treatment, while no ZO-1 gene promoter methylation was detected in the control group. With close tracking of 47 cases in the study group, consisting of 32 cases of T-NHL and 15 cases of B-NHL, the rates of ZO-1 gene promoter methylation prior to treatment were 72% and 67%, respectively, (P>0.572). The cases of T-NHL and B-NHL showed no significant changes in methylation rate in the early and middle phases of chemotherapy (P>0.05), but they showed significant changes in methylation rate in the late phase of chemotherapy (P<0.05). RT-PCR showed that the NHL cases carrying methylated ZO-1 gene had no mRNA expression of ZO-1, while all children in the control group had mRNA expression of ZO-1. There was no linear relationship between the total number of peripheral blood leukocytes and ZO-1 gene IOD (r=0.093, P=0.575); a positive correlation was found between the number of malignant cells in bone marrow and ZO-1 gene IOD (r=0.669, P<0.001). CONCLUSIONS: ZO-1 gene shows a hypermethylation status in children with NHL, and the methylation level is positively correlated with the number of malignant cells in bone marrow. ZO-1 may be used as a novel molecular marker in early diagnosis, outcome assessment, prognostic evaluation, and detection of minimal residual disease.

MiR-363 suppresses the tumor growth of natural killer/T-cell lymphoma via the SIRT6/PI3K/AKT axis.

Background: Natural killer/T cell lymphoma (NKTCL) is a rare and aggressive tumor of non-Hodgkin's lymphoma. The role of micro ribonucleic acid (RNA) (miR)-363 in NKTCL has not yet been elucidated. The present study aimed to investigate the potential role of miR-363 in NKTCL. Methods: The expression of the top five differentially expressed microRNAs (miRNAs) as well as sirtuin 6 (SIRT6) in NK normal cells and its tumor cell lines were explored. The clinical tissues of NKTCL patients were collected and analyzed for expression of miR-363 and SIRT6. In addition, human NK/T-cell lymphoma cells (SNK-6) were transfected into different groups to detect cell proliferation and apoptosis abilities through cell counting kit 8 (CCK-8) experiment and flow cytometry analysis. Western blot assay was employed to examine protein expression. NKTCL nude mice models were constructed by subcutaneous injection of stably transfected SNK-6 cells to validate the mechanism of miR-363 in NKTCL via SIRT6 in vivo. Results: MiR-363 was down-regulated in NKTCL tissues and cell lines. Overexpression of miR-363 inhibited cell proliferation and promoted cell apoptosis. In contrast, SIRT6 was up-regulated in NKTCL and proved to be a downstream target of miR-363. SIRT6 could activate the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Also, miR-363 mimic could suppress the proliferation and induce the apoptosis of NKTCL via the SIRT6/PI3K/AKT axis both in vitro and in vivo. Conclusions: MiR-363 suppresses the SIRT6/PI3K/AKT pathway to restrain cell proliferation and accelerate cell apoptosis during NKTCL progression.

Bifidobacterium may benefit the prevention of necrotizing enterocolitis in preterm infants: A systematic review and meta-analysis.

AIM: A systematic review and meta-analysis was designed to evaluate the efficacy and safety of Bifidobacterium for preventing necrotizing enterocolitis (NEC) in preterm infants. METHODS: We searched the Cochrane Library, PubMed, EMBASE and Web of Science to December 2017. Risk ratio (RR) with 95% confidence intervals (CIs) were estimated to compare the outcomes of the groups. For the pooled RR estimating the incidence of NEC, we also performed subgroup analysis. Besides, sensitivity analysis was performed to examine the stability of the combined results. Two reviewers assessed trial quality and extracted data independently. The work has been reported in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines. All statistical analyses were performed using standard statistical procedures provided in Review Manager 5.2. RESULTS: Twenty four randomized, placebo-controlled studies (N = 6155 participants) were included in this analysis, of which twenty two studies were used for assessing the efficacy of Bifidobacterium for preventing NEC and seventeen for assessing the safety (sepsis and death). When comparing Bifidobacterium groups with control groups, the relative risk of developing NEC (RR 0.38, 95% CI 0.25-0.58; P < 0.00001) or death (RR 0.74, 95% CI 0.60-0.92; P = 0.006) was significantly lower in the Bifidobacterium groups. No significant difference in the incidence of sepsis was found (RR 0.87, 95% CI 0.73-1.03; P = 0.11). In addition, significant results for NEC were also found in all subgroups we made. CONCLUSIONS: Bifidobacterium may have a beneficial effect and be safe in preventing necrotizing enterocolitis in preterm infants.

H3K27me3 and VEGF is associated with poor prognosis in patients with synovial sarcoma.

PURPOSE: Previous studies have shown a correlation between the expression of H3K27me3 and pathological characteristics of malignant tumors. This study aimed to investigate the association of H3K27me3 and VEGF expression with clinical outcomes of synovial sarcoma patients. METHODS: This study included 48 patients with synovial sarcoma. H3K27me3 and VEGF levels were evaluated by immunohistochemical staining, and their correlation with clinical parameters was analyzed by Spearman's and Pearson's test. Univariate and multivariate Cox regression analyses were used to identify potential prognostic factors. Kaplan-Meier method was used to analyze overall survival. RESULTS: Protein levels of both H3K27me3 and VEGF were significantly associated with histologic grade (P = 0.004, P = 0.042, respectively), metastasis (P = 0.009, P = 0.028, respectively), and AJCC staging (P < 0.001, P = 0.003, respectively). H3K27me3 and VEGF expression showed positive correlation (P < 0.001, R = 0.618). Both H3K27me3 and VEGF expression were significantly associated with shorter overall survival by univariate analysis, but the association was significant for H3K27me3 [P = 0.26, HR = 2.640 (1.124-6.200)] only by multivariate analysis. CONCLUSIONS: H3K27me3 and VEGF expression are both significantly associated with overall survival of synovial sarcoma, and H3K27me3 is a significant independent prognostic indicator in patients with synovial sarcoma.

[Methylation of Id4 gene and inhibitive effect of arsenic trioxide on it in Raji cells].

OBJECTIVE: To study methylation of Id4 gene and demethylation effect of arsenic trioxide (ATO) in Raji cells. METHODS: Human Burkitt's Raji lymphoma cells were cultared and treated with ATO at different concentrations and different time points. Methylated degree of Id4 gene was detected by methylation specificity polymerase chain reaction (MS-PCR), Id4 mRNA expression in Raji cell by reverse transcription polymerase chain reaction (RT-PCR), the growth of cell by MTT assay, and cell apoptosis and cycle distribution by Flow Cytometry (FCM). RESULTS: (1) The Id4 gene exhaustive methylation in control group, and hypermethylation in experimental group were reversed by ATO in a dose-dependent manner. (2) Id4 mRNA expression in Raji cells treated with ATO for 48 h increased gradually with ATO concentration increasing in experimental group. (3) Raji cell growth inhibited rates after different concentrations of ATO treatment for 24, 48, 72 h were 12.15% ∼ 92.17% in the experimental group (P < 0.05). (4) Apoptosis peak emerged after ATO treatment for 48 hours in experimental group, while a much lower apoptosis in control group. (5) After ATO treatment for 48 h in experiment group, the cells were arrested at G(0)/G(1) phase in a dose-dependent manner. CONCLUSION: Id4 gene presents exhaustive methylation in Raji cells. ATO can reverse the hypermethylation of Id4 gene and recover the expression of Id4 mRNA. Hypermethylation of Id4 gene is one of the reasons of Raji cells malignant proliferations.