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Investigation of the effects of resveratrol, lutein, and crocetin on ARPE-19 cells induced with oxidative damage by H2O2

Tissue Cell. 2025 Sep 9;98:103133. doi: 10.1016/j.tice.2025.103133. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to evaluate and compare the antioxidant effects, influence on autophagy and mitophagy, and impact on cell viability of resveratrol, lutein, and crocetin in hydrogen peroxide (H₂O₂)-induced oxidative damage in ARPE-19 cells as an in vitro model of age-related macular degeneration (AMD).

METHODS: Oxidative damage was induced in ARPE-19 cells by exposure to 800 μM H₂O₂ for 1 h. Cell viability was assessed using the WST-1 assay. Subsequently, ARPE-19 cells were treated with lutein (5 and 10 μM), crocetin (10 and 20 μM), or resveratrol (100 μM), and the levels of oxidative damage biomarkers including malondialdehyde (MDA), glutathione (GSH), and nitric oxide (NO) were quantified via spectrophotometry. The autophagy- and mitophagy-related markers, LC3B, PINK1, and PARKIN, were visualized using confocal microscopy, and LC3B and PARKIN were further evaluated by western blotting (WB).

RESULTS: Cell viability results were 100 % in the control group, decreased to 73.5 % and 69.1 % with 10 and 20 μM crocetin, 62.7 % and 59.3 % with 5 and 10 μM lutein, and 52.7 % with 100 μM resveratrol, respectively, while H₂O₂ exposure reduced viability to 0.04 %. Exposure to H₂O₂ (800 µM, 1 h) induced significant oxidative damage in ARPE-19 cells, as indicated by a reduction in GSH levels (p < 0.01) and an increase in MDA (p < 0.001) and NO (p < 0.001) compared to the control group, along with a notable decrease in WST-1 viability. Among the interventions, 10 µM crocetin significantly decreased MDA (p = 0.019) and NO (p = 0.05) levels compared to those in the damage group, although the 20 µM concentration also reduced these markers without achieving statistical significance. 5 µM Lutein significantly reduced NO levels compared to the damage group, whereas reductions in MDA at concentrations of 5-10 µM were not statistically significant. GSH levels exhibited a numerical, albeit non-significant, increase with 10 µM lutein (p = 0.09), and showed modest, non-significant increases with crocetin and resveratrol. The highest LC3B expression was observed in the 5 μM lutein group compared to control and other treatment groups, while PARKIN expression was significantly elevated in the 10 μM lutein, 20 μM crocetin, and 100 μM resveratrol groups, with 20 μM crocetin and resveratrol levels also exceeding lutein 5 μM.

CONCLUSIONS: 10 μM Crocetin demonstrated the strongest antioxidant protection, while 5 μM lutein primarily improved cell survival, likely through autophagy activation and 100 μM resveratrol also activated both autophagy and mitophagy. These results highlighted the complementary concentration-dependent mechanisms of natural antioxidants in protecting RPE cells from oxidative stress related to AMD.

PMID:40934544 | DOI:10.1016/j.tice.2025.103133

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Posterolateral Tibial Plateau Bone Loss in the Setting of ACL Insufficiency Leads to Altered Kinematics During a Simulated Pivot Shift That Can Be Corrected With Combined ACL Reconstruction and Lateral Extra-articular Tenodesis But Not ACL Reconstruction Alone

Am J Sports Med. 2025 Sep 11:3635465251371644. doi: 10.1177/03635465251371644. Online ahead of print.

ABSTRACT

BACKGROUND: Posterolateral tibial plateau impaction fractures commonly occur in the setting of anterior cruciate ligament (ACL) tears and have been reported to affect clinical outcomes after ACL reconstruction (ACLR), but their biomechanical significance is not well understood.

PURPOSE: To evaluate the biomechanical effect of increasing depths of anteroposterior lateral tibial plateau bone loss on knee kinematics in the ACL-deficient knee and to evaluate the effect of ACLR with and without lateral extra-articular tenodesis (LET) on knee kinematics in the setting of posterolateral tibial plateau bone loss.

STUDY DESIGN: Controlled laboratory study.

