The phytochemical analysis of the investigated Immortelle essential oil revealed the presence of monoterpenes and sesquiterpenes as major components that might be efficient as a wound healing potential agent. The present study aimed to develop an ointment based on the Immortelle essential oil and investigate its wound healing effects on excision wounds in diabetic rats. The topical formulated Immortelle ointment was subjected to pharmaco-technical characterization. Thirty-two diabetic rats with the induced excision wound were used to evaluate in vivo wound healing effects of ointment. The animals were randomly divided into four groups untreated or topically treated with either a 1% silver sulfadiazine, the ointment base, or Immortelle ointment. The response to the treatment was assessed by macroscopic, biochemical and histopathological analysis. The ointment, compatible with the skin remained stable for 6 months. Topical application of the Immortelle ointment showed the highest wound contraction with the highest content of hydroxyproline in comparison to the all examined groups. The Immortelle ointment showed significant wound contraction from day 7 to day 21 as compared to other groups. On the day 21, there was an average of 99.32% wound contraction in the Immortelle group, whereas the mean wound contraction in the negative control and ointment base group was 71.36% and 81.26% respectively. The histopathological results validated the potential wound healing effect of Immortelle ointment with evident post-excision scar maturation and increased collagen fibers density. Our findings revealed that the Immortelle ointment approach might serve as a promising and innovative tool for wound healing.

The beneficial effects of HBO in inflammatory processes make it an attractive type of treatment for chronic arthritis. In addition, the effects of combination therapy based on adipose stem cells and HBO on OA progression have not been fully investigated. The current study explored the efficacy of intra-articular injection of allogeneic adipose-derived mesenchymal stem cells (ADMSCs) combined with hyperbaric oxygenation treatment (HBO) in a rat osteoarthritis (OA) model. The rat OA model was induced by intra-articular injection of monoiodoacetate (MIA) and 7 days after application of MIA rats were divided into five groups: healthy control (CTRL), osteoarthritis (OA), ADMSCs (ADS), the HBO+ADS^21day and HBO+ADS^28day groups. A single dose of 1 × 10⁶ allogeneic ADMSCs suspended in sterile saline was injected into the knee joint alone or in combination with HBO treatment. Rats were sacrificed at 3 or 4 weeks after MIA injection. Treatment outcomes were evaluated by radiographic, morphological and histological analysis and by specific staining of articular cartilage. We also measured the level of inflammatory and pro/antioxidative markers. We confirmed that combined treatment of ADMSCs and HBO significantly improved the regeneration of cartilage in the knee joint. Rtg score of knee joint damage was significantly decreased in the HBO+ADS^21day and HBO+ADS^28day groups compared to the OA. However, the positive effect in the HBO+ADS^28day group was greater than the HBO+ADS^21day group. The articular cartilage was relatively normal in the HBO+ADS^28day group, but moderate degeneration was observed in the HBO+ADS^21day compared to the OA group. These findings are in line with the histopathological results. A significantly lower level of O₂⁻. was observed in the HBO+ADS^28day group but a higher NO level compared to the HBO+ADS^21day group. Moreover, in the HBO+ADS^28day group significantly higher concentrations of IL-10 were observed but there was no significant difference in proinflammatory cytokine in serum samples. These results indicate that a single intra-articular injection of allogeneic ADMSCs combined with HBO efficiently attenuated OA progression after 28 days with greater therapeutic effect compared to alone ADMSCs or after 3 weeks of combined treatment. Combined treatment might be an effective treatment for OA in humans.

The use of non-vitamin K antagonist oral anticoagulants (NOACs) has brought a significant progress in the management of cardiovascular diseases, considered clinically superior to vitamin K antagonists (VKAs) particularly in the prevention and treatment of thromboembolic events. In addition, numerous advantages such as fixed dosing, lack of laboratory monitoring, and fewer food and drug-to-drug interactions make the use of NOACs superior to VKAs. While NOACs are synthetic drugs prescribed for specific conditions, nattokinase (NK) is a natural enzyme derived from food that has potential health benefits. Various experimental and clinical studies reported the positive effects of NK on the circulatory system, including the thinning of blood and the dissolution of blood clots. This enzyme showed not only fibrinolytic activity due to its ability to degrade fibrin, but also an affinity as a substrate for plasmin. Recent studies have shown that NK has additional cardioprotective effects, such as antihypertensive and anti-atherosclerotic effects. In this narrative review, we presented the cardioprotective properties of two different approaches that go beyond anticoagulation: NOACs and NK. By combining evidence from basic research with clinical findings, we aim to elucidate the comparative cardioprotective efficacy of these interventions and highlight their respective roles in modern cardiovascular care.

Background/Objectives: The objective of this study was to investigate the effects of local zoledronate treatment during periapical lesion development on inflammatory and bone remodeling responses in two immunologically distinct inbred rat strains, Dark Agouti (DA) and Albino Oxford (AO). Methods: Periapical lesions were induced in the mandibular first molars of AO and DA rats (n = 44) by pulp exposure. Animals were assigned to four groups: DA + zoledronate, DA + saline, AO + zoledronate, and AO + saline. Zoledronate (0.15 mg/kg) or saline was locally administered on days 0, 7, 14, and 21 during lesion development. Animals were sacrificed on day 28. Mandibles were analyzed radiographically and histologically for lesion size, while osteogenic activity was assessed by osteocalcin immunohistochemistry. Gene expression was evaluated by qRT-PCR, and systemic oxidative stress parameters were analyzed spectrophotometrically. Statistical analysis included parametric or non-parametric tests according to data distribution, with significance set at p < 0.05. Results: Zoledronate -treated AO rats exhibited smaller periapical lesions and higher radiographic grayscale density than DA rats (p < 0.05). Histological analysis confirmed the radiographic findings and demonstrated smaller lesion areas in AO rats. Osteocalcin expression was significantly higher in AO rats (p < 0.05), indicating increased osteogenic activity. At the molecular level, DA rats showed higher expression of TNF-α and IL-1β, whereas AO rats exhibited higher expression of IL-10 and IL-4 (p < 0.05). In addition, expression of osteoclastogenic factor RANKL was significantly lower in AO rats than in DA rats (p < 0.05), while OPG expression showed a non-significant tendency toward higher levels in AO rats. Systemic redox analysis demonstrated lower NO₂⁻ and O₂⁻ levels in zoledronate-treated AO rats, whereas no significant differences were observed in the remaining oxidative stress parameters. Conclusions: Following local zoledronate treatment during lesion development, Th2-dominant AO rats exhibited reduced inflammatory responses and increased osteogenic activity compared with Th1-dominant DA rats. In contrast, DA rats primarily demonstrated attenuation of osteoclastogenic signaling without comparable osteogenic responses. These findings indicate that the biological effects of local zoledronate treatment in developing periapical lesions are influenced by the host immune phenotype.