Sex differences in gut microbiota are acknowledged, and evidence suggests that gut microbiota may have a role in higher incidence and/or severity of autoimmune diseases in females. Additionally, it ...has been suggested that oral, vaginal, and gut microbiota composition can be regulated by estrogen levels. The association of vaginal microbiota with vulvovaginal atrophy at menopause is well described in the literature. However, the relevance of oral and gut microbiota modulation in the immune system during estrogen deficiency and its effect on inflammatory diseases is not well explored. Estrogen deficiency is a condition that occurs in menopausal women, and it can last approximately 30 years of a woman's life. The purpose of this mini- review is to highlight the importance of alterations in the oral and gut microbiota during estrogen deficiency and their effect on oral and inflammatory diseases that are associated with menopause. Considering that hormone replacement therapy is not always recommended or sufficient to prevent or treat menopause-related disease, we will also discuss the use of probiotics and prebiotics as an option for the prevention or treatment of these diseases.
Control of Streptococcus pneumoniae colonisation at human mucosal surfaces is critical to reducing the burden of pneumonia and invasive pneumococcal disease, interrupting transmission, and achieving ...herd protection. Here, we use an experimental human pneumococcal carriage model (EHPC) to show that S. pneumoniae colonisation is associated with epithelial surface adherence, micro-colony formation and invasion, without overt disease. Interactions between different strains and the epithelium shaped the host transcriptomic response in vitro. Using epithelial modules from a human epithelial cell model that recapitulates our in vivo findings, comprising of innate signalling and regulatory pathways, inflammatory mediators, cellular metabolism and stress response genes, we find that inflammation in the EHPC model is most prominent around the time of bacterial clearance. Our results indicate that, rather than being confined to the epithelial surface and the overlying mucus layer, the pneumococcus undergoes micro-invasion of the epithelium that enhances inflammatory and innate immune responses associated with clearance.
Short-chain fatty acids (SCFAs) are fermentation end products produced by the intestinal microbiota and have anti-inflammatory and histone deacetylase-inhibiting properties. Recently, a dual ...relationship between the intestine and kidneys has been unraveled. Therefore, we evaluated the role of SCFA in an AKI model in which the inflammatory process has a detrimental role. We observed that therapy with the three main SCFAs (acetate, propionate, and butyrate) improved renal dysfunction caused by injury. This protection was associated with low levels of local and systemic inflammation, oxidative cellular stress, cell infiltration/activation, and apoptosis. However, it was also associated with an increase in autophagy. Moreover, SCFAs inhibited histone deacetylase activity and modulated the expression levels of enzymes involved in chromatin modification. In vitro analyses showed that SCFAs modulated the inflammatory process, decreasing the maturation of dendritic cells and inhibiting the capacity of these cells to induce CD4(+) and CD8(+) T cell proliferation. Furthermore, SCFAs ameliorated the effects of hypoxia in kidney epithelial cells by improving mitochondrial biogenesis. Notably, mice treated with acetate-producing bacteria also had better outcomes after AKI. Thus, we demonstrate that SCFAs improve organ function and viability after an injury through modulation of the inflammatory process, most likely via epigenetic modification.
Airborne exposure to microbial cell wall lipids such as lipopolysaccharide triggers innate immune responses that regulate susceptibility to allergic airway inflammation. α-Glycosylceramides represent ...another widespread class of microbial lipids that directly stimulate innate-like, IL-4- and IL-13-producing, CD1d-restricted NKT cells. In this study, we demonstrate that NKT cells constitutively accumulate and reside in the microvasculature of the mouse lung. After a single airborne exposure to lipid antigen, they promptly extravasate to orchestrate the formation of peribronchiolar and interstitial lymphohistiocytic granulomas containing numerous eosinophils. Concomitant airborne exposure to ovalbumin (OVA) induces the priming of OVA-specific Th2 cells and IgE antibodies by the same dendritic cell coexpressing CD1d and MHC class II. Although NKT cell activation remains confined to the lipid-exposed lung and draining lymph nodes, Th2 cells recirculate and seed the lung of a parabiotic partner, conferring susceptibility to OVA challenge months after the initial exposure, in a manner independent of NKT cells and CD1d. Thus, transient recruitment and activation of lung-resident intravascular NKT cells can trigger long-term susceptibility to allergic airway inflammation.
