Abstract The study of the liver as a lymphoid organ is a growing field fueled by our better knowledge of the different component of the immune system and how they orchestrate an immune-related ...response. The liver have highly specialized mechanisms of immune tolerance, mainly because is continuously exposed to microbial and environmental antigens, and dietary components from the gut. Accordingly, the liver contains specialized lymphoid subpopulations acting as antigen-presenting cells. Growing evidences show that the liver is also associated with obesity-associated diseases because of its immune-related capacity to sense metabolic stress induced by nutritional surplus. Finally, the liver produces a pletora of neo-antigens being the primary metabolic organ of the body. Common immune mechanisms play a key pathogenetic role in most of acute and chronic liver diseases and in the rejection of liver allografts. Any perturbations of liver-related immune functions have important clinical implications. This issue of the Journal of Autoimmunity is focused on the more recent advances in our knowledge related to the loss of liver tolerance, a paradox for a tolerogenic organ, that leads to overactivation of the innate and adaptive immune response and the development of autoimmune liver diseases, such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. The invited expert review articles capture the underlying immunomolecular mechanisms of the development and progression of autoimmune liver diseases, the novel field of the immune-related “liver-gut” axis influences to the development of liver autoimmunity, the predominant role of genetic factors, and the increasingly effective immuno-therapeutic possibilities.
Chronic autoimmune atrophic gastritis (CAAG) is an organ-specific autoimmune disease, which affects the corpus–fundus gastric mucosa. Although it has been described for several years, the real ...pathophysiological mechanisms, the natural history and the possible neoplastic complications are not completely known. Atrophy of the gastric mucosa is the endpoint of the chronic processes, with the loss of glandular cells and their replacement by intestinal-type epithelium, pyloric-type glands, and fibrous tissue. As a consequence, hydrochloric acid, pepsin and intrinsic-factor is impaired resulting in pernicious anemia. The exact causal agent is not yet known, but both genetic and environmental factors seem to play a decisive role.
Moreover, the clinical onset may assume different characteristics; differently from what previously observed, recent evidence has reported the onset of CAAG at a younger age, frequently with iron deficiency anemia or upper gastro-intestinal symptoms.
The diagnosis of CAAG might be challenging and usually requires the combination of clinical, serological and histopathologic data; moreover, CAAG patients are often misdiagnosed as refractory to HP eradication therapy, probably because achlorhydria might allow urease-positive bacteria other than H pylori to colonize the stomach, causing positive 13C-urea breath test results.
However, biopsy is the most reliable method to evaluate the presence of metaplastic atrophic gastritis. In order to assess the severity of gastric atrophy and intestinal metaplasia, OLGA and OLGIM staging systems have been proposed and seem to correlate with the risk of developing gastric adenocarcinoma. Indeed, CAAG represents a pre-neoplastic condition, as patients with CAAG are very likely to develop either type-1 gastric neuroendocrine tumors and gastric adenocarcinomas, as well as several other neoplastic diseases. To date, the need, the intervals and cost-effectiveness of endoscopic/histological surveillance for patients with CAAG/pernicious anemia are yet to be established.
Chronic inflammation is the hallmark of fibrotic disorders and is characterized by the activation of immune cells in the damaged tissues. Macrophages have emerged as central players in the fibrotic ...process since they initiate, sustain and amplify the inflammatory reaction. As regards the liver, distinct populations of phagocytic cells, like Kupffer cells and monocyte-derived macrophages, are indisputably key cells implicated in the pathogenesis of several chronic liver diseases. In this review, we summarize the current knowledge on the origin, role and functions of macrophages in fibrotic conditions, with a specific focus on liver fibrosis; then, we discuss some innovative therapeutic strategies targeting macrophages in fibrotic liver diseases.
Physical education (PE) researchers sustain that the teaching styles adopted by PE teachers play a key role in defining children’s positive experiences during lessons and have a relevant impact on ...their psychophysical health. However, a limited number of studies has examined the effect of teaching styles on these aspects. The aim of this study was to investigate the effectiveness of an integrated approach mainly based on integration of multi-teaching styles and active reflection (MTA) on the fitness level, motor competence, enjoyment, self-perception, amount of physical activity (PA), and children’s perception of PE, in Italian primary school children. Participants were 121 children from three elementary schools. Children were randomly assigned into two groups: (a) an intervention group (IG) that received PE lessons based on MTA provided by specifically trained PE students, and (b) a control group (CG) that received standard PE lessons (S-PE) from primary school classroom teachers. Both groups engaged in two PE lessons per week lasting 1 h each for 12 weeks. The findings revealed an increase in the children’s fitness level, motor competence, enjoyment and amount of PA in the IG compared to those in the CG. Furthermore, the children of the IG spent more time being engaged on a task, reflecting on it, and wasted less time during PE compared to the children of the CG. Finally, the children of the IG reported higher levels of satisfaction with PE lessons and teaching styles compared to children of the CG. Integration of different teaching styles lead by specifically trained educators can be suggested as a valuable strategy to provide learning experiences of children of primary school to have positive effects on their physical literacy development promoting healthy lifestyles.
