Songxue Guo

Burn-wound progression contributes to early deterioration of burn severity and is closely associated with oxidative stress-induced inflammation in the zone of stasis, where mitochondria play a central role in regulating inflammatory responses and tissue damage. Melatonin is known to exert antioxidant and anti-inflammatory effects and to protect organelles from injury, suggesting a potential role in mitigating ischemia-related tissue damage. In this study, a “comb” scald rat model was used to investigate whether melatonin could prevent early burn-wound progression and to elucidate the underlying mechanisms. Melatonin was administered intraperitoneally at different doses immediately after injury, and wound conversion was assessed by histological analysis. Oxidative stress markers, inflammatory cytokines, and autophagy/mitophagy-related signals were evaluated using enzyme-linked immunosorbent assay, immunostaining, quantitative real-time polymerase chain reaction, and western blotting, with additional pharmacological modulation of autophagy and mitophagy to clarify mechanistic involvement. The results showed that melatonin significantly attenuated burn-induced activation of the HMGB1-NLRP3 inflammasome and reduced inflammatory cytokine release, while also alleviating oxidative stress, as indicated by decreased malondialdehyde levels and restored superoxide dismutase and glutathione peroxidase activities. These protective effects were closely associated with preservation of mitochondrial integrity and regulation of reactive oxygen species through autophagy, particularly PINK1-PARKIN-dependent mitophagy. Importantly, the autophagy inhibitor 3-methyladenine abolished the beneficial effects of melatonin, confirming the essential role of autophagy-related pathways. Together, these findings demonstrate that melatonin prevents early burn-wound progression by promoting mitophagy-mediated mitochondrial repair and suppressing downstream inflammatory responses.

Background: The maintenance of physiological homeostasis in the human body depends on healthy skin, making optimal wound treatment crucial. In this study, a natural bioactive wound dressing combining astaxanthin and a hyaluronic acid hydrogel was developed. Methods: Mice with full-thickness skin wounds were divided into different groups: the untreated control group, the blank hyaluronic acid hydrogel group, the polyethylene glycol hyaluronic acid hydrogel group, and the 2%, 4%, and 8% astaxanthin-hyaluronic acid hydrogel groups. The wound healing process was evaluated by observing the general view of the wound and collecting skin samples for HE and Masson staining. The mRNA expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) in the wound tissue were analysed via qRT–PCR. The protein expression levels of collagen I, CD31, α-SMA, Nrf2, HO-1, and NF-κB were examined through Western blot analysis. Additionally, the levels of oxidative stress-related indicators (MDA and SOD) were quantified. Results: Compared with other hydrogels, ATX@HA gels accelerated full-thickness wound healing, promoting faster wound contraction. These gels enhanced vascularization, as shown by increased CD31 and α-SMA protein expression and increased granulation tissue formation. The ATX@HA gels improved collagen deposition, with a more regular arrangement of collagen fibres in the treated wounds. They reduced oxidative stress (lower MDA and higher SOD) and inflammation (less IL-1β and IL-6 and more IL-10). ATX@HA gels inhibited NF-κB activation and activated the Nrf2/HO-1 signalling pathway during wound healing. Conclusions: ATX@HA has a therapeutic effect on wounds by enhancing vascularization and facilitating orderly collagen formation at the wound site while exerting anti-inflammatory and antioxidant effects. Further investigation revealed that these effects may be attributed to the inhibition of NF-κB activation and promotion of Nrf2/HO-1 pathway activation.

As the intracellular “powerhouses”, mitochondria play a critical role in wound healing by maintaining structural and functional stability. The dynamic equilibrium of mitochondrial fusion and fission, together with mitophagy, constitutes the key pathway regulating mitochondrial structural integrity and functional stability. Mitochondria protect burn wounds via the dynamic balance of fusion and fission as well as mitophagy: moderate mitochondrial fission can promote wound healing, whereas excessive fission induces overproduction of reactive oxygen species and inflammatory cytokines, thereby impairing tissue repair; mitochondrial fusion may exert beneficial effects on wound healing. Mitophagy alleviates cellular apoptosis and oxidative stress, and modulates all stages of burn wound healing. This review focuses on the maintenance of mitochondrial fusion–fission balance and mitophagy, systematically elaborates their specific roles in burn wound repair, and discusses the clinical application prospects of these mechanisms in the prevention and treatment of post-burn injuries.

Significance: Refractory wounds are complicated multistep biological processes that can lead to severe complications in patients. Selective autophagy plays a crucial role in precisely controlling the quality of intracellular components and regulating biological behavior. This review explores the features and underlying mechanisms of various types of selective autophagy and highlights their implications in burn injury and wound healing. Recent Advances: In-depth studies have underscored the critical role of selective autophagy, including mitophagy, endoplasmic reticulum (ER)-phagy, pexophagy, xenophagy, lysophagy, ferritinophagy, and lipophagy, in effectively controlling the quality of intracellular components and regulating biological behavior, which may enhance wound-healing process. Critical Issues: Autophagy is a housekeeping and self-renewal process that utilizes lysosomal machinery to degrade and recycle cellular components, thereby enhancing cellular adaptability to stressful conditions. In addition to nonselective bulk degradation, autophagy selectively recycles specific cell constituents, including mitochondria, ER, peroxisomes, pathogens, lysosomes, lipid droplets, and ferritin. The effective management of the quality of cellular components during wound healing remains a challenge in clinical practice. Future Directions: Understanding the basic mechanisms and intricate crosstalk underlying selective autophagy may facilitate the development of comprehensive strategies and therapeutic targets for wound healing.

