Search Results (391)

Coastal wetlands play important environmental roles. However, their hydrogeomorphological dynamics remain poorly understood under scenarios of extreme climate events. The aim of this study was to characterize the temporal and spatial variability of hydrogeomorphological attributes (vegetation, water, and soil) in the wetlands of Lagoa do Peixe National Park, Brazil. The methodology involved applying Principal Component Analysis (PCA) in both temporal (T) and spatial (S) modes, decomposing spectral indices for each attribute to identify variability patterns. The results revealed that vegetation and water are strongly correlated with seasonal dynamics influenced by ENSO (El Niño/La Niña) events. Soils reflected their textural characteristics, with a distinct temporal response to the water balance. PCA proved to be a useful tool for synthesizing large volumes of multitemporal data and detecting dominant variability patterns. It highlighted the Lagoon Terraces and the Lagoon Fringe, where low slopes amplified hydrological variations. Temporal variability was more responsive to climate extremes, with implications for ecosystem conservation, while spatial variability was modulated by geomorphology. Full article

Glioblastoma is a highly aggressive brain tumor with an overall poor prognosis due to its immunosuppressive tumor microenvironment (TME). Microglia and tumor-associated macrophages (TAMs) with pro-tumorigenic properties are dominant populations of immune cells in the glioblastoma TME. To date, several studies targeting TAMs to fight tumor progression in different tumor entities have been initiated. However, the impact of standard therapy schemes of glioblastoma cells on macrophage polarization, activation, and phagocytosis remains controversial. The same applies to the relevance of PD-1/PD-L1 blockade in the interaction between macrophages and tumor cells. Our study, therefore, investigated patient-oriented treatment of GLIOBLASTOMA by examining the phagocytic capacity of polarized M1- and M2-like macrophages using GL261-luc2 tumor cells as a preclinical model system. Additionally, we analyzed the expression of activation and immune checkpoint markers on these macrophage subtypes following contact with tumor cells and their microenvironment. These factors were also determined after PD-1 blockade was initiated. The analyses revealed that the immunoregulatory M2-like macrophages generally exhibited a higher phagocytosis rate than the pro-inflammatory M1-like macrophages; however, this was not influenced by the pretreatment of glioblastoma cells with chemo- or radiotherapy. This could not be improved by blocking the PD-1 receptor. Furthermore, there were no modulations in the expression of differentiation, activation, or immune checkpoint molecules of M1- and M2-like macrophages after cell-to-cell contact with glioblastoma cells. But the medium conditioned by tumor cells strongly altered M1-like macrophages toward a more activated state, whereas M2-like cells were only mildly influenced. This was further enhanced by tumor cell treatment, with the most prominent effect after irradiation. These results suggest that conventional GLIOBLASTOMA tumor cell treatment affects the immunogenic status of macrophage subtypes, which is relevant for enhancing the anti-tumor immune response in brain tumors. Full article

The dynamics of large lake circulations are strongly modulated by wind forcing, thermal gradients, and shoreline topography, yet their integrated effects remain insufficiently quantified. To address this, numerical simulations were conducted in Lake Biwa to clarify the mechanisms underlying wind- and thermally driven gyres, with a focus on the influence of bathymetric asymmetry. In wind-driven cases, zonal and meridional wind stress gradients were imposed, revealing that cyclonic wind shear generated strong surface vorticity (up to 2.0 × 10⁻⁶ s⁻¹) in regions with gently sloped shores, while steep slopes suppressed anticyclonic responses. Cyclonic forcing induced upwelling in the lake center, with baroclinic return flows stabilizing the vertical circulation structure. In windless thermal experiments, surface temperature gradients of ±2.5 °C were applied to simulate seasonal heating and cooling. Cyclonic circulation predominated in warm seasons due to convergence and heat accumulation along gently sloping shores, whereas winter cooling produced divergent flows and anticyclonic gyres. The southern and eastern lake margins, characterized by mild slopes, consistently enhanced convergence and vertical mixing, while steep western and northern slopes limited circulation intensity. These results demonstrate that shoreline slope asymmetry plays a decisive role in regulating both wind- and thermally induced circulations, offering insights into physical controls on transport and stratification in enclosed lake systems. Full article

