Gut microbiome colonization during early life is significant for immunological and physiological development. Maternal microbiome is associated with proper development of infants. The aim of this ...study was to determine the gut microbiome profiles among Thai healthy pregnant women and its associated factors.
A multicenter, open trial prospective study was performed at three hospitals in Northern, Central, and Northeastern regions of Thailand. Thai healthy pregnant women attending antenatal clinics were recruited. Fecal samples of subjects at the third trimester of pregnancy were collected with sterilized techniques. The gut microbiome profiles and bacterial diversity were assessed using 16Ss RNA gene sequencing. Demographic data, dietary intake, and anthropometric data were recorded and analyzed.
There were 86 healthy pregnant women. The dominant of gut microbiome profiles were Bacteroidetes and Firmicutes. Pregnant women in the Central region had significantly higher of Ruminococcaceae and Lachnospiraceae than those in other regions (p < 0.001). Pregnant women in the Northern region significantly consumed more glutinous rice than those in other regions (p < 0.001). Glutinous rice intake was positively correlated with Bacteroidetes (rho = 0.405, p = 0.01) and negatively correlated with Firmicutes (rho = - 0.440, p = 0.001). Alpha diversity was not correlated with pre-pregnancy body mass index (BMI) or gestational weight gain.
The gut microbiome profiles mainly found in Thai healthy pregnant women were Bacteroidetes and Firmicutes. The gut microbiome profiles in pregnant women found in this study possibly depended on dietary patterns. Glutinous rice with high amylopectin is probably related to abundance of Bacteroidetes.
Poultry is an important high-quality food and protein source for humans. However, chicken is considered a primary source of foodborne diseases, especially Salmonella Enteritidis infection. Reducing ...Salmonella contamination in live poultry will thus lower the risk to consumers. Our previous studies reported that Lactobacillus reuteri KUB-AC5 can produce a substance with antimicrobial activity against pathogenic bacteria, especially Salmonella. In vivo testing revealed that this strain greatly influenced the ileal microbiota by improving chicken gastrointestinal health and inhibiting certain pathogenic bacteria. However, its activity against Salmonella in chicken is unknown. This study investigated the effects of the probiotic L. reuteri KUB-AC5 at various concentrations against Salmonella and the microbiota status in the gastrointestinal tract of broiler chickens. Four treatments groups were used: negative-control group (no Salmonella challenge), positive-control group (Salmonella challenge), and 5 or 7 log cfu probiotic supplementation to Salmonella-challenged chickens. The resultant microbial diversities at the growing and finisher stages were not significantly different among the groups (P>0.05). However, a high dosage of KUB-AC5 maintained similar microbial diversity in Salmonella-challenged chickens as observed in the non-challenged group in the early stage. The exposure Salmonella can affect the microbial diversity that consequently contributes to the disease progression in chicken. Low and high dosages of KUB-AC5 eliminated S. Enteritidis from the ileum and caecum at 14, 21 and 35 days of age. A high-dose of KUB-AC5 also enhanced Lactobacillaceae levels in the growing stage in both the ileum and caecum and suppressed Enterobacteriaceae levels in the finisher stage on day 35, whereas these effects were not observed in the low dose of KUB-AC5 or control groups. These results support the potential value of high-dose L. reuteri KUB-AC5 supplementation for three days after hatching in preventing Salmonella infection in chickens.
Heterochromatin protein 1 (HP1) is an evolutionarily conserved chromosomal protein that binds lysine 9-methylated histone H3 (H3K9me), a hallmark of heterochromatin, and plays a crucial role in ...forming higher-order chromatin structures. HP1 has an N-terminal chromodomain and a C-terminal chromo shadow domain, linked by an unstructured hinge region. Although biochemical and structural studies have revealed each domain's properties, little is known about the mechanisms by which these domains cooperate to carry out HP1's function in forming higher-order chromatin structures. In this review, we summarize HP1's biochemical and structural properties and highlight the latest findings regarding HP1's interactions with nucleosomes.
Background
Laparoscopic sleeve gastrectomy (LSG) is a well established treatment for severe obesity and type 2 diabetes. Although the gut microbiota is linked to the efficacy of LSG, the underlying ...mechanisms remain elusive. The effect of LSG for morbid obesity on the gut microbiota and bile acids was assessed here.
Methods
Severely obese subjects who were candidates for LSG were included and followed until 6 months after surgery. The composition and abundance of the microbiota and bile acids in faeces were assessed by 16S ribosomal RNA sequencing, quantitative PCR and liquid chromatography–mass spectrometry.
