Search Results (2,754)

Plants have a remarkable ability to regenerate tissues and organs from single cells, a property that underpins in vitro protoplast regeneration. Efficient protoplast-to-plant regeneration remains a major bottleneck for genome engineering in many crop species, including broccoli (Brassica oleracea var. italica). In this study, we established and optimized a regeneration system for broccoli cv. Claremont by evaluating enzyme composition, light quality, and culture media at successive stages of development. Among the tested enzyme mixtures, 1.5% Cellulase R-10 combined with 0.4% Macerozyme R-10 yielded the highest protoplast viability and recovery. Alginate-embedded protoplasts were cultured under control (dark), blue, and red + far-red LED illumination. Red + far-red treatment significantly enhanced microcolony formation, plating efficiency, and shoot regeneration compared with blue light, whereas blue illumination consistently reduced regenerative performance. The inclusion of activated charcoal in the regeneration medium further increased shoot production. The generalized linear model analyses identified light quality as a significant predictor of both shoot number and regeneration. To our knowledge, this study provides one of the first demonstrations of LED-assisted enhancement of protoplast regeneration in broccoli. The optimized protocol enables whole-plant recovery within approximately 5 months and offers a practical platform for CRISPR-based genome editing and advanced breeding applications in B. oleracea. Full article

Background and Objectives: Circulating microRNAs may provide minimally invasive biomarkers for laryngeal squamous cell carcinoma (LSCC), but clinically interpretable data for miR-99a-5p and miR-1246 remain limited. We compared circulating levels of these two miRNAs between LSCC patients and controls and explored stage-associated differences within the cancer cohort. Methods: This single-center case–control study was conducted in Timișoara, Romania. Circulating miRNAs were quantified by RT-qPCR. Expression was summarized as ΔCt [Ct(target) − Ct(miR-16)] and as the relative expression (2^−ΔΔCt) using the control group as a calibrator. Group comparisons used Mann–Whitney U tests, associations used Spearman correlation, and the diagnostic performance was assessed by ROC analysis and multivariable logistic regression. Results: Fourteen controls were compared with cancer patients with available miRNA measurements (miR-99a-5p, n = 53; miR-1246, n = 49). miR-99a-5p showed significantly higher ΔCt values in cancer patients than in the controls (5.308 [IQR 4.139–6.864] vs. 3.184 [2.142–3.708], p < 0.001), corresponding to a lower relative expression (fold-change 0.200 [0.068–0.449], p < 0.001). miR-1246 did not differ significantly between cancer and controls (p = 0.09). Within the cancer cohort, advanced-stage disease showed a lower relative miR-1246 expression than early-stage disease (ΔCt 5.820 [4.502–6.972] vs. 4.233 [3.109–5.372], p = 0.01; fold-change 0.363 vs. 1.091, p = 0.01), while miR-99a-5p showed a non-significant difference in the same direction (p = 0.052). miR-99a-5p discriminated cancer patients from the controls with an AUC of 0.842 (95% CI 0.744–0.931), sensitivity of 77.4%, and specificity of 92.9% at ΔCt = 4.018. In multivariable analysis, ΔCt(miR-99a-5p) remained independently associated with cancer status (OR 1.89, 95% CI 1.19–3.00; p = 0.007). Conclusions: Circulating miR-99a-5p showed the strongest diagnostic signal in LSCC, whereas miR-1246 appeared more informative for stage-associated biological stratification. Full article