•Nanocomposites between molybdenum-based materials (MoS2, amorphous molybdenum sulfide and oxide) and carbon nanotubes prepared as thin films through the liquid-liquid interfacial route.•Morphology ...and electrochemical properties of the nanocomposites are strongly dependent on the experimental parameters.•Films used as thin, transparent, and efficient anodes for aqueous K-ion batteries with capacities up to 517 mAh g−1.
Thin films of nanocomposites composed of different molybdenum-based materials and carbon nanotubes were prepared and their performance as anodes in aqueous potassium-ion batteries was verified. The films were obtained through an innovative methodology based on the liquid/liquid interfacial route in a single-step procedure, starting from carbon nanotubes dispersions in chloroform or toluene, and molybdenum disulfide (or a mixture of amorphous molybdenum oxide/sulfide) dispersed in acetonitrile/water. The samples were characterized using different spectroscopic, microscopic, and electrochemical techniques, and it was observed a strong correlation between morphology and electrochemical performance. Materials obtained from chloroform dispersion of carbon nanotubes present more effective and intimate interaction between the components, which improves the electrochemical response. All the nanocomposites showed a pseudo-capacitive behavior in an aqueous solution of KCl, with a particularly good specific capacity, allowing their application as anodes in K-ion batteries fully operating in water. The best sample showed a specific capacity of 517 mAh g−1 at 7 A g−1 with a recovery degree close to 100%.
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•Longer equilibration phase induces disturbances in oocyte phospholipid profile.•Lipid-based vitrification medium preserves phospholipids of the oocyte membrane.•Fatty acids and L-carnitine are ...promising ingredients in vitrification media.
Can exposure time to equilibration solutions during oocyte vitrification affect the lipid profile of oocytes and embryonic development? Could vitrification media supplemented with oleic, linoleic acids and L-carnitine effectively minimize damage induced by vitrification on embryo development and oocyte membrane lipid profile?
Experimental study including 936 oocytes from C57BL/6J mice, randomly divided into fresh IVF (control) and equilibration solution groups. Oocytes were exposed to equilibration solution from Irvine Scientific, Tvitri-4 or Tvitri-4 supplemented with L-carnitine and fatty acids for 7 or 10 min, vitrified–warmed, and submitted to IVF. The lipid profile of oocytes immediately after equilibration solution exposure was also asessed using the same equilibration times and solution compositions.
Longer equilibration time resulted in lower oocyte survival and blastocyst rates, and reduced relative abundance of structural lipids, i.e. phosphatidylcholines and sphingomyelins, varying according to equilibration solution composition. It also induced membrane disruptions resembling bubbles in the oocyte surface predominantly in equilibration solution from Irvine Scientific, rarely in Tvitri-4 and absent in Tvitri-4 supplemented with L-carnitine and fatty acids. To reveal the metabolic pathways associated with the equilibration phase of vitrification, lipid pathway analysis was conducted; both P-values and pathway impact values showed that the linoleic acid metabolism (P = 0.00223; impact =1) and alpha-Linolenic acid metabolism (P = 0.00084; impact = 0.33) were the most pathway perturbed, followed by glycerophospholipid metabolism (P = 0.0167; impact = 0.25)
A longer equilibration phase pre-vitrification can influence embryo development and induce changes in oocyte lipid composition related to membrane integrity. The results suggest internalization of oleic and linoleic acids added to equilibration solution by the oocyte, which, to some extent, contributed to membrane phospholipids preservation, regardless of the equilibration times assessed.
Heme crystallization as hemozoin represents the dominant mechanism of heme disposal in blood feeding triatomine insect vectors of the Chagas disease. The absence of drugs or vaccine for the Chagas ...disease causative agent, the parasite Trypanosoma cruzi, makes the control of vector population the best available strategy to limit disease spread. Although heme and redox homeostasis regulation is critical for both triatomine insects and T. cruzi, the physiological relevance of hemozoin for these organisms remains unknown. Here, we demonstrate that selective blockage of heme crystallization in vivo by the antimalarial drug quinidine, caused systemic heme overload and redox imbalance in distinct insect tissues, assessed by spectrophotometry and fluorescence microscopy. Quinidine treatment activated compensatory defensive heme-scavenging mechanisms to cope with excessive heme, as revealed by biochemical hemolymph analyses, and fat body gene expression. Importantly, egg production, oviposition, and total T. cruzi parasite counts in R. prolixus were significantly reduced by quinidine treatment. These effects were reverted by oral supplementation with the major insect antioxidant urate. Altogether, these data underscore the importance of heme crystallization as the main redox regulator for triatomine vectors, indicating the dual role of hemozoin as a protective mechanism to allow insect fertility, and T. cruzi life-cycle. Thus, targeting heme crystallization in insect vectors represents an innovative way for Chagas disease control, by reducing simultaneously triatomine reproduction and T. cruzi transmission.