Results
In total, 28 patients with a mean(s.d.) BMI of 44·2(6·6) kg/m2 were enrolled. These patients had achieved excess weight loss of 53·2(19·0) per cent and showed improvement in metabolic diseases by 6 months after LSG, accompanied by an alteration in the faecal microbial community. The increase in α‐diversity and abundance of specific taxa, such as Rikenellaceae and Christensenellaceae, was strongly associated with reduced faecal bile acid levels. These changes had a significant positive association with excess weight loss and metabolic alterations. However, the total number of faecal bacteria was lower in patients before (mean(s.d.) 10·26(0·36) log10 cells per g faeces) and after (10·39(0·29) log10 cells per g faeces) operation than in healthy subjects (10·83(0·27) log10 cells per g faeces).
Conclusion
LSG is associated with a reduction in faecal bile acids and greater abundance of specific bacterial taxa and α‐diversity that may contribute to the metabolic changes.
Antecedentes
La gastrectomía vertical laparoscópica (laparoscopic sleeve gastrectomy, LSG) es un tratamiento bien establecido para la obesidad grave y la diabetes tipo 2. Aunque la microbiota intestinal se ha vinculado con la eficacia de LSG, los mecanismos subyacentes siguen siendo poco conocidos. En este estudio se evaluó el efecto de LSG en la obesidad mórbida sobre la microbiota del intestino y de los ácidos biliares (bile acids, BA).
Métodos
Tras la aprobación del Comité ético y la obtención del consentimiento informado, los sujetos con obesidad grave que eran candidatos para LSG fueron incluidos en el estudio y seguidos durante 6 meses después de la operación. Se evaluaron la composición y abundancia de la microbiota y BA en las heces mediante secuenciación del gen 16S rRNA, PCR cuantitativa y cromatografía líquida‐espectrometría de masas.
Resultados
En total, 28 pacientes con una mediana (rango) del IMC de 43,9 kg/m2 (35,0‐61,9) fueron reclutados y a los 6 meses tras una LSG, consiguieron una pérdida del exceso de peso de 47,3% (20,7‐95,1) y mejoría de las enfermedades metabólicas acompañada de una alteración en la comunidad microbiana fecal. El aumento en la diversidad α y abundancia de especies taxonómicas específicas como Rikenellaceae y Christensenellaceae, se asociaba fuertemente con niveles fecales reducidos de BA. Estos cambios se asociaban de manera positiva y significativa con la pérdida del exceso de peso y las alteraciones metabólicas. Sin embargo, el número total de bacterias fecales en los pacientes fue inferior al de los sujetos sanos (10,84 log10 células/g heces (9,46‐11,35)) antes de la operación (10,26 log10 células/g heces (9,44‐10,91)) y después de la misma (10,42 log10 células/g heces (9,57‐10,96)).
Conclusión
LSG se asoció con menos BA fecal y mayor abundancia de especies bacterianas específicas y diversidad α lo que puede contribuir a los cambios metabólicos.
Obesity is the most common metabolic disease, with an increasing trend worldwide. Bariatric surgery has been proven to be the best line of treatment for morbid obesity. Laparoscopic sleeve gastrectomy (LSG) is a well established treatment for severe obesity and type 2 diabetes. To clarify the mechanisms underlying the efficacy of LSG, this study examined the effect of LSG on the gut microbiota and bile acids (BAs) in patients with morbid obesity. The findings indicated an increase in α‐diversity and abundance of specific taxa, such as Rikenellaceae and Christensenellaceae, which was strongly associated with reduced faecal BA levels. These changes were closely associated with excess weight loss and metabolic alterations. However, the total number of bacteria in patients before and after surgery was lower than that in healthy subjects. Quantitative abnormalities in major gut bacteria in patients with morbid obesity were not restored after operation. These findings indicate that LSG alone has limited effects on obesity‐related dysbiosis in the gut microbiota. %EWL, percentage excess weight loss; BW, bodyweight; HbA1c, haemoglobin A1c; HOMA‐R, homeostasis model assessment ratio; HOMA‐β, homeostasis model assessment of β‐cell function; CPI, C peptide immunoreactivity index; CPR, C peptide immunoreactivity; ALT, alanine aminotransferase; AST, aspartate aminotransferase; TG, triglyceride; HDL, high‐density lipoprotein; PD, phylogenetic diversity; F/B, Firmicutes/Bacteroidetes.
