Dieta com baixo teor de FODMAPs para distúrbios de dor abdominal funcional em crianças: revisão crítica do conhecimento atual (Low FODMAPs diet for functional abdominal pain disorders in children: critical review of current knowledge)

Objective: This narrative review aimed to provide practitioners a synthesis of the current knowledge on the role of a low Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols diet in reducing symptoms associated with functional abdominal pain disorders in children. This review is focused on the pathophysiology, efficacy and criticism of low Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols diet in children. / Sources: Cochrane Database, Pubmed and Embase were searched using specific terms for Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols diet interventions and functional abdominal pain disorders. / Summary of the findings: In children, only one Randomized Control Trial and one open‐label study reported positive results of low Fermentable Oligosaccharides Disaccharides Monosaccha‐rides and Polyols diet; one Randomized Control Trial showed exacerbation of symptoms with fructans in children with Irritable Bowel Syndrome; no effect was found for the lactose‐free diet whilst fructose‐restricted diets were effective in 5/6 studies. / Conclusions: In children there are few trials evaluating low Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols in functional abdominal pain disorders, with encour‐aging data on the therapeutic efficacy particularly of fructose‐restricted diet. Additional effort sare still needed to fill this research gap and clarify the most efficient way for tailoring dietary restrictions based on the patient's tolerance and/or identification of potential biomarkers of low Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols efficacy, to maintain nutritional adequacy and to simplify the adherence to diet by labeling FermentableOligosaccharides Disaccharides Monosaccharides and Polyols content in commercial products

Lineage specific composition of cyclin D–CDK4/CDK6–p27 complexes reveals distinct functions of CDK4, CDK6 and individual D-type cyclins in differentiating cells of embryonic origin

Objectives: This article is to study the role of G1/S regulators in differentiation of pluripotent embryonic cells. Materials and methods: We established a P19 embryonal carcinoma cell-based experimental system, which profits from two similar differentiation protocols producing endodermal or neuroectodermal lineages. The levels, mutual interactions, activities, and localization of G1/S regulators were analysed with respect to growth and differentiation parameters of the cells. Results and Conclusions: We demonstrate that proliferation parameters of differentiating cells correlate with the activity and structure of cyclin A/E–CDK2 but not of cyclin D–CDK4/6–p27 complexes. In an exponentially growing P19 cell population, the cyclin D1–CDK4 complex is detected, which is replaced by cyclin D2/3–CDK4/6–p27 complex following density arrest. During endodermal differentiation kinase-inactive cyclin D2/D3–CDK4–p27 complexes are formed. Neural differentiation specifically induces cyclin D1 at the expense of cyclin D3 and results in predominant formation of cyclin D1/D2–CDK4–p27 complexes. Differentiation is accompanied by cytoplasmic accumulation of cyclin Ds and CDK4/6, which in neural cells are associated with neural outgrowths. Most phenomena found here can be reproduced in mouse embryonic stem cells. In summary, our data demonstrate (i) that individual cyclin D isoforms are utilized in cells lineage specifically, (ii) that fundamental difference in the function of CDK4 and CDK6 exists, and (iii) that cyclin D–CDK4/6 complexes function in the cytoplasm of differentiated cells. Our study unravels another level of complexity in G1/S transition-regulating machinery in early embryonic cells

Placental determinants of fetal growth: identification of key factors in the insulin-like growth factor and cytokine systems using artificial neural networks

<p>Abstract</p> <p>Background</p> <p>Changes and relationships of components of the cytokine and IGF systems have been shown in placenta and cord serum of fetal growth restricted (FGR) compared with normal newborns (AGA). This study aimed to analyse a data set of clinical and biochemical data in FGR and AGA newborns to assess if a mathematical model existed and was capable of identifying these two different conditions in order to identify the variables which had a mathematically consistent biological relevance to fetal growth.</p> <p>Methods</p> <p>Whole villous tissue was collected at birth from FGR (N = 20) and AGA neonates (N = 28). Total RNA was extracted, reverse transcribed and then real-time quantitative (TaqMan) RT-PCR was performed to quantify cDNA for IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IL-6. The corresponding proteins with TNF-α in addition were assayed in placental lysates using specific kits. The data were analysed using Artificial Neural Networks (supervised networks), and principal component analysis and connectivity map.</p> <p>Results</p> <p>The IGF system and IL-6 allowed to predict FGR in approximately 92% of the cases and AGA in 85% of the cases with a low number of errors. IGF-II, IGFBP-2, and IL-6 content in the placental lysates were the most important factors connected with FGR. The condition of being FGR was connected mainly with the IGF-II placental content, and the latter with IL-6 and IGFBP-2 concentrations in placental lysates.</p> <p>Conclusion</p> <p>These results suggest that further research in humans should focus on these biochemical data. Furthermore, this study offered a critical revision of previous studies. The understanding of this system biology is relevant to the development of future therapeutical interventions possibly aiming at reducing IL-6 and IGFBP-2 concentrations preserving IGF bioactivity in both placenta and fetus.</p