Background: In burn injuries, wound healing effectiveness is complex and influenced significantly by the local biochemical environment and the physicochemical properties of topical preparations. pH lesions modulation can influence protection barrier integrity, inflammatory responses, and microbial colonization. Their antioxidant, antimicrobial, and anti-inflammatory properties, of the topical formulations enriched with plant extracts have demonstrated promising results. Objective: The aim of the study was to develop and characterize topical oleogel and hydrogel formulations containing ethanolic and hydroalcoholic extracts of medicinal plants (Boswellia serrata, Ocimum basilicum, Sambucus nigra, and Galium verum), and to evaluate the impact of their physicochemical properties, rheological behavior, in contrast with the wound pH modulation, and healing efficacy in an experimental burn model. Methods: Second-degree burns were induced uniformly on Wistar rats using the validated RAPID-3D device. All formulations were applied daily for 21 days, and wound healing was assessed through several measurements specific to the wound surface, skin temperature, pH, and, last but not least, histological analyses. Formulations’ physicochemical and rheological properties, including pH, viscosity, and spreadability, were also analyzed and systematically characterized. Results: Oleogel formulations demonstrated superior wound healing performance compared to hydrogels. Formulations containing Boswellia serrata and Ocimum basilicum extracts significantly reduced wound size, inflammation, and melanin production by days 9 and 21 (p < 0.05). The beneficial outcomes correlated strongly with formulation acidity (pH < 6), high viscosity, and enhanced thixotropic behavior, indicating improved adherence and sustained bioactive compound release. Histological evaluations confirmed enhanced epithelialization and reduced inflammation. Conclusions: Particularly Boswellia serrata and Ocimum basilicum in oleogel formulations in ethanolic solvent effectively modulated wound pH, enhanced topical adherence, and improved burn wound healing. These findings highlight their potential clinical application and justify further clinical investigations. Full article

Compelling clinical evidence strongly indicates that anti-angiogenesis therapeutics including Bevacizumab, a humanised anti-VEGF mAb, can alleviate the resistance to immunotherapy. We explored the direct modulation of Bevacizumab on endothelial cell (EC) immune response including surface expression of adhesion and MHC molecules and EC-elicited proliferation of immune cells under inflammatory conditions. Flow cytometry showed that addition of VEGF inhibited TNF-α stimulation of expression of ICAM-1 and VCAM-1 on HUVECs, whereas Bevacizumab enhanced this TNF-α-stimulated expression. The presence of MHC Class I on HUVECs was decreased by VEGF and increased by TNF-α, respectively. Bevacizumab reversed VEGF downregulation and promoted TNF-α upregulation of MHC class I expression, suggesting that anti-VEGF treatment can boost the endothelial immunological reaction, a prerequisite for immune cell trafficking. Functionally, real-time monitoring of the proliferation of human PBMCs co-cultured on HUVEC monolayers over 3 days showed opposing effects on the proliferation of PBMCs between VEGF and TNF-α. Consistently, Bevacizumab antagonised VEGF suppression and sensitized TNF-α activation of PBMC growth over the time course. In line with these findings, Bevacizumab increased the surface expression of CD69 on VEGF-treated T cells collected from PBMCs after 3-day co-cultures with HUVECs. Furthermore, the proliferation of CD3+, CD8+ and CD4+ T cells was promoted via Bevacizumab. Collectively, this study demonstrates that targeting VEGF can enhance the immune response of ECs required for T cell recruitment. Our findings provide insights to a deeper understanding of increased vascular inflammatory response conferred by anti-VEGF treatment in addition to inhibiting angiogenesis, which supports its favourable dual role in the positive immunological synergism with immunotherapy. Full article

Elderly individuals infected with SARS-CoV-2 are at higher risk of developing cytokine storms and severe outcomes, yet specific biomarkers remain unclear. In this study, we investigated the alteration of primary bile acid metabolism in elderly patients with severe COVID-19 using untargeted metabolomics (n = 31), followed by targeted metabolomics to compare patients with disease progression (n = 16) to those without (n = 48). Significant reductions in chenodeoxycholic acid (CDCA) and glycochenodeoxycholic acid (GCDCA) levels were identified in severe cases, with GCDCA levels at admission correlating strongly with peak inflammatory markers. In vitro, CDCA, GCDCA, and their receptors, Farnesoid X Receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5), effectively inhibited the inflammatory response induced by SARS-CoV-2. NOD-like receptor pathway, activated by SARS-CoV-2, may modulate inflammatory cytokines under the treatment of CDCA, GCDCA, and TGR5. CDCA and GCDCA levels at admission predicted disease progression, suggesting their potential as biomarkers for severe COVID-19 in the elderly and highlighting their regulatory role in inflammation, pointing to new therapeutic avenues. Full article

