Search Results (12,732)

Background: While trefoil factor 3 (TFF3) has been linked to cardiovascular disease, its role in peripheral artery disease (PAD) remains largely unexplored. In this prospective study, we assessed three pre-selected circulating biomarkers and found that TFF3 demonstrated the strongest association with the presence of PAD. Building on this finding, we integrated plasma TFF3 concentrations with clinical characteristics to construct predictive models aimed at identifying individuals with PAD and estimating their risk of major adverse limb events (MALE) over a two-year follow-up period. Methods: A total of 476 individuals were prospectively recruited, including 312 patients with PAD and 164 controls without PAD. At study entry, circulating concentrations of TFF3, oncostatin M (OSM), and brain-derived neurotrophic factor (BDNF) were quantified, and all participants were subsequently monitored for a two-year period. The primary endpoint was the occurrence of MALE within two years, comprising acute limb ischemia, major amputation, or lower extremity revascularization by either open surgical or endovascular approaches. PAD diagnosis served as the secondary outcome and was established by an ankle–brachial index (ABI) ≤ 0.9 or toe–brachial index (TBI) ≤ 0.67 in the presence of reduced or absent pedal pulses. For predictive model development, the cohort was randomly divided into training (70%) and testing (30%) sets. A random forest algorithm incorporating clinical variables and plasma TFF3 levels was developed and optimized using 10-fold cross-validation. Model discrimination was quantified using the area under the receiver operating characteristic curve (AUROC). For prognostic evaluation, patients were classified into low- and high-risk groups based on the optimal ROC-derived probability threshold of 0.60, and MALE-free survival between groups was assessed using Cox proportional hazards regression. Results: Among the three candidate biomarkers evaluated, only TFF3 demonstrated a significant association with PAD. Patients with PAD exhibited higher circulating TFF3 concentrations than those without PAD (7.27 ± 3.36 vs. 5.89 ± 2.67 pg/mL; p < 0.001), whereas OSM and BDNF showed no significant differences between groups. Over the two-year follow-up period, MALE occurred in 28 patients (9%). Predictive models combining plasma TFF3 measurements with clinical variables achieved strong performance for both PAD detection and 2-year MALE risk estimation, yielding AUROCs of 0.79 and 0.85, respectively. Furthermore, patients classified as high risk by the model experienced a significantly increased hazard of MALE during follow-up (HR 1.12, 95% CI 1.10–1.19; p = 0.003). Variable importance analysis revealed that TFF3 was the most influential predictor of MALE, followed by age and smoking history. Conclusions: Combining plasma TFF3 levels with readily available clinical characteristics enabled the development of a predictive model with good discriminatory ability for both PAD diagnosis and estimation of 2-year MALE risk. Such an approach may enhance risk stratification by identifying patients at elevated risk earlier in their disease course, thereby informing decisions related to vascular testing, referral for specialist evaluation, and implementation of targeted treatment strategies. Full article

Background: Background breast features are frequently noted in pathology reports alongside invasive breast cancer but rarely factor into prognosis or treatment decisions. Their relationship to tumor characteristics and patient outcomes remains incompletely characterized. Methods: We conducted a retrospective cohort study of 7603 patients with Stage I–III invasive breast cancer (diagnosed 1991–2022, age < 80 years) from the Joint Breast Cancer Registry in Singapore. Natural language processing (NLP) was applied to 9754 free-text pathology reports to extract co-existing background breast features, with accuracy validated by dual-reviewer assessment of 200 reports. Because background features are most reliably assessed on excision specimens, the primary analytic cohort comprised 3988 patients with available excision pathology reports. Unsupervised hierarchical clustering grouped extracted features into three categories. Associations with tumor characteristics were assessed with multinomial logistic regression and ten-year overall survival by Cox proportional hazards models (median follow-up 9.6 years; 620 deaths). Results: Here, we show that NLP-based extraction of background breast features from routine pathology reports achieves an accuracy of over 90% across features. Lobular neoplasia and benign proliferative changes are associated with less aggressive tumor characteristics, whereas early neoplastic and papillary lesions are more prevalent in HER2-enriched and luminal B tumor subtypes. Benign proliferative changes are associated with better survival in age- and year-adjusted models (hazard ratio 0.91, 95% CI 0.86–0.97), but this association is attenuated after adjustment for stage and subtype. Conclusions: NLP-enabled extraction of background breast features from pathology text is feasible at scale. These features reflect tumor biology but do not independently add prognostic information beyond established clinical variables. Full article

