A Purified Capsular Polysaccharide Markedly Inhibits Inflammatory Response during Endotoxic Shock

Capsular material of the opportunistic fungus Cryptococcus neoformans is mainly composed of a polysaccharide named glucuronoxylomannan (GXM). In this study, the effects of GXM were analyzed in an in vivo experimental system of LPS-induced shock. Endotoxic shock was induced in mice by a single intraperitoneal injection of LPS from Escherichia coli. GXM treatment reduced the mortality of mice at early stages. Mice treated with LPS alone showed markedly increased plasma levels of TNF-α, IL-1β, and IL-6, whereas mice treated with GXM too showed significantly lower plasma levels of these cytokines. This effect was related to a marked suppression of Akt and IkBα activation. Importantly, the inhibitory effect of GXM on pro-inflammatory cytokine secretion was reproduced by treatment with Wortmannin, an inhibitor of the Akt transcription pathway. Our results indicate that GXM has a beneficial effect on endotoxic shock, resulting in a significant increase in rate of survival by dampening the hyper-inflammatory response

In vivo induction of neutrophils chemotaxis by secretory aspartyl proteinases of Candida albicans

Secretory aspartyl proteinases (Saps) of Candida albicans are key virulence traits which cause inflammasome-dependent, aseptic inflammation in a mouse model of vaginitis. In this paper, neutrophil migration in response to Sap2, Sap6 and chemo-attractive products released from Sap-treated vaginal epithelium was measured in vitro, ex vivo and in vivo. Our results show that Sap2 and Sap6 induce neutrophil migration and production of potent chemoattractive chemokines such as IL-8 and MIP-2 by vaginal epithelial cells. Our data suggest that at least part of MIP-2 production depends upon IL-1β activity. The vaginal fluid of Candida-infected mice contained a heat-labile inhibitor of neutrophil candidacidal activity that was absent from the vaginal fluid of Sap-treated mice. Overall, our data provide additional information on the capacity of C. albicans Saps to cause aseptic vaginal inflammation and highlight the potential role of some chemokines released from vaginal epithelial cells in this phenomenon

Induction of caspase-11 by aspartyl proteinases of Candida albicans and implication in promoting inflammatory response

We recently demonstrated that the secreted aspartyl proteinases (Saps), Sap2 and Sap6, of Candida albicans have the potential to induce the canonical activation of NLRP3-inflammasome leading to the secretion of IL-1β and IL-18 via caspase-1 activation. We also observed that the activation of caspase-1 is partially independent from the NLRP3 activation pathway. In this study, we examined whether Sap2 and Sap6 are also able to activate the noncanonical inflammasome pathway in murine macrophages. Our data show that both, Sap2 and Sap6, can activate caspase-11 through type I IFN production. Caspase-11 concurs to activate caspase-1 with subsequent increase of IL-1β secretion. Endocytosis and internalization of Saps are required for the induction of type I IFN production, that is essential for induction of noncanonical inflammasome activation. Our study indicates a sophisticated interplay between caspase-1 and caspase-11 that connects canonical and noncanonical pathways of inflammasome activation in response to C. albicans Saps

Le varietà di sorgo da granella consigliate per le semine 2017

Nel 33º anno di prove di confronto tra ibridi di sorgo da granella sono stati realizzati 5 campi sperimentali, 2 nel Nord, 2 in Italia centrale e 1 in Sicilia. Le rese medie sono risultate simili a quelle del 2015, pur con notevoli differenze tra i diversi areali di coltivazion

Protein Pattern Formation

Protein pattern formation is essential for the spatial organization of many intracellular processes like cell division, flagellum positioning, and chemotaxis. A prominent example of intracellular patterns are the oscillatory pole-to-pole oscillations of Min proteins in \textit{E. coli} whose biological function is to ensure precise cell division. Cell polarization, a prerequisite for processes such as stem cell differentiation and cell polarity in yeast, is also mediated by a diffusion-reaction process. More generally, these functional modules of cells serve as model systems for self-organization, one of the core principles of life. Under which conditions spatio-temporal patterns emerge, and how these patterns are regulated by biochemical and geometrical factors are major aspects of current research. Here we review recent theoretical and experimental advances in the field of intracellular pattern formation, focusing on general design principles and fundamental physical mechanisms.Comment: 17 pages, 14 figures, review articl

Functional Improvement of Regulatory T Cells From Rheumatoid Arthritis Subjects Induced by Capsular Polysaccharide Glucuronoxylomannogalactan

Objective: Regulatory T cells (Treg) play a critical role in the prevention of autoimmunity, and the suppressive activity of these cells is impaired in rheumatoid arthritis (RA). The aim of the present study was to investigate function and properties of Treg of RA patients in response to purified polysaccharide glucuronoxylomannogalactan (GXMGal). Methods: Flow cytometry and western blot analysis were used to investigate the frequency, function and properties of Treg cells. Results: GXMGal was able to: i) induce strong increase of FOXP3 on CD4+ T cells without affecting the number of CD4+CD25+FOXP3+ Treg cells with parallel increase in the percentage of non-conventional CD4+CD25-FOXP3+ Treg cells; ii) increase intracellular levels of TGF-beta1 in CD4+CD25-FOXP3+ Treg cells and of IL-10 in both CD4+CD25+FOXP3+ and CD4+CD25-FOXP3+ Treg cells; iii) enhance the suppressive activity of CD4+CD25+FOXP3+ and CD4+CD25-FOXP3+ Treg cells in terms of inhibition of effector T cell activity and increased secretion of IL-10; iv) decrease Th1 response as demonstrated by inhibition of T-bet activation and down-regulation of IFN-gamma and IL-12p70 production; v) decrease Th17 differentiation by down-regulating pSTAT3 activation and IL-17A, IL-23, IL-21, IL-22 and IL-6 production. Conclusion: These data show that GXMGal improves Treg functions and increases the number and function of CD4+CD25-FOXP3+ Treg cells of RA patients. It is suggested that GXMGal may be potentially useful for restoring impaired Treg functions in autoimmune disorders and for developing Treg cell-based strategies for the treatment of these diseases