Abstract MicroRNAs (miRNAs) have recently emerged as a new class of modulators of gene expression at the post-transcriptional level. The function of miRNA is the control of protein production by ...targeting mRNAs for translational repression or degradation. MiRNAs play a critical role in many biological processes such as cellular proliferation and maturation, apoptosis, regulation of chronic inflammation and development of cancer. It has recently been discovered that miRNAs are differentially expressed in autoimmune diseases (AID) and miRNA regulation may impact in the development or prevention of AID. In this paper we review the importance of miRNAs in AID in particular in inflammatory bowel disease (IBD). IBD is an AID whose pathophysiology remains uncertain. It is generally hypothesized that IBD is caused by the enteric microflora in genetically predisposed patients with an immune dysregulation in the gastrointestinal tract. Knowing the typical miRNA pattern of IBD will improve our knowledge of the pathogenesis of this disease and will lead to future well-focused projects to study the regulatory function of such miRNAs. Furthermore, it is possible that some miRNAs are specific to IBD and could serve as biomarkers with clinical applications for the diagnosis or assessment of disease activity.
The humoral arm of innate immunity includes diverse molecules with antibody-like functions, some of which serve as disease severity biomarkers in coronavirus disease 2019 (COVID-19). The present ...study was designed to conduct a systematic investigation of the interaction of human humoral fluid-phase pattern recognition molecules (PRMs) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of 12 PRMs tested, the long pentraxin 3 (PTX3) and mannose-binding lectin (MBL) bound the viral nucleocapsid and spike proteins, respectively. MBL bound trimeric spike protein, including that of variants of concern (VoC), in a glycan-dependent manner and inhibited SARS-CoV-2 in three in vitro models. Moreover, after binding to spike protein, MBL activated the lectin pathway of complement activation. Based on retention of glycosylation sites and modeling, MBL was predicted to recognize the Omicron VoC. Genetic polymorphisms at the MBL2 locus were associated with disease severity. These results suggest that selected humoral fluid-phase PRMs can play an important role in resistance to, and pathogenesis of, COVID-19, a finding with translational implications.
Abstract The X chromosome is known to contain the largest number of immune-related genes of the whole human genome. For this reason, X chromosome has recently become subject of great interest and ...attention and numerous studies have been aimed at understanding the role of genes on the X chromosome in triggering and maintaining the autoimmune aggression. Autoimmune diseases are indeed a growing heath burden affecting cumulatively up to 10% of the general population. It is intriguing that most X-linked primary immune deficiencies carry significant autoimmune manifestations, thus illustrating the critical role played by products of single gene located on the X chromosome in the onset, function and homeostasis of the immune system. Again, the plethora of autoimmune stigmata observed in patients with Turner syndrome, a disease due to the lack of one X chromosome or the presence of major X chromosome deletions, indicate that X-linked genes play a unique and major role in autoimmunity. There have been several reports on a role of X chromosome gene dosage through inactivation or duplication in women with autoimmune diseases, for example through a higher rate of circulating cells with a single X chromosome (i.e. with X monosomy). Finally, a challenge for researchers in the coming years will be to dissect the role for the large number of X-linked microRNAs from the perspective of autoimmune disease development. Taken together, X chromosome might well constitute the common trait of the susceptibility to autoimmune diseases, other than to explain the female preponderance of these conditions. This review will focus on the available evidence on X chromosome changes and discuss their potential implications and limitations.
Summary Clinical complexity, anatomic diversity and molecular heterogeneity of cholangiocarcinoma (CCA) represent a major challenge in the assessment of effective targeted therapies. Molecular and ...cellular mechanisms underlying the diversity of CCA growth patterns remain a key issue of clinical concern. Crucial questions comprise the nature of the CCA-origin, the initial target for cellular transformation as well as the relationship with the cancer stem cells (CSC) concept. Additionally, since CCA often develops in the context of an inflammatory milieu (cirrhosis and cholangitis), the stromal compartment or tumour microenvironment (TME) likely promotes initiation and progression of this malignancy, contributing to its heterogeneity. This review will emphasize the dynamic interplay between stem-like intrinsic and TME-extrinsic pathways, which may represent novel options for multi-targeted therapies in CCA.
Physical education during adolescence, supported by evidenced-based methodologies, offers many different opportunities to practice structured physical activity and promote the development of motor ...skills, motor coordination, and conditioning. The present study aimed to assess differences in the levels of physical activity, enjoyment, and self-perception in a sample (
= 1029, M = 505, F = 524) of 11-12-year-old secondary schoolchildren according to gender and BMI and determine (a) the mediation effects of physical self-perception in the association between BMI and physical activity and (b) the role of enjoyment in mediating the relation between physical self-perception and physical activity. As part of the Regional Observatory of Motor Development Project (Apulia, Southern Italy), the assessment involved three questionnaires for physical activity levels (PAL), physical self-perception (PSP_C), and enjoyment (PACES). The results showed significant differences in PSP between normal-weight, overweight, and obese children (especially in girls), while there were no significant differences in enjoyment. Physical self-perception partially mediates the relationship between BMI and PAL (R
= 7.94% for males, 95% C.I.: -0.013, -0.004; R
= 14.70% for females, 95% C.I.: -0.25, -0.009), and the enjoyment partially mediates the relationship between physical self-perception and PAL (R
= 6.83% for males, 95% C.I. = 0.003, 0.012; R
= 13.45% for females, 95% C.I. = 0.002, 0.014). However, only a small percentage of variance was explained, precluding the extension and generalization of the results obtained.
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