Background: Multiple Myeloma (MM) remains the most common indication for Autologous Stem Cell Transplant (ASCT). ASCT use is disproportionately lower in older adults, Black patients with MM, as well as those living in rural areas and of low socioeconomic status (SES). Low utilization of ASCT is linked to poor outcomes. There are numerous barriers to ASCT access and limited interventions to address disparate outcomes in patients with MM. Methods: This is an ambispective study conducted at a single institution to identify and mitigate barriers to ASCT utilization. In aim one, we retrospectively evaluated ASCT utilization and overall survival (OS) for MM patients accounting for clinical, geographic (Rural Urban Commuting Area—RUCA), and socioeconomic factors (Yost). In aim two, based on the observations of the retrospective study, we conducted a prospective feasibility study to improve access for vulnerable patients with MM (older adults, Black patients, rural and/or Appalachian residence) using a virtual ASCT consultative model with patient navigation, coordinated with local oncology centers. Poisson regression estimated the relative risk of receiving ASCT. OS was calculated from MM diagnosis to the date of death censoring survivors at last contact and analyzed using Kaplan-Meir. Cox proportional hazard models estimated the hazard ratio for risk of death. The multivariable model was built including significant risk factors from the univariable models to estimate the independent effect of each risk factor. Results: Among 1799 patients, median age of diagnosis was 61 (range 17–87), race was self-identified as White (85.6%), Black (13.1%), or other (1.3%) and it was primarily metropolitan (n = 1205, 71.2%) and 1169 (65%) received a transplant. The hazard of death was lower for those who received a transplant (vs. no transplant, HR = 0.63, 95%CI 0.53–0.74, p < 0.001), patients identified as Black (vs. White, HR = 0.66, 95%CI 0.51–0.85, p = 0.001) and higher SES areas (quartile 2–4 vs. quartile 1, HR = 0.69, 95%CI 0.58–0.83, p < 0.001). Prospectively with patient navigation and virtual consultation (n = 35), half of the patients sought virtual consultation, 68% of patients were eligible for transplant, 43% went on to receive ASCT, of which 42% of patients were non-metropolitan and 15% of patients were from an Appalachian county. Using this strategy, no difference was observed in ASCT utilization by age (31% in age > 70 vs. 45% in age 65–70 vs. 78% in age < 65, p = 0.10), geographical area (47% in metro vs. 50% in non-metro, p = 0.99), or race (46% in White vs. 60% in Black, p = 0.66). Conclusions: Implementing patient navigation and virtual transplant consultation can effectively enhance access to ASCT among underserved MM populations while reducing the influence of racial and geographic differences. Full article

