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17 pages, 1485 KiB  
Article
Selective Inhibition of Vascular Smooth Muscle Cell Function by COVID-19 Antiviral Drugs: Impact of Heme Oxygenase-1
by Kelly J. Peyton, Giovanna L. Durante and William Durante
Antioxidants 2025, 14(8), 945; https://doi.org/10.3390/antiox14080945 (registering DOI) - 31 Jul 2025
Viewed by 41
Abstract
Coronavirus disease 2019 (COVID-19) causes cardiovascular complications, which contributes to the high mortality rate of the disease. Emerging evidence indicates that aberrant vascular smooth muscle cell (SMC) function is a key driver of vascular disease in COVID-19. While antivirals alleviate the symptoms of [...] Read more.
Coronavirus disease 2019 (COVID-19) causes cardiovascular complications, which contributes to the high mortality rate of the disease. Emerging evidence indicates that aberrant vascular smooth muscle cell (SMC) function is a key driver of vascular disease in COVID-19. While antivirals alleviate the symptoms of COVID-19, it is not known whether these drugs directly affect SMCs. Accordingly, the present study investigated the ability of three approved COVID-19 antiviral drugs to influence SMC function. Treatment of SMCs with remdesivir (RDV), but not molnupiravir or nirmatrelvir, inhibited cell proliferation, DNA synthesis, and migration without affecting cell viability. RDV also stimulated an increase in heme oxygenase-1 (HO-1) expression that was not observed with molnupiravir or nirmatrelvir. The induction of HO-1 by RDV was abolished by mutating the antioxidant responsive element of the promoter, overexpressing dominant-negative NF-E2-related factor-2 (Nrf2), or treating cells with an antioxidant. Finally, silencing HO-1 partly rescued the proliferative and migratory response of RDV-treated SMCs, and this was reversed by carbon monoxide and bilirubin. In conclusion, the induction of HO-1 via the oxidant-sensitive Nrf2 signaling pathway contributes to the antiproliferative and antimigratory actions of RDV by generating carbon monoxide and bilirubin. These pleiotropic actions of RDV may prevent occlusive vascular disease in COVID-19. Full article
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2 pages, 615 KiB  
Correction
Correction: Lin et al. Induction of HO-1 by Mevastatin Mediated via a Nox/ROS-Dependent c-Src/PDGFRα/PI3K/Akt/Nrf2/ARE Cascade Suppresses TNF-α-Induced Lung Inflammation. J. Clin. Med. 2020, 9, 226
by Chih-Chung Lin, Wei-Ning Lin, Rou-Ling Cho, Chien-Chung Yang, Yi-Cheng Yeh, Li-Der Hsiao, Hui-Ching Tseng and Chuen-Mao Yang
J. Clin. Med. 2025, 14(15), 5390; https://doi.org/10.3390/jcm14155390 (registering DOI) - 31 Jul 2025
Viewed by 44
Abstract
In the original publication [...] Full article
(This article belongs to the Special Issue Current and Emerging Uses of Statins in Clinical Therapeutics)
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28 pages, 2379 KiB  
Article
FADEL: Ensemble Learning Enhanced by Feature Augmentation and Discretization
by Chuan-Sheng Hung, Chun-Hung Richard Lin, Shi-Huang Chen, You-Cheng Zheng, Cheng-Han Yu, Cheng-Wei Hung, Ting-Hsin Huang and Jui-Hsiu Tsai
Bioengineering 2025, 12(8), 827; https://doi.org/10.3390/bioengineering12080827 - 30 Jul 2025
Viewed by 100
Abstract
In recent years, data augmentation techniques have become the predominant approach for addressing highly imbalanced classification problems in machine learning. Algorithms such as the Synthetic Minority Over-sampling Technique (SMOTE) and Conditional Tabular Generative Adversarial Network (CTGAN) have proven effective in synthesizing minority class [...] Read more.
