Nutraceuticals in the Modulation of the Intestinal Microbiota: Current Status and Future Directions

Pharmaceutical interest in the human intestinal microbiota has increased considerably, because of the increasing number of studies linking the human intestinal microbial ecology to an increasing number of non-communicable diseases. Many efforts at modulating the gut microbiota have been made using probiotics, prebiotics and recently postbiotics. However, there are other, still little-explored opportunities from a pharmaceutical point of view, which appear promising to obtain modifications of the microbiota structure and functions. This review summarizes all in vitro, in vivo and clinical studies demonstrating the possibility to positively modulate the intestinal microbiota by using probiotics, prebiotics, postbiotics, essential oils, fungus and officinal plants. For the future, clinical studies investigating the ability to impact the intestinal microbiota especially by using fungus, officinal and aromatic plants or their extracts are required. This knowledge could lead to effective microbiome modulations that might support the pharmacological therapy of most non-communicable diseases in a near future

Telomere Length as a Quantitative Trait: Genome-Wide Survey and Genetic Mapping of Telomere Length-Control Genes in Yeast

Telomere length-variation in deletion strains of Saccharomyces cerevisiae was used to identify genes and pathways that regulate telomere length. We found 72 genes that when deleted confer short telomeres, and 80 genes that confer long telomeres relative to those of wild-type yeast. Among identified genes, 88 have not been previously implicated in telomere length control. Genes that regulate telomere length span a variety of functions that can be broadly separated into telomerase-dependent and telomerase-independent pathways. We also found 39 genes that have an important role in telomere maintenance or cell proliferation in the absence of telomerase, including genes that participate in deoxyribonucleotide biosynthesis, sister chromatid cohesion, and vacuolar protein sorting. Given the large number of loci identified, we investigated telomere lengths in 13 wild yeast strains and found substantial natural variation in telomere length among the isolates. Furthermore, we crossed a wild isolate to a laboratory strain and analyzed telomere length in 122 progeny. Genome-wide linkage analysis among these segregants revealed two loci that account for 30%–35% of telomere length-variation between the strains. These findings support a general model of telomere length-variation in outbred populations that results from polymorphisms at a large number of loci. Furthermore, our results laid the foundation for studying genetic determinants of telomere length-variation and their roles in human disease

Brain CHID1 Expression Correlates with NRGN and CALB1 in Healthy Subjects and AD Patients

Alzheimer's disease is a progressive, devastating, and irreversible brain disorder that, day by day, destroys memory skills and social behavior. Despite this, the number of known genes suitable for discriminating between AD patients is insufficient. Among the genes potentially involved in the development of AD, there are the chitinase-like proteins (CLPs) CHI3L1, CHI3L2, and CHID1. The genes of the first two have been extensively investigated while, on the contrary, little information is available on CHID1. In this manuscript, we conducted transcriptome meta-analysis on an extensive sample of brains of healthy control subjects (n = 1849) (NDHC) and brains of AD patients (n = 1170) in order to demonstrate CHID1 involvement. Our analysis revealed an inverse correlation between the brain CHID1 expression levels and the age of NDHC subjects. Significant differences were highlighted comparing CHID1 expression of NDHC subjects and AD patients. Exclusive in AD patients, the CHID1 expression levels were correlated positively to calcium-binding adapter molecule 1 (IBA1) levels. Furthermore, both in NDHC and in AD patient's brains, the CHID1 expression levels were directly correlated with calbindin 1 (CALB1) and neurogranin (NRGN). According to brain regions, correlation differences were shown between the expression levels of CHID1 in prefrontal, frontal, occipital, cerebellum, temporal, and limbic system. Sex-related differences were only highlighted in NDHC. CHID1 represents a new chitinase potentially involved in the principal processes underlying Alzheimer's disease

Cycloastragenol as an exogenous enhancer of chondrogenic differentiation of human adipose-derived mesenchymal stem cells. A morphological study

Stem cell therapy and tissue engineering represent a promising approach for cartilage regeneration. However, they present limits in terms of mechanical properties and premature de-differentiation of engineered cartilage. Cycloastragenol (CAG), a triterpenoid saponin compound and a hydrolysis product of the main ingredient in Astragalus membranaceous, has been explored for cartilage regeneration. The aim of this study was to investigate CAG's ability to promote cell proliferation, maintain cells in their stable active phenotype, and support the production of cartilaginous extracellular matrix (ECM) in human adipose-derived mesenchymal stem cells (hAMSCs) in up to 28 days of three-dimensional (3D) chondrogenic culture. The hAMSC pellets were cultured in chondrogenic medium (CM) and in CM supplemented with CAG (CAG-CM) for 7, 14, 21, and 28 days. At each time-point, the pellets were harvested for histological (hematoxylin and eosin (H&E)), histochemical (Alcian-Blue) and immunohistochemical analysis (Type I, II, and X collagen, aggrecan, SOX9, lubricin). After excluding CAG's cytotoxicity (MTT Assay), improved cell condensation, higher glycosaminoglycans (sGAG) content, and increased cell proliferation have been detected in CAG-CM pellets until 28 days of culture. Overall, CAG improved the chondrogenic differentiation of hAMSCs, maintaining stable the active chondrocyte phenotype in up to 28 days of 3D in vitro chondrogenic culture. It is proposed that CAG might have a beneficial impact on cartilage regeneration approaches