Low FODMAPs diet for functional abdominal pain disorders in children: critical review of current knowledge

Objective This narrative review aimed to provide practitioners a synthesis of the current knowledge on the role of a low Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols diet in reducing symptoms associated with functional abdominal pain disorders in children. This review is focused on the pathophysiology, efficacy and criticism of low Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols diet in children. Sources Cochrane Database, Pubmed and Embase were searched using specific terms for Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols diet interventions and functional abdominal pain disorders. Summary of the findings In children, only one Randomized Control Trial and one open-label study reported positive results of low Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols diet; one Randomized Control Trial showed exacerbation of symptoms with fructans in children with Irritable Bowel Syndrome; no effect was found for the lactose-free diet whilst fructose-restricted diets were effective in 5/6 studies. Conclusions In children there are few trials evaluating low Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols in functional abdominal pain disorders, with encouraging data on the therapeutic efficacy particularly of fructose-restricted diet. Additional efforts are still needed to fill this research gap and clarify the most efficient way for tailoring dietary restrictions based on the patient's tolerance and/or identification of potential biomarkers of low Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols efficacy, to maintain nutritional adequacy and to simplify the adherence to diet by labeling Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols content in commercial products

R-Ras Regulates Migration through an Interaction with Filamin A in Melanoma Cells

Changes in cell adhesion and migration in the tumor microenvironment are key in the initiation and progression of metastasis. R-Ras is one of several small GTPases that regulate cell adhesion and migration on the extracellular matrix, however the mechanism has not been completely elucidated. Using a yeast two-hybrid approach we sought to identify novel R-Ras binding proteins that might mediate its effects on integrins.We identified Filamin A (FLNa) as a candidate interacting protein. FLNa is an actin-binding scaffold protein that also binds to integrin β1, β2 and β7 tails and is associated with diverse cell processes including cell migration. Indeed, M2 melanoma cells require FLNa for motility. We further show that R-Ras and FLNa interact in co-immunoprecipitations and pull-down assays. Deletion of FLNa repeat 3 (FLNaΔ3) abrogated this interaction. In M2 melanoma cells active R-Ras co-localized with FLNa but did not co-localize with FLNa lacking repeat 3. Thus, activated R-Ras binds repeat 3 of FLNa. The functional consequence of this interaction was that active R-Ras and FLNa coordinately increased cell migration. In contrast, co-expression of R-Ras and FLNaΔ3 had a significantly reduced effect on migration. While there was enhancement of integrin activation and fibronectin matrix assembly, cell adhesion was not altered. Finally, siRNA knockdown of endogenous R-Ras impaired FLNa-dependent fibronectin matrix assembly.These data support a model in which R-Ras functionally associates with FLNa and thereby regulates integrin-dependent migration. Thus in melanoma cells R-Ras and FLNa may cooperatively promote metastasis by enhancing cell migration

Systems microscopy approaches to understand cancer cell migration and metastasis

Cell migration is essential in a number of processes, including wound healing, angiogenesis and cancer metastasis. Especially, invasion of cancer cells in the surrounding tissue is a crucial step that requires increased cell motility. Cell migration is a well-orchestrated process that involves the continuous formation and disassembly of matrix adhesions. Those structural anchor points interact with the extra-cellular matrix and also participate in adhesion-dependent signalling. Although these processes are essential for cancer metastasis, little is known about the molecular mechanisms that regulate adhesion dynamics during tumour cell migration. In this review, we provide an overview of recent advanced imaging strategies together with quantitative image analysis that can be implemented to understand the dynamics of matrix adhesions and its molecular components in relation to tumour cell migration. This dynamic cell imaging together with multiparametric image analysis will help in understanding the molecular mechanisms that define cancer cell migration

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10−8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution