Biocompatibility evaluation for the developed hydrogel wound dressing – ISO-10993-11 standards – InVitro and InVivo study

Assessment of biocompatibility for the developed wound dressing plays a significant role in translational studies. In the present research work, a wound dressing has been developed using gelatin, hyaluronic acid and chondroitin sulfate using EDC as crosslinker in a specific manner. The characterized hydrogel wound dressing was evaluated for its biocompatibility studies by means of ISO-10993-11 medical device rules and standards. Various parameters like skin sensitization test, acute systemic toxic test, implantation study, intracutaneous reactivity test, in vitro cytotoxicity test and bacterial reverse mutation test, were evaluated and the results demonstrated its safety for the pre-clinical investigation.

Temporal and Quantitative Analysis of Aortic Immunopathologies in Elastase-Induced Mouse Abdominal Aortic Aneurysms

Objective. Elastase-induced abdominal aortic aneurysm (AAA) model is widely used for aneurysmal pathogenesis and translational research. However, temporal alternations in aneurysmal histologies remain unknown. This study is aimed at analyzing temporal immunopathologies of aneurysmal aorta following experimental AAA induction. Methods. Male C57BL/6J mice at the age of 10-14 weeks received intra-aortic infusion of elastase to induce AAAs. Aortic diameters at the baseline and indicated days after AAA induction were measured, and aortae were collected for histopathological analysis. Results. Aorta diameters increased from 0.52 mm at the baseline levels to 0.99 mm, 1.34 mm, and 1.41 mm at days 7, 14, and 28, respectively, corresponding 90%, 158%, and 171% increases over the baseline level. Average aortic diameters did not differ between days 14 and 28. Severe elastin degradation and smooth muscle cell depletion were found at days 14 and 28 as compared to the baseline and day 7. No difference in the scores of medial elastin and SMC destruction was noted between days 14 and 28. Consistent results were found for leukocyte accumulation, neoangiogenesis, and matrix metalloproteinase expression. Twenty-eight days after AAA induction, all aneurysmal pathologies showed an attenuated trend, although most histopathological parameters did no differ between days 14 and 28. Conclusion. Our data suggest that almost aneurysmal immunohistopathologies reach maximal 14 days following AAA induction. Analysis of day 14 histologies is sufficient for AAA pathogenesis and translational studies in elastase-induced mouse experimental AAAs.

Proteome of the Luminal Surface of the Blood–Brain Barrier

Interrogation of the molecular makeup of the blood–brain barrier (BBB) using proteomic techniques has contributed to the cataloguing and functional understanding of the proteins uniquely organized at this specialized interface. The majority of proteomic studies have focused on cellular components of the BBB, including cultured brain endothelial cells (BEC). Detailed proteome mapping of polarized BEC membranes and their intracellular endosomal compartments has led to an improved understanding of the processes leading to internalization and transport of various classes of molecules across the BBB. Quantitative proteomic methods have further enabled absolute and comparative quantification of key BBB transporters and receptors in isolated BEC and microvessels from various species. However, translational studies further require in vivo/in situ analyses of the proteins exposed on the luminal surface of BEC in vessels under various disease and treatment conditions. In vivo proteomics approaches, both profiling and quantitative, usually rely on ‘capturing’ luminally-exposed proteins after perfusion with chemical labeling reagents, followed by analysis with various mass spectrometry-based approaches. This manuscript reviews recent advances in proteomic analyses of luminal membranes of BEC in vitro and in vivo and their applications in translational studies focused on developing novel delivery methods across the BBB.

The Impact of Cultural and Translational Studies on Modern Comparative Literature Studies

Modern comparative literature with globalization phenomenon extends linguistic and political boundaries, even for conserving and revitalizing languages particularly minor languages with cultural and ethnic exchanges. Such this emergence of comparative literature might return from contemporary translational and cultural studies as crucial and effective factors in the study of comparative literature. The role, relationship, and impact of translation and cultural studies on modern comparative literature are explored via a descriptive analysis. Translational and cultural studies in current comparative literature studies facilitate the relevant studies and they play a supplementary role for literary study. This study confirms a significant relationship exists among contemporary translational, cultural, and literary works intangibly and inevitably that helps to study comparative literary works. The findings report cultural and translational studies can be fruity informing literary studies, new writing styles besides intercultural conversation; nevertheless, scholars of comparative literature have argued that their discipline has been significantly subsumed and substituted by translation studies. The results indicate contemporary translation and cultural studies have paved the way for comparative literature researchers to achieve cultural knowledge and to strengthen the culture with developing national literature.

Epithelial to Mesenchymal Transition: A Challenging Playground for Translational Research. Current Models and Focus on TWIST1 Relevance and Gastrointestinal Cancers

Resembling the development of cancer by multistep carcinogenesis, the evolution towards metastasis involves several passages, from local invasion and intravasation, encompassing surviving anoikis into the circulation, landing at distant sites and therein establishing colonization, possibly followed by the outgrowth of macroscopic lesions. Within this cascade, epithelial to mesenchymal transition (EMT) works as a pleiotropic program enabling cancer cells to overcome local, systemic, and distant barriers against diffusion by replacing traits and functions of the epithelial signature with mesenchymal-like ones. Along the transition, a full-blown mesenchymal phenotype may not be accomplished. Rather, the plasticity of the program and its dependency on heterotopic signals implies a pendulum with oscillations towards its reversal, that is mesenchymal to epithelial transition. Cells in intermixed EÛM states can also display stemness, enabling their replication together with the epithelial reversion next to successful distant colonization. If we aim to include the EMT among the hallmarks of cancer that could modify clinical practice, the gap between the results pursued in basic research by animal models and those achieved in translational research by surrogate biomarkers needs to be filled. We review the knowledge on EMT, derived from models and mechanistic studies as well as from translational studies, with an emphasis on gastrointestinal cancers (GI).

An Evolutionary Conserved Signaling Network Between Mouse and Human Underlies the Differential Osteoskeletal Potential of Frontal and Parietal Calvarial Bones

The mammalian calvarial vault is an ancient and highly conserved structure among species, however, the mechanisms governing osteogenesis of the calvarial vault and how they might be conserved across mammalian species remain unclear. The aim of this study was to determine if regional differences in osteogenic potential of the calvarial vault, first described in mice, extend to humans. We derived human frontal and parietal osteoblasts from fetal calvarial tissue, demonstrating enhanced osteogenic potential both in vitro and in vivo of human frontal derived osteoblasts compared to parietal derived osteoblasts. Furthermore, we found shared differential signaling patterns in the canonical WNT, TGF-β, BMP, and FGF pathways previously described in the mouse to govern these regional differences in osteogenic potential. Taken together, our findings unveil evolutionary conserved similarities both at functional and molecular level between the mouse and human calvarial bones, providing further support that studies employing mouse models, are suitable for translational studies to human.

Individualizing Representational Similarity Analysis

Representational similarity analysis (RSA) is a popular multivariate analysis technique in cognitive neuroscience that uses functional neuroimaging to investigate the informational content encoded in brain activity. As RSA is increasingly being used to investigate more clinically-geared questions, the focus of such translational studies turns toward the importance of individual differences and their optimization within the experimental design. In this perspective, we focus on two design aspects: applying individual vs. averaged behavioral dissimilarity matrices to multiple participants' neuroimaging data and ensuring the congruency between tasks when measuring behavioral and neural representational spaces. Incorporating these methods permits the detection of individual differences in representational spaces and yields a better-defined transfer of information from representational spaces onto multivoxel patterns. Such design adaptations are prerequisites for optimal translation of RSA to the field of precision psychiatry.