Over the last hundred years, groundbreaking research in oral microbiology has provided a broad and deep understanding about the oral microbiome, its interactions with our body, and how the community ...can affect our health, be protective, or lead to the development of dental diseases. During this exciting journey, hypotheses were proposed, and concepts were established, discarded, and later revisited from updated perspectives. Dental plaque, previously considered a polymicrobial community of unspecific pathogenicity, is recognized as microbial biofilms with healthy, cariogenic, or periodontopathogenic profiles, resulting from specific ecologic determinants and host factors. The “one pathogen, one disease” paradigm of oral infections has been replaced by a holistic concept of a microbial community as the entity of pathogenicity. Cutting-edge technology can now explore large microbial communities related to different clinical conditions, which has led to finding several novel disease-associated species and potential pathobionts and pathobiomes. This vast amount of data generated over time has widened our view of the etiology of caries and periodontal and peri-implant diseases and has promoted updated strategies to treat and prevent the oral diseases.
The majority of experiments investigating the immune response to gastrointestinal helminth infection use a single bolus infection. However, in situ individuals are repeatedly infected with low doses. ...Therefore, to model natural infection, mice were repeatedly infected (trickle infection) with low doses of Trichuris muris. Trickle infection resulted in the slow acquisition of immunity reflected by a gradual increase in worm burden followed by partial expulsion. Flow cytometry revealed that the CD4+ T cell response shifted from Th1 dominated to Th2 dominated, which coincided with an increase in Type 2 cytokines. The development of resistance following trickle infection was associated with increased worm expulsion effector mechanisms including goblet cell hyperplasia, Muc5ac production and increased epithelial cell turn over. Depletion of CD4+ T cells reversed resistance confirming their importance in protective immunity following trickle infection. In contrast, depletion of group 2 innate lymphoid cells did not alter protective immunity. T. muris trickle infection resulted in a dysbiotic mircrobiota which began to recover alpha diversity following the development of resistance. These data establish trickle infection as a robust and informative model for analysis of immunity to chronic intestinal helminth infection more akin to that observed under natural infection conditions and confirms the importance of CD4+ T cell adaptive immunity in host protection.
As the life expectancy and growth of the aging population increase globally, efforts to promote healthy longevity become more important. Holistic policy guidelines and actions have been designed to ...advocate and fortify healthy aging at multiple levels. Oral health, a fundamental contributor of overall health and well-being, forms a core part of the noncommunicable disease agenda within the sustainable development goals set by the World Health Organization. Aging significantly heightens the risk of myriad oral disorders and other noncommunicable diseases. As of 2019, oral disorders accounted for 8.9 million disability-adjusted life-years in individuals older than 60 y. In addition to the development of multidisciplinary aging-friendly policies to promote healthy aging, basic biology and translational research has been encouraged that focuses on deciphering the underlying mechanisms involved in age-related physical and cognitive decline or dysregulation of oral tissues. Given the relevance of oral health aging as a critical component of the One Health Initiative, this special issue encompasses a collection of articles dedicated to recent advances in the behavioral and social implications of age-related oral diseases and tooth loss on several aspects of the quality of life of adults as they age. Furthermore, it includes articles detailing molecular mechanisms associated with cellular aging and their implications for oral tissue health, periodontal disease severity, and the regenerative potential of stem cells.
Schistosomiasis is a parasitic disease affecting over 200 million people in multiple organs, including the lungs. Despite this, there is little understanding of pulmonary immune responses during ...schistosomiasis. Here, we show type-2 dominated lung immune responses in both patent (egg producing) and pre-patent (larval lung migration) murine Schistosoma mansoni (S. mansoni) infection. Human pre-patent S. mansoni infection pulmonary (sputum) samples revealed a mixed type-1/type-2 inflammatory cytokine profile, whilst a case-control study showed no significant pulmonary cytokine changes in endemic patent infection. However, schistosomiasis induced expansion of pulmonary type-2 conventional dendritic cells (cDC2s) in human and murine hosts, at both infection stages. Further, cDC2s were required for type-2 pulmonary inflammation in murine pre-patent or patent infection. These data elevate our fundamental understanding of pulmonary immune responses during schistosomiasis, which may be important for future vaccine design, as well as for understanding links between schistosomiasis and other lung diseases.
Infection with soil-transmitted helminths (STH) remains a major burden on global health and agriculture. Our understanding of the immunological mechanisms that govern whether an individual is ...resistant or susceptible to infection is derived primarily from model infections in rodents. Typically, experimental infections employ an artificially high, single bolus of parasites that leads to rapid expulsion of the primary infection and robust immunity to subsequent challenges. However, immunity
is generated slowly, and is only partially effective, with individuals in endemic areas retaining low-level infections throughout their lives. Therefore, there is a gap between traditional model STH systems and observations in the field. Here, we review the immune response to traditional model STH infections in the laboratory. We compare these data to studies of natural infection in humans and rodents in endemic areas, highlighting crucial differences between experimental and natural infection. We then detail the literature to date on the use of "trickle" infections to experimentally model the kinetics of natural infection.
