International Journal of Molecular Sciences

Radiation-induced chronic wounds remain a major clinical challenge owing to persistent non-healing and progressive tissue degeneration. Rather than simply representing delayed wound repair, they arise from a self-perpetuating pathological cascade involving DNA damage, oxidative stress, chronic inflammation, microvascular dysfunction, cellular senescence, stem cell impairment, and fibrosis. Current clinical management remains largely supportive and symptomatic, with limited efficacy and no standardized therapeutic regimens targeting the core pathological mechanisms. Emerging strategies—antioxidant, antifibrotic, senolytic, stem cell/exosome-based, and functional biomaterial approaches—show promise. This review critically summarizes recent advances in pathogenic mechanisms and mechanism-based therapeutic strategies, highlighting current translational challenges and future directions for microenvironment-oriented regenerative therapies.

Liposomal drug-delivery systems can improve the formulation performance of poorly soluble compounds by enhancing aqueous dispersion, protecting encapsulated agents, and modifying release behavior. Co-encapsulation of pharmacologically distinct compounds may provide a formulation strategy for comparing combined delivery with a single agent nanoliposomal system. This study aimed to develop and characterize atorvastatin–rutin co-loaded nanoliposomes and to compare their antioxidant, anti-inflammatory, and SRB-based cytotoxic activity with the corresponding free-drug and single-loaded nanoliposomal formulations. Nanoliposomes were prepared by thin-film hydration and characterized by particle size, polydispersity index, zeta potential, encapsulation efficiency, lyophilization-associated retention of encapsulation efficiency, morphology, and in vitro release. A reverse-phase HPLC method was validated for simultaneous atorvastatin and rutin quantification, and lyophilized formulations were evaluated for retention of encapsulation efficiency. In vitro assays included DPPH radical scavenging, nitrite inhibition in LPS-stimulated RAW 264.7 macrophages, and SRB-based cytotoxicity screening across human cancer cell lines and normal periodontal ligament fibroblasts. The co-loaded nanoliposomes achieved encapsulation efficiencies of 88.46% for atorvastatin and 81.74% for rutin; after lyophilization, encapsulation efficiency decreased to 72.31% for atorvastatin and 76.63% for rutin. The nanoliposomal formulations showed measurable DPPH radical-scavenging activity, nitrite-inhibition activity in LPS-stimulated macrophages, and SRB-based antiproliferative activity in several cancer cell lines, while showing no detectable cytotoxicity toward PDL fibroblasts within the tested concentration range. With exquisite similarity to apoptogenic Anti-VEGF antiangiogenesis chemotherapeutic efficacies ofcisplatin; nanoliposomal atorvastatin and co-loaded atorvastatin with rutin were remarkable comparable (in descending order of human VEGF mitigations) in mammary T47D> uterine cervix HeLa> lung A549 adherent monolayers post 72 h incubations. These findings support further investigation of atorvastatin–rutin co-loaded nanoliposomes as an in vitro formulation platform; however, formal synergy analysis, cellular uptake studies, mechanistic assays, pharmacokinetic evaluation, and in vivo safety testing remain necessary. Further in vivo studies are required to determine pharmacokinetic behavior, tissue distribution, therapeutic relevance, and systemic safety.

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the emerging leading cause of Chronic Liver Disease (CLD) worldwide, with a global prevalence of approximately 30% in the general population that parallels global rates of obesity and Type 2 Diabetes (T2D). Although two drugs (Resmetirom and Semaglutide) have been recently approved for clinical use, their ability to block or slow down disease progression to metabolic dysfunction-associated Steatohepatitis (MASH) and liver fibrosis is limited to a subset of patients, and no data are available at present for the efficacy of these drugs in compensated cirrhosis or in relation to hepatocellular carcinoma (HCC) development. Moreover, there is a lack of reliable biomarkers able to identify MASH patients at risk of disease progression and/or HCC development. In line with the knowledge that pro-inflammatory cytokines play a key role in MASLD/MASH progression and HCC development, in this review, we will discuss the role in this disease and other CLDs of Oncostatin M (OSM), a cytokine belonging to the IL6 family, and of pathways involving OSM and its receptor β (OSM/OSMRβ axis). OSM and related pathways are emerging as selective in sustaining disease progression by promoting chronic inflammation and fibrogenesis. The OSM/OSMRβ axis is proposed to be involved in MASH-related HCC development by affecting proliferation, angiogenesis, invasiveness and metastasis as well as by reshaping the MASH-related tumor immune microenvironment. OSM and the OSM/OSMRβ axis are emerging as a candidate biomarker and putative MASH-related therapeutic target.