Bench-to-bedside review: The role of glycosaminoglycans in respiratory disease.

The extracellular matrix (ECM) plays a significant role in the mechanical behaviour of the lung parenchyma. The ECM is composed of a three-dimensional fibre mesh that is filled with various macromolecules, among which are the glycosaminoglycans (GAGs). GAGs are long, linear and highly charged heterogeneous polysaccharides that are composed of a variable number of repeating disaccharide units. There are two main types of GAGs: nonsulphated GAG (hyaluronic acid) and sulphated GAGs (heparan sulphate and heparin, chondroitin sulphate, dermatan sulphate, and keratan sulphate). With the exception of hyaluronic acid, GAGs are usually covalently attached to a protein core, forming an overall structure that is referred to as proteoglycan. In the lungs, GAGs are distributed in the interstitium, in the sub-epithelial tissue and bronchial walls, and in airway secretions. GAGs have important functions in lung ECM: they regulate hydration and water homeostasis; they maintain structure and function; they modulate the inflammatory response; and they influence tissue repair and remodelling. Given the great diversity of GAG structures and the evidence that GAGs may have a protective effect against injury in various respiratory diseases, an understanding of changes in GAG expression that occur in disease may lead to opportunities to develop innovative and selective therapies in the future

Contribution of microscopy for understanding the mechanism of action against trypanosomatids

Transmission electron microscopy (TEM) has proved to be a useful tool to study the ultrastructural alterations and the target organelles of new antitrypanosomatid drugs. Thus, it has been observed that sesquiterpene lactones induce diverse ultrastructural alterations in both T. cruzi and Leishmania spp., such as cytoplasmic vacuolization, appearance of multilamellar structures, condensation of nuclear DNA, and, in some cases, an important accumulation of lipid vacuoles. This accumulation could be related to apoptotic events. Some of the sesquiterpene lactones (e.g., psilostachyin) have also been demonstrated to cause an intense mitochondrial swelling accompanied by a visible kinetoplast deformation as well as the appearance of multivesicular bodies. This mitochondrial swelling could be related to the generation of oxidative stress and associated to alterations in the ergosterol metabolism. The appearance of multilamellar structures and multiple kinetoplasts and flagella induced by the sesquiterpene lactone psilostachyin C indicates that this compound would act at the parasite cell cycle level, in an intermediate stage between kinetoplast segregation and nuclear division. In turn, the diterpene lactone icetexane has proved to induce the external membrane budding on T. cruzi together with an apparent disorganization of the pericellar cytoskeleton. Thus, ultrastructural TEM studies allow elucidating the possible mechanisms and the subsequent identification of molecular targets for the action of natural compounds on trypanosomatids.Fil: Lozano, Esteban Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Spina Zapata, Renata María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Tonn, Carlos Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

Dynamics of early establishment of SARS-CoV-2 VOC Omicron lineages in Minas Gerais, Brazil

Brazil is one of the nations most affected by Coronavirus disease 2019 (COVID-19). The introduction and establishment of new virus variants can be related to an increase in cases and fatalities. The emergence of Omicron, the most modified SARS-CoV-2 variant, caused alarm for the public health of Brazil. In this study, we examined the effects of the Omicron introduction in Minas Gerais (MG), the second-most populous state of Brazil. A total of 430 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) samples from November 2021 to June 2022 from Belo Horizonte (BH) city were sequenced. These newly sequenced genomes comprise 72% of all previously available SARS-CoV-2 genomes for the city. Evolutionary analysis of novel viral genomes reveals that a great diversity of Omicron sublineages have circulated in BH, a pattern in-keeping with observations across Brazil more generally. Bayesian phylogeographic reconstructions indicate that this diversity is a product of a large number of international and national importations. As observed previously, São Paulo state is shown as a significant hub for viral spread throughout the country, contributing to around 70% of all viral Omicron introductions detected in MG

Does the impact of a plant-based diet during pregnancy on birth weight differ by ethnicity? A dietary pattern analysis from a prospective Canadian birth cohort alliance

