Obesity and overweight are defined as abnormal fat accumulations. Adipose tissue consists of more than merely adipocytes; each adipocyte is closely coupled with the extracellular matrix. Adipose ...tissue stores excess energy through expansion. Obesity is caused by the abnormal expansion of adipose tissue as a result of adipocyte hypertrophy and hyperplasia. The process of obesity is controlled by several molecules, such as integrins, kindlins, or matrix metalloproteinases. In children with obesity, metabolomics studies have provided insight into the existence of unique metabolic profiles. As a result of low-grade inflammation in the system, abnormalities were observed in several metabolites associated with lipid, carbohydrate, and amino acid pathways. In addition, obesity and related hormones, such as leptin, play an instrumental role in regulating food intake and contributing to childhood obesity. The World Health Organization states that physical activity benefits the heart, the body, and the mind. Several noncommunicable diseases, such as cardiovascular disease, cancer, and diabetes, can be prevented and managed through physical activity. In this work, we reviewed pediatric studies that examined the molecular and hormonal control of obesity and the influence of physical activity on children with obesity or overweight. The purpose of this review was to examine some orchestrators involved in this disease and how they are related to pediatric populations. A larger number of randomized clinical trials with larger sample sizes and long-term studies could lead to the discovery of new key molecules as well as the detection of significant factors in the coming years. In order to improve the health of the pediatric population, omics analyses and machine learning techniques can be combined in order to improve treatment decisions.
The development of DNA microarray and RNA-sequencing technology has led to an explosion in the generation of transcriptomic differential expression data under a wide range of biologic systems ...including those recapitulating the monogenic muscular dystrophies. Data generation has increased exponentially due in large part to new platforms, improved cost-effectiveness, and processing speed. However, reproducibility and thus reliability of data remain a central issue, particularly when resource constraints limit experiments to single replicates. This was observed firsthand in a recent rare disease drug repurposing project involving RNA-seq-based transcriptomic profiling of primary cerebrocortical cultures incubated with clinic-ready blood-brain penetrant drugs. Given the low validation rates obtained for single differential expression genes, alternative approaches to identify with greater confidence genes that were truly differentially expressed in our dataset were explored. Here we outline a method for differential expression data analysis in the context of drug repurposing for rare diseases that incorporates the statistical rigour of the multigene analysis to bring greater predictive power in assessing individual gene modulation. Ingenuity Pathway Analysis upstream regulator analysis was applied to the differentially expressed genes from the Care4Rare Neuron Drug Screen transcriptomic database to identify three distinct signaling networks each perturbed by a different drug and involving a central upstream modulating protein: levothyroxine (
), hydroxyurea (
), dexamethasone (
). Differential expression of upstream regulator network related genes was next assessed in in vitro and in vivo systems by qPCR, revealing 5× and 10× increases in validation rates, respectively, when compared with our previous experience with individual genes in the dataset not associated with a network. The Ingenuity Pathway Analysis based gene prioritization may increase the predictive value of drug-gene interactions, especially in the context of assessing single-gene modulation in single-replicate experiments.
Abstract
Context
Despite the gut microbiome being widely studied in metabolic diseases, its role in polycystic ovary syndrome (PCOS) has been scarcely investigated.
Objective
Compare the gut ...microbiome in late fertile age women with and without PCOS and investigate whether changes in the gut microbiome correlate with PCOS-related metabolic parameters.
Design
Prospective, case–control study using the Northern Finland Birth Cohort 1966.
Setting
General community.
Participants
A total of 102 PCOS women and 201 age- and body mass index (BMI)-matched non-PCOS control women. Clinical and biochemical characteristics of the participants were assessed at ages 31 and 46 and analyzed in the context of gut microbiome data at the age of 46.
Intervention
(s): None
Main outcome measure(s)
Bacterial diversity, relative abundance, and correlations with PCOS-related metabolic measures.
Results
Bacterial diversity indices did not differ significantly between PCOS and controls (Shannon diversity P = .979, unweighted UniFrac P = .175). Four genera whose balance helps to differentiate between PCOS and non-PCOS were identified. In the whole cohort, the abundance of 2 genera from Clostridiales, Ruminococcaceae UCG-002, and Clostridiales Family XIII AD3011 group, were correlated with several PCOS-related markers. Prediabetic PCOS women had significantly lower alpha diversity (Shannon diversity P = .018) and markedly increased abundance of genus Dorea (false discovery rate = 0.03) compared with women with normal glucose tolerance.
Conclusion
PCOS and non-PCOS women at late fertile age with similar BMI do not significantly differ in their gut microbial profiles. However, there are significant microbial changes in PCOS individuals depending on their metabolic health.