In recent years, data augmentation techniques have become the predominant approach for addressing highly imbalanced classification problems in machine learning. Algorithms such as the Synthetic Minority Over-sampling Technique (SMOTE) and Conditional Tabular Generative Adversarial Network (CTGAN) have proven effective in synthesizing minority class samples. However, these methods often introduce distributional bias and noise, potentially leading to model overfitting, reduced predictive performance, increased computational costs, and elevated cybersecurity risks. To overcome these limitations, we propose a novel architecture, FADEL, which integrates feature-type awareness with a supervised discretization strategy. FADEL introduces a unique feature augmentation ensemble framework that preserves the original data distribution by concurrently processing continuous and discretized features. It dynamically routes these feature sets to their most compatible base models, thereby improving minority class recognition without the need for data-level balancing or augmentation techniques. Experimental results demonstrate that FADEL, solely leveraging feature augmentation without any data augmentation, achieves a recall of 90.8% and a G-mean of 94.5% on the internal test set from Kaohsiung Chang Gung Memorial Hospital in Taiwan. On the external validation set from Kaohsiung Medical University Chung-Ho Memorial Hospital, it maintains a recall of 91.9% and a G-mean of 86.7%. These results outperform conventional ensemble methods trained on CTGAN-balanced datasets, confirming the superior stability, computational efficiency, and cross-institutional generalizability of the FADEL architecture. Altogether, FADEL uses feature augmentation to offer a robust and practical solution to extreme class imbalance, outperforming mainstream data augmentation-based approaches. Full article
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17 pages, 1160 KiB  
Article
Enhanced Antioxidant and Antiproliferative Activities of Apple and Korean Green Chili Pepper Extracts Cultivated with Mineral Supplementation
by Ji-Sun Lim, Mi-Hee Yu, Dong Kyu Choi, Hae Won Kim, Seung-Hwan Park, Sin-Il Sin and Jong-Sang Kim
Foods 2025, 14(15), 2685; https://doi.org/10.3390/foods14152685 - 30 Jul 2025
Viewed by 153
Abstract
Apples and Korean green chili peppers are rich in phytochemicals and recognized for their diverse bioactive properties. Given the potential to enhance these beneficial compounds, this study investigated the effects of mineral supplementation during cultivation on the antioxidant and antiproliferative activities of extracts [...] Read more.
Apples and Korean green chili peppers are rich in phytochemicals and recognized for their diverse bioactive properties. Given the potential to enhance these beneficial compounds, this study investigated the effects of mineral supplementation during cultivation on the antioxidant and antiproliferative activities of extracts from both crops. Mineral-enriched cultivation significantly increased the total phenolic and flavonoid contents in both crops, which was accompanied by enhanced DPPH and ABTS radical scavenging activities. Moreover, the mineral-supplemented extracts of Korean green chili pepper activated the Nrf2 signaling pathway and upregulated downstream antioxidant enzymes, including heme oxygenase-1 (HO-1), γ-glutamylcysteine ligase (GCL), and glutathione peroxidase (GPx). Notably, the mineral-supplemented Korean green chili pepper extract significantly suppressed the proliferation of human colorectal cancer cells. These findings suggest that mineral supplementation during cultivation may improve the functional quality of apples and Korean green chili peppers, supporting their potential application in cancer prevention and complementary therapeutic strategies. Full article
(This article belongs to the Special Issue Bioactive Phenolic Compounds from Agri-Food and Its Wastes)
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26 pages, 11108 KiB  
Article
Warming in the Maternal Environment Alters Seed Performance and Genetic Diversity of Stylosanthes capitata, a Tropical Legume Forage
by Priscila Marlys Sá Rivas, Fernando Bonifácio-Anacleto, Ivan Schuster, Carlos Alberto Martinez and Ana Lilia Alzate-Marin
Genes 2025, 16(8), 913; https://doi.org/10.3390/genes16080913 (registering DOI) - 30 Jul 2025
Viewed by 203
Abstract
Background/Objectives: Global warming and rising CO2 concentrations pose significant challenges to plant systems. Amid these pressures, this study contributes to understanding how tropical species respond by simultaneously evaluating reproductive and genetic traits. It specifically investigates the effects of maternal exposure to [...] Read more.