Background: Spread through air spaces (STAS) is a recognized histologic pattern of invasion associated with poor prognosis in non-small-cell lung cancer (NSCLC), particularly adenocarcinoma. However, its presence in pulmonary squamous cell carcinoma (SCC), whether primary or metastatic, remains largely unexplored. Given the limited available evidence, this study was designed as an exploratory analysis to evaluate the prevalence and potential prognostic significance of STAS in pulmonary SCC. Material and Methods: In this exploratory retrospective study, we analyzed 57 patients who underwent surgical resection for pulmonary squamous cell carcinoma (P-SCC) at the Department of Thoracic Surgery at the University Hospital Erlangen between 2008 and 2020. The cohort included both primary lung SCC and metastatic SCC to the lung from extrapulmonary sites, primarily from ear, nose, and throat (ENT) tumors. Histological slides were reviewed to assess the presence of STAS, as defined by established morphological criteria. The Chi-square test was used to investigate the presence of STAS. Disease-free survival (DFS) and overall survival (OS) was evaluated using Kaplan–Meier analysis, and the prognostic impact of STAS along other variables were assessed using Cox proportional hazards regression. Results: A total of 57 patients with squamous cell carcinoma (SCC), 22 (39%) had primary lung SCC and 35 (61%) had metastatic SCC from head and neck tumours (ENT). Spread through air spaces (STAS) was detected in 20 patients (35%). Disease-free survival (DFS) differed according to primary tumour location (p-value of 0.009), with higher 1-, 3-, and 5-year DFS in patients with primary lung SCC (86.4%, 77.3%, 63.3%) than in those with head and neck SCC (54.3%, 31.4%, 22.2%). DFS was also significantly higher in patients undergoing solitary resections compared with multiple resections (78.6%, 64.3%, 49.5% vs. 33.3%, 6.7%, not estimable; p-value < 0.001). DFS was slightly longer in STAS-negative patients compared with STAS-positive patients (1-, 3-, 5-year DFS: 64.9%, 51.4%, 40.5% vs. 70%, 45%, not estimable), (median DFS 36 vs. 25 months; p-value of 0.776). Overall survival (OS) was significantly longer in patients with primary lung SCC (median OS 125 months) than in those with head and neck SCC (27 months; p-value of 0.039). STAS-negative patients had also a longer OS than STAS-positive patients (median OS 46 vs. 38 months; HR = 1.11, 95% CI 0.56–2.20; p-value of 0.771). Conclusions: STAS was identified in metastatic pulmonary SCC lesions as well as in primary lung SCC, occurring in approximately one-third of cases. However, due to the limited cohort size and the exploratory univariate design of the study, the prognostic significance of STAS could not be definitively established and requires further investigation in larger, adequately powered studies. Full article

Background and Objectives: The COVID-19 pandemic disrupted cancer diagnosis and treatment pathways worldwide. Glioblastoma is an aggressive primary brain malignancy requiring timely multimodal care. This study evaluated survival outcomes among glioblastoma patients diagnosed before and during the COVID-19 pandemic and prepared a dataset for machine learning-based prediction of 12-month mortality. Materials and Methods: Patients aged ≥20 years diagnosed with glioblastoma between 2018 and 2021 were identified from the SEER database using ICD-O-3 histology codes 9440/3, 9441/3, and 9442/3. Patients were categorized as pre-COVID period (2018–2019) or COVID period (2020–2021). OS and CSS were evaluated using Kaplan–Meier curves, log-rank tests, and Cox regression models. Machine learning models predicted 12-month all-cause mortality using registry variables. Results: The final cohort included 9914 patients; 4819 were diagnosed pre-COVID and 5095 during COVID. Median OS was 11 months pre-COVID and 10 months during COVID; 12-month OS was 44.3% and 41.2%, respectively. Median CSS was 11 months in both periods; 12-month CSS was 46.9% and 44.1%, respectively. COVID-period diagnosis was modestly associated with poorer OS (adjusted HR 1.050, 95% CI 1.006–1.095, p = 0.025) and CSS (adjusted HR 1.048, 95% CI 1.003–1.095, p = 0.035). Machine learning models showed moderate discrimination for 12-month mortality prediction. Conclusions: Glioblastoma patients diagnosed during the COVID period had modestly poorer OS and CSS in conventional survival analyses; however, competing-risk analysis did not show a significant association with cancer-specific death. Registry-based machine learning models provided moderate 12-month mortality prediction, supporting their potential utility for population-level prognostic assessment. Full article

Background and Objectives: Tracheostomy is frequently performed in critically ill patients requiring prolonged invasive mechanical ventilation; however, factors associated with intermediate-term mortality after tracheostomy remain poorly characterized. This study aimed to identify clinical and procedural factors associated with 90-day all-cause mortality after tracheostomy in ICU patients. Materials and Methods: This retrospective multicenter cohort study included 292 adult patients who underwent tracheostomy in two tertiary ICUs between 1 October 2023 and 1 June 2025. Demographic characteristics, admission diagnoses, comorbidities, clinical severity scores, procedural variables, microbiological culture results, and survival data were collected. Univariate analyses, multivariable binary logistic regression, Cox proportional hazards regression, receiver operating characteristic (ROC) analysis, and Kaplan–Meier survival analysis were performed. Results: The overall 90-day all-cause mortality rate was 74.7%. Age, Charlson Comorbidity Index, and APACHE II score were significantly associated with 90-day mortality in univariate analyses, whereas tracheostomy timing and technique were not. In multivariable logistic regression analysis, the Charlson Comorbidity Index and APACHE II score were independently associated with mortality. Cox proportional hazards regression confirmed that both APACHE II score and Charlson Comorbidity Index were independently associated with mortality over time. ROC analysis demonstrated moderate discriminative performance for age, Charlson Comorbidity Index, and APACHE II score. Conclusions: In critically ill patients undergoing tracheostomy, 90-day mortality was high and was driven primarily by acute illness severity and comorbidity burden rather than procedural characteristics. These findings support incorporating biological vulnerability, expected recovery potential, and goals-of-care discussions into tracheostomy decision-making. Full article

Introduction: During the COVID-19 pandemic, drug overdose deaths increased significantly, providing a potential cohort of donor organs. However, graft failure and mortality rates among those receiving organs from donors who died from drug overdose related to the pandemic have not previously been assessed. We compared graft failure and mortality up to one year after transplant of those receiving a kidney or liver pre-pandemic and during the pandemic. Methods: A retrospective analysis between pre-pandemic (1 January 2018 to 31 December 2019) and pandemic (1 January 2020 to 31 December 2021) periods was performed using the United Network for Organ Sharing (UNOS) database. Recipients aged 17 or below and those with multiple-organ transplants were excluded. ANOVA tests for continuous variables and Chi-squared or Fisher’s exact tests were utilized to compare graft failure and mortality of transplant outcomes. The Kaplan–Meier (KM) Product Limit method was employed to estimate transplant outcomes and survival curves. For graft failure analysis, graft survival was the endpoint. For survival analysis, recipient death was the endpoint. Multivariate Cox regression analyses were performed for suspected risk factors (i.e., recipient and donor demographics, clinical factors, donor characteristics, including cause of death and transplant-related variables). Results: Pandemic-era kidney recipients experienced significantly higher one-year graft failure and mortality than pre-pandemic recipients. Liver recipients also had higher one-year graft failure during the pandemic, but no statistically significant change in mortality. ODD liver recipients had a 22% reduction in one-year graft failure compared with other causes of death (p = 0.009). ODD kidneys were not inferior to non-ODD donors and were independently protective in several period-stratified comparisons. Conclusions: Pandemic-era recipients experienced worse one-year outcomes than pre-pandemic recipients across both organs, driven primarily by kidney graft failure and mortality. Drug overdose donor organs were not inferior to other donor sources in either period and were independently protective in several period-stratified comparisons. These data support continued and expanded use of drug overdose donor organs, including during periods of systemic strain. Full article

Background/Objectives: Stroke-induced cardiac damage may lead to lifelong cardiac problems, such as heart failure (HF). We aimed to compare the incidence of HF between stroke survivors and the general non-stroke population. Methods: We performed a population-based study of individuals in the Korean National Health Insurance Service database. We included 220,231 stroke survivors between 2010 and 2018 and 1:1 age- and sex-matched non-stroke controls. The study outcome was HF and the cohort was followed up until 2019. Cox hazards models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for HF risk. Results: At baseline, stroke survivors had a substantially higher comorbidity burden than matched controls (Charlson Comorbidity Index 4.1 vs. 1.6), with higher rates of hypertension, type 2 diabetes, and dyslipidemia, and were more likely to be current smokers and heavy drinkers. Stroke survivors showed a higher risk for HF (aHR 1.69, 95% CI 1.65–1.73) compared to controls. The risks were further increased with disability, as demonstrated in comparison of those with mild disability (aHR 1.78, 95% CI 1.70–1.87) and those with severe disability (aHR 2.22, 95% CI 2.10–2.36). Before applying the 1-year lag period, the association appeared more prominent among hemorrhagic stroke survivors than ischemic stroke survivors. However, following the 1-year lag period, the HF risk was similar between stroke subtypes (hemorrhagic stroke with disability: aHR 1.77, 95% CI 1.62–1.93; ischemic stroke with disability: aHR 1.71, 95% CI 1.63–1.80). Propensity score matching incorporating all baseline characteristics confirmed the robustness of the primary findings. Conclusions: Stroke survivors, who had a greater burden of cardiovascular risk factors, were at significantly greater risk for incident HF compared with age- and sex-matched non-stroke controls, particularly those with disability. Clinicians need to be aware of the importance of HF in stroke survivors who have multiple comorbidities and disability. Full article

