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The article focuses on the evaluation of the potential beneficial effects of the probiotic Lactiplantibacillus Plantarum (HEAL9) in counteracting cognitive decline and intestinal alterations associated with Alzheimer's disease through the microbiota-gut-brain axis.

The article discusses a study conducted to examine mucosal permeability, immune/inflammatory responses and colonic motility in mice with high-fat diet (HFD)-induced obesity. In the setting of obesity, the activation of NLRP3 inflammasome in tissue-resident macrophages contributes to colonic dysmotility, through the modulation of tachykininergic neurogenic responses, thus identifying NLRP3 as a therapeutic target for the treatment of bowel symptoms related to obesity.

Background: Nucleotide-binding oligomerization domain leucine rich repeat and pyrin domain containing protein 3 (NLRP3) inflammasome activation in immune/inflammatory cells contributes to enteric inflammation and bowel dysmotility in obesity (1). However, the involvement of NLRP3 inflammasome in enteric glial activation and gut barrier alterations associated with obesity has not yet been investigated. Aim: This study examined the interplay among enteric glia NLRP3 inflammasome activation and intestinal barrier impairments in high-fat diet (HFD)-induced obesity Methods: Wild-type C57BL/6J mice were fed with HFD or standard diet for 8 weeks. The remodelling of intestinal epithelial barrier in the colonic wall were assessed by standard histological staining, immunohistochemistry and immunofluorescence and western blot. Double-immunofluorescence of ASC and GFAP-positive glial cells was performed to characterize inflammasome activation in enteric glial cells. The molecular mechanisms underlying the interplay between altered intestinal barrier, enteric gliosis and NLRP3 activation in the setting of obesity were investigated with in vitro co-culture experiments enteric glial cells (EGCs) and intestinal epithelial cells (IECs). Results: After 8 weeks of HFD, animals displayed a remodeling of mucus layer, decrease in expression of tight junction proteins along with an increase in proliferating epithelial cells in colonic crypts. HFD animals were also characterized by increased ASC immunopositivity in GFAP-positive glial cells. In co-culture experiments, exposure to palmitate and lipopolysaccharide, besides to induce intestinal epithelial barrier alterations, promotes enteric gliosis with consequent hyperactivation of enteric glial NLRP3/caspase-1/IL-1β signaling pathway. The glial-derived IL-1β release contributes to exacerbate the disruption of IEB. Such an effect was abrogated upon incubation with IL-1β receptor antagonist, anakinra. Conclusions: Glial NLRP3 inflammasome acts as a regulatory hub linking EGCs and IECs, representing a promising therapeutic target for the treatment of gut barrier alterations related to obesity. [ABSTRACT FROM AUTHOR]

The carotid bodies (CBs) are small organs localized bilaterally at the bifurcation of the common carotid artery into the internal and external carotids. They work as peripheral chemoreceptors that sense changes in arterial blood O2, CO2 and pH levels and activate sympathetic-mediated cardiorespiratory reflexes thought their sensory nerve, the carotid sinus nerve (CSN) to restore the altered parameters1. Across all mammalian species, CBs are mainly formed by chemoreceptor cells (glomus cells) surrounded by glia-like sustentacular cells in small highly vascularized cell clusters called "glomoids". A variable quantity of connective tissue surrounds glomoids and defines the capsule of the CB, giving to the organ a discrete and compact aspect in some species whilst in others is rather diffuse2,5. CBs have been recently addressed as peripheral metabolic sensors involved in glucose homeostasis and sympathetic drive control in metabolic diseases like type II diabetes3.Despite the pig represents one of the best pre-clinical model of type II diabetes available4, surprisingly a proper anatomical characterization of pig CBs is lacking in this species5.In the present work we provide a detailed and updated anatomical characterization of pig CBs as a fundamental step for further studies in this species. We firstly focused on the surgical identification of the CBs in pigs (n=7) followed by classic haematoxylin-eosin histological analysis of carotids bifurcation sections. We identified the CB bilaterally as a small compact corpuscle attached to internal carotid wall in the proximity of the carotid bifurcation. We observed a lobular structure where it was possible to recognize glomus and sustentacular cells in clusters resembling the glomoids as described in other species5. Neurofilament immunolabeling revealed a rich amount of neural fibers arising from the CBs that were dispersed in the surrounding adipose tissue without forming a well identifiable nerve structure. Further studies beyond routine histological preparations will be carried on for a deeper characterization of CBs. We aim at giving a proper anatomical basis for future functional studies of this intriguing organ in a key animal model of metabolic diseases like the pig. [ABSTRACT FROM AUTHOR]

