Activation of Sestrin2 accelerates deep second-degree burn wound healing through PI3K/AKT pathway.

Deep second-degree burns heal slowly, and promoting the healing process is a focus of clinical research. Sestrin2 is a stress-inducible protein with antioxidant and metabolic regulatory effects. However, its role during acute dermal and epidermal re-epithelialization in deep second-degree burns is unknown. In this study, we aimed to explore the role and molecular mechanism of sestrin2 in deep second-degree burns as a potential treatment target for burn wounds. To explore the effects of sestrin2 on burn wound healing, we established a deep second-degree burn mouse model. Then we detected the expression of sestrin2 by western blot and immunohistochemistry after obtaining the wound margin of full-thickness burned skin. The effects of sestrin2 on burn wound healing were explored in vivo and in vitro through interfering sestrin2 expression using siRNAs or the small molecule agonist of sestrin2, eupatilin. We also investigated the molecular mechanism of sestrin2 in promoting burn wound healing by western blot and CCK-8 assay. Our in vivo and in vitro deep second-degree burn wound healing model demonstrated that sestrin2 was promptly induced at murine skin wound edges. The small molecule agonist of sestrin2 accelerated the proliferation and migration of keratinocytes, as well as burn wound healing. Conversely, the healing of burn wounds was delayed in sestrin2-deficient mice and was accompanied by the secretion of inflammatory cytokines as well as the suppression of keratinocyte proliferation and migration. Mechanistically, sestrin2 promoted the phosphorylation of the PI3K/AKT pathway, and inhibition of PI3K/AKT pathway abrogated the promoting role of sestrin2 in keratinocyte proliferation and migration. Therefore, sestrin2 plays a critical role in activation of the PI3K/AKT pathway to promote keratinocyte proliferation and migration, as well as re-epithelialization in the process of deep second-degree burn wound repair.

Preparation, characterization, and pharmacodynamic study on deep second degree burns of total flavonoids composite phospholipids liposome gel of Oxytropis falcata Bunge.

Wound healing is the treatment problem after deep second degree (II°) burns. The p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-κB/inhibitory factor-κB (NF-κB/IκB) signal pathways play significant role in angiogenesis and wound repair after burns.This study aimed to investigate the preparation, characterization and pharmacodynamics of the total flavonoids composite phospholipids liposome of Oxytropis falcata Bunge (TFOFB-CPL) on deep II° burns to research its biological activity and underlying mechanism. The TFOFB-CPL was prepared by thin-film dispersion method and the preparation process was optimized via central composite design. The TFOFB-CPL was then characterized by using particle size, polydispersity indexes (PDIs), zeta potential, encapsulation efficiency (EE) and morphology. Moerover, in vitro transdermal test and in vivo pharmacodynamic study included wound healing rate, hematoxylin-eosin (HE) staining, masson staning, western blotting and RT-PCR. The results showed that the therapeutic effects of TFOFB-CPL gel on deep II° burns, especially during wound healing were significant. TFOFB-CPL gel has a sustained-release effect during the treatment of deep II° burns with forming drug depot in the dermis layer. The wound healing rate of TFOFB-CPL gel group was near positive group and better than the other groups. TFOFB-CPL gel could promote the growth of epidermis, skin appendages, fibrovascular and collagen fibers, and had obvious anti-inflammatory effects. Moreover, TFOFB-CPL gel inhibited the activation of p38MAPK and the degradation of IκBα, and promoted the neonatal wounds during the early stage. Therefore, TFOFB-CPL gel could be considered as a novel preparation for treating deep II° burns.

Spontaneous healing and scar control following enzymatic debridement of deep second-degree burns.

Scarring after a burn injury remains the greatest unmet challenge in the treatment of functional and psychosocial sequelae of burns. The hypertrophic scar represents the most common type of cicatrix after burns, and it has a prevalence of up to 70%. We present a case of upper and lower extremity partial-thickness burns in a female patient treated in two different modalities. Superficial seconddegree burns on the upper extremities were treated with conservative dressing with fairly early wound closure but they developed hypertrophic scars. Deeper, lower extremity burns were debrided with a new bromelain-based debriding agent, resulting in scar-free healing. The pathophysiology of hypertrophic scar formation is based on the perturbation of collagen production or degradation or both. The duration and magnitude of the inflammatory phase of wound healing also appears to play a role in hypertrophic scarring. Bromelain has demonstrated an anti-angiogenic effect in various cancer cell lines and it has been shown to regulate a variety of pro-angiogenic growth factors. This case raises the classical question of the relationship between time to healing and formation of hypertrophic scars after burn injury, pointing to other potential factors that may play an important role in burn healing.

La cicatrisation après une brûlure reste le plus grand défi du traitement des séquelles à la fois sur le plan fonctionnel et sur le plan psychologique. La cicatrisation hypertrophique représente l'évolution la plus fréquente après brûlure et sa prévalence est supérieure à 70 %. Nous présentons une observation de brûlures du 2e degré au niveau du membre supérieur et du membre inférieur chez une patiente traitée suivant deux modalités différentes. Les brûlures du second degré superficiel du membre supérieur furent traitées par un pansement classique avec une cicatrisation précoce, mais suivie de cicatrices hypertrophiques. Les brûlures plus profondes du membre inférieur furent détergées avec le nouvel agent à base de bromelaïne, et permirent une guérison sans cicatrice. La physiopathologie de la cicatrisation hypertrophique est basée sur les troubles de production des fibres de collagène, ou de leur dégradation, ou des deux. La durée et l'amplitude de la phase inflammatoire de la cicatrisation paraît aussi jouer un rôle dans l'hypertrophie cicatricielle. La bromelaïne a démontré son effet anti-angiogénique dans plusieurs lignées cellulaires cancéreuses ; elle a montré aussi son aptitude à réguler les divers facteurs de croissance pro-angiogéniques. Cette observation soulève la question classique de la relation entre le temps de cicatrisation et l'apparition de cicatrices hypertrophiques après brûlure, en soulignant les autres facteurs potentiels jouant un rôle important dans la cicatrisation des brûlures.

Cultured allogenic keratinocytes for extensive burns: a retrospective study over 15 years.

UNLABELLED: The aim was to review the use and indications of cultured allogenic keratinocytes (CAlloK) in extensive burns and their efficiency. MATERIALS AND METHODS: This retrospective study comprised 15 years (1997-2012). INCLUSION CRITERIA: all patients who received CAlloK. EXCLUSION CRITERIA: patients who died before complete healing. Evaluation criteria were clinical. Time and success of wound healing after CAlloK use were evaluated. RESULTS: The CAlloK were used for 2 indications - STSG donor sites and deep 2nd degree burns in extensively burned patients. A total of 70 patients were included with severity Baux score of 99.2 (from 51 to 144) and mean percentage of TBSA of 63.49% (from 21 to 96%). Fifty nine patients received CAlloK for STSG donor sites with a mean number of applications of 4 and mean surface of 3800 cm(2) per patient. Treated donor sites were re-harvested 2.5 times. The mean time of complete epithelialization was 7 days. In 11 patients, CAlloK were used for deep 2nd degree burns. The mean percentage of burned surface was 73.7%. The mean surface of CAlloK per patient was 2545 cm(2). Complete healing was achieved in 6.4 days. CONCLUSION: The CAlloK allow rapid healing of STSG donor-sites and deep 2nd second degree burns in extensively burned patients.