This study investigates the influence of chirality on the dynamic susceptibility of concentric nanotori via micromagnetic simulations. The aim is to analyze the ferromagnetic resonance characteristics of coupled nanotori structures and compare them across various ring separation distances, thus providing an insight into how vortex configurations with identical or differing chiralities affect their dynamic properties. We analyze the energetic differences between the two vortex configurations and find them to be negligible; however, these minor differences suffice to explain the significant discrepancies in the demagnetization field observed between the nanotori. We examine the dynamic susceptibility spectrum and the spatial localization of the ferromagnetic resonance modes for different nanotori separations. Our findings demonstrate that the resonant oscillation frequencies are significantly influenced by the magnetostatic interactions between the nanotori, which can be effectively modulated by varying the distance between them. Furthermore, for smaller separations, the frequency peaks in the dynamic susceptibility markedly diverge between the two vortex configurations, demonstrating that the observed differences in the demagnetization field between the rings strongly influence the frequency response. In summary, our results indicate that both the inter-ring distance and the vortex configuration play a crucial role in determining the frequency response of the system. Full article

Objectives: Innate lymphoid cells (ILCs) and natural killer (NK) cells represent a diverse group of innate immune populations that modulate immune responses and tissue equilibrium across various diseases, including cancer. In the present study, we analyzed single-cell RNA sequencing (scRNA-seq) data to explore the landscape and functional status of ILC subsets in patients with head and neck squamous cell carcinoma (HNSCC). Methods: The GSE164690 dataset, which includes preprocessed scRNA-seq and clinical data, was acquired from the Gene Expression Omnibus database. The Cancer Genome Atlas database was used to develop the survival prediction model. Results: A total of 95,809 immune cells were clustered into 16 immune cell clusters, among which 7278 NK cells were further subdivided into 11 clusters. Among the 11 clusters, eight NK cell clusters, two intraepithelial ILC1 (ieILC1) clusters, and one ieILC1–NK-intermediate (ieILC1-NK-int) cluster were identified. Among the ieILC1/NK clusters, ieILC1-1 exhibited the highest immunological activity and was mainly derived from human papillomavirus-positive samples. Further, ieILC1s showed higher enrichment of pathways related to inflammation and effector functions—such as inflammatory response, interferon-gamma response, and interferon-alpha response—compared to the other clusters. Moreover, we developed prognostic prediction models based on differentially expressed genes in the ieILC1/NK clusters. Risk scores of the ieILC1-1, ieILC1-NK-int, and NK clusters were identified as independent prognostic factors for shorter overall survival (OS) and progression-free survival (PFS). Recursive partitioning revealed that combining ieILC1-1 and the NK clusters strongly predicted shorter OS and PFS. Conclusions: Our findings highlight the diverse landscape and prognostic significance of ieILC1/NK cells in patients with HNSCC. Full article

Background/Objectives: Nocturnal glucose regulation is a critical but underexplored determinant of next-day fasting glucose (FG), particularly in individuals with dysglycemia. This study examined the role of glucose levels after the last eating occasion (LEO) and during the overnight fast in predicting FG, considering the potential influence of carbohydrate content in LEO and insulin sensitivity. Methods: In a controlled 24 h protocol, 33 adults (50–75 years) with prediabetes or diet-controlled type 2 diabetes followed a standardized feeding schedule with meals at fixed times, including a LEO at 10:00 p.m. Continuous glucose monitoring was used to assess glucose during the 3 h postprandial period (LEO-PPGR) and two fasting intervals: chronological overnight fast (COF) and biological overnight fast (BOF). Associations with FG were tested using general linear models, adjusting for carbohydrate intake and insulin sensitivity (Matsuda index). Results: Glucose responses during LEO-PPGR—assessed by mean glucose, peak, and AUC—were strongly correlated with FG the next morning (r = 0.704, 0.535, and 0.708, p < 0.001). Similarly, glucose levels during COF and BOF were also correlated with FG (r = 0.878, p < 0.001 for both), but these associations weakened after adjustment for LEO carbohydrate content. The Matsuda index was positively correlated with glucose in all three periods (p < 0.05), yet its inclusion in the model attenuated all previously significant associations with FG. Conclusions: These findings suggest that the glycemic response to the last meal and subsequent overnight glucose levels contribute to next-day FG, but their impact is modulated by carbohydrate content and individual insulin sensitivity. Understanding nocturnal glycemic dynamics may inform strategies for improving metabolic outcomes in dysglycemia. Full article

