Xiao-Yu Zhou

A meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates

Necrotizing enterocolitis (NEC) is one of the most common acquired diseases of the gastrointestinal tract in preterm infants. Some randomized, controlled trials (RCTs) have indicated that probiotics may potentially lower the incidence of NEC and mortality. However, debate still remains about the safety of probiotics and their influence on normal infant growth. We performed this meta-analysis to assess the safety and benefits of probiotic supplementation in preterm infants. We searched in PubMed, Embase, and Cochrane databases for English references, and in Wanfang, VIP, and CNKI databases for Chinese references. Ultimately, 27 RCTs (including 9 Chinese articles) were incorporated into this meta-analysis. Relative risk (RR) and weighted mean difference (WMD) were calculated using a random-effects or fixed-effects model, depending on the data type and heterogeneity. A total of 6655 preterm infants, including the probiotic group (n=3298) and the placebo group (n=3357), were eligible for inclusion in this meta-analysis. For Bell stage ≥I and gestational age <37 weeks, risk of NEC incidence was significantly lower in the probiotic group [RR=0.35, 95% confidence interval (CI)=0.27-0.44, P<0.00001]. For Bell stage ≥II or gestational age <34 weeks, there were likewise significant differences between the probiotic and placebo groups concerning NEC incidence (RR=0.34, 95%CI=0.25-0.48, P<0.00001; and RR=0.39, 95%CI=0.27-0.56, P<0.00001). Risk of death was significantly reduced in the probiotic group (RR=0.58, 95%CI=0.46-0.75, P<0.0001). In contrast, there was no significant difference concerning the risk of sepsis (RR=0.94, 95%CI=0.83-1.06, P=0.31). With respect to weight gain and the age at which infants reached full feeds, no significant differences were found between the probiotic and placebo groups (WMD=1.07, 95%CI=−0.21-2.34, P=0.10; and WMD=−1.66, 95%CI=−3.6-0.27, P=0.09). This meta-analysis has shown that, regardless of gestational age and NEC stage, probiotic supplementation could significantly reduce the risk of NEC in preterm infants. Analysis also indicated that such supplementation did not increase the incidence risk of sepsis or of mortality. Finally, the study showed that probiotic supplementation may have no adverse effect on normal feeding and growth.

Neuroprotective effects of microRNA-210 against oxygen-glucose deprivation through inhibition of apoptosis in PC12 cells

Although several reports have demonstrated the specific roles of microRNAs (miRs) in neuronal differentiation, neurogenesis, neural cell specification and neurodevelopmental function, there have been no studies with regard to the importance of miRs in hypoxic-ischemic encephalopathy (HIE). In the present study, we aimed to investigate the effect of miR-210 on neuronal cell apoptosis caused by HI injury. We established an ex vivo model of HIE using oxygen-glucose deprivation (OGD) and demonstrated that miR-210 expression was upregulated in pheochromocytoma (PC12) cells after 4 h of OGD compared with normoxic controls. Furthermore, miR-210 suppressed cell apoptosis by inhibiting caspase activity and by regulating the balance between Bcl-2 and Bax levels. In conclusion, the present study revealed that miR-210 exerts neuroprotective effects by inhibiting cell apoptosis. This work represents a potential novel therapeutic approach to combat neonatal HI injury.

Neuroprotective Effects of MicroRNA-210 on Hypoxic-Ischemic Encephalopathy

Objectives. To reveal the effect of microRNA-210 on cell apoptosis caused by HIE. Methods. Postnatal day 7 rats after HI injury were intraventricularly injected with microRNA-210 mimic, microRNA-210 inhibitor, or physiological saline. 72 h after the injection, rats were sacrificed and the left hemispheres were collected. The expression level of microRNA-210 was identified by quantitative real-time PCR analysis. Apoptosis in brain sections was investigated by TUNEL assay. Apoptosis-related protein expressions were studied by Western blot analysis. Results. The results showed that microRNA-210, whose expression was downregulated in the brain 72 h after HI injury, suppressed neuronal apoptosis by inhibiting caspase activity and regulating the balance between bcl-2 and bax levels. Discussion. Recent study demonstrated that microRNA-210 has neuroprotective effects through inhibiting apoptosis in a murine model of HIE. It represents a potential novel therapeutic approach for the treatment of HIE.

