Crohn's disease (CD)-associated dysbiosis is characterised by a loss of Faecalibacterium prausnitzii, whose culture supernatant exerts an anti-inflammatory effect both in vitro and in vivo. However, ...the chemical nature of the anti-inflammatory compounds has not yet been determined.
Peptidomic analysis using mass spectrometry was applied to F. prausnitzii supernatant. Anti-inflammatory effects of identified peptides were tested in vitro directly on intestinal epithelial cell lines and on cell lines transfected with a plasmid construction coding for the candidate protein encompassing these peptides. In vivo, the cDNA of the candidate protein was delivered to the gut by recombinant lactic acid bacteria to prevent dinitrobenzene sulfonic acid (DNBS)-colitis in mice.
The seven peptides, identified in the F. prausnitzii culture supernatants, derived from a single microbial anti-inflammatory molecule (MAM), a protein of 15 kDa, and comprising 53% of non-polar residues. This last feature prevented the direct characterisation of the putative anti-inflammatory activity of MAM-derived peptides. Transfection of MAM cDNA in epithelial cells led to a significant decrease in the activation of the nuclear factor (NF)-κB pathway with a dose-dependent effect. Finally, the use of a food-grade bacterium, Lactococcus lactis, delivering a plasmid encoding MAM was able to alleviate DNBS-induced colitis in mice.
A 15 kDa protein with anti-inflammatory properties is produced by F. prausnitzii, a commensal bacterium involved in CD pathogenesis. This protein is able to inhibit the NF-κB pathway in intestinal epithelial cells and to prevent colitis in an animal model.
Purpose
Gestational diabetes mellitus (GDM) and thyroid dysfunction during gestation (GTD) are the two most prevalent endocrinopathies during pregnancy. The aim of the present review is to provide an ...overview of the peculiar aspects of GDM and GTD, to highlight the potential interactions and clinical consequences of these two frequent clinical conditions.
Methods
A literature review regarding GDM and GTD was carried out with particular interest on meta-analyses and human studies dealing with the (i) shared risk factors between GDM and GTD, (ii) the epidemiological link between GTD and GDM, (iii) physiopathologic link between GTD and GDM, (iv) clinical consequences of GDM and GTD, and (v) post-partum implications of GDM and GTD.
Results
The association between GDM and GTD is common and may be explained by the insulin-resistance state due to maternal GTD, to alterations in the placentation process or to the many shared risk factors. Discrepant results of epidemiologic studies can be explained, at least in part, by the changes in diagnostic criteria and screening strategies throughout the years for both conditions. GDM and GTD impact pregnancy outcome and have post-partum long-term consequences, but more studies are needed to prove an additional adverse effect.
Conclusions
Based on the epidemiological and physio-pathological link between GDM and GTD, it could be suggested that a diagnosis of GTD could lead to screen GDM and the other way round.
Nous rapportons le cas d’une patiente de 30 ans en échec d’une sleeve gastrectomie réalisée en 2014 au poids de 120kg (taille 173cm). Son obésité, dans un contexte d’obésité familiale, remonte à ...l’enfance, associée à une croissance staturale à +2DS et à une aménorrhée primaire rapportée à une atrophie ovarienne. Elle a perdu 58kg après l’intervention, a manqué les visites de suivi et repris du poids, atteignant 121kg à la consultation de décembre 2019. L’enquête alimentaire ne relève pas d’erreurs notables et l’activité physique parait adéquate. Elle a un phénotype féminin et des signes cliniques d’acromégalie. Les explorations préopératoires ont trouvé une forte augmentation paradoxale de GH à l’HGPO, un taux d’IGF1 augmenté à 325ng/mL (N 95-304), FSH et LH élevées (47,2UI/L et 28,5UI/L). L’IRM hypophysaire est normale, ainsi que le scanner thoraco-abdomino-pelvien et l’octréoscan pratiqués à la recherche d’une production ectopique de GH. L’ostéodensitométrie trouve une ostéoporose avec une densité minérale augmentée malgré l’absence d’œstrogènes et la chirurgie bariatrique, compatible avec une acromégalie. En postopératoire, l’IGF1 dosé à 2 reprises était normal. Aucune mutation n’a été retrouvée concernant l’atrophie ovarienne. L’hypersécrétion de GH pourrait s’inscrire avec l’obésité massive familiale d’installation précoce dans un syndrome génétique. Une mutation de MC4R, qui peut s’accompagner de taux modérément élevés de GH et d’IGF1 secondairement à la baisse d’ARNm de la somatostatine dans le noyau périventriculaire, a été écartée. Une autre étiologie génétique pouvant expliquer ce profil ainsi que l’atrophie ovarienne est recherchée.