Osteosarcoma, the most prevalent primary malignant bone tumor in children and adolescents, is characterized by high rates of metastasis, recurrence, and chemotherapy resistance, leading to suboptimal patient survival. The MDM2-p53 pathway plays a pivotal role in its tumorigenesis and progression, where dysregulation leads to loss of p53 function. This review systematically elucidates the molecular mechanisms of this pathway and summarizes diverse targeted therapeutic strategies, including small-molecule MDM2 inhibitors, mutant p53 reactivators, and innovative modalities such as gene therapy and Proteolysis Targeting Chimeras (PROTACs). Despite demonstrating potent preclinical activity with low IC₅₀ values, the clinical translation of these agents has faced significant challenges. Early-generation MDM2 inhibitors (e.g., RG7112, Idasanutlin) showed limited monotherapy efficacy and dose-limiting toxicities like thrombocytopenia, halting their development at early-phase clinical trials. In contrast, novel MDM2 inhibitors like APG-115 have advanced to Phase II trials, marking a significant breakthrough. Although not yet tested in dedicated osteosarcoma cohorts, their safety and efficacy in MDM2-amplified solid tumors provide a critical foundation for the development of precision medicine and combination regimens for osteosarcoma. Future efforts to accelerate drug development may leverage single-cell sequencing and AI-aided drug design to decipher osteosarcoma heterogeneity and optimize drug profiles for reduced toxicity. Full article

Background and Objectives: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers and remains a leading cause of cancer-related mortality worldwide. EGFR-targeted tyrosine kinase inhibitors (TKIs) have substantially improved outcomes in EGFR-mutant NSCLC; however, primary and acquired resistance continues to limit their long-term efficacy. HER3 (receptor tyrosine-protein kinase ErbB3), a member of the ErbB receptor family, has been implicated in TKI resistance through heterodimerization with EGFR and HER2, leading to downstream PI3K/AKT pathway activation. Despite its biological plausibility as a resistance mediator, the clinical significance of HER3 expression as a prognostic and predictive biomarker in EGFR-mutant NSCLC has not been thoroughly characterized in real-world cohorts. Materials and Methods: This retrospective, single-center study included 52 patients diagnosed with EGFR-mutant NSCLC who received TKI therapy at Afyonkarahisar Health Sciences University between January 2011 and September 2023. HER3 protein expression was evaluated by immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded tumor tissue sections using the Huabio anti-HER3 antibody (clone PD00-44, 1:2000 dilution). Staining in more than 30% of tumor cells was considered HER3-positive; membranous staining intensity was scored on a 1–3 scale. Progression-free survival (PFS1, PFS2) and overall survival (OS) were analyzed using the Kaplan–Meier method and log-rank test. Statistical significance was set at p < 0.05. Results: Of 52 patients (55.8% female; mean age 64.5 years), 59.6% received chemotherapy and 40.4% received an EGFR TKI as first-line treatment; erlotinib constituted 71.2% of targeted therapies. In the first-line TKI group, HER3-negative patients had a numerically longer median PFS1 compared with HER3-positive patients (14.0 vs. 7.1 months; p = 0.285); however, this difference did not reach statistical significance and should be interpreted with caution given the small sample size. In contrast, among patients receiving first-line chemotherapy, HER3 staining status did not meaningfully affect PFS1 (4.1 vs. 2.5 months; p = 0.063). In second-line treatment, HER3-positive patients who received TKI after prior chemotherapy demonstrated a PFS2 comparable to or slightly exceeding that of HER3-negative patients (21.8 vs. 19.8 months; p = 0.49), suggesting that the sequencing of chemotherapy before TKI may attenuate the adverse effect of HER3 positivity. Median OS was 15.1 months in HER3-negative patients and 12.7 months in HER3-positive patients (p = 0.824); this numerical difference of approximately 3 months did not reach statistical significance and should therefore be interpreted cautiously. Among patients receiving TKI in the first line, HER3-positive patients had a shorter median OS than HER3-negative patients (9.6 vs. 14.2 months), whereas those receiving TKI in the second line showed a trend toward longer OS in HER3-positive patients (20.5 vs. 17.2 months). Conclusions: HER3 expression was associated with reduced first-line TKI efficacy in EGFR-mutant NSCLC, suggesting a possible role for HER3 in primary TKI resistance; however, these findings are exploratory and did not reach statistical significance. The observation that HER3-positive patients who received chemotherapy before TKI demonstrated outcomes comparable to HER3-negative patients raises the hypothesis that treatment sequencing may potentially influence the impact of HER3 positivity, though this requires prospective validation before any clinical conclusions can be drawn. These results suggest that HER3 expression may warrant further investigation as a candidate biomarker for treatment sequencing decisions and as a potential therapeutic target in EGFR-mutant NSCLC. Prospective studies evaluating chemotherapy–TKI sequencing and HER3-directed agents such as patritumab deruxtecan (HER3-DXd) in HER3-positive patients are needed to confirm these preliminary observations. Full article