The increasing use of terrestrial plant lipids to replace of fish oil in commercial aquafeeds requires understanding synthesis and storage of long chain-polyunsaturated fatty acids (LC-PUFA) in ...farmed fish. Manipulation of dietary fatty acids may maximize tissue storage of LC-PUFA, through increased production and selective utilization. A data synthesis study was conducted to estimate optimal levels of fatty acids that may maximize the production and storage of LC-PUFA in the edible portion of salmonids. Data were compiled from four studies with Atlantic salmon, rainbow trout, and steelhead trout (total n = 180) which were fed diets containing different terrestrial-based oils to replace fish oil. LC-PUFA (%) were linearly correlated between diet and muscle tissue (p < 0.001; r2 > 44%), indicating proportional storage after consumption. The slope, or retention rate, was highest for docosahexaenoic acid (DHA) at 1.23, indicating that an additional 23% of DHA was stored in the muscle. Dietary saturated fatty acids were positively related to DHA stored in the muscle (p < 0.001; r2 = 22%), which may involve membrane structural requirements, as well as selective catabolism. DHA was found to be optimally stored with a dietary n-3: n-6 ratio of 1.03: 1. These new results provide a baseline of optimal dietary ratios that can be tested experimentally to determine the efficacy of balancing dietary fatty acids for maximum LC-PUFA storage.
This open-label, multicentre, phase 2 trial evaluated the efficacy and tolerability of the mammalian target of rapamycin inhibitor ridaforolimus in women with advanced endometrial cancer.
Women with ...measurable recurrent or persistent endometrial cancer and documented disease progression were treated with ridaforolimus 12.5 mg intravenously once daily for 5 consecutive days every 2 weeks in a 4-week cycle. The primary end point was clinical benefit response, defined as an objective response or prolonged stable disease of 16 weeks or more.
In all, 45 patients were treated with single-agent ridaforolimus. Clinical benefit was achieved by 13 patients (29%), including 5 (11%) with confirmed partial responses and 8 (18%) with prolonged stable disease. All patients with clinical benefit response received ridaforolimus for more than 4 months. In this heavily pretreated population, the 6-month progression-free survival was 18%. Ridaforolimus was generally well tolerated: adverse events were predictable and manageable, consistent with prior studies in other malignancies. Overall, the most common adverse events were diarrhoea (58%) and mouth sores (56%); most common grade 3 or higher adverse events were anaemia (27%) and hyperglycaemia (11%).
Single-agent ridaforolimus has antitumor activity and acceptable tolerability in advanced endometrial cancer patients. Further clinical evaluation of ridaforolimus is warranted.
Nippostrongylus brasiliensis is a well-defined model of type-2 immunity but the early lung-migrating phase is dominated by innate IL-17A production. In this study, we confirm previous observations ...that Il17a-KO mice infected with N. brasiliensis exhibit an impaired type-2 immune response. Transcriptional profiling of the lung on day 2 of N. brasiliensis infection revealed an increased Ifng signature in Il17a-KO mice confirmed by enhanced IFNγ protein production in lung lymphocyte populations. Depletion of early IFNγ rescued type-2 immune responses in the Il17a-KO mice demonstrating that IL-17A-mediated suppression of IFNγ promotes type-2 immunity. Notably, later in infection, once the type-2 response was established, IL-17A limited the magnitude of the type-2 response. IL-17A regulation of type-2 immunity was lung-specific and infection with Trichuris muris revealed that IL-17A promotes a type-2 immune response in the lung even when infection is restricted to the intestine. Together our data reveal IL-17A as a major regulator of pulmonary type-2 immunity such that IL-17A supports early development of a protective type-2 response by suppression of IFNγ but subsequently limits excessive type-2 responses. A failure of this feedback loop may contribute to conditions such as severe asthma, characterised by combined elevation of IL-17 and type-2 cytokines.
Consumers are increasingly demanding for natural and beneficial foods, in order to improve their health and well-being. Probiotics play an important role in such demand, and dairy foods are commonly ...used as vehicles for such bacteria, represented predominantly by lactic acid bacteria. Due to consumers demand, food industry is constantly looking for novel bacterial strains, leading to studies that aims the isolation and characterization of their beneficial features. This study aimed to characterize the naturally occurring lactic acid bacteria obtained from a dairy environment, in order to assess their potential use as probiotics.
Preliminary screening and PCR analysis, based on 16S rRNA sequencing, were applied to select and identify 15 LAB strains from the genera Lactobacillus (n = 11), Pediococcus (n = 2) and Weissella (n = 2). All strains showed resistance to low pH and the evaluated bile salt concentrations in vitro. The API ZYM test characterized the enzymatic activity of the strains, and a high β-galactosidase activity was observed in 13 strains. All strains presented resistance to simulated gastric (3 h) and intestinal (4 h) conditions in vitro, the ability to auto- and co-aggregate with indicator microorganisms and a high cell surface hydrophobicity. Most of the strains were positive for map and EFTu beneficial genes. All strains exhibited strong deconjugation of bile salts in vitro and all assimilated lactose.
The phenotypes exhibited in vitro and the presence of beneficial genes revealed the beneficial potential of the studied strains, demanding further analyses in a food matrix and in vivo to allow the development of a functional product, with health-related properties.
Desmoid-type fibromatosis (DF) is a rare locally aggressive monoclonal proliferation of myofibroblasts lacking metastatic capacity. It may be observed in nearly every part of the body. Considering ...the variable clinical presentations, anatomic locations, and biologic behaviors, an individualized treatment approach is required. The pathogenesis of DF is not completely understood even if a high prevalence (∼85%) of CTNNB1 mutations discovered in sporadic DF underlies the importance of the Wnt/&bgr;-catenin pathway. No established and evidence-based approach for the treatment of this neoplasm is available as of today. Considering the unpredictable behavior and the heterogeneity of this disease, we propose a treatment algorithm approved by the French and the Italian Sarcoma Group, based on a front-line wait and see approach and subsequent therapy in the case of progression. A careful counseling at a referral center is mandatory and should be offered to all patients affected by sporadic DF from the time of their diagnosis.
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