Background/Objectives: The prognostic value of serial coronary artery calcium (CAC) progression remains uncertain in Asian populations and statin-treated patients. We evaluated the association between CAC progression and subsequent major adverse cardiovascular events (MACE) in a Taiwanese cohort. Methods: We retrospectively studied 1791 individuals undergoing two CAC-scoring cardiac CT scans at a tertiary center in Taiwan from 2006 to 2021, excluding those with MACE before the second scan. CAC progression was defined as an annualized Agatston score increase of ≥20 units/year. Time-to-event analyses used landmark Cox models beginning at the second scan, with inverse probability weighting (IPW), balance diagnostics, multivariable Cox regression, and multiple-imputation sensitivity analyses. Results: CAC progression occurred in 365 participants (20.4%). Progressors were older and had greater cardiometabolic risk and baseline CAC burden. In a landmark IPW analysis, CAC progression was associated with higher subsequent MACE risk (HR 2.02, 95% CI 1.49–2.74), with a graded association across annualized CAC change categories: HR 1.72 (95% CI 1.17–2.74) for 21–49 units/year and HR 2.86 (95% CI 2.29–3.57) for ≥50 units/year. The association remained consistent in multiple-imputation analysis (HR 1.90, 95% CI 1.36–2.66) and across major clinical subgroups. Discrimination for 10-year MACE was stronger among statin users than non-statin users (AUC 0.774 vs. 0.571), although statin-stratified analyses were exploratory. Conclusions: CAC progression was independently associated with subsequent MACE and showed a graded risk relationship. Serial CAC assessment may serve as a useful dynamic marker for refining longitudinal cardiovascular risk stratification, while prospective studies are needed to validate progression-guided management. Full article

Background: Multiple arterial grafting (MAG) is associated with superior long-term outcomes in coronary artery bypass grafting (CABG). The influence of prior myocardial infarction (MI) on outcomes following MAG remains uncertain. This study evaluates in-hospital outcomes and long-term survival of MAG in patients with and without previous MI. Methods: A retrospective single-center observational analysis of 2468 patients undergoing MAG was performed. Propensity score matching yielded 911 pairs based on preoperative variables. Kaplan–Meier survival analysis and Cox regression were used to assess long-term survival and predictors of mortality. Results: In the unmatched cohort, patients with prior MI had significantly higher rates of diabetes (30.6% vs. 23.9%, p < 0.001), smoking history (p < 0.001), and impaired left ventricular function (fair/poor LVEF: 32.4% vs. 11.1%, p < 0.001), along with higher logistic EuroSCORE (3.81 vs. 3.11, p < 0.001). After matching, baseline characteristics were balanced. In-hospital outcomes, including 30-day mortality (1.5% vs. 1.9%, p = 0.587), stroke, reoperation, and renal complications, were similar. Long-term survival at 10, 15, and 20 years was comparable (log-rank p = 0.814). Multivariate Cox regression identified age (HR 1.065, p < 0.001), NYHA class, diabetes (HR 0.779, p = 0.008), and off-pump CABG (HR 1.444, p < 0.001) as independent predictors of mortality. Prior MI was not associated with increased long-term mortality (HR 0.872, p = 0.105). Conclusions: Despite worse baseline risk profiles, patients with prior MI undergoing MAG had equivalent in-hospital outcomes and long-term survival. MAG remains a robust revascularization strategy irrespective of MI history, supporting its broader use in CABG. These findings should be interpreted in the context of a single-center experience from a high-volume arterial grafting program. Full article

