19 research outputs found
New genetic loci link adipose and insulin biology to body fat distribution.
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (PÂ <Â 5Â ĂÂ 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms
Serotonin and Melatonin in Human Lower Gastrointestinal Tract
Background and Aims. Melatonin is a ubiquitous hormone produced not only by the pineal gland but also by other organs and tissues. It is involved in the regulation of several gastrointestinal functions. The main cells responsible for the production and release of extrapineal melatonin are the enterochromaffin (EC) cells that produce serotonin. They are involved in the pathogenesis of neuromotor disorders that characterize functional gastrointestinal disorders and in the pathophysiology of inflammatory intestinal diseases. Our aim was the immunohistochemical highlighting on biopsy samples of normal gastrointestinal mucosa and in ulcerative colitis (UC) of immunoreactive cells for melatonin and serotonin in order to identify any differences in their distribution. Materials and Methods. Our prospective case-control study involves the highlighting on human mucosal biopsies of immunoreactive cells for melatonin and serotonin. All patients undergoing colonoscopy + ileoscopy were considered eligible for the study, divided into two groups: 1. patients with active ulcerative colitis (UC); 2. control group consisting of patients undergoing endoscopic examination for colorectal cancer screening. Results. Twenty-one patients were enrolled. The controls had a higher concentration of EC cells containing 5HT particularly in the rectum (p value †0.05). In patients with active colitis the expression of 5-HT-iR was greater in all tracts of the colon. The correlation analysis in UC patients shows that a higher expression of 5-HT-iR+ cells corresponds to a lower extension of the disease and a greater severity of the same. Conclusions. 5HT+ cells decreased in the case of UC compared to healthy controls. In the severe disease, there was an increase in the expression of melatonin-secreting cells, probably as a compensatory response to the inflammation and oxidative stress. This increase is negatively correlated with the extent of the disease and positively with the severity of the same
Gender-differences of in vitro colonic motility after chemo- and radiotherapy in humans
Abstract Background The aim of the present in vitro study was to investigate, in different genders, motor responses in surgical colonic specimens from patients with rectal cancer undergoing and not undergoing chemotherapy with capecitabine and radiotherapy. Methods This in vitro study was conducted from October 2015 to August 2017 at the Experimental Pharmacology Laboratory at the National Institute âS. de Bellisâ after collecting samples at the Department of Surgery. Segments of sigmoid colon were obtained from 15 patients (Male (M)/Female (F)â=â8/7; control group, CG) operated on for elective colorectal resection for rectal cancer without obstruction and 14 patients (M/Fâ=â7/7; study group, SG) operated on for elective colorectal resection for rectal cancer who also received chemotherapy, based on capecitabine twice daily, and radiotherapy. Isometric tension was measured on colonic circular muscle strips exposed to increasing carbachol or histamine concentrations to obtain concentration-response curves. The motor responses to electrically evoked stimulation were also investigated. Results In males, carbachol and histamine caused concentration-dependent contractions in the CG and SG. An increased sensitivity and a higher response to carbachol and histamine were observed in SG than CG (Pâ<â0.01). On the contrary, in females, the response to carbachol was not significantly different in CG from the SG and the maximal responses to carbachol were greater in CG than in SG (Pâ<â0.001). The same applied to histamine for half-maximal effective concentrations and maximal response in that they were not significantly different in CG from the SG. Electrically evoked contractions were significantly more pronounced in males, especially in the SG (Pâ<â0.05). Conclusions This preliminary in vitro study has shown gender differences in motor responses of colonic circular muscle strips in patients who had received chemotherapy with capecitabine and radiotherapy
Vaginal microbiome signatures in Chlamydia trachomatis infected women
Introduction: In healthy women, lactobacilli play a crucial role in maintaining the microbial homeostasis of the vaginal niche. In case
of bacterial vaginosis (BV), a condition characterised by a depletion of lactobacilli and an increasing number of anaerobes, a higher risk of urogenital and sexually transmitted infections (STIs) is reported. The vaginal environment of healthy and BV-positive women have been extensively studied, leading to the identification of the microbial species dominating these opposite conditions and to the description of specific metabolic profiles. Besides that, less is known about the vaginal microbiome in case of STIs, as Chlamydia trachomatis (CT) infections. The aim of this study was to analyse the composition of the endogenous microbiota and the metabolic signatures of the vaginal niche in 3 different conditions: healthy, BV and CT infections.