The importance of gut microbiota in health and disease is being highlighted by numerous research groups worldwide. Atherosclerosis, the leading cause of heart disease and stroke, is responsible for ...about 50% of all cardiovascular deaths. Recently, gut dysbiosis has been identified as a remarkable factor to be considered in the pathogenesis of cardiovascular diseases (CVDs). In this review, we briefly discuss how external factors such as dietary and physical activity habits influence host-microbiota and atherogenesis, the potential mechanisms of the influence of gut microbiota in host blood pressure and the alterations in the prevalence of those bacterial genera affecting vascular tone and the development of hypertension. We will also be examining the microbiota as a therapeutic target in the prevention of CVDs and the beneficial mechanisms of probiotic administration related to cardiovascular risks. All these new insights might lead to novel analysis and CVD therapeutics based on the microbiota.
Taste disorders (TDs) are common among systemically treated cancer patients and negatively impact their nutritional status and quality of life. The novel food approved by the European Commission ...(EFSA), dried miracle berries (DMB), contains the natural taste-modifying protein miraculin. DMB, also available as a supplement, has emerged as a possible alternative treatment for TDs. The present study aimed to evaluate the efficacy and safety of habitual DMB consumption in malnourished cancer patients undergoing active treatment. An exploratory clinical trial was carried out in which 31 cancer patients were randomized into three arms standard dose of DMB (150 mg DMB/tablet), high dose of DMB (300 mg DMB/tablet) or placebo (300 mg freeze-dried strawberry) for three months. Patients consumed a DMB tablet or placebo daily before each main meal (breakfast, lunch, and dinner). Throughout the five main visits, electrochemical taste perception, nutritional status, dietary intake, quality of life and the fatty acid profile of erythrocytes were evaluated. Patients consuming a standard dose of DMB exhibited improved taste acuity over time (% change right/left side: −52.8 ± 38.5/−58.7 ± 69.2%) and salty taste perception (2.29 ± 1.25 vs. high dose: 2.17 ± 1.84 vs. placebo: 1.57 ± 1.51 points, p < 0.05). They also had higher energy intake (p = 0.075) and covered better energy expenditure (107 ± 19%). The quality of life evaluated by symptom scales improved in patients receiving the standard dose of DMB (constipation, p = 0.048). The levels of arachidonic (13.1 ± 1.8; 14.0 ± 2.8, 12.0 ± 2.0%; p = 0.004) and docosahexaenoic (4.4 ± 1.7; 4.1 ± 1.0; 3.9 ± 1.6%; p = 0.014) acids in erythrocytes increased over time after DMB intake. The standard dose of DMB increased fat-free mass vs. placebo (47.4 ± 9.3 vs. 44.1 ± 4.7 kg, p = 0.007). Importantly, habitual patients with DMB did not experience any adverse events, and metabolic parameters remained stable and within normal ranges. In conclusion, habitual consumption of a standard 150 mg dose of DMB improves electrochemical food perception, nutritional status (energy intake, fat quantity and quality, fat-free mass), and quality of life in malnourished cancer patients receiving antineoplastic treatment. Additionally, DMB consumption appears to be safe, with no changes in major biochemical parameters associated with health status. Clinical trial registered (NCT05486260).
The vaginal microbiota has importance in preserving vaginal health and defending the host against disease. The advent of new molecular techniques and computer science has allowed researchers to ...discover microbial composition in depth and associate the structure of vaginal microbial communities. There is a consensus that vaginal flora is grouped into a restricted number of communities, although the structure of the community is constantly changing. Certain Community-Sate Types (CSTs) are more associated with poor reproductive outcomes and sexually transmitted diseases (STDs) meanwhile, CSTs dominated by
species-particularly
-are more related to vaginal health. In this work, we have reviewed how modifiable and non-modifiable factors may affect normal vaginal microbiota homeostasis-including sexual behavior, race or ethnicity, and hygiene. Special interest has been given to how the use of probiotics, diet intake, and use of hormone replacement therapies (HRTs) can potentially impact vaginal microbiota composition.
Mechanisms of Action of Probiotics Plaza-Diaz, Julio; Ruiz-Ojeda, Francisco Javier; Gil-Campos, Mercedes ...