METHODS: This study used 16 cadaveric knee specimens subjected to simulated pivot-shift, anterior tibial translation (ATT), and internal rotation (IR) testing via a robotic system. ACL-deficient specimens with 5, 10, and 15 mm of posterolateral tibial plateau bone loss were examined in addition to specimens that underwent ACLR with and without LET in the setting of 15-mm bone loss. Statistical analysis was performed using 1-factor, random-intercepts mixed-effects models to compare ATT, IR, and valgus angulation during a simulated pivot-shift test.

RESULTS: During pivot-shift testing, we observed significant increases in ATT, IR, and valgus angulation when comparing between the ACL intact with no bone loss state and all deficient ACL with bone loss states. For the reconstruction with 15-mm bone loss states, ACLR + LET was able to significantly improve ATT and IR, although valgus angulation remained significantly increased compared with the intact state (mean difference, 0.6 ± 4.0 mm, -4.8° ± 5.7°, and 2.0° ± 3.3°, respectively), while significant differences in ATT, IR, and valgus angulation remained when comparing isolated ACLR to the intact state (mean difference, 4.1 ± 2.8 mm, 3.2° ± 2.1°, and 3.4° ± 2.5°, respectively).

CONCLUSION: With increasing amounts of posterolateral tibial plateau bone loss, there were increased values of ATT, IR, and valgus angulation observed with a simulated pivot shift in ACL-deficient knees in a cadaveric model. In the setting of 15-mm posterolateral tibial plateau bone loss, ACLR combined with LET resulted in a significant decrease in both ATT and IR, but these parameters remained significantly elevated with isolated ACLR.

CLINICAL RELEVANCE: In the setting of high-grade posterolateral tibial plateau bone loss, significant laxity remained after ACLR compared with the ACL-intact state, whereas ACLR with LET was able to better restore kinematics to the ACL-intact state. This suggests that the addition of LET to ACLR should be considered in the setting of high-grade posterolateral tibial plateau bone loss.

PMID:40934532 | DOI:10.1177/03635465251371644

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Mid-term outcomes of covered and bare metal stents for femoropopliteal atherosclerotic disease

Vascular. 2025 Sep 11:17085381251379289. doi: 10.1177/17085381251379289. Online ahead of print.

ABSTRACT

ObjectiveEndovascular modality used in peripheral vascular intervention (PVI) varies widely. Long-term outcomes are poorly studied between covered stents (CS) and bare metal stents (BMS) for the SFA.MethodsPatients (2017-2021) undergoing CS and BMS to the SFA were identified at an academic institution. Comparative statistics and Kaplan-Meier analysis were used to evaluate outcomes by group.ResultsOne hundred and nineteen patients undergoing stenting were included with 60 patients undergoing CS (50%) and BMS in 59 (50%). There were no differences in sex (p = 0.5), preoperative ABI (p = 0.2) or indication for surgery between groups (p = 0.8). CS patients had undergone more prior SFA interventions (p = 0.03) and were younger (62 vs. 66 years; p = 0.04). Regarding anatomic and operative characteristics, CS patients had more TASC C/D lesions (69 vs. 47%; p = 0.006) less severe calcification (8 vs.17%; p = 0.0006) and more often underwent angioplasty and stenting (90 vs 51%; p < 0.0001) and less often angioplasty, DCB and stenting (5 vs. 43%; p < 0.0001). CS patients had larger SFA (5.7 vs 4; p < .0001), longer lesions (119 vs. 89 mm; p = 0.0008), higher popliteal runoff score (8.3 vs. 6.4; p = 0.02), longer surgery (140 vs. 118 min; p = 0.03), less fluoroscopy time (21 vs. 26 min; p = 0.03), larger SFA stent (6.2 vs. 5.6 mm; p < 0.0001), and longer stented length (260 vs. 171 mm; p < 0.0001). There were no differences in concomitant iliac/tibial treatment between groups (p = 0.3). Regarding outcomes, there were no differences in amputation (CS 10 vs. BMS 10.2%; p = 1) but overall mortality was lower in CS patients (8 vs 22%; p = 0.04) as was acute limb ischemia (17 vs. 34%; p = 0.03). CS patients underwent fewer endovascular (p = 0.03) and open reinterventions (p = 0.005) but a shorter time to first endovascular reintervention (5.6 vs. 17.8 months; p = 0.0002) on unadjusted analysis. Kaplan-Meier estimated survival at 48 months was 83% for CS and 75% for BMS (p = 0.28). At 36 months, primary patency was 35% for CS vs. 41% for BMS (p = 0.09), primary-assisted patency was 57% for CS vs. 68% for BMS (p = 0.04) and secondary patency for CS was 61% vs. 61% for BMS (p = 0.99).ConclusionsIn this series, CS was associated with lower reintervention rates than BMS despite higher TASC classification, longer lesions, and higher popliteal runoff scores. CS was more often used to salvage previous SFA intervention. At 3 years, however, patency was similar between groups. These data suggest some advantages for CS over BMS in endovascular salvage of failed SFA intervention and potentially a preferred modality for more complex SFA lesions than BMS.