Insights into the altered microenvironment
Reactive oxygen species (ROS)-generating enzyme Nox1 is important in the induction of oncogenic Ras transformation phenotypes, but it is not defined whether Nox1 is involved in Ras-induced ...upregulation of vascular endothelial growth factor (VEGF), a potent stimulator of tumor angiogenesis. Here we describe that ablation of the Nox1 activity by Nox1 small-interference RNAs (siRNAs) or diphenylene iodonium (DPI) inhibited synthesis of both VEGF proteins and VEGF mRNAs in K-Ras transformed normal rat kidney (KNRK) cells. Nox1siRNAs and DPI suppressed extracellular signal-regulated kinase (ERK)-dependent phosphorylation of a transcription factor Sp1 and Sp1 binding to a VEGF promoter. Furthermore, tumors derived from Nox1siRNA-transfected KNRK cells markedly decreased neovascularization. The Nox1 activity was required for VEGF production in human colon cancer CaCO-2 cells, as in the case of KNRK cells. However, since overexpression of Nox1 in normal rat kidney cells failed to induce VEGF, the Nox1 activity alone was not sufficient to upregulate VEGF expression, which suggests that unlike the previously proposed model, Nox1 may act in concert with other effectors integrated into the Ras network. We propose that Nox1 mediates oncogenic Ras-induced upregulation of VEGF and angiogenesis by activating Sp1 through Ras-ERK-dependent phosphorylation of Sp1.
Background
Psoriasis affecting sites such as the hands, feet and nails can be particularly difficult to treat. There are limited data on the efficacy of biological agents to treat these specific ...localizations.
Objective
This analysis of a phase 2 regimen‐finding study evaluated the efficacy of secukinumab in subjects with moderate‐to‐severe psoriasis and non‐pustular involvement of the hands, feet and/or nails.
Methods
Subjects were randomized (1 : 2 : 2 : 1) to one of three subcutaneous secukinumab 150‐mg induction regimens Single (Week 0), Monthly (Weeks 0, 4, 8), Early (Weeks 0, 1, 2, 4) or placebo. In the subgroup (n = 131) with hand and/or foot psoriasis baseline 5‐point hand/foot Investigator's Global Assessment (IGA) score ≥2, efficacy was assessed as percentage of subjects achieving an IGA response a score of 0 (clear) or 1 (minimal) and an improvement of ≥2 points on the 5‐point hand/foot scale vs. baseline at Week 12. In the subgroup (n = 304) with fingernail psoriasis (baseline composite score ≥1), efficacy was assessed as mean percentage change from baseline to Week 12 in a composite score.
Results
At Week 12, a markedly higher percentage of subjects with hand and/or foot psoriasis achieved an IGA response with the Early regimen vs. placebo (54.3% vs. 19.2%, P = 0.005). The composite fingernail score improved with the Early and Monthly regimens, but worsened with placebo percentage mean change from baseline (SE): −19.1% (6.12) and −10.6% (7.06) vs. 14.4% (11.92); P = 0.010 vs. placebo for Early, P = 0.027 for Monthly). Secukinumab was well tolerated.
Conclusion
Secukinumab demonstrated a beneficial effect on psoriasis of the hands/feet/nails in this short‐term assessment.
The probiotic strain Lactobacillus reuteri KUB-AC5, which was originally isolated from chicken intestine, was fed to newborn broiler chicks for the first week post-hatch. The growth and ileum ...microbiota of the chickens were carefully monitored for 6 wk. The inclusion of 5 log cfu/g of feed statistically increased the BW gain in the first week compared with that of the control group, but this effect did not continue thereafter. Significant effects on host feed consumption and the feed-to-growth conversion ratio were not detected. The total amount and composition of ileum bacteria were investigated by quantitative PCR and pyrosequencing of the 16S rRNA gene (rDNA), respectively, and were compared between the control and the probiotic-treated groups. The amount of total bacterial 16S rDNA in ileum samples at d 42 was 5 times higher in the probiotic group than in the control, whereas no significant difference was observed at d 21. A composition analysis revealed the establishment of lactobacilli-enriched microbiota in the probiotic-treated chickens at d 42. At this point, the population level and species diversity of lactobacilli were significantly enhanced compared with those of the control group. In addition, Actinobacteria, mainly genera Corynebacterium and Dietzia, were also statistically higher in the probiotic group. However, Proteobacteria, including those of the family Campylobacterales and some other nonbeneficial bacterial groups, were decreased in the probiotic group at the growing stage. Therefore, with probiotic supplementation, it was demonstrated that Lactobacillus reuteri KUB-AC5 in the early post-hatching period had a delayed effect on ileum microbiota, which resulted in the enrichment of potentially beneficial lactobacilli and the suppression of Proteobacteria, including nonbeneficial bacterial groups.