Quorum sensing in Burkholderia cenocepacia H111 involves two signalling systems that depend on different signal molecules, namely N-acyl homoserine lactones (AHLs) and the diffusible signal factor ...cis-2-dodecenoic acid (BDSF). Previous studies have shown that AHLs and BDSF control similar phenotypic traits, including biofilm formation, proteolytic activity and pathogenicity. In this study we mapped the BDSF stimulon by RNA-Seq and shotgun proteomics analysis. We demonstrate that a set of the identified BDSF-regulated genes or proteins are also controlled by AHLs, suggesting that the two regulons partially overlap. The detailed analysis of two mutually regulated operons, one encoding three lectins and the other one encoding the large surface protein BapA and its type I secretion machinery, revealed that both AHLs and BDSF are required for full expression, suggesting that the two signalling systems operate in parallel. In accordance with this, we show that both AHLs and BDSF are required for biofilm formation and protease production.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
L’hyperprolactinémie inhibe l’axe gonadotrope et entraîne un hypogonadisme chez l’homme. Très rarement, les patients avec un prolactinome sont eugonadiques au diagnostic (eugPRL). L’évolution de la ...testostérone et des signes cliniques chez ces personnes après normalisation de la PRL est inconnue.
Objectif. Analyser l’évolution des paramètres cliniques et biologiques de patients eugPRL en comparaison d’une population témoin eugonadique appariée sur l’âge et la durée de suivi.
Les concentrations de testostérone, LH, FSH et peptides testiculaires ainsi que les signes cliniques de 28 patients eugPRL (âge=41±19ans, PRL=2077±3768ng/mL, testostéronémie=4,7±1,4ng/mL, volume testiculaire=24±10mL) suivis jusqu’à normalisation de la PRL, ont été comparés à ceux de 22 témoins (âge=47±19ans, PRL=8±5ng/mL, testostérone=4,6±1,3ng/mL, volume testiculaire=19,6±7,8mL).
La PRL s’est normalisée (10±7ng/mL) après 17±27 mois de traitement et la testostérone est passée de 4,7±1,4 à 5,7±1,9ng/mL (p=0,035) chez les patients eugPRL, la variation de testostéronémie entre le diagnostic et la normalisation de la PRL étant supérieure à celle des témoins (+0,87±2,1 vs –0,47±2,0, p=0,028). Les autres paramètres hormonaux n’ont pas varié significativement. Le pourcentage de patients présentant des signes cliniques d’hypogonadisme est passé de 39,3 % à 14,3 % après normalisation de la PRL (p=0,034).
Chez les patients porteurs d’un prolactinome mais eugonadiques au diagnostic, les concentrations de testostérone augmentent après normalisation de la PRL, contrairement à une population témoin. L’amélioration des signes cliniques d’hypogonadisme après traitement indique que ces variations biologiques ont un retentissement clinique.