Respiratory viruses continue to present serious health challenges to human wellness. Growing evidence suggests that the more severe and damaging effects and symptoms of influenza, rhinovirus (RV), respiratory syncytial virus (RSV), and COVID-19 may primarily result from their common ability to disorganize the body’s healthy immune response. The simultaneous over-stimulation of several reactive oxygen species (ROS) pathways and concurrent suppression of bioavailable Nitic Oxide (NO) contribute to an immune disbalance that can lead to cellular oxidative distress and an excessive inflammatory response. This study evaluated the real-time, acute ability of a single, orally administered 50 mg encapsulated dose of a plant-based dietary supplement (“PB-Blend”), compared to 1000 mg of Vitamin C as a positive control, to modulate multiple ROS associated with a dampened immune response, as well as NO and other markers of inflammation, in a cohort recovering from a moderate course of COVID-19. This randomized, double-blind study was performed on 28 individuals 18–24 days after a moderate COVID-19 infection. Participants were orally supplemented with a single encapsulated dose of either 50 mg of PB-Blend or 1000 mg Vitamin C as a positive control. Changes in the levels of bioavailable NO (measured as circulating NOHb) were assessed, as well as the ex vivo cellular formation of mitochondrial, NOX2-, iNOS-, and TNFα-dependent ROS. All parameters were measured in real time before ingestion (baseline), and then at 30, 60, 120, and 180 min after administration. ROS were measured using a portable electron paramagnetic resonance (EPR) spectrometer. Inflammatory, immunity (hsCRP and TNFα plasma levels), interleukin (IL1, IL6, IL8, and IL10), cytokine (IFNγ, TNFα, and NF-κB), and immunoglobulin (IgA, IgM, IgG, and IgE) profiles were also followed. In addition to laboratory and cell function investigations, we performed clinical cardio ergometry, blood O₂ saturation, and respirometry examinations. As hypothesized, the collected baseline data from this study group confirmed that mitochondrial, NOX2, and iNOS enzymatic systems were strongly involved in the generation of ROS at 18–24 days following a positive COVID-19 PCR test. Acute single-dose supplementation of 50 mg PB-Blend had a multifunctional impact on ROS and significantly inhibited the following: (a.) mitochondrial ROS levels by up to 56%; (b.) iNOS by up to 60%; and (c.) NOX2-dependent ROS generation by up to 49%. Moreover, 1000 mg Vitamin C supplementation exhibited narrower ROS-mitigating activity by solely inhibiting NOX2-dependent ROS generation by 45%. Circulating NOHb levels were significantly increased after PB-Blend administration (33%), but not after Vitamin C administration. PB-Blend and Vitamin C exhibited similar potential to reduce ex vivo high dose TNFα (200 ng/mL)-induced H₂O₂ formation. These results suggest that 50 mg of PB-Blend has the potential to modulate disbalanced mitochondria, iNOS, and NOX2 enzymatic systems that can be engendered during respiratory viral infection and subsequent recovery. Moreover, PB-Blend, but not Vitamin C, showed potential to upregulate bioavailable NO, which is known to decline under these conditions. Based upon these observations, PB-Blend could be considered an alternative to, or to be used in tandem with Vitamin C in applications that promote immune support and recovery during seasons of heightened respiratory viral risk (e.g., “flu season”). Full article