Background/Objectives: There has been a growing concern about excessive caffeine consumption among heavy green tea drinkers on health outcomes, such as cardiovascular diseases or cancer. We evaluated the association between green tea consumption and risk of all-cause mortality in Vietnam. Methods: We used data from the Hanoi Prospective Cohort Study, an ongoing study comprising 42,146 participants aged 10 or older in Northern Vietnam who have been followed up between 2007 and 2019. Green tea intake was derived from a validated semi-quantitative food frequency questionnaire. We performed a Cox proportional hazard regression model to calculate the hazard ratio (HR) and respective 95% confidence intervals (95% CIs) for the association between green tea consumption and risk of all-cause mortality, adjusted for potential confounding factor. Results: After a median follow-up of 11 years (range: 0.13–11.64 years), we identified 2494 deaths. Overall, there was an inverse association between green tea intake and risk of all-cause mortality (HR_{perSDincrement} = 0.93; 95% CI, 0.89–0.97, P_trend < 0.001). This pattern was more pronounced in males (HR_{perSDincrement} = 0.93; 95% CI, 0.89–0.97, P_trend < 0.001) but not in females (HR_{perSDincrement} = 0.94; 95% CI, 0.86–1.02, P_trend = 0.12; P_{heterogeneity} = 0.81). In stratified analysis, the inverse association pattern was seen in both younger and old age groups, in individuals with BMI < 23 kg/m², in both ever and never smokers, among ever alcohol drinkers and never coffee drinkers, and in individuals with and without history of type 2 diabetes (P_{heterogeneity} = 0.31). Conclusions: Findings from the current study, the first prospective cohort study in Vietnam, suggest a protective effect of green tea consumption on risk of all-cause mortality. Further studies are warranted to validate our findings in similar population and settings. Full article

Background/Objectives: To evaluate the clinical outcomes and prognostic factors of Baerveldt glaucoma implant (BGI) surgery performed as a primary filtering procedure in eyes without prior glaucoma filtering surgery. Methods: This retrospective cohort study included 148 eyes of 148 patients who underwent BGI surgery with a 350-mm² endplate at a single tertiary center. Surgical success was defined using three intraocular pressure (IOP)-based criteria: IOP > 21 mmHg (criterion A), >17 mmHg (criterion B), or >14 mmHg (criterion C), failure to achieve ≥ 20% IOP reduction, need for additional glaucoma surgery, loss of light perception, or persistent hypotony. Kaplan–Meier survival analysis and multivariable Cox proportional hazards regression were used to evaluate surgical outcomes and prognostic factors. Results: The 5-year cumulative probability of surgical success was 70.6%, 49.8%, and 27.6% for criteria A, B, and C, respectively. Mean IOP decreased significantly from 33.5 ± 10.0 mmHg preoperatively to 13.9 ± 4.0 mmHg at 5 years (p < 0.01); number of glaucoma medications decreased from 4.0 ± 1.2 to 1.8 ± 1.9 (p < 0.01). Younger age was associated with a higher risk of surgical failure (criterion A: hazard ratio [HR] 0.97, p < 0.01; criterion B: HR 0.98, p = 0.011; criterion C: HR 0.97, p < 0.01). More previous intraocular surgeries were associated with failure under criterion B (HR 1.30, p = 0.048). Early and late postoperative complications occurred in 34.5% and 14.2% of eyes, respectively; 20.9% required additional postoperative interventions. Conclusions: BGI surgery performed as a primary filtering procedure demonstrated favorable long-term IOP control in eyes without prior glaucoma filtering surgery. Younger age was identified as a consistent risk factor for surgical failure. Full article

