Background and Objectives: Cartilage repair remains a critical challenge in orthopaedic medicine due to the tissue’s limited self-healing ability, contributing to degenerative joint conditions such as osteoarthritis (OA). In response, regenerative medicine has developed advanced therapeutic strategies, including cell-based therapies, gene editing, and bioengineered scaffolds, to promote cartilage regeneration and restore joint function. This narrative review aims to explore the latest developments in cartilage repair techniques, focusing on mesenchymal stem cell (MSC) therapy, gene-based interventions, and biomaterial innovations. It also discusses the impact of patient-specific factors, such as age, defect size, and cost efficiency, on treatment selection and outcomes. Materials and Methods: This review synthesises findings from recent clinical and preclinical studies published within the last five years, retrieved from the PubMed, Scopus, and Web of Science databases. The search targeted key terms such as “cartilage repair”, “stem cell therapy”, “gene editing”, “biomaterials”, and “tissue engineering”. Results: Advances in MSC-based therapies, including autologous chondrocyte implantation (ACI) and platelet-rich plasma (PRP), have demonstrated promising regenerative potential. Gene-editing tools like CRISPR/Cas9 have facilitated targeted cellular modifications, while novel biomaterials such as hydrogels, biodegradable scaffolds, and 3D-printed constructs have improved mechanical support and tissue integration. Additionally, biophysical stimuli like low-intensity pulsed ultrasound (LIPUS) and electromagnetic fields (EMFs) have enhanced chondrogenic differentiation and matrix production. Treatment decisions are influenced by patient age, cartilage defect size, and financial considerations, highlighting the need for personalised and multimodal approaches. Conclusions: Combining regenerative techniques, including cell-based therapies, gene modifications, and advanced scaffolding, offers a promising pathway towards durable cartilage repair and joint preservation. Future research should focus on refining integrated therapeutic protocols, conducting long-term clinical evaluations, and embracing personalised treatment models driven by artificial intelligence and predictive algorithms.

Over the past two decades, the use of tumor necrosis factor alpha (TNF-α) inhibitors has significantly improved the treatment of patients with immune-mediated inflammatory diseases. Firstly, introduced for rheumatoid arthritis, these inhibitors are currently approved and used for a variety of conditions, including ankylosing spondylitis, Crohn’s disease, juvenile idiopathic arthritis, psoriasis, psoriatic arthritis, ulcerative colitis, and chronic uveitis. Despite their immense therapeutic efficacy, TNF-α inhibitors have been associated with neurological adverse effects that bring new clinical challenges. The present review collects data from multiple studies to evaluate the incidence and the relationship between TNF-α inhibitors and neurological side effects and to explore the potential underlying mechanisms of this association. Moreover, it highlights the importance of patient selection, particularly in the case of individuals with a history of demyelinating diseases, raises awareness for clinicians, and calls for ongoing research that will improve TNF-α targeting strategies and offer safer and more effective therapeutic options.

The current study proposes the in vitro and in silico anticancer evaluation of clove (Syzygium aromaticum L.) essential oil (CEO). The steam hydrodistillation method used yielded 10.7% (wt) CEO. GC-MS analysis revealed that the obtained oil is rich in eugenol (75%), β-caryophyllene (20%), and α- caryophyllene (2.8%) and also contains several other minor components accounting for approximately 1.5%. The DPPH-based scavenging antioxidant activity was assessed for the obtained CEO, exhibiting an IC₅₀ value of 158 μg/mL. The cytotoxic effects of CEO, its major component eugenol, and CEO solubilized with Tween-20 and PEG-400 were tested against both noncancerous HaCaT cells and HT-29 human colorectal adenocarcinoma, RPMI-7951 melanoma, A431 skin carcinoma, and NCI-H460 non-small lung cancer cells, using the Alamar Blue and LDH assay after 48 h treatment. The Tween-20 and PEG-400 CEO formulations, at 200 μg/mL, recorded the highest cytotoxic and selective effects against RPMI-7951 (72.75% and 71.56%), HT-29 (71.51% and 45.43%), and A431 cells (61.62% and 59.65%). Furthermore, CEO disrupted mitochondrial function and uncoupled oxidative phosphorylation. This effect was more potent for the CEO against the RPMI-7951 and HT-29 cells, whereas for the other two tested cell lines, a more potent inhibition of mitochondrial function was attributed to eugenol. The present study is the first to specifically investigate the effects of CEO and Tween-20 and PEG-400 CEO formulations on the mitochondrial function of RPMI-7951, HT-29, A431, and NCI-H460 cancer cell lines using high-resolution respirometry, providing novel insights into their impact on mitochondrial respiration and bioenergetics in cancer cells. The results obtained may explain the increased ROS production observed in cancer cell lines treated with eugenol and CEO. Molecular docking identified potential protein targets, related to the CEO anticancer activity, in the form of PI3Kα, where the highest active theoretical inhibitor was calamenene (−7.5 kcal/mol). Docking results also showed that calamenene was the overall most active theoretical inhibitor for all docked proteins and indicated a potential presence of synergistic effects among all CEO constituents.

Betulinic acid is a lupane-type pentacyclic triterpene mostly found in birch bark and thoroughly explored for its wide range of pharmacological activities. Despite its impressive biological potential, its low bioavailability has challenged many researchers to develop different formulations for achieving better in vitro and in vivo effects. We previously reported the synthesis of fatty acid esters of betulinic acid using butyric, stearic, and palmitic acids (But-BA, St-BA, and Pal-BA) and included them in surfaced-modified liposomes (But-BA-Lip, St-BA-Lip, Pal-BA-Lip). In the current study, we evaluated the cytotoxic effects of both fatty acid esters and their respective liposomal formulations against MCF-7, HT-29, and NCI-H460 cell line. The cytotoxic assessment of BA derivatives revealed that both the fatty esters and their liposomal formulations acted as cytotoxic agents in a dose- and time-dependent manner. But-BA-Lip exerted stronger cytotoxic effects than the parent compound, BA and its liposomal formulation, and even stronger effects than 5-FU against HT-29 cells (IC₅₀ of 30.57 μM) and NCI-H460 cells (IC₅₀ of 30.74 μM). BA’s fatty esters and their respective liposomal formulations facilitated apoptosis in cancer cells by inducing nuclear morphological changes and increasing caspase-3/-7 activity. The HET-CAM assay proved that none of the tested compounds induced any irritative effect, suggesting that they can be used safely for local applications.

This study aims to assess the potential anticancer activity of lemongrass essential oil (LEO) using in vitro and in silico methods. The steam hydrodistillation of the aerial parts yielded 3.2% (wt) LEO. The GC-MS analysis of the LEO revealed the presence of α-citral (37.44%), β-citral (36.06%), linalool acetate (9.82%), and d-limonene (7.05%) as major components, accompanied by several other minor compounds. The antioxidant activity, assessed using the DPPH assay, revealed that LEO exhibits an IC₅₀ value of 92.30 μg/mL. The cytotoxic effect of LEO, as well as LEO solubilized with Tween-20 (LEO-Tw) and PEG-400 (LEO-PEG), against a series of cancer cell lines (A375, RPMI-7951, MCF-7, and HT-29) was assessed using the Alamar Blue assay; the results revealed a high cytotoxic effect against all cell lines used in this study. Moreover, neither one of the tested concentrations of LEO, LEO-PG, or LEO-TW significantly affected the viability of healthy HaCaT cells, thus showing promising selectivity characteristics. Furthermore, LEO, LEO-PG, and LEO-TW increased ROS production and decreased the mitochondrial membrane potential (MMP) in all cancer cell lines. Moreover, LEO treatment decreased all mitochondrial respiratory rates, thus suggesting its ability to induce impairment of mitochondrial function. Molecular docking studies revealed that LEO anticancer activity, among other mechanisms, could be attributed to PDK1 and PI3Kα, where the major contributors are among the minor components of the essential oil. The highest active theoretical inhibitor against both proteins was β-caryophyllene oxide.

Due to their high content of bioactive compounds with anticancer properties, essential oils (EO) are increasingly viewed as valuable therapeutic strategies in oncology. The aim of this study was to evaluate the chemical composition and anticancer activity of Cedrus atlantica EO (CAEO) and its PEG-400 and Tween 20 formulations. The gas-chromatography (GC) analysis revealed a sesquiterpene-rich profile, with β-himachalene (39.32%) as the major constituent, followed by α-Himachalene (16.76%) and γ-Himachalene (12.92%). The cytotoxicity studies, performed using Alamar Blue assay on normal HaCaT human keratinocytes and A375 human melanoma and HT-29 colorectal carcinoma cell lines, revealed that CAEO displayed minimal toxicity on HaCaT cells, while significantly reducing A735 and HT-29 cell viability, at any of the concentrations tested. The PEG- and Tween-based formulations of CAEO exhibited the same effect on cell viability as the simple water dispersion of CAEO. The immunofluorescence-based examination of cellular morphology suggested that CAEO induces apoptosis in both cancer cell lines: A375 and HT-29; this apoptosis-related mechanism was further supported by the caspase-3/7 assay, which revealed a significant increase in caspase-3/7 activity after CAEO treatment. To further investigate the underlying mechanism, the JC-1 staining and high-resolution respirometry assays demonstrated that CAEO induces mitochondrial membrane depolarization and reduced mitochondrial active respiration (OXPHOS). Molecular docking further indicated that isoledene and β-himachalene exhibit the highest predicted affinity for PI3Kγ, suggesting a potential involvement of PI3K-related signaling in the pro-apoptotic activity of CAEO. Together, these results suggest that CAEO induces apoptosis through a mitochondria-mediated mechanism.