Mice with Type 2 Diabetes Present Significant Alterations in Their Tissue Biomechanical Properties and Histological Features.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disease often associated with severe complications that may result in patient morbidity or death. One T2DM etiological agent is chronic hyperglycemia, a condition that induces damaging biological processes, including impactful extracellular matrix (ECM) modifications, such as matrix components accumulation. The latter alters ECM stiffness, triggering fibrosis, inflammation, and pathological angiogenesis. Hence, studying ECM biochemistry and biomechanics in the context of T2DM, or obesity, is highly relevant. With this in mind, we examined both native and decellularized tissues of obese B6.Cg-Lepob/J (ob/ob) and diabetic BKS.Cg-Dock7m+/+LeprdbJ (db/db) mice models, and extensively investigated their histological and biomechanical properties. The tissues analyzed herein were those strongly affected by diabetes-skin, kidney, adipose tissue, liver, and heart. The referred organs and tissues were collected from 8-week-old animals and submitted to classical histological staining, immunofluorescence, scanning electron microscopy, rheology, and atomic force microscopy. Altogether, this systematic characterization has identified significant differences in the architecture of both ob/ob and db/db tissues, namely db/db skin presents loose epidermis and altered dermis structure, the kidneys have clear glomerulopathy traits, and the liver exhibits severe steatosis. The distribution of ECM proteins also pinpoints important differences, such as laminin accumulation in db/db kidneys and decreased hyaluronic acid in hepatocyte cytoplasm in both obese and diabetic mice. In addition, we gathered a significant set of data showing that ECM features are maintained after decellularization, making these matrices excellent biomimetic scaffolds for 3D in vitro approaches. Importantly, mechanical studies revealed striking differences between tissue ECM stiffness of control (C57BL/6J), obese, and diabetic mice. Notably, we have unveiled that the intraperitoneal adipose tissue of diabetic animals is significantly stiffer (G* ≈ 10,000 Pa) than that of ob/ob or C57BL/6J mice (G* ≈ 3000-5000 Pa). Importantly, this study demonstrates that diabetes and obesity selectively potentiate severe histological and biomechanical alterations in different matrices that may impact vital processes, such as angiogenesis, wound healing, and inflammation.

Factors associated with the development of Congenital Zika Syndrome: a case-control study.

BACKGROUND: We aim to investigate possible maternal- and pregnancy-related factors associated with the development of Congenital Zika Syndrome (CZS) in children of mothers with probable gestational infection. METHODS: This case-control study, we recruited mother-infant pairs between May 2015 and October 2017 in a pediatric infectious disease clinic in Rio de Janeiro. Inclusion criteria required either that the mother reported Zika infection symptoms during pregnancy or that the infant presented with clinical or imaging features of the CZS. Exclusion criteria included detection of an alternative cause for the patient's presentation or negative polymerase chain reaction assays for Zika in all specimens tested within 12 days from the beginning of maternal symptoms. Infants with CZS (CDC definition) were selected as cases and infants without CZS, but with probable maternal Zika virus infection during pregnancy, were selected as controls. Maternal and pregnancy-related informations were collected and their relationship to the presence of congenital anomalies due to CZS was assessed by Fisher exact or Mann-Whitney test. RESULTS: Out of the 42 included neonates, 24 (57.1%) were diagnosed with CZS (cases). The mean maternal age at the birth was 21 years old. The early occurrence of maternal symptoms during pregnancy was the only variable associated with CZS (odds ratio = 0.87, 95% CI: 0.78-0.97). Case's mothers presented symptoms until the 25th week of gestational age (GA), while control's mothers presented until 36th weeks of GA. Income; illicit drug, alcohol, or tobacco use during pregnancy; other infections during pregnancy (including previous dengue infection) were not associated with CZS. CONCLUSIONS: Our study corroborates the hypothesis that Zika virus infection earlier in pregnancy is a risk factor to the occurrence of congenital anomalies in their fetuses.

Injectable in situ crosslinkable RGD-modified alginate matrix for endothelial cells delivery.

Cell-based therapies offer an attractive approach for revascularization and regeneration of tissues. However, and despite the pressing clinical needs for effective revascularization strategies, the successful immobilization of viable vascular cells within 3D matrices has been difficult to achieve. In this paper the in vitro potential of a natural, injectable RGD-alginate hydrogel as an in situ forming matrix to deliver endothelial cells was evaluated. Several techniques were employed to investigate how these microenvironments could influence the behavior of vascular cells, namely their ability to promote the outward migration of viable, proliferative cells, retaining the ability to form a 3D arrangement. Cells within RGD-grafted alginate hydrogel were able to proliferate and maintained 80% of viability for at least 48 h post-immobilization. Additionally, entrapped cells created a 3D organization into cellular networks and, when put in contact with matrigel, cells migrated out of the RGD-matrix. Overall, the obtained results support the idea that the RGD peptides conjugated to alginate provide a 3D environment for endothelial cells adhesion, survival, migration and organization.