Vitex madiensis Oliv. (Lamiaceae) is a species growing in tropical and subtropical regions throughout the world. In several African countries, the different organs of this plant, leaves, fruits, stem bark and roots are used in folk medicine for the treatment of headaches, toothaches, aches and pains. In this study, we investigated the phytochemical profile of Vitex madiensis leaf extracts using LC-MS. The antioxidant and anti-inflammatory potential of crude extracts, fractions, and pure molecules was evaluated using reactive oxygen species (ROSs) production assays and cyclooxygenase-2 inhibition assays. A bio-guided fractionation was carried out to identify the most active fractions and resulted in the isolation of four phytoecdysteroids from the n-butanol fraction: 20-hydroxyecdysone, ajugasterone C, vitexirone, and pterosterone. 20-hydroxyecdysone showed very good anti-inflammatory properties with a significant reduction of more than 70% of COX-2 expression in induced LPS-stimulated human blood leukocytes compared to the control. This study confirmed the therapeutic potential of phytoecdysteroids. Full article

This study assessed the potential of Oleaster leaves as a valuable cosmetic ingredient by comparing aqueous and hydroalcoholic ultrasound-assisted extracts of Oleaster leaves to those of the Olive tree. The hydroalcoholic Oleaster leaf extract showed a higher content in phenolic and flavonoid compounds, with an oleuropein and verbascoside content of 58 mg/g of dry leaves and 3.2 mg/g of dry leaves, respectively. To refine the comparison of their molecular composition, the extracts were analyzed using UHPLC-HRMS/MS. About twenty compounds, including secoiridoids, flavonoids and triterpenic acid derivatives, were annotated in both extracts, demonstrating their similarity. DPPH, CUPRAC and enzymatic SOD assays showed a good antioxidant activity with high inhibition (60–90%) for both Oleaster and Olive tree leaf extracts. The hydroalcoholic extracts at 62.5 µg/mL also exhibited 60–80% of protection against reactive oxygen species (ROS) in H₂O₂-stressed HaCaT cells, confirming this antioxidant capacity without demonstrating a severe cytotoxicity, which remained below 40%. The anti-inflammatory potential of the extracts was also demonstrated using COX-2 inhibition, which was around 70%, and by measuring the concentration of IL-8 in HaCaT cells under pro-inflammatory conditions, which decreased in the presence of extracts at a concentration of 50 pg/mL, similar to that observed for the positive control. Thus, the hydroalcoholic ultrasound extract of Oleaster leaves demonstrated its high potential to develop sustainable and active cosmetic ingredients. Full article

With the increasing demand for sustainable animal production, the utilization of agricultural and processing by-products as functional feed ingredients has gained growing attention. However, the application of Xiasangju processing residues, a by-product generated during the industrial processing of the traditional Chinese herbal formula Xiasangju, in poultry nutrition remains poorly understood. This study aimed to evaluate the nutritional composition, bioactive components, and potential functional effects of Xiasangju processing by-products as a dietary supplement for late-laying hens. Chemical composition was characterized using LC-MS and conventional nutritional analysis, while potential anti-inflammatory mechanisms were predicted via network pharmacology. A total of 288 Jingfen laying hens (55 weeks old) were randomly assigned to four dietary treatments supplemented with 0, 0.5%, 1.0%, or 1.5% Xiasangju processing by-products for 56 days. Results showed that 11 major active compounds were identified, including relatively high levels of linarin and rosmarinic acid, along with abundant crude protein, fiber, minerals, and amino acids. Dietary supplementation at 1.5% was associated with higher egg production rate, egg weight, and yolk color without obvious adverse effects on organ indices or serum biochemical parameters. This treatment was also associated with lower inflammatory gene expression, including IL-6 and COX-2 in the ileum and NF-κB, IL-6, COX-2, and TNF-α in the cecum. No significant effects were observed on antioxidant status in yolk or liver, or intestinal morphology. Integrated analyses using network pharmacology, molecular docking, and in vitro COX-2 inhibition suggested that anti-inflammatory-related responses may involve COX-2-related pathways, while 16S rRNA sequencing indicated changes in gut microbiota composition. In conclusion, Xiasangju processing by-products may serve as a potential functional feed ingredient for late-laying hens, with 1.5% inclusion showing favorable overall performance under the conditions of this study. These effects may be associated with the combined contribution of residual nutrients and bioactive compounds in the residues. Full article