Several plant species of the genus Psychotria (Rubiaceae) harbor Burkholderia sp. bacteria within specialized leaf nodules. The bacteria are transmitted vertically between plant generations and have ...not yet been cultured outside of their host. This symbiosis is considered to be obligatory because plants devoid of symbionts fail to develop into mature individuals. The genome of 'Candidatus Burkholderia kirkii' has been sequenced recently and has revealed evidence of reductive genome evolution, as shown by the proliferation of insertion sequences and the presence of numerous pseudogenes. We employed shotgun proteomics to investigate the expression of 'Ca. B. kirkii' proteins in the leaf nodule. Drawing from this dataset and refined comparative genomics analyses, we designed a new pseudogene prediction algorithm and improved the genome annotation. We also found conclusive evidence that nodule bacteria allocate vast resources to synthesis of secondary metabolites, possibly of the C7N aminocyclitol family. Expression of a putative 2-epi-5-valiolone synthase, a key enzyme of the C7N aminocyclitol synthesis, is high in the nodule population but downregulated in bacteria residing in the shoot apex, suggesting that production of secondary metabolites is particularly important in the leaf nodule.
Summary
Like many other bacteria, Burkholderia sp. take up iron in its ferric form via siderophore‐dependent transporters. We observed that mutant strains of B. cenocepacia H111 unable to synthesize ...siderophores did not exhibit any growth defect under iron limited conditions. This finding suggested that this opportunistic pathogen can adopt an alternative iron uptake strategy to compensate for the loss of siderophores. We identified a putative iron uptake locus, ftrBccABCD, in the genome of B. cenocepacia H111, which is also conserved in other members of the genus Burkholderia. Mutants deficient in both siderophore‐dependent and FtrBccABCD systems failed to grow under iron‐limited conditions and radiolabelled iron transport assays showed that these mutants were impaired in iron uptake. In addition, expression of ftrBccABCD can restore growth of an E. coli strain lacking all known high‐affinity iron transport systems under iron‐limited conditions. We show that all four proteins encoded by ftrBccABCD are essential for iron uptake. Furthermore, our results indicate that the expression of ftrBccABCD is regulated at the transcriptional level by iron concentration. This study provides evidence of an alternative, siderophore‐independent, iron uptake system in Burkholderia species.
Summary
Several plant species of the genus Psychotria (Rubiaceae) harbour Burkholderia sp. bacteria within specialized leaf nodules. The bacteria are transmitted vertically between plant generations ...and have not yet been cultured outside of their host. This symbiosis is also generally described as obligatory because plants devoid of symbionts fail to develop into mature individuals. We sequenced for the first time the genome of the symbiont of Psychotria kirkii in order to shed some light on the nature of their symbiotic relationship. We found that the 4 Mb genome of Candidatus Burkholderia kirkii (B. kirkii) is small for a Burkholderia species and displays features consistent with ongoing genome erosion such as large proportions of pseudogenes and transposable elements. Reductive genome evolution affected a wide array of functional categories that may hinder the ability of the symbiont to be free‐living. The genome does not encode functions commonly found in plant symbionts such as nitrogen fixation or plant hormone metabolism. Instead, a collection of genes for secondary metabolites' synthesis is located on the 140 kb plasmid of B. kirkii and suggests that leaf nodule symbiosis benefits the host by providing protection against herbivores or pathogens.
Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic member of the Bcl-2 family proteins. Its amplification is one of the most frequent genetic aberrations found in human cancers. Pyridoclax, a ...promising BH3 mimetic inhibitor, interacts directly with Mcl-1 and induces massive apoptosis at a concentration of 15 µM in combination with anti-Bcl-x
L
strategies in chemo-resistant ovarian cancer cell lines. In this study, a combined experimental and theoretical approach was used to investigate the binding mode of Pyridoclax to Mcl-1. The representative poses generated from dynamics simulations compared with NMR data revealed: (i) Pyridoclax bound to P1 and P2 pockets of Mcl-1 BH3 binding groove through its styryl and methyl groups establishing mainly hydrophobic contacts, (ii) one of the ending pyridines interacts through electrostatic interaction with K234 side chain, a negatively charged residue present only in this position in Mcl-1.
Communicated by Ramaswamy H. Sarma
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