Effect of Virulence Factors on the Photodynamic Inactivation of Cryptococcus neoformans

Opportunistic fungal pathogens may cause an array of superficial infections or serious invasive infections, especially in immunocompromised patients. Cryptococcus neoformans is a pathogen causing cryptococcosis in HIV/AIDS patients, but treatment is limited due to the relative lack of potent antifungal agents. Photodynamic inactivation (PDI) uses the combination of non-toxic dyes called photosensitizers and harmless visible light, which produces singlet oxygen and other reactive oxygen species that produce cell inactivation and death. We report the use of five structurally unrelated photosensitizers (methylene blue, Rose Bengal, selenium derivative of a Nile blue dye, a cationic fullerene and a conjugate between poly-L-lysine and chlorin(e6)) combined with appropriate wavelengths of light to inactivate C. neoformans. Mutants lacking capsule and laccase, and culture conditions that favoured melanin production were used to probe the mechanisms of PDI and the effect of virulence factors. The presence of cell wall, laccase and melanin tended to protect against PDI, but the choice of the appropriate photosensitizers and dosimetry was able to overcome this resistance.Fundação de Amparo à Pesquisa do Estado de São Paulo (2010/13313–9

Saccharomyces cerevisiae CNCM I-3856 as a New Therapeutic Agent Against Oropharyngeal Candidiasis

Oropharyngeal candidiasis is a common opportunistic mucosal infection of the oral cavity, mainly caused by an overgrowth of Candida albicans. This infection can inhibit nutritional intakes and strongly affect quality of life. To date, standard therapeutic strategies involving the administration of antifungal drugs can bring several side effects, not least the emergence of drug-resistant strains. The purpose of this study is to investigate the effectiveness of Saccharomyces cerevisiae CNCM I-3856 (live or inactivated cells) against oropharyngeal candidiasis. Our results show that administration of S. cerevisiae CNCM I-3856 (live or inactivated cells) in the oral cavity of C57BL/6J mice resulted in a protective effect against oropharyngeal candidiasis. The strongest effect was obtained with live S. cerevisiae CNCM I-3856. This was related to: (1) a decrease in C. albicans load in the oral cavity, esophagus, stomach, and duodenum; (2) an early resolution of inflammatory process in the tongue; (3) a marked reduction in C. albicans virulence factors; and (4) a consistent increase in neutrophil antimicrobial capacity. These findings suggest that S. cerevisiae products are potentially beneficial in the treatment of oropharyngeal candidiasis

In vivo antiphytoviral and aphid repellency activity of essential oils and hydrosols from Mentha suaveolens and Foeniculum vulgare to control zucchini yellow mosaic virus and its vector Aphis gossypii

In recent years, natural compounds have gained attention in many fields due to their wide-range biological activity. In particular, essential oils and their associated hydrosols are being screened to control plant pests, exerting antiviral, antimycotic and antiparasitic actions. They are more quickly and cheaply produced and are generally considered safer for the environment and non-target organisms than conventional pesticides. In this study, we report the evaluation of the biological activity of two essential oils and their corresponding hydrosols obtained from Mentha suaveolens and Foeniculum vulgare in the control of zucchini yellow mosaic virus and its vector, Aphis gossypii, in Cucurbita pepo plants. The control of the virus was ascertained with treatments applied either concurrently with or after virus infection; choice tests were performed to verify repellency activity against the aphid vector. The results indicated that treatments could decrease virus titer as measured using real-time RT-PCR, while the experiments on the vector showed that the compounds effectively repelled aphids. The extracts were also chemically characterized using gas chromatography-mass spectrometry. Mentha suaveolens and Foeniculum vulgare hydrosol extracts mainly comprised fenchone and decanenitrile, respectively, while essential oils analysis returned a more complex composition, as expected

Sex and stressor modality influence acute stress-induced dynamic changes in corticolimbic endocannabinoid levels in adult Sprague Dawley rats

Research over the past few decades has established a role for the endocannabinoid system in contributing to the neural and endocrine responses to stress exposure. The two endocannabinoid ligands, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), both play roles in regulating the stress response and both exhibit dynamic changes in response to stress exposure. Most of this previous research, however, was conducted in male rodents. Given that, especially in rodents, the stress response is influenced by sex, an understanding of how these dynamic responses of endocannabinoids in response to stress is influenced by sex could provide insight into sex differences of the acute stress response. We exposed adult, Sprague Dawley rats to different commonly utilized acute stress modalities, specifically restraint, swim and foot shock stress. Thirty minutes following stress onset, we excised the amygdala, hippocampus and medial prefrontal cortex, corticolimbic brain regions involved in the stress response, to measure endocannabinoid levels. When AEA levels were altered in response to restraint and swim stress, they were reduced, whereas exposure to foot shock stress led to an increase in the amygdala. 2-AG levels, when they were altered by stress exposure were only increased, specifically in males in the amygdala following swim stress, and in the hippocampus and medial prefrontal cortex overall following foot shock stress. This increase in 2-AG levels following stress only in males was the only sex difference found in stress-induced changes in endocannabinoid levels. There were no consistent sex differences observed. Collectively, these data contribute to our further understanding of the interactions between stress and endocannabinoid function