Manual microscopy for malaria diagnosis is labor-intensive and prone to inter-observer variability. This study presents an automated binary classification approach for detecting malaria ring-form infections in thin blood smear single-cell images using a parallel neural network framework. Utilizing a balanced Kaggle dataset of 27,558 erythrocyte crops, images were standardized to 128 × 128 pixels and subjected to on-the-fly augmentation. The proposed architecture employs a dual-branch fusion strategy, integrating a convolutional neural network for local morphological feature extraction with a multi-head self-attention branch to capture global spatial relationships. Performance was rigorously evaluated using 10-fold stratified cross-validation and an independent 10% hold-out test set. Results demonstrated high-level discrimination, with all models achieving an ROC–AUC of approximately 0.99. The primary model (Model#1) attained a peak mean accuracy of 0.9567 during cross-validation and 0.97 accuracy (macro F1-score: 0.97) on the independent test set. In contrast, increasing architectural complexity in Model#3 led to a performance decline (0.95 accuracy) due to higher false-positive rates. These findings suggest that moderate-capacity feature fusion, combining convolutional descriptors with attention-based aggregation, provides a robust and generalizable solution for automated malaria screening without the risks associated with over-parameterization. Despite a strong performance, immediate clinical use remains limited because the model was developed on pre-segmented single-cell images, and external validation is still required before routine implementation. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a five-year survival rate of approximately 13%, partly because of limited treatment options and resistance to therapies. Although the recently discovered KRAS G12D inhibitor MRTX1133 has shown promising efficacy in preclinical models, its clinical efficacy as a single agent is expected to be limited, as is the case with KRAS G12C inhibitors. Therefore, in this study, we evaluated potential combination strategies to enhance the therapeutic effect of MRTX1133. We combined MRTX1133 with the BCL-xL proteolysis-targeting chimera (PROTAC) DT2216 and the mTOR inhibitor everolimus. Methods: The sensitization of MRTX1133 by the combination of DT2216 + everolimus was tested in KRAS G12D-mutant PDAC cell lines using colony formation and apoptosis assays. The effects of MRTX1133 and/or DT2216 + everolimus on KRAS signaling and BCL-2 family proteins were assessed by immunoblotting and/or RT-PCR. The functional roles of BIM/NOXA were elucidated via immunoprecipitation (IP) and siRNA knockdown. Triple combination efficacy was evaluated in AsPC1 parental and MRTX1133-resistant xenografts, with pharmacodynamic effects confirmed by immunoblotting and immunohistochemistry. Results: The triple combination leads to significantly greater colony growth inhibition and apoptosis induction as compared with single agents or two-drug combinations in multiple KRAS G12D-mutant PDAC cell lines. Mechanistically, MRTX1133 treatment increased BIM and decreased NOXA levels, and the combination of DT2216/everolimus simultaneously enhanced BIM release and stabilized NOXA. In vivo, DT2216/everolimus combination significantly potentiated the anti-tumor activity of MRTX1133 in the AsPC1 PDAC xenograft model. Furthermore, the triple combination effectively overcame acquired MRTX1133 resistance in vitro and in the AsPC1 xenograft model. Conclusions: Collectively, our findings suggest that the combination of DT2216/everolimus potentiates the anti-tumor efficacy of MRTX1133 associated with enhanced apoptosis induction and inhibition of compensatory survival signaling. Full article

Background: Clotrimazole (CLZ) is an approved antifungal with reported pleiotropic effects. Beyond its antifungal use, CLZ can perturb glycolytic flux and ionic homeostasis, motivating its evaluation as a repurposing candidate in oncology. Objective: We aimed to evaluate CLZ and nitazoxanide (NTZ) as drug repurposing candidates for pancreatic ductal adenocarcinoma (PDAC) in comparison with standard chemotherapeutics gemcitabine (GEM) and 5-fluorouracil (5-FU). Methods: T3M4 PDAC cells were treated (0.1–100 µM; 48–72 h) with 5-FU, GEM, CLZ, and NTZ. Cell viability (MTT) and morphology were assessed, and CLZ-based combinations were analyzed by the Chou–Talalay method. In silico studies provided physicochemical descriptors and ADMET profiles, along with predicted interactions with relevant bioorganic targets (e.g., KCa3.1/KCNN4 ion channels). Results: CLZ produced marked cytotoxicity at 72 h (IC₅₀ ≈ 9 µM) and achieved a greater reduction in cell viability at higher concentrations compared to 5-FU and GEM under identical conditions, whereas NTZ showed modest and inconsistent effects. CLZ combinations with 5-FU or GEM were mainly antagonistic. In silico analyses indicated high membrane permeability and suggested potential interactions with KCa3.1, supporting a hypothesis-generating interpretation of the observed in vitro effects. Conclusions: Within a drug repurposing framework, CLZ exhibited consistent cytotoxic activity as a single agent in a PDAC cell model, whereas NTZ revealed limited effects and CLZ-based combinations were not beneficial under the tested conditions. These findings position CLZ as a monotherapy-oriented repurposing candidate for PDAC and motivate further mechanistic and translational studies to clarify the biological basis of its in vitro activity. Full article

Background/Objectives: TP53 mutation or deletion status is important for determining cellular responses to DNA-damaging drugs. Oxaliplatin (OXA) is combined with the fluoropyrimidine (FP) drug 5-fluorouracil (5-FU) in the FOLFOX regimen used to treat advanced colorectal cancer (CRC). However, the effects of TP53 deletion on 5-FU + OXA synergy are not well known. We investigated potential synergy between OXA and 5-FU and compared it with OXA synergy with a novel polymeric FP, CF10, in four cell lines harboring either wild-type (WT) or TP53-null status. Methods: Using CompuSyn and the highest single agent (HSA) models, we compared synergy between CF10 and OXA (COXA) and between 5-FU and OXA (FOXA). Cell cycle analysis was performed, as was Western blot quantification of canonical DNA damage pathway proteins. Likewise, immunofluorescent and confocal analysis allowed us to compare topoisomerase 1 cleavage complex and double-strand DNA break formation. Results: COXA synergy displayed minimal TP53 dependence with greatly improved potency compared to FOXA. COXA synergy resulted from OXA increasing: (i) Topoisomerase 1 (Top1) cleavage complex formation; (ii) DNA double-strand breaks (DSBs), and (iii) Checkpoint Kinase 1 and 2 (p-Chk1/2) phosphorylation, consistent with increased replication stress. Additionally, increased S-phase entry in TP53-null cells enhanced synergy between CF10, 5-FU, and OXA as S-phase drugs. Conclusions: Our results demonstrate that OXA synergizes with CF10 more effectively than with 5-FU through enhanced replication stress in both WT and TP53-null cells by causing greater Top1-mediated DNA double-strand breaks. Our studies provide a foundation for further testing of this combination in an orthotopic liver metastatic setting and eventual clinical development. Full article

Dynamic wavefront control plays a crucial role in advancing terahertz (THz) high-precision non-destructive testing, wireless communication and high-resolution imaging. However, existing approaches to THz dynamic wavefront control suffer from inherent limitations, such complex structures, narrow operational bandwidth, and the ability to tune only a single function, significantly restricting their practical applications. To overcome these challenges, we propose a dynamic reflective THz metasurface based on nested split-ring unit cells. The nested unit cell consists of an outer double-split VO₂ ring resonator and an inner single-split aluminum ring deposited on a central VO₂ circular patch. By, respectively, rotating the inner and outer rings in the insulator and metal states of VO₂, independent full 2π phase coverage at 1.07 THz can be achieved in both VO₂ states while maintaining high polarization-conversion efficiency with a PCR exceeding 0.98, thereby enabling efficient dynamic wavefront control. Using these unit cells, we constructed three distinct reflective metasurfaces that, respectively, generate broadband focusing beams with tunable focal lengths, broadband vortex beams with different topological charges, and a broadband beam that can be switched between focusing and vortex modes by changing the state of VO₂. The design offers considerable flexibility for developing compact, multifunctional THz devices, with promising potential for integrated THz systems, high-capacity communications, and high-resolution imaging. Full article

Green-synthesis routes for producing CuO nanoparticles offer a simplified, sustainable, and low-cost replacement for conventional chemical methods, eliminating the need for harsh chemicals and providing an easily scalable process for industrial-level production. Although numerous studies have investigated synthesizing CuO nanoparticles from single plant extracts, comparative assessments of multi-plant-mediated CuO nanoparticles alongside synthetic CuO remain limited. In this work, CuO nanoparticles were green-synthesized from three different plant sources, namely ginger, red onion peels, and garlic, and their physicochemical and biological properties were tested against the synthetic CuO. All plant extracts produced pure-phased monoclinic CuO nanoparticles as confirmed by UV–Vis, XRD, FTIR, and SEM/EDX analyses. SEM showed distinct nanoparticle morphologies, with CuO from ginger extract exhibiting uniform nanocubes, while nanoparticles from red onion and garlic extracts exhibited more aggregated and irregular structures. Their crystallite sizes were 8–9 nm lower than the ~11 nm observed for the synthetic CuO, highlighting the phytochemical role in shaping the nanoparticles’ morphology. The antibacterial efficacy against S. aureus and E. coli showed that ginger-derived and synthetic CuO had the strongest bacterial inhibition and bactericidal potency compared to onion- and garlic-derived CuO samples. However, synthetic CuO had the highest cytotoxicity risk, hindering its suitability for biological uses, while CuO-ginger maintained good cell viability at moderate concentrations. CuO-onion and CuO-garlic gave lower antibacterial cytocompatibility performance due to their thicker capping layers, which led to decreased Cu²⁺ release and ROS production. Ginger-derived CuO achieved an optimal trade-off between antibacterial and cytotoxic efficiency, highlighting its prospects as a candidate for biomedical applications. Full article

Background/Objectives: Ofatumumab is a fully human anti-CD20 monoclonal antibody approved for the treatment of relapsing forms of multiple sclerosis (MS). While its efficacy and safety have been demonstrated in clinical trials, real-world data focusing on laboratory changes and detailed immunophenotyping during treatment remain limited. The objective of this study was to assess routine laboratory parameters and immunophenotyping profiles in ofatumumab-treated patients in a real-world setting. Methods: We conducted a retrospective, single-center real-world study including 59 patients with relapsing–remitting MS treated with ofatumumab. Routine laboratory parameters were analyzed at the baseline and 6–12 months after treatment initiation. Immunophenotyping by flow cytometry was available for a subset of 29 patients. Infections were assessed during a follow-up period of at least six months. Paired comparisons were performed using the Wilcoxon signed-rank test. Results: Ofatumumab induced a profound and sustained depletion of CD19+ B cells (p < 0.001). Total T cells, CD4+ and CD8+ T-cell counts, the CD4/CD8 ratio, and natural killer (NK) cells remained largely stable over time. NK cells and helper T cells showed a numerical increase without statistical significance. IgM levels and relative lymphocyte percentages showed a statistically significant decrease compared with baseline (p = 0.047 and p = 0.016, respectively), while remaining within reference ranges. Other routine laboratory parameters remained stable. Reported infections were infrequent and predominantly mild. Conclusions: In this real-world cohort, ofatumumab demonstrated a favorable immunological and laboratory profile consistent with its known mechanism of action. These findings suggest that routine laboratory monitoring is sufficient for most patients, while immunophenotyping may be reserved for selected clinical scenarios. Further prospective studies integrating clinical and radiological outcomes are needed to better define the clinical relevance of these immunological findings. Full article