Altered syntactic abilities in first episode patients: An inner phenomenon characterizing psychosis

Background: Research has consistently shown that language abilities represent a core dimension of psychosis; however, to date, very little is known about syntactic comprehension performance in the early stages of psychosis. This study aims to compare the linguistic abilities involved in syntactic comprehension in a large group of First Episode Psychosis (FEP) patients and healthy controls (HCs). Methods: A multiple choice test of comprehension of syntax was administered to 218 FEP patients (166 non-affective FEP patients [FEP-NA] and 52 affective FEP patients [FEP-A]) and 106 HCs. All participants were asked to match a sentence they listen with one out of four vignettes on a pc screen. Only one vignette represents the stimulus target, while the others are grammatical or non-grammatical (visual) distractors. Both grammatical and non-grammatical errors and performance in different syntactic constructions were considered. Results: FEP committed greater number of errors in the majority of TCGB language domains compared to HCs. Moreover, FEP-NA patients committed significantly more non-grammatical (z = −3.2, p = 0.007), locative (z = −4.7, p < 0.001), passive-negative (z = −3.2, p = 0.02), and relative (z = −4.6, p < 0.001) errors compared to HCs as well as more passive-affirmative errors compared to both HCs (z = −4.3, p < 0.001) and FEP-A (z = 3.1, p = 0.04). Finally, we also found that both FEP-NA and FEP-A committed more grammatical (FEP-NA: z = −9.2, p < 0.001 and FEP-A: z = −4.4, p < 0.001), total (FEP-NA: z = −8.2, p < 0.001 and FEP-A: z = 3.9, p = 0.002), and active-negative (FEP-NA: z = −5.8, p < 0.001 and FEP-A: z = −3.5, p = 0.01) errors compared to HCs. Conclusions: This study shows that the access to syntactic structures is already impaired in FEP patients, especially in those with FEP-NA, ultimately suggesting that language impairments represent a core and inner feature of psychosis even at early stages

Differential Regulation of the Period Genes in Striatal Regions following Cocaine Exposure

Several studies have suggested that disruptions in circadian rhythms contribute to the pathophysiology of multiple psychiatric diseases, including drug addiction. In fact, a number of the genes involved in the regulation of circadian rhythms are also involved in modulating the reward value for drugs of abuse, like cocaine. Thus, we wanted to determine the effects of chronic cocaine on the expression of several circadian genes in the Nucleus Accumbens (NAc) and Caudate Putamen (CP), regions of the brain known to be involved in the behavioral responses to drugs of abuse. Moreover, we wanted to explore the mechanism by which these genes are regulated following cocaine exposure. Here we find that after repeated cocaine exposure, expression of the Period (Per) genes and Neuronal PAS Domain Protein 2 (Npas2) are elevated, in a somewhat regionally selective fashion. Moreover, NPAS2 (but not CLOCK (Circadian Locomotor Output Cycles Kaput)) protein binding at Per gene promoters was enhanced following cocaine treatment. Mice lacking a functional Npas2 gene failed to exhibit any induction of Per gene expression after cocaine, suggesting that NPAS2 is necessary for this cocaine-induced regulation. Examination of Per gene and Npas2 expression over twenty-four hours identified changes in diurnal rhythmicity of these genes following chronic cocaine, which were regionally specific. Taken together, these studies point to selective disruptions in Per gene rhythmicity in striatial regions following chronic cocaine treatment, which are mediated primarily by NPAS2. © 2013 Falcon et al

Measurement of the atmospheric muon flux with the NEMO Phase-1 detector

The NEMO Collaboration installed and operated an underwater detector including prototypes of the critical elements of a possible underwater km3 neutrino telescope: a four-floor tower (called Mini-Tower) and a Junction Box. The detector was developed to test some of the main systems of the km3 detector, including the data transmission, the power distribution, the timing calibration and the acoustic positioning systems as well as to verify the capabilities of a single tridimensional detection structure to reconstruct muon tracks. We present results of the analysis of the data collected with the NEMO Mini-Tower. The position of photomultiplier tubes (PMTs) is determined through the acoustic position system. Signals detected with PMTs are used to reconstruct the tracks of atmospheric muons. The angular distribution of atmospheric muons was measured and results compared with Monte Carlo simulations.Comment: Astrop. Phys., accepte

Measurement of the atmospheric muon depth intensity relation with the NEMO Phase-2 tower

The results of the analysis of the data collected with the NEMO Phase-2 tower, deployed at 3500 m depth about 80 km off-shore Capo Passero (Italy), are presented. Cherenkov photons detected with the photomultipliers tubes were used to reconstruct the tracks of atmospheric muons. Their zenith-angle distribution was measured and the results compared with Monte Carlo simulations. An evaluation of the systematic effects due to uncertainties on environmental and detector parameters is also included. The associated depth intensity relation was evaluated and compared with previous measurements and theoretical predictions. With the present analysis, the muon depth intensity relation has been measured up to 13 km of water equivalent.Comment: submitted to Astroparticle Physic