Regulation of pulmonary surfactant synthesis in fetal rat type II alveolar epithelial cells by microRNA-26a.

Pulmonary surfactant, a unique developmentally regulated, phospholipid‐rich lipoprotein, is synthesized by the type II epithelial cells (AECII) of the pulmonary alveolus, where it is stored in organelles termed lamellar bodies. The synthesis of pulmonary surfactant is under multifactorial control and is regulated by a number of hormones and factors, including glucocorticoids, prolactin, insulin, growth factors, estrogens, androgens, thyroid hormones, and catecholamines acting through beta‐adrenergic receptors, and cAMP. While there is increasing evidence that microRNAs (miRNAs) are involved in the regulation of almost every cellular and physiological process, the potential role of miRNAs in the regulation of pulmonary surfactant synthesis remains unknown. miRNA‐26a (miR‐26a) has been predicted to target SMAD1, one of the bone morphogenetic protein (BMP) receptor downstream signaling proteins that plays a key role in differentiation of lung epithelial cells during lung development. In this study, we explored the regulation role of miR‐26a in the synthesis of pulmonary surfactant. An adenoviral miR‐26a overexpression vector was constructed and introduced into primary cultured fetal AECII. GFP fluorescence was observed to determinate the transfection efficiency and miR‐26a levels were measured by RT‐PCR. MTT was performed to analyze AECII viability. qRT‐PCR and Western blotting were used to determine the mRNA and protein level of SMAD1 and surfactant‐associated proteins. The results showed that miR‐26a in fetal AECII was overexpressed after the transfection, and that the overexpression of miR‐26a inhibited pulmonary surfactant synthesis in AECII. There was no significant change in cell proliferation. Our results further showed that overexpression of miR‐26a reduced the SMAD1 expression both in mRNA and protein level in fetal AECII. These findings indicate that miR‐26a regulates surfactant synthesis in fetal AECII through SMAD1. Pediatr Pulmonol. 2014; 49:863–872.

Gene expression profiles of adipose tissue of obese rats after central administration of neuropeptide Y-Y5 receptor antisense oligodeoxynucleotides by cDNA microarrays.

To investigate the gene expression profiles of adipose tissue of obese rats after central administration of neuropeptide Y-Y5 receptor antisense oligodeoxynucleotides (ODNs), Y5 receptor antisense, mismatched ODNs or vehicle was intracerebroventricularly injected and cDNA microarrays were undertaken. Central administration of NPY-Y5 receptor antisense ODNs decreased food intake, body weight and serum insulin compared with both vehicle and mismatched ODNs. The average area of adipocytes both at retroperitoneal and epididymal adipose tissue were fall in antisense group while only the weight of the retroperitoneal fat pats was reduced in antisense group. cDNA microarrays containing 18,000 genes/Ests were used to investigate gene expression of adipose tissue. Autoradiographic analysis showed that 404, 81, and 34 genes were differently expressed over twofold, threefold, and fivefold, respectively. The analysis of gene expression profiles indicated that 332 genes were up-regulated and 187 genes were down-regulated in response to Y5 receptor antisense ODNs treatment. Different clusters of genes associated with apoptosis, signal transduction, energy metabolism, lipid metabolism, etc., such as FXR1, PHLDA1, MAEA, PIK3R1, ICAM2, PITPN, CALM2, CAMK2D, PKIA, DRD2, SLC25A14, CKB, AADAC, LIPA, ACOX3, FADS1, were concerned. Analysis of differentially expressed genes will help to understand the effects of Y5 receptor antisense ODNs therapy.

Effects of antenatal application of ambroxol and glucocorticoid on lung morphometry and signal transduction of bone morphogenetic protein in the fetal rat.

Antenatal ambroxol, dexamethasone (Dex) and betamethasone (Beta) are used to prevent neonate respiratory distress syndrome. The present study aimed to investigate the role of ambroxol, Dex and Beta administered antenatally on lung morphogenesis and signal transduction of bone morphogenetic protein (BMP) in rat embryo. Fetal lungs treated with ambroxol, 1-day Beta, 3-day Dex and 3-day Beta were more mature compared to the controls as determined by light microscopy and transmission electron microscopy. Expression of BMP4 and bone morphogenetic protein receptor II (BMPR‑II) mRNA was upregulated in the 1-day-Beta-, 3-day-Dex- and 3-day-Beta-treated animals. BMP4 and BMPR-II protein were significantly increased in the 1-day-Beta-, 3-day-Dex- and 3-day-Beta-treated animals. Ambroxol, Dex and Beta promoted the morphological development of rat fetal lung; Beta was more effective than Dex. A multi-dose of glucocorticoids exhited a more beneficial effect than a single dose. The effects of Beta and Dex may be mediated by regulation of BMP signal transduction in rat fetal lung.

