FOXO1, TGF-β Regulation and Wound Healing

Re-epithelialization is a complex process that involves migration and proliferation of keratinocytes, in addition to the production of cytokines and growth factors that affect other cells. The induction of transcription factors during these processes is crucial for successful wound healing. The transcription factor forkhead boxO-1 (FOXO1) has recently been found to be an important regulator of wound healing. In particular, FOXO1 has significant effects through regulation of transforming growth factor-beta (TGF-β) expression and protecting keratinocytes from oxidative stress. In the absence of FOXO1, there is increased oxidative damage, reduced TGF-β1 expression, reduced migration and proliferation of keratinocytes and increased keratinocytes apoptosis leading to impaired re-epithelialization of wounds

FOXO1 Deletion in Keratinocytes Improves Diabetic Wound Healing through MMP9 Regulation

Keratinocyte migration is a key aspect of re-epithelialization during wound healing. Matric metalloproteinase 9 (MMP9) contributes to this process and deificiencies in the MMP9 lead to impaired healing. Inappropriate expression of MMP9 also contributes to impaired re-epithelialization. Previously we demonstrated that FOXO1 was activated in wound healing but to higher levels in diabetic wounds. To address mechanisms of impaired re-epithelialization we examined MMP0 expression in vivo in full thickness dermal scalp wounds creared in experimental K14.Cre+.Foxo1L/L mice with lineage-specific Cre recombinase deletion of floxed FOXO1 and compared the results to control littermates. MMP9 was induced during wound healing but at a significantly higher level in diabetic compared to normal wounds. FOXO1 deletion substantially blocked this increase. By chromatin immunoprecipitation FOXO1 was shown to bind to the MMP9 promoter, FOXO1 overexpression increased MMP9 transcriptional activity and increased MMP9 expression simulated by high glucose that was blocked by FOXO1 deletion or FOXO1 knockdown. We also show for the first time that high glucose impairs keratinocyte migration by inducing high levels of MMP9 expression in diabetic wound healing, which represents a novel mechanism for impaired re-epithelialization in diabetic wounds

Characterization of adipose tissue macrophages and adipose-derived stem cells in critical wounds

Background. Subcutaneous adipose tissue is a rich source of adipose tissue macrophages and adipose-derived stem cells which both play a key role in wound repair. While macrophages can be divided into the classically-activated M1 and the alternatively-activated M2 phenotype, ASCs are characterized by the expression of specific stem cell markers. Methods. In the present study, we have investigated the expression of common macrophage polarization and stem cell markers in acutely inflamed adipose tissue. Subcutaneous adipose tissue adjacent to acutely inflamed wounds of 20 patients and 20 healthy subjects were harvested and underwent qPCR and flow cytometry analysis. Results. Expression levels of the Ml-specific markers CD80, iNOS, and IL-lb were significantly elevated in inflammatory adipose tissue when compared to healthy adipose tissue, whereas the M2-specific markers CD163 and TGF-beta were decreased. By flow cytometry, a significant shift of adipose tissue macrophage 1populations tow ards the M1 phenotype was confirmed. Furthermore, a decrease in the mesenchymai stem cell markers CD29, CD34, and CD105 was observed whereas CD73 and CD90 remained unchanged. Discussion. This is the first report describing the predominance pf M1 adipose tissue macrophages and the reduction of stem cell marker expression in acutely inflamed, non-healing wounds

Adaptive Façades’ Technologies to Enhance Building Energy Performance and More

With the increased enrolment the digital technologies and modern computer applications in AEC industry, a parallel increase and upgrade happened in the work competition leading to new benchmarks in such fields. The importance of these technologies increased with their investment of improving energy consumption in buildings, which represents a world crisis. The problem got worse in hot arid desert zones, as the case of some regions in KSA, where most users tend to spend most of their time in internal air-conditioned spaces, which led to the increase of the consumption of cooling energy, that reach 40% of the total Energy consumed in buildings. Despite the widespread global use and investment of the benefits of the new technologies in many projects in different climatic regions all over the world, the high percentage of energy consumption in buildings in the KSA may be an indication that the use of such technologies is not well invested, and that its application has not taken the needed weight and importance. This represents the research problem of this study that aims to explore and confirm the importance of adaptive facades’ technologies that could not only enhance building energy performance, but also achieve more benefits to building users and environments. The study adopted the descriptive analytical approach through the review and analysis of literature and case studies to achieve its goal. The results confirm the importance of the new adaptive facades’ technologies and the preference of combining more than one technology as per the building surrounding context, in addition to identifying the main technologies’ features used in the analysed case-studies and the resulted benefits on the level of enhancing energy and the additional benefits resulted from investing these technologies. The significances of this paper emerges from the importance of its subject, results and conclusions that matches Saudi Vision 2030 initiatives related to digital transformation, current and future research trends related to adaptive facades’ technologies, and the global energy crisis responsive actions.