Background/Objectives: Global warming and rising CO2 concentrations pose significant challenges to plant systems. Amid these pressures, this study contributes to understanding how tropical species respond by simultaneously evaluating reproductive and genetic traits. It specifically investigates the effects of maternal exposure to warming and elevated CO2 on progeny physiology, genetic diversity, and population structure in Stylosanthes capitata, a resilient forage legume native to Brazil. Methods: Maternal plants were cultivated under controlled treatments, including ambient conditions (control), elevated CO2 at 600 ppm (eCO2), elevated temperature at +2 °C (eTE), and their combined exposure (eTEeCO2), within a Trop-T-FACE field facility (Temperature Free-Air Controlled Enhancement and Free-Air Carbon Dioxide Enrichment). Seed traits (seeds per inflorescence, hundred-seed mass, abortion, non-viable seeds, coat color, germination at 32, 40, 71 weeks) and abnormal seedling rates were quantified. Genetic diversity metrics included the average (A) and effective (Ae) number of alleles, observed (Ho) and expected (He) heterozygosity, and inbreeding coefficient (Fis). Population structure was assessed using Principal Coordinates Analysis (PCoA), Analysis of Molecular Variance (AMOVA), number of migrants per generation (Nm), and genetic differentiation index (Fst). Two- and three-way Analysis of Variance (ANOVA) were used to evaluate factor effects. Results: Compared to control conditions, warming increased seeds per inflorescence (+46%), reduced abortion (−42.9%), non-viable seeds (−57%), and altered coat color. The germination speed index (GSI +23.5%) and germination rate (Gr +11%) improved with warming; combined treatments decreased germination time (GT −9.6%). Storage preserved germination traits, with warming enhancing performance over time and reducing abnormal seedlings (−54.5%). Conversely, elevated CO2 shortened GSI in late stages, impairing germination efficiency. Warming reduced Ae (−35%), He (−20%), and raised Fis (maternal 0.50, progeny 0.58), consistent with the species’ mixed mating system; A and Ho were unaffected. Allele frequency shifts suggested selective pressure under eTE. Warming induced slight structure in PCoA, and AMOVA detected 1% (maternal) and 9% (progeny) variation. Fst = 0.06 and Nm = 3.8 imply environmental influence without isolation. Conclusions: Warming significantly shapes seed quality, reproductive success, and genetic diversity in S. capitata. Improved reproduction and germination suggest adaptive advantages, but higher inbreeding and reduced diversity may constrain long-term resilience. The findings underscore the need for genetic monitoring and broader genetic bases in cultivars confronting environmental stressors. Full article
(This article belongs to the Special Issue Genetics and Breeding of Forage)
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26 pages, 4256 KiB  
Review
Progress in Pharmacokinetics, Pharmacological Effects, and Molecular Mechanisms of Swertiamarin: A Comprehensive Review
by Hao-Xin Yang, Ying-Yue Hu, Rui Liang, Hong Zheng and Xuan Zhang
Cells 2025, 14(15), 1173; https://doi.org/10.3390/cells14151173 - 30 Jul 2025
Viewed by 234
Abstract
Swertiamarin (SW), a natural iridoid glycoside primarily isolated from the genus Swertia, Gentianaceae family, has been extensively utilized in traditional medicine systems, including Ayurveda, Traditional Chinese Medicine, and Tibetan medicine, for treating fever, diabetes, liver disorders, and inflammatory conditions. Pharmacokinetic studies reveal [...] Read more.