PMID:40934524 | DOI:10.1177/17085381251379289

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Assessment of corneal topographical and endothelial cell parameters in hypothyroidism before and after thyroid replacement therapy

Clin Exp Optom. 2025 Sep 11:1-8. doi: 10.1080/08164622.2025.2558756. Online ahead of print.

ABSTRACT

CLINICAL RELEVANCE: Hypothyroidism is a common endocrine disorder that can influence various physiological processes throughout the human body.

BACKGROUND: Despite its clinical significance, there is a notable gap in directly comparing corneal characteristics between hypothyroid and euthyroid individuals within the same study cohort. This study aimed to explore the impact of hypothyroid and euthyroid states in the same participants on corneal topometry, tomography, densitometry, and aberrometry parameters.

METHODS: Thirty eyes from 30 newly diagnosed hypothyroid patients with clinically clear corneas were enrolled in this study. Corneal parameter analyses using Scheimpflug corneal topography (Pentacam®HR, Wetzlar, Germany) and specular microscopy (EM-4000; Tomey Corp. Nagoya, Japan) were performed at the time of hypothyroidism diagnosis and after thyroid replacement therapy.

RESULTS: The flat and mean keratometric readings of the anterior surface of the cornea were significantly higher in the euthyroid state than in the hypothyroid state (p < 0.001 and p = 0.002). After euthyroidism was provided, mean central corneal thickness and thinnest pachymetry values significantly decreased by 4.5 µm and 5.2 µm, respectively (p = 0.003 and p = 0.001). Significantly lower corneal densitometry values were detected in the euthyroid state (p < 0.05). Although there was no difference in pupil diameter, spherical aberration measurements were significantly higher at the time of diagnosis than during the euthyroidism period (p = 0.001). Average and maximal progression index significantly increased in the euthyroidism phase compared to the hypothyroidism phase, while maximum Ambrόsio relational thickness decreased (p < 0.05). The endothelial characteristics were statistically similar (p > 0.05).

CONCLUSION: The study suggests that patients with hypothyroidism may experience subtle corneal changes. The evaluation of a hypothyroid patient with corneal imaging devices may underestimate the risk of keratoconus and overestimate optic aberrations.

PMID:40934523 | DOI:10.1080/08164622.2025.2558756

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Decline in Rate of Radical Hysterectomies Performed by Gynecologic Oncologists in the United States

Obstet Gynecol. 2025 Sep 11. doi: 10.1097/AOG.0000000000006068. Online ahead of print.

ABSTRACT

Trends in cervical cancer epidemiology and physician workforces have converged to make radical hysterectomy an increasingly rare procedure for gynecologic oncologists practicing in the United States. Using data from the National Cancer Database and the Centers for Disease Control and Prevention’s United States Cancer Statistics and published gynecologic oncology workforce data, we assessed trends in radical hysterectomy performed in the United States from 2004 to 2020. Over this period, the annual rate of radical hysterectomies per gynecologic oncologist declined significantly, by an average of 6.9% per year (95% CI, 6.4-7.5), corresponding to a decrease from 4.5 to 1.5 cases per oncologist per year. The increasing rarity of radical hysterectomy may pose a challenge to those seeking to acquire and maintain competency in this complex operation.

