RESUMEN
Wound management in obesity is complicated by excessive exudates from wounded areas, pressure ulcerations due to stacking of the fat layer, and vascular rarefaction. The current study explored the development of biomaterials for reprogramming the altered wound microenvironment under obese conditions. Self-assembled collagen biomatrix with trans and de novo browning activator, apigenin, was fabricated as a soft tissue regenerative wound dressing material. The as-synthesized self-assembled collagen biomatrix exhibited excellent thermal, mechanical, and biological stability with a superior wound exudate absorption capacity. The apigenin self-assembled collagen biomatrix exhibited porous 3-D microstructure that mimicked the extracellular matrix that promoted cell adhesion and proliferation. The apigenin self-assembled collagen multifunctional biomatrix triggered adaptive localized thermogenesis in the subcutaneous fat layer, resulting in the activation of angiogenesis and fibroblast spreading and migration. The in vivo wound healing assay performed in DIO-C57BL6 mice showed faster tissue regeneration within 9 days, with well-defined neo-epidermis, blood vessel formation, thick collagen deposition, minimal inflammation, and significant activation of browning in the subcutaneous adipose layer. This study paves the way forward for the development of specialized regenerative biomatrices that reprogram the obese wound bed for faster tissue regeneration.
Asunto(s)
Apigenina , Colágeno , Animales , Ratones , Apigenina/farmacología , Apigenina/uso terapéutico , Ratones Endogámicos C57BL , Colágeno/química , Cicatrización de Heridas , ObesidadRESUMEN
The wound exudates, hypoperfusion of the subcutaneous fat layer, and poor vasculature worsen wound management in obese subjects. In the current study, a multifunctional Caffeine-reinforced collagen biomaterial is developed that can simultaneously modulate lipid metabolism and angiogenesis in obese wound microenvironments for faster tissue regeneration. The biomaterial is fabricated specialized for obese conditions to initiate simultaneous lipolysis and angiogenesis locally in the hypoxic subcutaneous fat in wound margins of obese subjects. Caffeine-reinforced collagen biomatrix shows better structural integrity, thermal stability, bio-compatibility, and lesser proteolytic susceptibility. Caffeine-collagen biomaterial promote angiogenesis, fibroblast migration, and localized browning of white adipocytes to activate thermogenesis in the subcutaneous fat layer at the wound site. Full-thickness excision wound healing studies performed in obese C57BL6 mice shows faster wound closure within day 9 when compare to control mice. The Caffeine-reinforced collagen biomaterial remodeled the wound site locally by activating fibroblast to secrete collagen, activate endothelial cells to promote angiogenesis, and induce browning in white adipocytes in subcutaneous fat. The study opens a new direction in bariatric tissue regenerative medicine by locally modulating lipid metabolism, angiogenesis, and trans-browning at the injured site for faster complete restoration of the damaged tissue.
Asunto(s)
Bariatria , Cafeína , Humanos , Animales , Ratones , Cafeína/farmacología , Células Endoteliales , Ratones Endogámicos C57BL , Colágeno , Materiales Biocompatibles , ObesidadRESUMEN
Thermogenic activation via trans-and de novo browning of white adipocytes is a promising strategy to accelerate lipid metabolism for regulating obesity-related disorders. In this study, we investigated the intricate interplay between angiogenic regulation and browning in white adipocytes using the bioactive compound, resveratrol (Rsv). Rsv has previously been documented for its regulatory influence on the trans and de novo browning of white adipocytes. Our findings revealed that concurrent activation of angiogenesis is prerequisite for inducing browning within the microenvironment of white adipocytes when exposed to browning activators. Additionally, we observed a significant browning effect on white adipocytes when the local adipose tissue environment was prompted to undergo angiogenesis, notably facilitated by a proangiogenic molecule known as Vascular endothelial growth factor (VEGF). Intriguingly, this effect was reversed when angiogenesis was inhibited by treatment with the antiangiogenic agent thalidomide. Furthermore, the study revealed the role of VEGF in paracrine activation of white adipocytes resulting in the induction of browning in both 3T3-L1 cell lines and primary mouse white adipocytes. The cross-talk between angiogenesis and browning was found to be initiated via the transcriptional activation of Estrogen receptor α (ERα) triggering the VEGF/VEGFR2 signaling pathway leading to browning and a reconfiguration of lipid metabolism within adipocytes. In conclusion, this study sheds light on the intricate cross-talk between angiogenesis and browning of white adipocytes. Notably, the findings underscore the reciprocal relationship between these processes, wherein inhibition of one process exerts discernible effects on the other.
Asunto(s)
Adipocitos Blancos , Metabolismo de los Lípidos , Animales , Ratones , Adipocitos Blancos/metabolismo , Factor A de Crecimiento Endotelial Vascular , Transducción de SeñalRESUMEN
Coconut (Cocos nucifera L.), an important source of vegetable oil, nutraceuticals, functional foods, and housing materials, provides raw materials for a repertoire of industries engaged in the manufacture of cosmetics, soaps, detergents, paints, varnishes, and emulsifiers, among other products. The palm plays a vital role in maintaining and promoting the sustainability of farming systems of the fragile ecosystems of islands and coastal regions of the tropics. In this study, we present the genome of a dwarf coconut variety "Chowghat Green Dwarf" (CGD) from India, possessing enhanced resistance to root (wilt) disease. Utilizing short reads from the Illumina HiSeq 4000 platform and long reads from the Pacific Biosciences RSII platform, we have assembled the draft genome assembly of 1.93 Gb. The genome is distributed over 26,855 scaffolds, with â¼81.56% of the assembled genome present in scaffolds of lengths longer than 50 kb. About 77.29% of the genome was composed of transposable elements and repeats. Gene prediction yielded 51,953 genes, which upon stringent filtering, based on Annotation Edit Distance, resulted in 13,707 genes, which coded for 11,181 proteins. Among these, we gathered transcript level evidence for a total of 6828 predicted genes based on the RNA-Seq data from different coconut tissues, since they presented assembled transcripts within the genome annotation coordinates. A total of 112 nucleotide-binding and leucine-rich repeat loci, belonging to six classes, were detected. We have also undertaken the assembly and annotation of the CGD chloroplast and mitochondrial genomes. The availability of the dwarf coconut genome shall prove invaluable for deducing the origin of dwarf coconut cultivars, dissection of genes controlling plant habit and fruit color, and accelerated breeding for improved agronomic traits.