Advances in nutrition (Bethesda, Md.),
01/2019, Letnik:
10, Številka:
suppl_1
Journal Article
Recenzirano
Odprti dostop
ABSTRACT
Probiotics are living microorganisms that confer health benefits to the host when administered in adequate amounts; however, dead bacteria and their components can also exhibit probiotic ...properties. Bifidobacterium and strains of lactic acid bacteria are the most widely used bacteria that exhibit probiotic properties and are included in many functional foods and dietary supplements. Probiotics have been shown to prevent and ameliorate the course of digestive disorders such as acute, nosocomial, and antibiotic-associated diarrhea; allergic disorders such as atopic dermatitis (eczema) and allergic rhinitis in infants; and Clostridium difficile–associated diarrhea and some inflammatory bowel disorders in adults. In addition, probiotics may be of interest as coadjuvants in the treatment of metabolic disorders, including obesity, metabolic syndrome, nonalcoholic fatty liver disease, and type 2 diabetes. However, the mechanisms of action of probiotics, which are diverse, heterogeneous, and strain specific, have received little attention. Thus, the aim of the present work was to review the main mechanisms of action of probiotics, including colonization and normalization of perturbed intestinal microbial communities in children and adults; competitive exclusion of pathogens and bacteriocin production; modulation of fecal enzymatic activities associated with the metabolization of biliary salts and inactivation of carcinogens and other xenobiotics; production of short-chain and branched-chain fatty acids, which, in turn, have wide effects not only in the intestine but also in peripheral tissues via interactions with short-chain fatty acid receptors, modulating mainly tissue insulin sensitivity; cell adhesion and mucin production; modulation of the immune system, which results mainly in the differentiation of T-regulatory cells and upregulation of anti-inflammatory cytokines and growth factors, i.e., interleukin-10 and transforming growth factor; and interaction with the brain-gut axis by regulation of endocrine and neurologic functions. Further research to elucidate the precise molecular mechanisms of action of probiotics is warranted.
Myotonic Dystrophy Type 1 (DM1) is the most common form of adult muscular dystrophy (~1:8000). In DM1, expansion of CTG trinucleotide repeats in the 3’ untranslated region of the dystrophia myotonica ...protein kinase (DMPK) gene results in DMPK mRNA hairpin structures which aggregate as insoluble ribonuclear foci and sequester several RNA-binding proteins. The resulting sequestration and misregulation of important splicing factors, such as muscleblind-like 1 (MBNL1), causes the aberrant expression of fetal transcripts for several genes that contribute to the disease phenotype. Previous work has shown that antisense oligonucleotide-mediated disaggregation of the intranuclear foci has the potential to reverse downstream anomalies. To explore whether the nuclear foci are, to some extent, controlled by cell signalling pathways, we have performed a screen using a small interfering RNA (siRNA) library targeting 518 protein kinases to look at kinomic modulation of foci integrity. RNA foci were visualized by
in situ
hybridization of a fluorescent-tagged (CAG)
10
probe directed towards the expanded DMPK mRNA and the cross-sectional area and number of foci per nuclei were recorded. From our screen, we have identified PACT (
p
rotein kinase R (PKR)
act
ivator) as a novel modulator of foci integrity and have shown that PACT knockdown can both increase MBNL1 protein levels; however, these changes are not suffcient for significant correction of downstream spliceopathies.
The most common cancer in women is breast cancer, which is also the second leading cause of death in this group. It is, however, important to note that some women will develop or will not develop ...breast cancer regardless of whether certain known risk factors are present. On the other hand, certain compounds are produced by bacteria in the gut, such as short-chain fatty acids, secondary bile acids, and other metabolites that may be linked to breast cancer development and mediate the chemotherapy response. Modeling the microbiota through dietary intervention and identifying metabolites directly associated with breast cancer and its complications may be useful to identify actionable targets and improve the effect of antiangiogenic therapies. Metabolomics is therefore a complementary approach to metagenomics for this purpose. As a result of the combination of both techniques, a better understanding of molecular biology and oncogenesis can be obtained. This article reviews recent literature about the influence of bacterial metabolites and chemotherapy metabolites in breast cancer patients, as well as the influence of diet.
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•Cinnamon EO showed a highest antibacterial activity against intestinal pathogenic bacteria.•Essential oils inhibits probiotic bacteria growth at the 0.1% (v/v) ...concentration.•Cinnamon EO present better inhibitory and immunomodulatory properties than the rest of the EOs.•Cinnamon EO seems to modulate IL-2 secretion and TLR signalling pathway in Caco-2 cells.
The present study was conducted to evaluate the in vitro antimicrobial effect of three essential oils (cinnamon, white thyme, and clove) on selected intestinal pathogen bacteria, probiotic strains, and commensal bacteria. Additionally, their effects on inflammatory gene expression were also evaluated in a well-known intestinal human cellular model (Caco-2 cells). Cinnamon showed the highest antipathogenic microbial activity, followed by white thyme and clove. In the case of the probiotic strains, the inhibitory effect was observed at 0.1% (v/v), although growth recovery was seen after 24 h of incubation. Besides, cinnamon down-regulated the expression of genes related to the Toll-like receptor, nitric oxide, and apoptosis pathways. Similarly, secretion of interleukin 2 was inhibited by cinnamon. Results support the potential use of essential oils in the food industry for their antimicrobial and immunomodulatory effects; however, the underlying mechanisms are unknown and warrant further research.
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