The Mutyh Base Excision Repair Gene Influences the Inflammatory Response in a Mouse Model of Ulcerative Colitis

Background

The Mutyh DNA glycosylase is involved in the repair of oxidized DNA bases. Mutations in the human MUTYH gene are responsible for colorectal cancer in familial adenomatous polyposis. Since defective DNA repair genes might contribute to the increased cancer risk associated with inflammatory bowel diseases, we compared the inflammatory response of wild-type and Mutyh^−/− mice to oxidative stress.

Methodology/Principal Findings

The severity of colitis, changes in expression of genes involved in DNA repair and inflammation, DNA 8-oxoguanine levels and microsatellite instability were analysed in colon of mice treated with dextran sulfate sodium (DSS). The Mutyh^−/− phenotpe was associated with a significant accumulation of 8-oxoguanine in colon DNA of treated mice. A single DSS cycle induced severe acute ulcerative colitis in wild-type mice, whereas lesions were modest in Mutyh^−/− mice, and this was associated with moderate variations in the expression of several cytokines. Eight DSS cycles caused chronic colitis in both wild-type and Mutyh^−/− mice. Lymphoid hyperplasia and a significant reduction in Foxp3⁺ regulatory T cells were observed only in Mutyh^−/− mice.

Conclusions

The findings indicate that, in this model of ulcerative colitis, Mutyh plays a major role in maintaining intestinal integrity by affecting the inflammatory response.     

Histochemical and ultrastructural analysis of the epidermal gland cells of Branchiomma luctuosum (Polychaeta, Sabellidae)

Abstract. This histochemical and ultrastructural study describes the epidermal gland cells of a tubicolous polychaete, Branchiomma luctuosum . The histochemistry was carried out using standard techniques and FITC-labelled lectins. Four types of secretory cells were identified in two categories: orthochromatic cells (Type 1) and metachromatic cells (Types 2, 3, and 4). The secretory product of the Type-1 orthochromatic cells contains neutral glycoproteins with Galβ1,3GalNAc residues. Metachromatic cells produce acidic, mainly sulfated, glycoconjugates with Galβ1,3GalNAc residues (Type 2) or glucosidic and/or mannosidic residues (Types 3 and 4). In sialylated chains, terminal sialic acid is bound to the penultimate GalNAc and Galβ1,3GalNAc residues. The complex composition of the mucus produced by epidermal gland cells of B. luctuosum may be correlated with its different functions. Ultrastructural studies of the epidermal gland cells showed differing morphology, and the presence in the gland cells of Types 3 and 4 of a funnel-shaped structure for the extrusion of the secretory material.     

Knowledge Integration and Good Marine Governance: A Multidisciplinary Analysis and Critical Synopsis

Human Ecology - Our research addresses knowledge integration for the good governance of the environment and the oceans: (a) through a comprehensive legal, political science, and anthropological...     

In vitro leaf-derived organogenesis and somaclonal variant detection in Humulus lupulus L

In Vitro Cellular & Developmental Biology - Plant - The exploitation of somaclonal variation potentially could be a valid strategy to overcome the depletion of hop intraspecific...     

Neuroprotective potential of choline alfoscerate against β‐amyloid injury: Involvement of neurotrophic signals

Alzheimer's disease represents the most prevalent neurodegeneration worldwide, clinically characterized by cognitive and memory impairment. New therapeutic approaches are extremely important to counteract this disorder. This research is focused on the potential use of choline alfoscerate in preventing neuronal death using in vitro models of Alzheimer's disease, representing the early stage of the disease, treated before or after the insult with glycerylphosphorylcholine. On the light of the results collected, we can postulate that choline alfoscerate, by the activation of the neurotrophin survival pathway, was able to counteract the detrimental effect of β‐amyloid in both in vitro models, reducing apoptotic cell death and preserving the neuronal morphology.     

Distribution of substance P immunoreactive cell bodies and fibers in cranial sensory and autonomic ganglia of the chick

Substance P-immunoreactive neurons were demonstrated in chick embryonic and adult trigeminal ganglion and jugular-superior ganglionic complex using FITC-immunohistochemical methods. Both small-size and large ganglion cells exhibited SP immunoreactivity, without apparent changes during embryonic and post-hatching development. SP-positive fibers could be detected in a good number in the sympathetic cranial cervical ganglion, either during embryonic development or in adult chick. No immunoreactive perikarya were observed in this ganglion. In the ciliary ganglion, both choroidal and ciliary neurons were SP-negative, whereas SP immunoreactive fibers surrounded the perikarya of both cell populations.     

Chick heart peptidergic innervation: localization and development

Localization and development of chick heart peptidergic innervation (Substance P, VIP and Somatostatin) were investigated by means of immunofluorescence technique. The peptidergic component of the heart innervation was observed, for the first time, in older than 11 day chick embryos, i.e., subsequently to the appearance of the cholinergic component. The peptidergic structures achieve nearly full development in about 16-17 day embryos. Substance P is the most represented of the three peptides. It is localized both in nerve bundle fibers and in isolated fibers within the myocardium, the pericardium, the vessel walls; it is also present in fibers of some heart base ganglia. VIP is mostly contained in some thick single fibers travelling along the vessel walls of the heart base, the myocardium and the pericardium. Some VIP immunoreactive cells were also observed in the base ganglia. Somatostatin is mostly contained in some ganglia cells, whilst thin Somatostatin-immunoreactive fibers form a rich plexus among the atrial and ventricular myofibers, without contacting the vessel walls.     

Susceptibility of different strains of mice to various levels of infection with the eggs of Taenia taeniaeformis

Susceptibility of different mouse strains to varying levels of Taenia taeniaeformis eggs has been studied. C3H are shown to be susceptible to any quantity of eggs. However C57 and NMRI are only susceptible to 1–2 eggs, while larvae from an infection of 30–50 eggs are precociously destroyed. Sometimes fertile larvae can also develop in resistant strains of mice infected with some hundred eggs. In C3H the challenge larvae are unable to survive even from an infection given 24–48 h post-first inoculum. The hypothesis is proposed that in resistant strains, infection with 30–50 eggs induces a more rapid immune response which becomes effective while the larva is still vulnerable; in massive infections, however, immune paralysis may occur. Although susceptible strains allow primary infections to develop, they show resistance to challenge infections because larvae are destroyed before they become insusceptible to host attack.     

Organoid systems to study the human female reproductive tract and pregnancy

Both the proper functioning of the female reproductive tract (FRT) and normal placental development are essential for women’s health, wellbeing, and pregnancy outcome. The study of the FRT in humans has been challenging due to limitations in the in vitro and in vivo tools available. Recent developments in 3D organoid technology that model the different regions of the FRT include organoids of the ovaries, fallopian tubes, endometrium and cervix, as well as placental trophoblast. These models are opening up new avenues to investigate the normal biology and pathology of the FRT. In this review, we discuss the advances, potential, and limitations of organoid cultures of the human FRT.Subject terms: Cell biology, Physiology, Diseases

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