PMID:40934516 | DOI:10.1097/AOG.0000000000006068

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Explainable AI for Depression Detection and Severity Classification From Activity Data: Development and Evaluation Study of an Interpretable Framework

JMIR Ment Health. 2025 Sep 11;12:e72038. doi: 10.2196/72038.

ABSTRACT

BACKGROUND: Depression is one of the most prevalent mental health disorders globally, affecting approximately 280 million people and frequently going undiagnosed or misdiagnosed. The growing ubiquity of wearable devices enables continuous monitoring of activity levels, providing a new avenue for data-driven detection and severity assessment of depression. However, existing machine learning models often exhibit lower performance when distinguishing overlapping subtypes of depression and frequently lack explainability, an essential component for clinical acceptance.

OBJECTIVE: This study aimed to develop and evaluate an interpretable machine learning framework for detecting depression and classifying its severity using wearable-actigraphy data, while addressing common challenges such as imbalanced datasets and limited model transparency.

METHODS: We used the Depresjon dataset and applied Adaptive Synthetic Sampling (ADASYN) to mitigate class imbalance. We extracted multiple statistical features (eg, power spectral density mean and autocorrelation) and demographic attributes (eg, age) from the raw activity data. Five machine learning algorithms (logistic regression, support vector machines, random forest, XGBoost, and neural networks) were assessed via accuracy, precision, recall, F1-score, specificity, and Matthew correlation constant. We further used Shapley Additive Explanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME) to elucidate prediction drivers.

RESULTS: XGBoost achieved the highest overall accuracy of 84.94% for binary classification and 85.91% for multiclass severity. SHAP and LIME revealed power spectral density mean, age, and autocorrelation as top predictors, highlighting circadian disruptions’ role in depression.

CONCLUSIONS: Our interpretable framework reliably identifies depressed versus nondepressed individuals and differentiates mild from moderate depression. The inclusion of SHAP and LIME provides transparent, clinically meaningful insights, emphasizing the potential of explainable artificial intelligence to enhance early detection and intervention strategies in mental health care.

PMID:40934462 | DOI:10.2196/72038

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Fatty Acids Analysis of Four Pistacia Species by Gas Chromatography Coupled With Mass Spectrometry via Multivariate Chemometrics

Chem Biodivers. 2025 Sep 11:e01787. doi: 10.1002/cbdv.202501787. Online ahead of print.

ABSTRACT

Pistacia species are widely used in traditional medicine, particularly for wound healing. This study investigated the fatty acid composition of fruits from four Pistacia species collected from various regions of Algeria. Dried fruits of Pistacia lentiscus L. were extracted using hexane in a Soxhlet apparatus. The extracted lipids were subjected to acid hydrolysis and then converted into their corresponding methyl esters by refluxing with methanolic sulfuric acid prior to analysis. These methylated fatty acids were analyzed by gas chromatography coupled with mass spectrometry. The major fatty acids identified were oleic acid (C18:1n9c), palmitic acid (C16:0), linoleic acid (C18:2n6c), palmitoleic acid (C16:1), and stearic acid (C18:0). Multivariate statistical analysis using R software (version 4.3.3), including principal component analysis and hierarchical clustering, was applied to explore patterns among the fatty acid profiles. Oleic acid was dominant in PL3 (51.18%), linoleic acid in PL1 (21.86%), and palmitoleic acid in PL2 (3.26%). These findings support the ethnomedicinal relevance of Pistacia species and provide the first detailed chemometric profiling of their fruit fatty acid content.

PMID:40934461 | DOI:10.1002/cbdv.202501787

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Ischemic Lesion Net Water Uptake for the Prediction of Very Poor Functional Outcomes at 90 Days

Neurology. 2025 Oct 7;105(7):e214068. doi: 10.1212/WNL.0000000000214068. Epub 2025 Sep 11.

ABSTRACT

BACKGROUND AND OBJECTIVES: Recent trials have shown the efficacy of endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO) and large infarcts on admission. However, many patients still experience poor outcomes despite treatment. The aim of this study was to investigate whether quantitative ischemic lesion net water uptake (NWU) on noncontrast head CT (NCCT) could identify AIS-LVO patients with large baseline infarcts who may require constant care or die despite successful EVT.

