Biology subjects

Nawilaijaroen, Y.

Publications and source records attributed to Nawilaijaroen, Y..

3 recordsLinked to original sources

bioRxiv2026

Persistent CCL3 expression sustains neutrophil recruitment and contributes to delayed wound healing in advanced age

Delayed wound healing in advanced age is associated with prolonged inflammation, but the mechanisms that impair inflammatory resolution in this context remain poorly defined. Neutrophils are essential for early repair, but their persistence is predicted to disrupt resolution and delay healing. Here we show that aged mice exhibit impaired wound closure accompanied by sustained neutrophil infiltration from days 7-14 post-injury, long after neutrophils have resolved in young wounds. In aged skin, macrophage abundance and neutrophil-macrophage interactions were reduced, consistent with reduced macrophage-mediated clearance. Instead, neutrophils preferentially localised to perivascular regions, consistent with ongoing recruitment. Transcriptomic profiling demonstrated that young wounds transitioned from inflammatory to reparative programs, whereas aged wounds retained inflammatory signatures, including enrichment for neutrophil chemotaxis and LPS-response pathways. Notably, Ccl3, Cxcl2 and Cxcl3 remained elevated in aged wounds. Analysis of human chronic ulcers identified macrophages as a major source of these transcripts, and aged mouse wounds possessed more CCL3+ macrophages than in young. Targeted blockade of CCL3 beginning at day 4 post-injury reduced neutrophil accumulation, accelerated wound closure, and rescued key features of age-impaired healing, when administered after the initial inflammatory phase. Together, these findings identify persistent CCL3 expression as a contributor to sustained neutrophil recruitment and impaired repair in advanced age. Therapeutically targeting this pathway offers a strategy to restore timely resolution and improve healing outcomes.

immunology↗

bioRxiv2025

Establishing a preclinical chronic wound model to characterise the pathophysiology of snakebite envenoming

Snakebite claims 138,000 lives a year with an additional 400,000 patients left permanently disabled or disfigured1. Morbidity following envenoming includes the development of chronic wounds around the bite site. The understanding of the underlying pathophysiology of chronic snakebite wounds has been severely limited by the historical reliance on a preclinical model that only captures acute local envenoming pathology. Through the application of three medically important snake venoms (Echis ocellatus, Bothrops atrox and Naja nigricollis) to a recently developed preclinical model of chronic wounds, we have been able to characterise key features of venom wounds. We have been able to show that venom wounds share consistencies with non-venom induced preclinical wounds, and also display unique characteristics such as extracellular matrix degradation and eosinophilic infiltrate. This model will not only serve to increase our understanding the underlying pathophysiology of venom wounds, but will also provide a platform for exploring therapeutic interventions to reduce or resolve snakebite wounds.

pathology↗

bioRxiv2022

MC1R drives cutaneous repair by promoting angiogenesis and lymphangiogenesis

Cutaneous healing results in scarring with significant functional and psychological sequelae, while chronic non-healing wounds represent repair failure often with devastating consequences, including amputation and death. Due to a lack of effective therapies, novel interventions addressing scarring and chronic wounds are urgently needed. Here, we demonstrate that harnessing melanocortin 1 receptor with a selective agonist (MC1R-Ag) confers multifaceted benefits to wound repair. MC1R-Ag accelerates wound closure and re-epithelialization while improving wound bed perfusion and lymphatic drainage by promoting angiogenesis and lymphangiogenesis. Concomitant reductions in oxidative stress, inflammation and scarring were also observed. To evaluate the therapeutic potential of targeting MC1R in pathological healing, we established a novel murine model that recapitulates the hallmarks of human non-healing wounds. This model combines advanced age and locally elevated oxidative stress. Remarkably, topical application of MC1R-Ag restored repair, whereas disrupting MC1R signalling exacerbated the chronic wound phenotype. Our study highlights MC1R agonism as a promising therapeutic approach for scarring and non-healing wound pathologies, and our chronic wound model as a valuable tool for elucidating ulcer development mechanisms.

pathology↗