Methods: From July 2016, all the pre-menopausal women attending the STI Outpatients Clinic of SantâOrsola-Malpighi Hospital in Bologna (Italy) and meeting one of the following criteria were enrolled: presence of vaginal symptoms or presence of risk factors for CT infection. Patients with vaginal candidiasis were excluded. For all the patients, a vaginal swab was collected for molecular CT detection (Versant CT/GC DNA 1.0 Assay; Siemens), whereas Amsel criteria were used for BV assessment. Moreover, for each woman, an additional vaginal swab stored in saline was collected and centrifuged. Cell pellets were examined with a DNA-microarray platform including 17 probe sets specific for the most representative vaginal bacterial groups and with a quantitative real-time PCR targeting 16s rRNA gene of Gardnerella vaginalis (GV). Cell-free supernatants were used for metabolomic analysis by means of 1H-NMR spectroscopy. NMR spectra were recorded with an AVANCE spectrometer (Bruker). Similarities among microbial and metabolic profiles of samples were investigated by means of a principal component analysis (PCA). Differences in GV DNA loads and metabolites concentrations were analysed by ANOVA test. The study was approved by the Hospital Ethical Committee.
Results: Among all the women enrolled, 25 were considered healthy, 18 received a diagnosis of BV and 22 were positive for CT. PCA revealed that the vaginal microbiome of healthy and BV-subjects were clearly distinct and that CT-positive women were more similar to healthy women rather than to BV-positives, both for microbial composition and for metabolic profile. The mean GV DNA load was significantly different between the groups (p=0.03): healthy and CT positive women showed similar and lower mean loads compared to BV group. At a metabolic level, significantly higher concentrations of formate, ethanolamine and methylamine were found in BV-patients, while tryptophan and lactate were more present in healthy and CT-positive women.
Conclusion: Specific microbial and metabolic signatures characterise different clinical conditions of the vaginal tract. In this context, CT-positive women are definitely more similar to healthy than BV-subjects
Artichoke Polyphenols Produce Skin Anti-Age Effects by Improving Endothelial Cell Integrity and Functionality
Artichoke is a characteristic crop of the Mediterranean area, recognized for its nutritional value and therapeutic properties due to the presence of bioactive components such as polyphenols, inulin, vitamins and minerals. Artichoke is mainly consumed after home and/or industrial processing, and the undersized heads, not suitable for the market, can be used for the recovery of bioactive compounds, such as polyphenols, for cosmetic applications. In this paper, the potential skin anti-age effect of a polyphenolic artichoke extract on endothelial cells was investigated. The methodology used was addressed to evaluate the antioxidant and anti-inflammatory activities and the improvement of gene expression of some youth markers. The results showed that the artichoke extract was constituted by 87% of chlorogenic, 3,5-O-dicaffeoylquinic, and 1,5-O-dicaffeoylquinic acids. The extract induced important molecular markers responsible for the microcirculation and vasodilatation of endothelial cells, acted as a potential anti-inflammatory agent, protected the lymphatic vessels from oxidative damage by ROS formation, and enhanced the cellular cohesion by reinforcing the tight junction complex. In addition, the artichoke extract, through the modulation of molecular pathways, improved the expression of genes involved in anti-ageing mechanisms. Finally, clinical testing on human subjects highlighted the enhancement by 19.74% of roughness and 11.45% of elasticity from using an artichoke extract cosmetic formulation compared to placebo cream
MICROBIOTA VAGINALE IN CORSO DI INFEZIONI DEL TRATTO GENITALE
Introduzione. Nel tratto genitale femminile coesistono diverse specie batteriche in un equilibrio dinamico, che pu\uf2 variare in risposta a molteplici fattori quali et\ue0, gravidanza, uso di farmaci, infezioni o patologie croniche.