Skin wound repair is critically regulated by peripheral nerves, whose injury or dysfunction represents a key factor impairing the healing of pathological wounds such as diabetic ulcers and deep burns. The mechanisms through which peripheral nerves participate in cutaneous wound healing primarily involve the modulation of immune responses, the regulation of stem cell niches, and the promotion of angiogenesis. Sensory neurons initiate and mediate essential local immune responses, contribute to the epidermal stem cell microenvironment, and support regenerative potential. Sympathetic nerves bidirectionally regulate immune homeostasis through the release of various neuromodulators and finely control the activation of hair follicle stem cells and the homeostasis of melanocyte stem cells. Schwann cells also play pivotal roles in immune modulation, balancing repair processes and mitigating scar formation. During revascularization, sensory and autonomic nerve terminals release neurotransmitters that precisely regulate vasomotor activity and angiogenesis, while Schwann cells facilitate the reconstruction of functional vascular networks through potent paracrine signaling. This review systematically summarizes the crucial roles of peripheral nerves in skin wound repair, with emphasis on their regulatory mechanisms in immune responses, stem cell activation and homeostasis, and vascular dynamics, thereby providing insights for developing novel therapeutic strategies targeting neuroregulation.

Poor wound healing is a refractory process that places an enormous medical and financial burden on diabetic patients. Exosomes have recently been recognized as crucial players in the healing of diabetic lesions. They have excellent stability, homing effects, biocompatibility, and reduced immunogenicity as novel cell-free therapies. In addition to transporting cargos to target cells to enhance intercellular communication, exosomes are beneficial in nearly every phase of diabetic wound healing. They participate in modulating the inflammatory response, accelerating proliferation and reepithelization, increasing angiogenesis, and regulating extracellular matrix remodeling. Accumulating evidence indicates that hydrogels or dressings in conjunction with exosomes can prolong the duration of exosome residency in diabetic wounds. This review provides an overview of the mechanisms, delivery, clinical application, engineering, and existing challenges of the use of exosomes in diabetic wound repair. We also propose future directions for biomaterials incorporating exosomes: 2D or 3D scaffolds, biomaterials loaded with wound healing-promoting gases, intelligent biomaterials, and the prospect of systematic application of exosomes. These findings may might shed light on future treatments and enlighten some studies to improve quality of life among diabetes patients.

Vascularized composite allotransplantation (VCA), which can effectively improve quality of life, is a promising therapy for repair and reconstruction after face or body trauma. However, intractable issues are associated with VCA, such as the inevitable multiple immunogenicities of different tissues that cause severe rejection, the limited protocols available for clinical application, and the shortage of donor sources. The existing regimens used to extend the survival of patients receiving VCAs and suppress rejection are generally the lifelong application of immunosuppressive drugs, which have side effects. Consequently, studies aiming at tissue engineering methods for VCA have become a topic. In this review, we summarize the emerging therapeutic strategies for tissue engineering aimed to prolong the survival time of VCA grafts, delay the rejection and promote prevascularization and tissue regeneration to provide new ideas for future research on VCA treatment.

We found a strong correlation between travel volumes departing from Wuhan, Hubei Province before the Spring Festival and the extent of amplification of the outbreak of COVID-19 in China in 2020, with 100 top cities. Almost 70% of exportations were within cities in Hubei province.

Early brain injury (EBI) is involved in the process of cerebral tissue damage caused by subarachnoid hemorrhage (SAH), and multiple mechanisms, such as apoptosis and inflammation, participate in its development. Mangiferin (MF), a natural C-glucoside xanthone, has been reported to exert beneficial effects against several types of organ injury by influencing various biological progresses. The current study aimed to investigate the potential of MF to protect against EBI following SAH via histological and biological assessments. A rat perforation model of SAH was established, and MF was subsequently administered via intraperitoneal injection at a low and a high dose. High-dose MF significantly lowered the mortality of SAH animals and ameliorated their neurological deficits and brain edema. MF also dose-relatedly attenuated SAH-induced oxidative stress and decreased cortical cell apoptosis by influencing mitochondria-apoptotic proteins. In addition, MF downregulated the activation of the NLRP3 inflammasome and NF-κB as well as the production of inflammatory cytokines, and the expression of Nrf2 and HO-1 was upregulated by MF. The abovementioned findings indicate that MF is neuroprotective against EBI after SAH and Nrf2/HO-1 cascade may play a key role in mediating its effect through regulation of the mitochondrial apoptosis pathway and activation of the NLRP3 inflammasome and NF-κB.

Early acute kidney injury (AKI) in severely burned patients predicts a high mortality that is multi-factorial. Hydrogen has been reported to alleviate organ injury via selective quenching of reactive oxygen species. This study investigated the potential protective effects of hydrogen against severe burn-induced early AKI in rats. Severe burn were induced via immersing the shaved back of rats into a 100°C bath for 15 s. Fifty-six Sprague–Dawley rats were randomly divided into Sham, Burn + saline, and Burn + hydrogen-rich saline (HS) groups, and renal function and the apoptotic index were measured. Kidney histopathology and immunofluorescence staining, quantitative real-time PCR, ELISA and western blotting were performed on the sera or renal tissues of burned rats to explore the underlying effects and mechanisms at varying time points post burn. Renal function and tubular apoptosis were improved by HS treatment. In addition, the oxidation–reduction potential and malondialdehyde levels were markedly reduced with HS treatment, whereas endogenous antioxidant enzyme activities were significantly increased. HS also decreased the myeloperoxidase levels and influenced the release of inflammatory mediators in the sera and renal tissues of the burned rats. The regulatory effects of HS included the inhibition of p38, JNK, ERK and NF-κB activation, and an increase in Akt phosphorylation. Hydrogen can attenuate severe burn-induced early AKI; the mechanisms of protection include the inhibition of oxidative stress induced apoptosis and inflammation, which may be mediated by regulation of the MAPKs, Akt and NF-κB signalling pathways.