Objective. To determine the role of sodium butyrate in intestinal inflammation via regulation of high-mobility group box-1 (HMGB1), we analyzed the potential mechanism in necrotizing enterocolitis (NEC) in a neonatal mouse model. Methods. A NEC model was created with hypoxia and cold exposure and artificial overfeeding. C57BL/6 neonatal mice were randomized into three groups: the control, untreated NEC, and sodium butyrate (150 mM)-pretreated NEC groups. Pathological variations in ileocecal intestinal tissue were observed by HE staining and scored in a double-blind manner. The mRNA expression levels of HMGB1, Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), and inflammatory cytokines in intestinal tissues were determined by quantitative real-time PCR. The protein levels of HMGB1 and associated cytokines in intestinal tissues were evaluated using ELISA. The relative protein expression levels of TLR4 and NF-κB in intestinal tissues were quantified by western blot. Results. Sodium butyrate administration improved the body weight and survival rate of NEC mice; relieved intestinal pathological injury; reduced the intestinal expression of HMGB1, TLR4, NF-κB, interleukin- (IL-) 1β, IL-6, IL-8, and TNF-α; and increased the intestinal expression of IL-10 ( P < 0.05 ). Treatment with butyrate decreased the proportion of opportunistic Clostridium_sensu_stricto_1 and Enterococcus and increased the proportion of beneficial Firmicutes and Lactobacillus in the NEC model. Conclusions. Sodium butyrate intervention relieves intestinal inflammation and partially corrects the disrupted intestinal flora in mice with NEC.

This study investigated the effect of Lactobacillus plantarum strain 299v on gut health in suckling piglets. Sixty newborn piglets were assigned to control and probiotic treatments, with three litters per treatment (ten piglets/litter). From days 1 to 20 of life, piglets were orally administered a placebo of 0.1% peptone or 1.0 ×  1010 CFU L. plantarum 299v daily. Six piglets per treatment were sacrificed on day 20, and intestinal tissues (including duodenum, jejunum, ileum and colon) and the intestinal contents from colon segments were collected. The results demonstrated that piglets treated with L. plantarum 299v had a lower diarrhoea incidence than the controls. L. plantarum 299v administration significantly increased the ratio of the villus height to the crypt depth in the jejunum and ileum, as well as the mRNA expression of jejunal occludin and ileal zonula occludens 1 (ZO‐1). The L. plantarum treatment also increased the mRNA abundance of porcine β‐defensin 2 (pBD2) and pBD3 in the jejunum and ileum and of toll‐like receptors (TLRs), such as TLR2, TLR4, TLR6 and TLR9 in the ileum, and significantly upregulated the mRNA abundances of ileal pBD1 and colonic TLR4. Additionally, the L. plantarum 299v treatment significantly changed the structure of the colonic microbiota, as evidenced by the obvious increases in the relative abundances of the phyla Firmicutes and Actinobacteria and of the genus Lactobacillus. Our findings indicate that L. plantarum 299v facilitates the gut health of suckling piglets, probably by improving the intestinal morphology and intestinal barrier function and by modifying the structure of the gut microbiota.

Autoinducer-2 (AI-2) is believed to be a bacterial interspecies signaling molecule that plays an important role in the regulation of the physiological behaviors of bacteria. The effect of AI-2 on the process of necrotizing enterocolitis (NEC) is unknown, and the aim of this study was to study the effect of AI-2 in a mouse NEC model. C57BL/6 mouse pups were randomly divided into three groups: the control group, the NEC group, and the NEC+AI-2 (NA) group. Exogenous AI-2 (500 nM) was added to the formula milk of the NA group. The concentrations of fecal AI-2 and flora were tested. The expression of cytokines, TLR4 and NF-κB in intestinal tissue was detected. The AI-2 level was significantly decreased in the NEC group (P&lt;0.05). Compared with the NEC group, the intestinal injury scores, expression of TLR4, NF-kB, and proinflammatory factors (IL-1β, IL-6, IL-8 and TNF-α) were reduced, and expression of anti-inflammatory factor (IL-10) was increased in the NA group mice (P&lt;0.05). At the phylum level, the Proteobacteria abundance in the NA group was significantly increased, while the Bacteroidota abundance in the control group was significantly increased (P&lt;0.05). At the genus level, Helicobacter and Clostridium_sensu_stricto_1 exhibited significantly greater abundance in the NEC group than in the other two groups, while Lactobacillus had the opposite trend (P&lt;0.05). In addition, the abundances of Klebsiella, Rodentibacter and Enterococcus were significantly higher in the NA group than in the NEC and control groups (P &lt; 0.05). Exogenous AI-2 partially reverses flora disorder and decreases inflammation in an NEC mouse model.