Ethylene-insensitive 3/ethylene-insensitive 3-like (EIN3/EIL) transcription factors are central regulators of ethylene signaling and stress adaptation in plants. However, their roles in Osmanthus fragrans, a globally cherished ornamental and aromatic plant with significant economic value, remain poorly characterized. Here, we identified nine OfEIL genes across eight chromosomes in the O. fragrans “Liuye Jingui” genome. Conserved motif analysis revealed core domains (Motif1/2/4/7), and promoter cis-elements highlighting hormone-related, stress-related, and growth-related regulatory potential. During late flowering stages, six OfEILs (3/4/5/6/7/9) were significantly upregulated. Under 5-azacytidine (AZA, a DNA demethylation agent), OfEIL2 and OfEIL7 were downregulated, whereas the ETH treatment activated OfEIL3/7/8/9. Strikingly, OfEIL7 exhibited dual regulatory roles, correlating strongly with natural flowering progression, AZA-induced demethylation, and ETH responses. Functional divergence was observed in petal senescence, with OfEIL2–5 and OfEIL7–9 showing stage-specific and tissue-specific expression patterns. These results position OfEIL7 as a key hub integrating epigenetic and hormonal signals to modulate floral longevity and stress adaptation. Our study provides the first genome-wide characterization of the EIL family in O. fragrans, offering critical insights for molecular breeding aimed at enhancing ornamental traits and environmental resilience in this economically significant species. Full article

Acne vulgaris is a common dermatological condition strongly associated with disruptions in the skin microbiota, specifically involving key species such as Cutibacterium acnes and Staphylococcus epidermidis. This study investigates the efficacy of SkinDuo^TM, a topical probiotic containing Lactiplantibacillus plantarum, in modulating the skin microbiota and improving clinical outcomes in patients with acne vulgaris. Over a 4-week to 8-week observational study period, microbial composition and diversity shifts were analyzed using full-length 16S rRNA sequencing. Patient responses were categorized into “good” responders (showing significant clinical improvement) and “no_change” responders (with minimal or no improvement). SkinDuo^TM treatment resulted in lower post-treatment Cutibacterium acnes abundance in the “good” group compared to the “no_change” group. The “good” group maintained a stable level of alpha diversity following treatment. In contrast, the “no_change” group exhibited a marked reduction in microbial diversity. Beta diversity analysis revealed distinct clustering patterns associated with improved clinical outcomes. These findings suggest that the preservation of microbial richness and evenness may serve as a potential biomarker for positive response to probiotic therapy. This study highlights the potential of SkinDuo^TM to restore microbial balance and alleviate acne symptoms, contributing to the growing body of evidence supporting microbiome-based therapeutic strategies in dermatology. Full article

Bone fracture activates the immune system and induces inflammation crucial for fracture healing but may also affect trauma-distant organs like the liver. Acute alcohol intoxication (AAI) dysregulates immune responses and affects organ damage post-trauma. However, the bone–liver axis and alcohol’s role in this process remain poorly understood. This study explores liver inflammation and damage following fracture, with and without prior AAI. Twenty-four male C57BL/6J mice were randomly assigned to four groups (n = 6) and received either NaCl (control) or 35% ethanol via gavage. Mice underwent femur osteotomy with external fixation or sham surgery. After 24 h, liver damage was assessed using hematoxylin–eosin and activated caspase-3 staining. Liver inflammation was evaluated through CXCL1 and polymorphonuclear leukocyte (PMNL) immunostaining, cytokine gene and protein expression analyses, and immune cell profiling in the liver via flow cytometry. Western blotting assessed NF-κB and Wnt signaling. Neither fracture alone nor with AAI caused significant liver damage. However, fracture significantly increased PMNL infiltration and altered monocyte populations, effects that were amplified by AAI. The hepatic neutrophil-to-monocyte ratio significantly decreased after fracture and was absent in the fracture AAI group. CXCL1 increased post-fracture, while MCP-1 and IL-10 decreased significantly, with AAI further significantly amplifying these changes. Wnt1 and Wnt3a levels increased significantly after fracture and were further strongly elevated by AAI. AAI completely abolished fracture-induced significant β-catenin reduction and significantly increased its phosphorylation, effects that potentially involve an AAI-induced β-catenin stabilization as well as its increased degradation. NF-κB activation was significantly decreased, while A20 expression significantly increased after fracture and AAI. Fracture influences the inflammatory liver response and signaling pathways, effects which were further modulated by AAI. Full article