Swertiamarin (SW), a natural iridoid glycoside primarily isolated from the genus Swertia, Gentianaceae family, has been extensively utilized in traditional medicine systems, including Ayurveda, Traditional Chinese Medicine, and Tibetan medicine, for treating fever, diabetes, liver disorders, and inflammatory conditions. Pharmacokinetic studies reveal that SW exhibits rapid absorption but demonstrates low oral bioavailability due to the first-pass effect. Pharmacological studies have demonstrated that SW possesses a wide range of pharmacological activities, including antioxidant, anti-inflammatory, anti-tumor, anti-diabetic, and neuroprotective activities. Our analysis demonstrates that SW exerts remarkable therapeutic potential across multiple pathological conditions through coordinated modulation of key signaling cascades, including Nrf2/HO-1, NF-κB, MAPK, PI3K/Akt, and PPAR pathways. This comprehensive review systematically consolidates current knowledge on SW’s pharmacokinetic characteristics, toxicity, diverse biological activities, and underlying molecular mechanisms based on extensive preclinical evidence, establishing a scientific foundation for future drug development strategies and potential clinical applications of the potential natural lead compound. Full article
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18 pages, 1800 KiB  
Article
Chemometric Evaluation of Official and Advanced Methods for Detecting Olive Oil Authenticity in Canned Tuna
by Marjeta Mencin, Milena Bučar-Miklavčič, Maja Podgornik and Nives Ogrinc
Foods 2025, 14(15), 2667; https://doi.org/10.3390/foods14152667 - 29 Jul 2025
Viewed by 207
Abstract
This study evaluated the authenticity of olive oil in canned tuna products from the Slovenian market using both official methods, including fatty acid (FA) profiling, determination of the equivalent carbon number difference (ΔECN42), and sterol analysis, and an advanced method: stable carbon isotope [...] Read more.
This study evaluated the authenticity of olive oil in canned tuna products from the Slovenian market using both official methods, including fatty acid (FA) profiling, determination of the equivalent carbon number difference (ΔECN42), and sterol analysis, and an advanced method: stable carbon isotope analysis (δ13C) of FAs obtained through compound-specific isotope analysis (CSIA). Results from both methods confirmed that all 10 samples were authentic, as per the limits set by EU Regulation 2022/2104 and supported by the scientific literature. Method performance was further evaluated by adulterating the olive oil from the canned tuna with 5–20% vegetable oil (VO) or hazelnut oil (HO). While FA analysis struggled to differentiate adulterants with similar FA profiles, CSIA of FAs significantly improved detection. However, distinguishing between VO and HO blended samples remained challenging. PLS-DA analysis further supported the potential of using δ13C values of FA for food authentication. Storage of adulterated samples also influenced FA composition, leading to significant changes in MUFA/PUFA ratios and δ13C values, which became less negative, likely due to oxidative degradation. In summary, the combination of official and advanced methods, supported by chemometric analysis, offers a robust approach to ensuring the authenticity of olive oil in canned tuna. Full article
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23 pages, 2594 KiB  
Article
A Natural Polyphenol, Chlorogenic Acid, Attenuates Obesity-Related Metabolic Disorders in Male Rats via miR-146a-IRAK1-TRAF6 and NRF2-Mediated Antioxidant Pathways
by Rashid Fahed Alenezi, Adel Abdelkhalek, Gehad El-Sayed, Ioan Pet, Mirela Ahmadi, El Said El Sherbini, Daniela Pușcașiu and Ahmed Hamed Arisha
Biomolecules 2025, 15(8), 1086; https://doi.org/10.3390/biom15081086 - 27 Jul 2025
Viewed by 214
Abstract
Chronic high-fat diet (HFD) feeding in male rats causes significant metabolic as well as inflammatory disturbances, including obesity, insulin resistance, dyslipidemia, liver and kidney dysfunction, oxidative stress, and hypothalamic dysregulation. This study assessed the therapeutic effects of chlorogenic acid (CGA), a natural polyphenol, [...] Read more.