In this work, an A-site deficient perovskite, (La_0.3Sr_0.6Ce_0.1)_0.9Co_0.1Ti_0.9O_3−δ (LSCCoT) was applied as an additional catalytic layer on Ni–YSZ anode for biogas-fuelled SOFC. Under reducing conditions, the formation of well-dispersed, socketed Co nanoparticles was observed due to the cobalt exsolution from the perovskite lattice. The structural and microstructural characterization confirmed phase stability of the perovskite after high-temperature reduction in hydrogen and the presence of exsolved nanoparticles on the grains’ surface. Electrical conductivity measurements showed thermally activated semiconducting behavior in air (E_a = 0.582 ± 0.121 eV) and a strongly enhanced conductivity with weak temperature dependence in hydrogen (E_a = 0.057 ± 0.001 eV). Single-cell tests performed under a CH₄/CO₂ (60/40 vol%) biogas mixture revealed a 30% increase in maximum power density at 800 °C compared to the reference cell. During 100 h of operation, the modified cell exhibited reduced performance degradation, improved internal reforming activity, and a more stable outlet gas composition. Full article

Background/Objectives: Tissue-agnostic therapy has transformed oncology by enabling treatment selection based on molecular alterations rather than tumor origin. Since 2017, nine U.S. Food and Drug Administration approvals across six biomarker classes have defined this paradigm. Thoracic and head and neck (H&N) cancers have been underrepresented in the registrational evidence supporting these approvals. This review systematically evaluated biomarker representation, histologic distribution, and clinical applicability of tissue-agnostic therapies in thoracic and H&N malignancies. Methods: A narrative systematic review was conducted using PubMed, ClinicalTrials.gov, and regulatory documents for all tissue-agnostic approvals between January 2017 and October 2025. Data were extracted from pivotal trials, including total enrollment, objective response rate (ORR), histologic distribution, and thoracic/H&N representation. Emerging biomarkers and resistance mechanisms were assessed from phase I–III studies and basket trials. Results: Nine tissue-agnostic approvals encompassing six biomarkers were identified: MSI-H/dMMR, TMB-High, NTRK, RET, BRAF V600E, and HER2 (IHC 3+). Across pivotal datasets (3800 patients), thoracic and H&N cancers accounted for fewer than 8% (n = 290) of enrolled patients. Thoracic representation was dominated by non-small-cell lung cancer (NSCLC) in RET, NTRK, and HER2 programs (150 patients, 4%), while small-cell lung, mesothelioma, and thymic carcinomas contributed <1% combined. H&N cancers comprised 140 patients (3–4%), primarily secretory salivary carcinoma in NTRK trials (n = 12–20), thyroid carcinoma in BRAF (n = 36) and RET (n = 45) programs, and rare HER2-positive salivary duct carcinomas. Conventional HNSCC and sinonasal cancers were limited to 1–2 cases per trial. Only two of nine trials (22%) reported prespecified CNS endpoints, and RNA-based fusion testing was employed in <40%, underscoring diagnostic variability and limited applicability. Conclusions: Although tissue-agnostic therapy has expanded the reach of precision oncology, thoracic and H&N cancers remain underrepresented in registrational evidence. Most approvals rely on single-arm basket studies with small, heterogeneous subsets that preclude histology-specific conclusions. Future research should prioritize histology-enriched trial designs, standardized molecular diagnostics, and real-world validation to establish reliable, equitable standards of care for these underrepresented malignancies. Full article