A detailed characterization of evapotranspiration (ET) patterns is of paramount importance for optimizing irrigation scheduling and enhancing water-use efficiency in the North China Plain. To delve into this, a two-season study was conducted at the National Experimental Station for Precise Agriculture in Beijing. Using 12 weighing lysimeters, the study compared two summer maize varieties with contrasting canopy sizes: Jingke 968 (JK), characterized by a large canopy, and CF 1002 (CF), with a small canopy. The comprehensive analysis yielded the following significant findings: (1) The daily average ET rates exhibited consistent trends across cultivars, yet with notable disparities in magnitude. JK consistently demonstrated higher water consumption throughout the growth seasons. In the first season, at the V13–R1 stage, the peak daily ET of JK and CF reached 5.91 mm/day and 5.52 mm/day, respectively. In the second season, during the R1–R3 stage, these values were 5.21 mm/day for JK and 5.22 mm/day for CF, highlighting the nuanced differences in water use between the varieties under varying growth conditions. (2) Regardless of canopy size, the hourly ET fluctuations across different growth stages followed similar temporal patterns. However, the most striking inter-varietal differences in ET emerged during the R1–R3 reproductive stages, when both cultivars had achieved peak canopy development (leaf area index, LAI > 4.5). Notably, the ET differences between JK and CF adhered to a characteristic diurnal “increase–decrease” pattern. These differences peaked during mid-morning (09:00–11:00) and early afternoon (13:00–15:00), while minimal divergence was observed at solar noon. This pattern suggests complex interactions between canopy structure, microclimate, and plant physiological processes that govern water loss over the course of a day. (3) Analysis of the pooled data pinpointed two critical time periods that significantly contributed to the cumulative ET differences between the varieties. The first period was from 12:00–17:00 during the R1–R3 (anthesis) stage, and the second was from 08:00–16:00 during the R3–R5 (grain filling) stage. JK maintained significantly higher transpiration rates (Tr) compared to CF, especially during the morning hours (09:00–12:00). On average, the Tr of JK exceeded that of CF by 5.3% during the pre-anthesis stage and by 16.0% during the post-anthesis stage. These observed Tr differentials strongly indicate that canopy architecture plays a pivotal role in modulating stomatal regulation patterns. Maize varieties with large canopies, such as JK, demonstrated enhanced morning photosynthetic activity, which likely contributed to increased transpiration. At the same time, both varieties seemed to employ similar midday water conservation strategies, possibly as an adaptive response to environmental stress. In summary, this study has comprehensively elucidated the intricate relationship between the leaf area index and the evapotranspiration of summer maize across multiple timescales, encompassing periodic, daily, and hourly variations. The findings provide invaluable data-driven insights that can underpin the development of precise and quantitative irrigation strategies, ultimately promoting sustainable and efficient maize production in the North China Plain. Full article

Polycystic ovary syndrome (PCOS), a common and multifactorial endocrine disorder in reproductive-aged women, is strongly associated with insulin resistance (IR) and type 2 diabetes mellitus (T2DM), and also affects up to one in four women with type 1 diabetes mellitus (T1DM). The current study explored the potential of Plantago ovata (P. ovata) seed ethanol extract (POEE) to modulate oxidative stress (OS), inflammatory responses, metabolic profiles, and hormonal levels in rat Streptozotocin (STZ)-induced DM and Letrozole (LET)-induced PCOS. Phytochemical analysis measured total phenolic content (TPC) and total flavonoid content (TFC) using HPLC-DAD-ESI MS for compound identification. POEE’s antioxidant activity was evaluated in vitro through DPPH, H₂O₂, FRAP, and NO scavenging assays. Rats received POEE, metformin, or Trolox (TX) for 10 days. PCOS confirmation was achieved via ultrasound and histopathology. Serum levels of OS markers (TOS, TAC, OSI, MDA, AOPP, 8-OHdG, NO, 3-NT, AGEs, and SH), inflammatory markers (NF-κB, IL-1β, IL-18, Gasdermin D, and IL-10), metabolic parameters (fasting blood glucose, lipid profile, and liver enzymes), and hormone levels (LH, FSH, estrogen, testosterone, and insulin) were assessed. Additionally, the Triglyceride–Glucose index (TyG) and HOMA-IR were calculated. POEE had a medium content of polyphenols and a good in vitro antioxidant effect. In vivo, POEE administration in diabetic rats led to a reduction in OS markers and an increase in antioxidant levels, alongside decreases in inflammatory cytokines, blood glucose levels, and transaminase activity and improvements in lipid profile. In the PCOS model, POEE treatment effectively reduced total OS and lowered levels of LH, FSH, and testosterone, while elevating estrogen concentrations and reducing insulin resistance. These therapeutic effects were dose-dependent, with higher doses producing more pronounced outcomes, comparable to those observed with metformin and TX treatment. Full article