Objective: Birth weight is an indicator of newborn health and a strong predictor of health outcomes in later life. Signicant variation in diet during pregnancy between ethnic groups in high-income countries provides an ideal opportunity to investigate the influence of maternal diet on birth weight. Setting: Four multiethnic birth cohorts based in Canada (the NutriGen Alliance). Participants: 3997 full-term mother–infant pairs of diverse ethnic groups who had principal component analysis-derived diet pattern scores—plant-based, Western and health-conscious—and birth weight data. Results: No associations were identified between the Western and health-conscious diet patterns and birth weight; however, the plant-based dietary pattern was inversely associated with birth weight (β=−67.6 g per 1-unit increase; P<0.001), and an interaction with non-white ethnicity and birth weight was observed. Ethnically stratified analyses demonstrated that among white Europeans, maternal consumption of a plant-based diet associated with lower birth weight (β=−65.9 g per 1-unit increase; P<0.001), increased risk of small-for-gestational age (SGA; OR=1.46; 95% CI 1.08 to 1.54;P=0.005) and reduced risk of large-for-gestational age (LGA; OR=0.71; 95% CI 0.53 to 0.95;P=0.02). Among South Asians, maternal consumption of a plant-based diet associated with a higher birth weight (β=+40.5 g per 1-unit increase; P=0.01), partially explained by cooked vegetable consumption. Conclusions: Maternal consumption of a plant-based diet during pregnancy is associated with birth weight. Among white Europeans, a plant-based diet is associated with lower birth weight, reduced odds of an infant born LGA and increased odds of SGA, whereas among South Asians living in Canada, a plant-based diet is associated with increased birth weight

Evaluation of the effects of Quercetin and Kaempherol on the surface of MT-2 cells visualized by atomic force microscopy

AbstractThis study investigated the anti-viral effects of the polyphenolic compounds Quercetin and Kaempherol on the release of HTLV-1 from the surface of MT-2 cells. Atomic force microscopy (AFM) was used to scan the surface of the MT-2 cells. MT-2 cells were fixed with 100% methanol on round glass lamina or cleaved mica and dried under UV light and laminar flow. The images were captured on a Multimode equipment monitored by a NanoScope IIId controller from Veeco Instruments Inc operated in tapping mode and equipped with phase-imaging hardware. The images demonstrated viral budding structures 131±57nm in size, indicating profuse viral budding. Interestingly, cell-free viruses and budding structures visualized on the surface of cells were less common when MT-2 was incubated with Quercetin, and no particles were seen on the surface of cells incubated with Kaempherol. In summary, these data indicate that HTLV-1 is budding constantly from the MT-2 cell surface and that polyphenolic compounds were able to reduce this viral release. Biological samples were analyzed with crude cell preparations just after cultivation in the presence of Quercetin and Kaempherol, showing that the AFM technique is a rapid and powerful tool for analysis of antiviral activity of new biological compounds

Higher Expression of CCL2, CCL4, CCL5, CCL21, and CXCL8 Chemokines in the Skin Associated with Parasite Density in Canine Visceral Leishmaniasis

Several previous studies correlated immunopathological aspects of canine visceral leishmaniasis (CVL) with tissue parasite load and/or the clinical status of the disease. Recently, different aspects of the immune response in Leishmania-infected dogs have been studied, particularly the profile of cytokines in distinct compartments. However, the role of chemokines in disease progression or parasite burdens of the visceralising species represents an important approach for understanding immunopathology in CVL. We found an increase in inflammatory infiltrate, which was mainly composed of mononuclear cells, in the skin of animals presenting severe forms of CVL and high parasite density. Our data also demonstrated that enhanced parasite density is positively correlated with the expression of CCL2, CCL4, CCL5, CCL21, and CXCL8. In contrast, there was a negative correlation between parasite density and CCL24 expression. These findings represent an advance in the knowledge of the involvement of skin inflammatory infiltrates in CVL and the systemic consequences and may contribute to developing a rational strategy for the design of new and more efficient prophylactic tools and immunological therapies against CVL