The mainstream treatments for non-melanoma skin cancer (NMSC) include photodynamic therapy (PDT), surgery excision (SE), cryotherapy (CT), imiquimod (IM), radiotherapy (RT), 5-fluorouracil (FU), and vehicle (VE). Our network meta-analysis (NMA) was aimed at evaluating the efficacy and safety of these seven treatments and providing superior ones. After searching the trials from Embase and PubMed and screening with our criteria, we conducted the NMA with software R 3.2.3 and STATA 13.0. Complete lesion response (CLR), complete lesion clearance (CLC), cumulative recurrence probabilities (CRP), and adverse effects (AEs) were considered as outcomes and displayed as odds ratios (ORs) and 95% credible intervals (CrI). The surface under the cumulative ranking curve (SUCRA) was calculated to rank each treatment on each index. The consistency of direct and indirect evidence was also assessed by node-splitting and heat plot methods. Data from 18 trials with 3706 patients were included. Both IM and SE were demonstrated significantly higher CLR rate than VE (OR = 9.12, 95% CrI = 1.92-47.5; OR = 26.1, 95% CrI = 1.92-347; respectively), while only IM was proved to be statistically better than VE in CLC rate (OR = 7.03, 95% CrI = 1.51-32.8). No significant difference was observed concerning CRP, and IM was more likely to induce AEs than VE (OR = 4.44, 95% CrI = 1.58-13.9). The SUCRA results indicated that SE was the treatment with best ranking in the entire three efficacy indexes and a relatively high safety. Taking efficacy and safety into account, our study recommended SE as the optimal regimen for NMSC with high efficacy considering CLR, CLC, and CRP and moderate AEs when compared with other interventions. J. Cell. Biochem. 118: 3686-3695, 2017. © 2017 Wiley Periodicals, Inc.

We previously identified an association of rapid engraftment of patient-derived leukemia cells transplanted into NOD/SCID mice with early relapse in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In search for the cellular and molecular profiles associated with this phenotype, we investigated the expression of microRNAs (miRNAs) in different engraftment phenotypes and patient outcomes and found high miR-497/195 expression in patient-derived xenograft samples with slow engraftment, derived from patients with favorable outcome. In contrast, epigenetic repression and low expression of these miRNAs was observed in rapidly engrafting samples associated with early relapse. Overexpression of miR-497/195 in patient-derived leukemia cells suppressed in vivo growth of leukemia and prolonged recipient survival. Conversely, inhibition of miR-497/195 led to increased leukemia cell growth. Key cell cycle regulators were downregulated upon miR-497/195 overexpression and we identified CDK4/CCND3-mediated control of G1/S transition as a principal mechanism for the suppression of BCP-ALL progression by miR-497/195. The critical role for miR-497/195-mediated cell cycle regulation was underscored by the finding in an additional independent series of patient samples, showing that high miR-497/195 expression together with a full sequence of CDKN2A/B was associated with excellent outcome, while deletion of CDKN2A/B together with low expression of miR-497/195 was associated with clearly inferior relapse-free survival. These findings point to the cooperative loss of cell cycle regulators as new prognostic factor indicating possible therapeutic targets for pediatric BCP-ALL.

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ObjectiveTo explore the main variations in gut microbiota compositions, short-chain fatty acids (SCFAs) concentrations and autoinducer-2 (AI-2) levels in very-low-birth-weight (VLBW) infants with feeding intolerance (FI).MethodsTwenty-seven VLBW infants with gestational ages of ≤30 weeks were divided into the FI group (n=14) and feeding tolerance (FT) group (n=13). The gut microbiota composition and SCFAs concentrations and AI-2 levels in feces were detected at 2 and 4 weeks after birth.ResultsThere was no difference in alpha diversity between the two groups at 2 and 4 weeks after birth (P&gt;0.05). Although the Chao index decreased (P&lt;0.05), there was no difference in the Shannon index from 2 weeks to 4 weeks in either the FI or FT group (P&gt;0.05). Additionally, there was no difference in beta diversity between the FI and FT groups at 2 weeks (P&gt;0.05), but there was a significant difference in beta diversity between the two groups at 4 weeks (P&lt;0.05) and a large difference from 2 weeks to 4 weeks in both the FI and FT groups (P&lt;0.05). Furthermore, the composition of the microbiota at 4 weeks was significantly different from that at 2 weeks in the FI group (P&lt;0.05). The Veillonella abundance was lower at 4 weeks in the FI group (P&lt;0.05), but there were no differences in the compositions of the other main microbes between the two groups (P&gt;0.05). Proteobacteria and Firmicutes were dominant in both the FI and FT groups. The concentrations of propanoic, valeric and hexanoic acids were lower in the FI group at 2 weeks, and the levels of isobutyric and valeric acids were lower at 4 weeks after birth (P&lt;0.05). The areas under the curves (AUCs) of propanoic, butanoic and valeric acids in predicting FI were 0.878, 0.816 and 0.744, respectively. Compared with that in the FT group, the relative bioluminescence of AI-2 was lower in the FI group at 2 weeks (P&lt;0.05), and the AUC was 0.736.ConclusionsThe main composition of the microbiota was not obviously different in infants with FI. Some SCFAs and AI-2 have moderate value in predicting FI.