Graphene quantum dots based on cannabis seeds for efficient wound healing in a mouse incisional wound model: Link with stress and neurobehavioral effect.

Graphene quantum dots (GQDs) are promising biomaterials with potential applicability in several areas due to their many useful and unique features. Among different applications, GQDs are photodynamic therapy agents that generate single oxygen and improve antimicrobial activity. In the present study, and for the first time, GQD were isolated from the Cannabis sativa L. seeds to generate C-GQDs as a new biomaterial for antibacterial and wound healing applications. Detailed characterization was performed using FTIR, UV-vis, Raman spectra, photoluminescence, TEM examination, HRTEM, ζ-potential, and XRD. Our results revealed in vitro and in vivo antibacterial activity of C-GQDs against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) with reduced minimal inhibitory concentration of 236 µg/mL for both strains. In addition, the C-GQDs confirmed the in vitro analysis and exhibited anti-inflammatory activity by reducing the level of neutrophils in blood and skin tissue. C-GQDs act by accelerating re-epithelization and granulation tissue formation. In addition, C-GQDs restored neurobehavioral alteration induced by incisional wounds by reducing oxidative stress, decreasing cortisol levels, increasing anxiolytic-like effect, and increasing vertical locomotor activity. The wound-healing effects of C-GQDs support its role as a potential therapeutic agent for diverse skin injuries.

The Role of Skin Substitutes in Acute Burn and Reconstructive Burn Surgery: An Updated Comprehensive Review.

Burns disrupt the protective skin barrier with consequent loss of cutaneous temperature regulation, infection prevention, evaporative losses, and other vital functions. Chronically, burns lead to scarring, contractures, pain, and impaired psychosocial well-being. Several skin substitutes are available and replace the skin and partially restore functional outcomes and improve cosmesis. We performed a literature review to update readers on biologic and synthetic skin substitutes to date applied in acute and reconstructive burn surgery. Improvement has been rapid in the development of skin substitutes in the last decade; however, no available skin substitute fulfills criteria as a perfect replacement for damaged skin.

Reduced Postburn Hypertrophic Scarring and Improved Physical Recovery With Yearlong Administration of Oxandrolone and Propranolol.

BACKGROUND: Massive burns induce a hypermetabolic response that leads to total body wasting and impaired physical and psychosocial recovery. The administration of propranolol or oxandrolone positively affects postburn metabolism and growth. The combined administration of oxandrolone and propranolol (OxProp) for 1 year restores growth in children with large burns. Here, we investigated whether the combined administration of OxProp for 1 year would reduce scarring and improve quality of life compared with control. STUDY DESIGN: Children with large burns (n = 480) were enrolled into this institutional review board-approved study; patients were randomized to control (n = 226) or administration of OxProp (n = 126) for 1 year postburn. Assessments were conducted at discharge and 6, 12, and 24 months postburn. Scar biopsies were obtained for histology. Physical scar assessments and patient reported outcome measures of physical and psychosocial function were obtained. RESULTS: Reductions in cellularity, vascular structures, inflammation, and abnormal collagen (P < 0.05) occurred in OxProp-treated scars. With OxProp, scar severity was attenuated and pliability increased (both P < 0.05). Analyses of patient-reported outcomes showed improved general and emotional health within the OxProp-treated group (P < 0.05). CONCLUSIONS: Here, we have shown improvements in objective and subjective measures of scarring and an increase in overall patient-reported physical function. The combined administration of OxProp for up to a year after burn injury should be considered for the reduction of postburn scarring and improvement of long-term psychosocial outcomes in children with massive burns.

IGF-1 protects dopamine neurons against oxidative stress: association with changes in phosphokinases.