Le infezioni genitali e le disbiosi colpiscono ogni anno oltre un miliardo di donne, con un significativo impatto sulla qualit\ue0 di vita e sulla salute riproduttiva. La vaginosi batterica (BV) \ue8 la disbiosi pi\uf9 comune, caratterizzata da una riduzione delle specie normalmente dominanti (Lactobacillus), che vengono sostituite da una comunit\ue0 polimicrobica anaerobia. Tra le infezioni urogenitali pi\uf9 comuni si riscontrano la candidiasi vulvovaginale e le infezioni da Chlamydia trachomatis (CT), che rappresentano la pi\uf9 comune infezione batterica a trasmissione sessuale nel mondo. L\u2019obiettivo di tale lavoro \ue8 stato quello di analizzare la composizione del microbiota vaginale in donne con diverse condizioni fisiologiche e patologiche del tratto genitale.
Materiali e metodi. Sono state incluse nello studio 21 donne sane, 20 donne con BV, 18 con candidiasi vaginale e 21 con infezione da CT. Per lo studio del microbiota, \ue8 stato estratto il DNA genomico a partire da un tampone vaginale e successivamente sono state amplificate e sequenziate le regioni V3-V4 del gene 16S rRNA batterico (MiSeq Illumina).
La classificazione tassonomica \ue8 stata condotta fino al livello di genere per tutti i microrganismi, ad eccezione dei lattobacilli, che sono stati identificati fino a livello di specie, per mezzo di un database specifico di riferimento. Per valutare la variabilit\ue0 della composizione del microbiota inter- e intra-gruppo, sono state eseguite valutazioni di \u3b1- e \u3b2-diversit\ue0, rispettivamente.
Risultati. Le donne sane erano caratterizzate da un basso indice di \u3b1-diversit\ue0, con un microbiota dominato da diverse specie di lattobacilli (Firmicutes). Al contrario, le donne con BV mostravano il pi\uf9 alto grado di diversit\ue0 microbica, con un microbiota depleto di lattobacilli e ricco di molteplici specie batteriche differenti.
Nelle donne con infezione da CT e candidiasi, la composizione del microbiota \ue8 apparsa simile, pi\uf9 vicina a quella delle donne sane rispetto, che a quelle con BV. Il microbiota vaginale di questi ultimi due gruppi, infatti, era sempre dominato da Firmicutes, ma la loro abbondanza relativa diminuiva progressivamente passando dalle donne sane a quelle con clamidia, candidiasi e BV.
Conclusioni. I nostri risultati hanno confermato l\u2019elevato grado di diversit\ue0 tra il microbiota vaginale di donne sane e di donne con BV, e hanno dimostrato come la candidiasi e l\u2019infezione da CT rappresentino una condizione intermedia fra questi due estremi
The vaginal microbiome of healthy, bacterial vaginosis and Chlamydia trachomatis-infected women
Recombinant Expression of Archaeal Superoxide Dismutases in Plant Cell Cultures: A Sustainable Solution with Potential Application in the Food Industry
Superoxide dismutase (SOD) is a fundamental antioxidant enzyme that neutralises superoxide ions, one of the main reactive oxygen species (ROS). Extremophile organisms possess enzymes that offer high stability and catalytic performances under a wide range of conditions, thus representing an exceptional source of biocatalysts useful for industrial processes. In this study, SODs from the thermo-halophilic Aeropyrum pernix (SODAp) and the thermo-acidophilic Saccharolobus solfataricus (SODSs) were heterologously expressed in transgenic tomato cell cultures. Cell extracts enriched with SODAp and SODSs showed a remarkable resistance to salt and low pHs, respectively, together with optimal activity at high temperatures. Moreover, the treatment of tuna fillets with SODAp-extracts induced an extension of the shelf-life of this product without resorting to the use of illicit substances. The results suggested that the recombinant plant extracts enriched with the extremozymes could find potential applications as dietary supplements in the nutrition sector or as additives in the food preservation area, representing a more natural and appealing alternative to chemical preservatives for the market