Characterization of microRNA expression profiles in 3T3-L1 adipocytes overexpressing C10orf116

Our data in the previous report demonstrated that C10orf116 (AFRO) is an adipocyte lineage-specific nuclear factor that can modulate the master adipogenesis transcription factors early during differentiation. However, more precise functional properties of this gene need to be clarified and await further investigation. Therefore, in this study, we performed an expression profile of cellular MicroRNAs (miRNAs) in the C10orf116 overexpression 3T3-L1 adipocytes and performed target prediction and functional enrichment of the differentially expressed miRNAs. Our study identified 34 miRNAs up-regulated in the 3T3-L1 adipocytes stably overexpressing C10orf116, whereas 43 miRNAs up-regulated in the control cells. The target genes of differentially expressed miRNAs were found to be involved in multiple signalling pathways, such as Wnt, TGF-beta, MAPK, Jak-STAT, insulin signalling pathway, et al. Our data provided novel information for the identification of C10orf116.

Expression profile of plasma microRNAs in premature infants with respiratory distress syndrome

As well-known regulators of gene expression, microRNAs (miRNAs) are important not only in cell proliferation and differentiation, but also in tumorigenesis and organ development. It has been estimated that miRNAs may be responsible for regulating the expression of almost one third of the human genome. Simultaneously, with advances in neonatal care in the clinic, an increased number of premature infants are being saved and, thus, respiratory distress syndrome (RDS) has become more common. However, previous non-miRNA studies have suggested their connection with RDS. In the present study, a miRNA microarray, including >1,891 capture probes was used to compared the expression profiles of plasma miRNAs between RDS and control groups. miRNAs, which were observed to have consistent fold-changes (fold-change ≥ 1.3) between the two groups were selected and validated using reverse transcription-quantitative polymerase chain reaction. As a result, 171 differentially expressed miRNAs were identified, including two upregulated and seven downregulated miRNAs. Of these miRNAs, four were selected as having higher fold-changes between the two groups. This is the first time, to the best of our knowledge, that these nine miRNAs have been reported in RDS. It was hypothesized that these novel miRNAs may be important in RDS, and may provide meaningful biomarkers for the diagnosis of RDS.

Reference values for serum cystatin C in very low-birthweight infants: From two centres of China

To determine the level of cystatin C (Cys‐C) values in preterm babies for the purpose of becoming a good endogenous marker of renal function.

Does neutrophil/lymphocyte ratio have good diagnostic value in neonatal necrotizing colitis?

Abstract Objective: The diagnostic value of neutrophil/lymphocyte (N/L) ratio in the early diagnosis of neonatal necrotizing colitis (NEC) was evaluated. Methods: This is a cross-sectional study. From the 103 NEC cases, the preterm infants were randomly recruited into this study, including NEC I 41 cases, NEC II 34 cases, and NEC III 28 cases. The control group included 58 preterm infants without NEC. Routine clinical data and blood samples of all NEC patients were collected within 24 h after the established diagnosis of NEC. Besides comparing laboratory data (white blood cell count, C-reactive protein, pre-albumin and N/L ratio) between NEC and control groups, the sensitivity, specificity, and Youden index were also compared. Results: (1) Baseline data including gender, age of admission, and contamination of amniotic fluid showed no difference. But, laboratory data all have significant differences between NEC and control groups (including NEC subgroups analysis). (2) Except pre albumin (PA), there are not significant correlations between N/L ratio and PA, C-reactive protein (CRP) as well as white blood cell count (white blood cell (WBC) count) in NEC stage I. In contrast, good correlation could be found between N/L ratio and other indicators in NEC stage II and stage III. (3) N/L ratio has higher sensitivity, specificity and Youden index when compared with WBC count, CRP, and PA. Conclusion: N/L ratio has better continuity and could be good marker for the early diagnosis of NEC, and could distinguish the severity. However, large sample, multicenter studies are still needed.