Insulin-like growth factor-1 (IGF-1) is an endogenous peptide transported across the blood brain barrier that is protective in several brain injury models, including an acute animal model of Parkinson's disease (PD). Motor deficits in PD are due largely to the progressive loss of nigrostriatal dopaminergic neurons. Thus, we examined the neuroprotective potential of IGF-1 in a progressive model of dopamine deficiency in which 6-hydroxydopamine (6-OHDA) is infused into the striatum. Rats received intrastriatal IGF-1 (5 or 50 µg) 6 h prior to infusion of 4 µg 6-OHDA into the same site and were euthanized 1 or 4 weeks later. Both concentrations of IGF-1 protected tyrosine hydroxylase (TH) immunoreactive terminals in striatum at 4 weeks but not at 1 week, indicating that IGF-induced restoration of the dopaminergic phenotype occurred over several weeks. TH-immunoreactive cell loss was only attenuated with 50 µg IGF-1. We then examined the effect of striatal IGF-1 on the Ras/ERK1/2 and PI3K/Akt pathways to ascertain whether their activation correlated with IGF-1-induced protection. Striatal and nigral levels of phospho-ERK1/2 were maximal 6 h after IGF-1 infusion and, with the exception of an increase in nigral pERK2 at 48 h, returned to basal levels by 7 days. Phospho-Akt (Ser473) was elevated 6-24 h post-IGF-1 infusion in both striatum and substantia nigra concomitant with inhibition of pro-death GSK-3ß, a downstream target of Akt. These results suggest that IGF-1 can protect the nigrostriatal pathway in a progressive PD model and that this protection is preceded by activation of key pro-survival signaling cascades.

Effects of the nephrilin peptide on post-burn glycemic control, renal function, fat and lean body mass, and wound healing.

The mechanisms underlying the effects of severe burn trauma are not well understood. We previously demonstrated the ability of nephrilin peptide (an iron-binding peptide believed to enter cells through iron-uptake pathways) to suppress aspects of the neuroinflammatory response in a rat scald model, as well as sepsis mortality in a mouse model. This study explores the effect of nephrilin on other clinically relevant outcomes in the rat scald model. In a rat scald model, animals were treated with nephrilin either in week 1 or week 2 post-burn. Measurements were made of serum glucose and creatinine as well as wound area by planimetry and body composition by DEXA. Given the potential role of iron, results were analyzed both for the entire cohort of animals and for the normoferremic (>100 ug/dL serum iron) subset of animals. Nephrilin improved body composition, wound healing, kidney function, and glycemic control. The first two effects were significant in normoferremic but not in hypoferremic animals suggesting an effect of iron status on burn injury outcomes. Nephrilin treatment modulates a number of relevant variables in the rat scald model.

Topically applied metal chelator reduces thermal injury progression in a rat model of brass comb burn.

UNLABELLED: Oxidative stress may be involved in the cellular damage and tissue destruction as burn wounds continues to progress after abatement of the initial insult. Since iron and calcium ions play key roles in oxidative stress, this study tested whether topical application of Livionex formulation (LF) lotion, that contains disodium EDTA as a metal chelator and methyl sulfonyl methane (MSM) as a permeability enhancer, would prevent or reduce burns. METHODS: We used an established brass comb burn model with some modifications. Topical application of LF lotion was started 5 min post-burn, and repeated every 8 h for 3 consecutive days. Rats were euthanized and skin harvested for histochemistry and immunohistochemistry. Formation of protein adducts of 4-hydroxynonenal (HNE), malonadialdehyde (MDA) and acrolein (ACR) and expression of aldehyde dehydrogenase (ALDH) isozymes, ALDH1 and ALDH2 were assessed. RESULTS: LF lotion-treated burn sites and interspaces showed mild morphological improvement compared to untreated burn sites. Furthermore, the lotion significantly decreased the immunostaining of lipid aldehyde-protein adducts including protein -HNE, -MDA and -ACR adducts, and restored the expression of aldehyde dehydrogenase isozymes in the unburned interspaces. CONCLUSION: This data, for the first time, demonstrates that a topically applied EDTA-containing lotion protects burns progression with a concomitant decrease in the accumulation of reactive lipid aldehydes and protection of aldehyde dehydrogenase isozymes. Present studies are suggestive of therapeutic intervention of burns by this novel lotion.