METHODS: This retrospective study included AIS-LVO patients with large baseline infarcts (Alberta Stroke Program Early CT Score ≤5) and occlusion of the intracranial internal carotid artery or first (M1) or second (M2) segments of the middle cerebral artery. Patients underwent EVT in 2 centers between 2012 and 2020. NWU was assessed on admission CT images by comparing density measurements of the ischemic core with the matching area of the contralateral hemisphere. The primary end point was a very poor outcome determined by functional neurologic status at 90 days on the modified Rankin Scale (mRS, score 5 or 6). Statistical analyses included group comparisons and evaluation of the predictive accuracy of an NWU ≥11.5% for very poor outcomes.

RESULTS: A total of 103 patients with AIS-LVO were included, of whom 57.3% were female, with a mean age of 72.1 years. Among patients with NWU ≥11.5%, 85% experienced very poor outcomes, compared with 51.8% of patients with an NWU <11.5% (p = 0.007). Patients with very poor outcomes had higher mean NWU compared with those without very poor outcomes (10.3% vs 6.0%, p < 0.001). An NWU threshold of 11.5% showed high specificity (93.0%, 95% CI 81.4-97.6) and positive predictive value (85%, 95% CI 64.0-94.8) for predicting very poor outcomes, which increased after combining it with other clinical and imaging parameters.

DISCUSSION: Elevated ischemic lesion NWU (≥11.5%) on admission NCCT was strongly associated with very poor functional outcomes at 90 days in AIS-LVO patients with large baseline infarcts treated by EVT. NWU assessment may serve as a valuable imaging biomarker for identifying patients who are likely to require constant care or die despite EVT.

PMID:40934458 | DOI:10.1212/WNL.0000000000214068

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Reply to: “NOTCH1: A Potential New Biomarker in the Era of Immunotherapy?” and “Caution in Interpreting NOTCH1 Mutation as a Predictive Biomarker of Tislelizumab Response in Esophageal Squamous Cell Carcinoma”

J Clin Oncol. 2025 Sep 11:JCO2501535. doi: 10.1200/JCO-25-01535. Online ahead of print.

NO ABSTRACT

PMID:40934453 | DOI:10.1200/JCO-25-01535

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How Sticky Are Clinical Trial Interventions? Site-Level Clinical Trial Participation and Differential Post-Trial Use of a Genomic Test

JCO Oncol Pract. 2025 Sep 11:OP2500475. doi: 10.1200/OP-25-00475. Online ahead of print.

ABSTRACT

PURPOSE: A provider’s participation in a randomized clinical trial (RCT) may influence their use of the trial intervention outside of trial contexts. We explored the association between site-level participation in a trial evaluating a postradical prostatectomy (RP) genomic classifier (GC; Genomics in Michigan Impacting Observation or Radiation [G-MINOR], ClinicalTrials.gov identifier: NCT02783950) and use of post-RP GC after completion of the trial’s enrollment window.

METHODS: The Michigan Urological Surgery Improvement Collaborative (MUSIC) data registry, in which G-MINOR was embedded, was queried for G-MINOR-eligible patients outside of the trial context (nonparticipating sites, chronology). A logistic regression model compared time with a patient’s receipt of post-RP GC testing at G-MINOR participating and nonparticipating sites, before and after the trial’s enrollment window.

RESULTS: A total of 7,144 patients (5,822 at G-MINOR sites, 1,322 non-G-MINOR sites) met study inclusion criteria between October 2015 and October 2020. Post-RCT, GC testing peaked among G-MINOR sites at 0.122 tests per eligible patient-quarter; no testing was observed among nonparticipating sites. Adjusting for patient characteristics, an interaction term between site-level RCT participation and pre-/postenrollment was statistically significant (hazard ratio, 21.9 [95% CI, 3.57 to 134]; P < .001).

CONCLUSION: Site-level participation in the G-MINOR RCT was significantly associated with a differential change in post-RCT GC use, where trial sites showed a greater post-RCT increase compared with nontrial sites. Whether this is caused by trial participation or represents a pre-existing intention to adopt an intervention remains unknown. Implementation and deimplementation considerations should be included in trial design.

PMID:40934443 | DOI:10.1200/OP-25-00475