This study investigates the therapeutic potential of human placental mesenchymal stem cells (P-MSCs) and their extracellular vesicles (EVs) in a murine model of acute respiratory distress syndrome (ARDS), a condition with growing relevance due to its association with severe COVID-19. We induced ARDS-like lung injury in mice using intranasal LPS instillation and evaluated histological changes, neutrophil accumulation via immunohistochemistry, bronchoalveolar lavage fluid cell count, total protein, and cytokine concentration, as well as lung gene expression changes at three time points: 24, 72, and 168 h. We found that both P-MSCs and EV treatments reduced the histological evidence of lung injury, decreased neutrophil infiltration, and improved alveolar barrier integrity. Analyses of cytokines and gene expression revealed that both treatments accelerated inflammation resolution in lung tissue. Biodistribution studies indicated negligible cell engraftment, suggesting that intraperitoneal P-MSC therapy functions mostly through soluble factors. Overall, both P-MSC and EV therapy ameliorated LPS-induced lung injury. Notably, at the tested dose, EV therapy was more effective than P-MSCs in reducing most aspects of lung injury.

Elsholtzia ciliata essential oil (E. ciliata) has been reported to have an impact on the cardiovascular system. However, its toxicity remains unknown. Therefore, the objective of this investigation was to evaluate the toxicological aspects of the E. ciliata extract. Male Balb/c mice were subjected to either acute (a single dose administered for 24 h) or sub-chronic (daily dose for 60 days) intraperitoneal injections of the E. ciliata extract. The mice were assessed for blood hematological/biochemical profiles, mitochondrial functions, and histopathological changes. Additionally, in vitro cytotoxicity assessments of the E. ciliata extract were performed on immobilized primate kidney cells (MARC-145, Vero) and rat liver cells (WBF344) to evaluate cell viability. The control groups received an equivalent volume of olive oil or saline. Our results demonstrated no significant detrimental effects on hematological and biochemical parameters, mitochondrial functions, cellular cytotoxicity, or pathological alterations in vital organs following the intraperitoneal administration of the E. ciliata extract over the 60-day sub-chronic toxicity study. In general, E. ciliata displayed no indications of toxicity, suggesting that the E. ciliata extract is a safe natural product with a well-defined therapeutic and protective index (found to be 90 and 54, respectively) in Balb/c mice.

Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) develops through inflammation-driven preneoplastic alterations characterized by epidermal hyperplasia, dysplasia, and increased proliferative activity. C-phycocyanin (C-PC) possesses antioxidant and anti-inflammatory properties; however, its topical potential to attenuate a tumour-promoting cutaneous microenvironment is limited by poor skin penetration. This study evaluated the effects of C-PC-loaded transfersomes in a 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse model of skin carcinogenesis. Methods: Male BALB/c mice were assigned to six groups (n = 10 per group). Carcinogenesis was initiated with a single topical application of DMBA, followed by twice-weekly TPA application for 16 weeks. C-PC-loaded transfersomes (1 mg/mL or 10 mg/mL) were applied topically. Histopathological assessment included epidermal thickness, rete ridge depth, mitotic activity, mast cell density, and semi-quantitative scoring of hyperplasia, dysplasia, and inflammation. Ki-67 immunohistochemistry was used to evaluate basal and suprabasal proliferation. Results: Carcinogen exposure induced marked epidermal thickening, severe dysplasia, increased mitotic activity, elevated Ki-67 expression, and pronounced dermal inflammation. Treatment with C-PC-loaded transfersomes significantly reduced epidermal thickness, rete ridge depth, mast cell density, mitotic counts, and suprabasal Ki-67 index. The 1 mg/mL concentration demonstrated the most consistent attenuation of dysplasia severity and inflammatory changes. No adverse histopathological alterations were observed in internal organs. Conclusions: These findings indicate that transfersome-mediated topical delivery of C-PC attenuates early inflammation-driven epidermal remodelling and tumour-promoting alterations in experimental skin carcinogenesis, supporting its potential as a topical preventive strategy.

Background/Objectives: Furan derivatives are commonly encountered in food and environmental matrices and may exert biological effects, but their acute cardiovascular actions and potential mitochondrial targets remain insufficiently characterised. This study examined the effects of two simple furan compounds, 2-acetylfuran (2AF) and 5-methylfurfural (5MFF), on arterial blood pressure in vivo and on oxidative phosphorylation in isolated rat liver mitochondria. Methods: Arterial blood pressure was recorded invasively in anaesthetised rats after intraperitoneal administration of 2AF or 5MFF (0.3 µL/g). Systolic, diastolic, and mean arterial pressures, as well as heart rate, were monitored over time. Mitochondrial respiration was assessed in isolated rat liver mitochondria using high-resolution respirometry. Results: Both 2AF and 5MFF induced a rapid hypotensive response, with significant reductions in systolic, diastolic, and mean arterial pressures within 10–15 min after administration. MAP was reduced to a similar extent by both compounds. However, their chronotropic and pulse pressure responses differed: 5MFF increased heart rate and pulse pressure, whereas 2AF induced a delayed bradycardic response without a significant change in pulse pressure. In isolated liver mitochondria, both compounds markedly reduced ADP-stimulated respiration and decreased the respiratory control index, indicating reduced coupling efficiency. Both compounds also increased the cytochrome c effect, suggesting partial impairment of outer mitochondrial membrane integrity. Conclusions: 2AF and 5MFF exert acute hypotensive effects in anaesthetised rats and impair oxidative phosphorylation in isolated rat liver mitochondria. This study provides the first in vivo evidence that 2AF and 5MFF exert hypotensive effects and identifies them as bioactive furan compounds with dual haemodynamic and bioenergetic actions.

Acute kidney injury (AKI) is widely recognized as a precursor to the onset or rapid progression of chronic kidney disease (CKD). However, there is currently no effective treatment available for AKI, underscoring the urgent need for the development of new strategies to improve kidney function. Human placental mesenchymal stromal cells (hpMSCs) were isolated from donor placentas, cultured, and characterized with regard to yield, viability, flow cytometry, and potency. To mimic AKI and its progression to CKD in a rat model, a dedicated sensitive non-clinical bilateral kidney ischemia-reperfusion injury (IRI) model was utilized. The experimental group received 3 × 10⁵ hpMSCs into each kidney, while the control group received IRI and saline and the untreated group received IRI only. Urine, serum, and kidney tissue samples were collected over a period of 28 days. The hpMSCs exhibited consistent yields, viability, and expression of mesenchymal lineage markers, and were also shown to suppress T cell proliferation in a dose-dependent manner. To ensure optimal donor selection, manufacturing optimization, and rigorous quality control, the rigorous Good Manufacturing Practice (GMP) conditions were utilized. The results indicated that hpMSCs increased rat survival rates and improved kidney function by decreasing serum creatinine, urea, potassium, and fractionated potassium levels. Furthermore, the study demonstrated that hpMSCs can prevent the initial stages of kidney structural fibrosis and improve kidney function in the early stages by mitigating late interstitial fibrosis and tubular atrophy. Additionally, a robust manufacturing process with consistent technical parameters was established.