Pancreatic adenocarcinoma is an aggressive human malignancy and is characterized by resistance to apoptosis. Recently, NADPH oxidase (Nox) 4-mediated generation of intracellular reactive oxygen ...species (ROS) was proposed to confer antiapoptotic activity and thus a growth advantage to pancreatic cancer cells. The signaling mechanism by which Nox4 transmits cell survival signals remains unclear. Here, we show that both a flavoprotein inhibitor, diphenylene iodonium (DPI), and small interfering RNAs designed to target Nox4 mRNA (siNox4RNAs) inhibited superoxide production in PANC-1 pancreatic cancer cells, and depletion of ROS by DPI or siNox4RNAs induced apoptosis. Parallely, DPI treatment and siNox4RNA transfection blocked activation of the cell survival kinase AKT by attenuating phosphorylation of AKT. Furthermore, AKT phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) on Ser-83 was reduced by DPI and siNox4RNAs. When ASK1Ser83Ala (an AKT phosphorylation-defective ASK1 mutant) was introduced into PANC-1 cells, this mutant alone induced apoptosis. But, addition of DPI or co-transfection of siNox4RNA had no additive effect, indicating that the mutant can substitute for these reagents in apoptosis induction. Taken together, these findings suggest that ROS generated by Nox4, at least in part, transmit cell survival signals through the AKT-ASK1 pathway in pancreatic cancer cells and their depletion leads to apoptosis.
Aims: To identify and characterize novel bacteriocins from Weissella hellenica QU 13. Methods and Results: Weissella hellenica QU 13, isolated from a barrel used to make Japanese pickles, produced ...two novel bacteriocins termed weissellicin Y and weissellicin M. The primary structures of weissellicins Y and M were determined, and their molecular masses were determined to be 4925·12 and 4968·40 Da, respectively. Analysis of the DNA sequence encoding the bacteriocins revealed that they were synthesized and secreted without N‐terminal extensions such as leader sequences or sec signal peptides. Weissellicin M showed significantly high and characteristic homology with enterocins L50A and L50B, produced by Enterococcus faecium L50, while weissellicin Y showed no homology with any other known bacteriocins. Both bacteriocins showed broad antimicrobial spectra, with especially high antimicrobial activity against species, which contaminate pickles, such as Bacillus coagulans, and weissellicin M showed relatively higher activity than weissellicin Y. Furthermore, the stability of weissellicin M against pH and heat was distinctively higher than that of weissellicin Y. Conclusions: Weissella hellenica QU 13 produced two novel leaderless bacteriocins, weissellicin Y and weissellicin M, and weissellicin M exhibited remarkable potency that could be employed by pickle‐producing industry. Significance and Impact of the Study: This study is the first report, which represents a complete identification and characterization of novel leaderless bacteriocins from Weissella genus.
Abstract Aim The use of sentinel node biopsy (SNB) has not been established for cutaneous squamous cell carcinoma (SCC), and its clinical significance has not been clarified. We investigated the ...usefulness of and indication criteria for SNB for cutaneous SCC. Materials and methods Twenty-six patients with high-risk cutaneous SCC that had undergone SNB were retrospectively reviewed. SNB was performed with either the dye method or a combined dye and radioisotope method. Results Of the 26 patients, recurrence or metastasis was observed in 5 cases (19.2%). Six cases (23.1%) were sentinel node (SN) metastasis-positive. All cases that were SN metastasis-negative survived, and 4 of 6 SN metastasis-positive (66.7%) cases died of the original disease. The 3-year survival rates of all cases, SN metastasis-negative cases, and SN metastasis-positive cases were 82.2%, 100%, and 20.8%, respectively. Tumour thickness was a significant risk factor for SN metastasis ( p = 0.049). Recurrence occurred in 4 of 7 cases involving external genitalia, 3 of which died. The 3-year survival rates of external genitalia and nongenital cases were 47.6% and 94.1%, respectively ( p = 0.016). Conclusions SNB aided the early discovery and treatment of latent lymph node metastasis and helped predict whether SN metastasis had occurred, and therefore helped predict patient prognosis. These results suggest that thickness of the primary lesion is an indication criterion for the use of SNB in cases of cutaneous SCC. SNB should be considered in cases where tumour thickness is ≥2 mm and actively performed in cases ≥5 mm.
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