Background. Essential hypertension is a chronic multifactorial disease that arises from combined actions among polygenic/environmental/behavioral factors (diet, physical activity, obesity) [1] and aging. It is associated with cardiovascular, cerebrovascular and renal complications [2], which are causes of mortality in hypertensive patients. Surprisingly, to date detailed morphological studies on the histopathological wall rearrangement of the resistance vessels in essential hypertension are lacking and, therefore, are highly expected. Aim. To analyze the morphological remodeling of the wall of small arteries from young (<30 years) to old (>60 years) normotensive subjects (NT) and hypertensive patients (HT) and to connect the hypertensive effect on age-related vascular changes. Methods. Formalin fixed and paraffin embedded small arteries (150-300 µm diameter) were isolated from the subcutaneous tissue of the region undergoing abdominal surgery; cross-sectioned samples were examined to evaluate the histopathological vessels architecture and detect collagen by double histochemical staining Sirius Red/Fast Green. Confocal laser scanning microscopy highlighted the production of reactive superoxide anion (ROS) by dihydroethidium fluorescent staining in frozen section. Morphometric parameters were obtained from fresh small arteries mounted in a pressurized myograph. Results and Conclusions. In small arteries morphological and functional remodeling was found. Deposition of collagen fibers, ROS generation along with values of the media/lumen ratio and media transversal area in the vascular wall were increased with aging and, even more, with HT. Taken together these data suggest that in normotensive subjects the physiological aging of small resistance arteries entails eutrophic and, only late, hypertrofic remodeling. On the contrary, in HT the vascular fibrotic/hypertrofic remodeling occurs precociously, suggesting an early vascular aging in this pathological condition. [ABSTRACT FROM AUTHOR]

Background and Aim. Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor clinical signs, among which gastrointestinal disturbances represent relevant manifestations [1]. Nevertheless, the morphological alterations associated with intestinal dysfunctions in PD have been barely investigated [2]. The present study was aimed at investigating the remodelling of colonic wall in a rat model of PD with central dopaminergic denervation by intra-nigral injection of the neuro-toxin 6-hydroxydopamine (6-OHDA). Methods. Histopathological analysis of the whole colonic wall was performed 4 and 8 weeks after central 6-OHDA injection. Inflammatory infiltrates, collagen deposition as well as the remodelling of intestinal epithelial barrier and tunica muscularis were examined by microscopic techniques (histochemistry/immunohistochemistry/confocal immunofluorescence). Results. Colonic tissue from 8-week 6-OHDA rats were significantly altered, as compared with controls. The tunica mucosa showed: eosinophil infiltration; altered lining epithelium (reduced claudin-1 and transmembrane 16A protein expression) and goblet cells (increased mucus expression); enhanced glial fibrillar acid protein-positive cells and vimentin-positive fibroblast-like cells. Along with transmural collagen deposition, significant changes were observed also in the tunica muscularis: reduced expression of alphasmooth muscle actin/desmin and increased proliferation index in smooth muscle cells; increased vimentin expression and proliferative phenotype in myenteric ganglia. Conclusions. A full-thickness structural remodelling occurs in the colon of PD rats 8 weeks after central dopaminergic denervation; the main changes include an alteration of the colonic epithelial barrier along with the activation of the mucosal defence and fibrotic switch of the colonic wall. Overall, these findings suggest that: a) early histological modifications occur in the colon of rats with experimental PD at both mucosal and muscular level; b) these changes and the fibrotic alterations might contribute to bowel motor dysfunctions associated with PD. [ABSTRACT FROM AUTHOR]

Background and Aim. Obesity is a metabolic disorder with an increasing incidence in Western countries and childhood. It is characterized by low-grade systemic inflammation and several comorbidities, including alterations of gastrointestinal (GI) functions, which impact negatively on patients' quality of life. There is currently limited information on the morpho-functional features of the GI tract in obese subjects. Of note, the intestinal barrier function has been found to be altered in obese subjects, even before the occurrence of body weight increase [1]. In this light, the present study was carried out to assess, in a mouse model of diet-induced obesity, whether high fat diet (HFD) is associated with morphological alterations of the colonic mucosal barrier. Methods. C57BL/6 mice (n=5/group) were fed with standard diet (SD, 18% calories from fat) or HFD (60% calories from fat). After 8 weeks, body weight, and levels of blood cholesterol, triglycerides and glucose were evaluated. Malondialdehyde (MDA, colorimetric assay), IL-1β and IL-6 levels (ELISA assays) were examined in colonic tissues. Morphological features of colonic mucosal structures (lining epithelial cells, goblet cells, inflammatory infiltrates and enteric glia) were examined by histochemistry and immunohistochemistry. Results. HFD mice displayed significant differences at both molecular and histomorphological level, as compared with SD animals: increased body weight and blood metabolic indexes; increased MDA, IL-1β and IL-6 levels in colonic tissues; altered pattern of claudin-1 expression along with upregulation of transmembrane 16A protein and induced nitric oxide synthase in the enteric epithelium facing the lumen; increased proliferation rate of crypts; altered composition of goblet cell mucous; mucosal gliosis and infiltrates with mixed inflammatory cells. Conclusions. After 8 weeks, HFD intake led to significant alterations of systemic metabolic indexes, colonic tissue inflammation, and colonic mucosal barrier in obese mice, as compared with controls. Morphological studies can be useful to allow the characterization of histopathological patterns of colonic wall remodelling and inflammation underlying bowel motor dysfunctions associated with obesity. [ABSTRACT FROM AUTHOR]