Introduction: In children with acute leukemia, gut microbiota is modified secondary to chemotherapy administration, leading to gastrointestinal side effects. Probiotics are microorganisms that can restore gut microbiota and may help alleviate gastrointestinal symptoms. The aim of this pilot study was to assess the effects of probiotic supplementation on chemotherapy-induced gastrointestinal side effects in children with acute leukemia (AL). Methods: In this randomized pilot study, patients under 17 years of age diagnosed with AL who were on remission induction or remission reinduction chemotherapy were randomly assigned to receive probiotic supplementation (a concentration of 5×109 CFU per sachet was administered at a standard dose twice daily, by mouth) or no probiotic supplementation. The primary endpoint was the prevalence of gastrointestinal side effects. Vomiting, nausea, flatulence, dyspepsia, diarrhea, constipation, abdominal pain, and abdominal distention were assessed in both groups. Results: Gastrointestinal side effects were less prevalent in the probiotic group, and 3 of the 8 gastrointestinal side effects (nausea, vomiting, and abdominal distension) significantly decreased in the probiotic group (P<0.05). We found for diarrhea a relative risk of 0.5 (95% confidence interval [CI], 0.2-1.2; P=0.04); for nausea an RR of 0.5 (95% CI, 0.4-0.8; P=0.04) and for vomiting an RR of 0.4 (95% CI, 0.2-0.9; P=0.04). Conclusions: Daily supplementation with Lactobacillus rhamnosus reduced chemotherapy-induced gastrointestinal side effects in children with AL.

Objective To evaluate the taxonomic composition of the gut microbiome in gout patients with and without tophi formation, and predict bacterial functions that might have an impact on urate metabolism. Methods Hypervariable V3–V4 regions of the bacterial 16S rRNA gene from fecal samples of gout patients with and without tophi (n = 33 and n = 25, respectively) were sequenced and compared to fecal samples from 53 healthy controls. We explored predictive functional profiles using bioinformatics in order to identify differences in taxonomy and metabolic pathways. Results We identified a microbiome characterized by the lowest richness and a higher abundance of Phascolarctobacterium, Bacteroides, Akkermansia, and Ruminococcus_gnavus_group genera in patients with gout without tophi when compared to controls. The Proteobacteria phylum and the Escherichia-Shigella genus were more abundant in patients with tophaceous gout than in controls. Fold change analysis detected nine genera enriched in healthy controls compared to gout groups (Bifidobacterium, Butyricicoccus, Oscillobacter, Ruminococcaceae_UCG_010, Lachnospiraceae_ND2007_group, Haemophilus, Ruminococcus_1, Clostridium_sensu_stricto_1, and Ruminococcaceae_UGC_013). We found that the core microbiota of both gout groups shared Bacteroides caccae, Bacteroides stercoris ATCC 43183, and Bacteroides coprocola DSM 17136. These bacteria might perform functions linked to one-carbon metabolism, nucleotide binding, amino acid biosynthesis, and purine biosynthesis. Finally, we observed differences in key bacterial enzymes involved in urate synthesis, degradation, and elimination. Conclusion Our findings revealed that taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism.

No abstract

Resumen Objetivo. Investigar la correlación entre las citocinas proinflamatorias o antiinflamatorias y los dos principales filos de la microbiota intestinal en niños obesos. Material y métodos. Se obtuvieron mediciones antropométricas de 890 niños de 6 a 14 años; posteriormente se clasificaron en normopeso y sobrepeso/obeso. Las concentraciones sé-ricas fueron medidas por el método de ELISA. La abundancia relativa de la microbiota intestinal en heces se evaluó por PCR tiempo real. Resultados. Los parámetros bioquímicos y antropométricos fueron estadísticamente más altos en niños con sobrepeso / obesidad que en niños delgados. Se encontraron niveles más altos de FNT-α en niños obesos que también tenían una abundancia relativa alta de Firmicutes. Conclusiones. Los niños obesos tienen una alta abundancia relativa de Firmicutes, la cual se correlaciona con un incremento de los niveles de FNT-α. Este es el primer estudio que evalúa la reacción entre la abundancia de Firmicutes y la concentración sérica de FNT-α en niños obesos.

Beractant, a natural surfactant, induces an antifibrogenic phenotype and apoptosis in normal human lung fibroblasts (NHLF). As intracellular Ca2+ signalling has been related to programmed cell death, we aimed to assess the effect of beractant on intracellular Ca2+ concentration ([Ca2+]i) in NHLF in vitro. Cultured NHLF were loaded with Fura-2 AM (3 μM) and Ca2+ signals were recorded by microfluorimetric techniques. Beractant causes a concentration-dependent increase in [Ca2+]i with a EC50 of 0.82 μg/ml. The application of beractant, at a concentration of 500 μg/ml, which has been shown to exert an apoptotic effect in human fibroblasts, elicited different patterns of Ca2+ signals in NHLF: a) a single Ca2+ spike which could be followed by b) Ca2+ oscillations, c) a sustained Ca2+ plateau or d) a sustained plateau overlapped by Ca2+ oscillations. The amplitude and pattern of Ca2+ transients evoked by beractant were dependent on the resting [Ca2+]i. Pharmacological manipulation revealed that beractant activates a Ca2+ signal through Ca2+ release from intracellular stores mediated by phospholipase Cβ (PLCβ), Ca2+ release from inositol 1,4,5-trisphosphate receptors (IP3Rs) and Ca2+ influx via a store-operated pathway. Moreover, beractant-induced Ca2+ release was abolished by preventing membrane depolarization upon removal of extracellular Na+ and Ca2+. Finally, the inhibition of store-operated channels prevented beractant-induced NHLF apoptosis and downregulation of α1(I) procollagen expression. Therefore, beractant utilizes SOCE to exert its pro-apoptotic and antifibrinogenic effect on NHLF.

Experiments with T cells from healthy donors in the presence TGF-beta1 or IL-10 suggest that these cytokines have a relevant role in T cell responses during CC progression.

Oct3/4 is a transcription factor involved in maintenance of the pluripotency and self-renewal of stem cells. The E7 oncoprotein and 17β-estradiol (E) are key factors in cervical carcinogenesis. In the present study, we aimed to investigate the effect of the HPV16 E7 oncoprotein and E on the expression pattern of Oct3/4, Sox2, Nanog and Fgf4. We also determined whether the E7 oncoprotein is associated with cell self-renewal. The results showed that Oct3/4, Sox2, Nanog and Fgf4 were upregulated by the E7 oncoprotein in vivo and in vitro and implicate E in the upregulation of these factors in vivo. We also demonstrated that E7 is involved in cell self-renewal, suggesting that the HPV16 E7 oncoprotein upregulates Oct3/4, Sox2, Nanog and Fgf4 expression to maintain the self-renewal capacity of cancer stem cells.

No abstract