The ability of Rhodotorula toruloides DSM 4444 to metabolize low-cost carbon sources such as fatty acids was comprehensively studied. This organism is shown, for the first time, to simultaneously accumulate microbial oils (biofuel precursors) and carotenoids from acetic acid obtained from CO₂ fermentation. This fatty acid is typically the single end product of acetogenic bioconversion of one-carbon gas pollutants (e.g., CO₂ and CO). In the first set of experiments, different aerobic fermentations were carried out in automated bioreactors, with acetic acid in one case and with glucose, a more conventional carbon source, as a control, in another bioreactor. R. toruloides consumed around 80 g/L substrate under both conditions. Maximum lipid content (27.2% g/g dry weight) was reached from 38 g/L glucose, while carotenoid content was higher with acetic acid (1.4 mg/g cell after 54.1 g/L acetic acid consumed), representing a 40% increase compared to glucose (1.0 mg/g cell after 64.2 g/L glucose consumed). Additionally, in the second set of assays, a fermented broth produced by Acetobacterium woodii from CO₂ fermentation, containing residual nutrients and metabolites, was tested. Despite its complex composition, R. toruloides grew and produced carotenoids (up to 0.141 mg/g), showing potential adaptability. To the best of our knowledge, this is the first report on a greenhouse gas-based biotechnological process as a promising sustainable alternative for the valorization of pollutants, e.g., gas emissions, their bioconversion to VFAs, such as acetic acid, and subsequent fermentation of the carboxylic acid into microbial oils, as a source of renewable energy, as well as carotenoids as a high-value nutraceutical product. Full article

Growing interest in natural therapies has increased the demand for essential oils; however, the complex interactions within their mixtures that dictate their final efficacy remain poorly understood. This study aimed to optimize a blend of ginger, cinnamon, tea tree, and geranium essential oils to develop an active ingredient, with synergistic multifunctional bioactivities, that was relevant to cutaneous healing. Initially, the composition and cytotoxicity for individual oils were determined; subsequently, a D-optimal mixture design was employed to evaluate three biological responses related to skin recovery: ultraviolet B radiation absorption, red blood cell lysis inhibition, and catalase enzyme activity. GC-FID analysis revealed the following major components (% w/w): cinnamon (cinnamaldehyde, 77.56%), ginger (α-zingiberene, 33.77%), geranium (citronellol, 33.6%), and tea tree (terpinen-4-ol, 38.38%). Dose–response data from essential oils tested against Detroit ATCC 551 skin fibroblasts revealed a clear cytotoxic hierarchy (IC₅₀ µg/mL): cinnamon (21.03) > ginger (25.3) > tea tree (41.67) > geranium (92.51). Cinnamaldehyde content was the primary contributor to photoprotective capacity, with a maximum sun protection factor (SPF) of 4.5. Inhibition against erythrocyte membrane lysis was not attributable to a single component; maximum protection (98.4%) was achieved through synergy between oxygenated monoterpenoids (geranium and tea tree), sesquiterpenes (ginger), and aromatic aldehydes (cinnamon). Highest catalase activity (160.86 kU/g Hb) was reached in mixtures with high cinnamaldehyde and eugenol contents, whereas an antagonistic effect was observed between tea tree and geranium oils. Finally, an optimal formulation (desirability = 0.927) was identified (% w/w): 31.7% ginger, 39.1% cinnamon, 14.5% tea tree, and 14.7% geranium. Experimental validation confirmed no significant difference compared with developed predictive models. This optimized mixture constitutes a bioactive natural component with potential for use in products aimed at promoting skin health, warranting further investigation into direct models of skin healing. Full article