Butyrate is a short‐chain fatty acid derived from the metabolism of indigestible carbohydrates by the gut microbiota. Butyrate contributes to gut homeostasis, but it may also control inflammatory ...responses and host physiology in other tissues. Butyrate inhibits histone deacetylases, thereby affecting gene transcription, and also signals through the metabolite‐sensing G protein receptor (GPR)109a. We produced an mAb to mouse GPR109a and found high expression on podocytes in the kidney. Wild‐type and Gpr109a–/– mice were induced to develop nephropathy by a single injection of Adriamycin and treated with sodium butyrate or high butyrate‐releasing high‐amylose maize starch diet. Butyrate improved proteinuria by preserving podocyte at glomerular basement membrane and attenuated glomerulosclerosis and tissue inflammation. This protective phenotype was associated with increased podocyte‐related proteins and a normalized pattern of acetylation and methylation at promoter sites of genes essential for podocyte function. We found that GPR109a is expressed by podocytes, and the use of Gpr109a–/– mice showed that the protective effects of butyrate depended on GPR109a expression. A prebiotic diet that releases high amounts of butyrate also proved highly effective for protection against kidney disease. Butyrate and GPR109a play a role in the pathogenesis of kidney disease and provide one of the important molecular connections between diet, the gut microbiota, and kidney disease.—Felizardo, R. J. F., de Almeida, D. C., Pereira, R. L., Watanabe, I. K. M., Doimo, N. T. S., Ribeiro, W. R., Cenedeze, M. A., Hiyane, M. I., Amano, M. T., Braga, T. T., Ferreira, C. M., Parmigiani, R. B., Andrade‐Oliveira, V., Volpini, R. A., Vinolo, M. A. R., Mariño, E., Robert, R., Mackay, C. R., Camara, N. O. S. Gut microbial metabolite butyrate protects against proteinuric kidney disease through epigenetic‐ and GPR109a‐mediated mechanisms. FASEB J. 33, 11894–11908 (2019). www.fasebj.org
Asthma is a worldwide public health issue, affecting the sufferer's quality of life. Many researchers are extensively studying the cellular processes involved in the affected airways. Experimental ...asthma using animals has been performed for a long time, mainly applying murine models due to well-known advantages. The aim of this study is to present an allergic airway inflammation protocol in mice. Basically, the allergic airway inflammation is induced by intraperitoneal sensitization and intratracheal challenge with ovalbumin (OVA). The model provided here mimics acute asthma characteristics including excessive mucus production, airway hyperresponsiveness, and eosinophilic airway inflammation.
White adipose tissue (WAT) represents a major site of triacylglycerol energy storage and is directly associated with metabolic disorders. Mitochondria regulate cellular energy expenditure and are ...active in WAT. Although isolated mitochondria have been classically used to assess their functions, several artifacts can be introduced by this approach. Furthermore, important limitations exist in the available methods to determine mitochondrial physiology in permeabilized WAT. Here, we established and validated a method for functional evaluation of mice mesenteric WAT (mWAT) mitochondria by using MEchanical Permeabilization and LIpid DEpletion (MEPLIDE) coupled to high-resolution respirometry. We observed that mild stirring of mWAT for 20 min at room temperature with 4% fatty acid-free albumin (FAF-BSA) followed by 50 min without FAF-BSA selectively permeabilized white adipocytes plasma membrane. In these conditions, mWAT mitochondria were intact, exhibiting succinate-induced respiratory rates that were sensitive to classical oxidative phosphorylation modulators. Finally, the respiratory capacity of mWAT in female mice was significantly higher than in males, an observation that agrees with reported data. Therefore, the functional assessment of mWAT mitochondria through MEPLIDE coupled to high resolution respirometry proposed here will contribute to a better understanding of WAT biology in several pathophysiological contexts.
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•Assessment of mitochondrial function in permeabilized tissue has key advantages.•A new method for permeabilization of white adipose tissue was described.•White adipocyte plasma membrane was permeabilized by mild mechanical stirring.•Assessment of mitochondrial function requires optimal lipid depletion.