Chronic high-fat diet (HFD) feeding in male rats causes significant metabolic as well as inflammatory disturbances, including obesity, insulin resistance, dyslipidemia, liver and kidney dysfunction, oxidative stress, and hypothalamic dysregulation. This study assessed the therapeutic effects of chlorogenic acid (CGA), a natural polyphenol, administered at 10 mg and 100 mg/kg/day for the last 4 weeks of a 12-week HFD protocol. Both CGA doses reduced body weight gain, abdominal circumference, and visceral fat accumulation, with the higher dose showing greater efficacy. CGA improved metabolic parameters by lowering fasting glucose and insulin and enhancing lipid profiles. CGA suppressed orexigenic genes (Agrp, NPY) and upregulated anorexigenic genes (POMC, CARTPT), suggesting appetite regulation in the hypothalamus. In abdominal white adipose tissue (WAT), CGA boosted antioxidant defenses (SOD, CAT, GPx, HO-1), reduced lipid peroxidation (MDA), and suppressed pro-inflammatory cytokines including TNF-α, IFN-γ, and IL-1β, while increasing the anti-inflammatory cytokine IL-10. CGA modulated inflammatory signaling via upregulation of miR-146a and inhibition of IRAK1, TRAF6, and NF-κB. It also reduced apoptosis by downregulating p53, Bax, and Caspase-3, and restoring Bcl-2. These findings demonstrate that short-term CGA administration effectively reverses multiple HFD-induced impairments, highlighting its potential as an effective therapeutic for obesity-related metabolic disorders. Full article
(This article belongs to the Special Issue Antioxidant and Anti-Inflammatory Activities of Phytochemicals)
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15 pages, 1081 KiB  
Article
Dosimetric and Radiobiological Evaluation of Inhomogeneity-Corrected Dose Distribution in Prophylactic Radiotherapy for Heterotopic Ossification
by Than S. Kehwar and Indra J. Das
J. Clin. Med. 2025, 14(15), 5291; https://doi.org/10.3390/jcm14155291 - 26 Jul 2025
Viewed by 283
Abstract
Background/Objectives: The aim of this study was to evaluate the impact of inhomogeneity correction (IC) of dose distribution on the dosimetric and radiobiological efficacy of radiation treatment for heterotopic ossification (HO). Methods: This study involved a retrospective analysis of 21 patients treated using [...] Read more.
Background/Objectives: The aim of this study was to evaluate the impact of inhomogeneity correction (IC) of dose distribution on the dosimetric and radiobiological efficacy of radiation treatment for heterotopic ossification (HO). Methods: This study involved a retrospective analysis of 21 patients treated using a homogeneous dose distribution plan for hip prophylactic HO. These IC-off plans were evaluated against an IC-on dose distribution plan. Dosimetric and corresponding radiobiological parameters (gEUD, LQ-EUD, LQ, EQD2 for α/β = 3 and 10 Gy) were calculated. These parameters were compared for both treatment plans. Additionally, Monte Carlo simulations were performed using mean and standard deviation values from baseline data to generate 10,000 synthetic datasets, allowing for robust statistical modeling of variability in dose distributions and biological outcomes. Results: The homogeneous (IC-off) plans demonstrated overestimation of dose conformity and uniformity, reflected in lower HI values (0.10 ± 0.05 vs. 0.18 ± 0.05) and higher D90%–D98% coverage. Radiobiologically, these plans yielded higher gEUD (7.02 Gy vs. 6.80 Gy) and EQD2 values across all α/β scenarios (e.g., EQD2[α/β=3]_gEUD = 14.07 Gy vs. 13.35 Gy), with statistically significant differences (p < 0.001). Although IC-on plans demonstrated steeper dose gradients (higher GIs), this came at the expense of internal dose variability and potentially compromised biological effectiveness. Conclusions: Our results suggest that plans without IC deliver suboptimal biological effectiveness if continued preferentially in routine HO prophylaxis. With advanced radiation dose calculation algorithms available in all centers, inhomogeneity-corrected doses warrant prospective validation. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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26 pages, 5270 KiB  
Article
Gallic Acid and Taurine Attenuate Thiamethoxam-Induced Hepatotoxicity in Rats by Modulating SIRT-1/PGC-1α, NF-κB/iNOS, and p53/Bax/Caspase-3 Pathways
by Sara T. Elazab, Fatmah A. Safhi, Rasha K. Al-Akeel, Raghda H. Deraz, Souvarish Sarkar and Rania Essam Ali Gamal Eldin
Pharmaceuticals 2025, 18(8), 1112; https://doi.org/10.3390/ph18081112 - 25 Jul 2025
Viewed by 379
Abstract
Background/Objectives: Thiamethoxam (TMX) is one of the most extensively utilized insecticides of the neonicotinoid family; however, its application is associated with notable toxic effects on multiple organs of mammals. Our purpose was to explore the potential hepatoprotective effect of taurine (TAU) and/or [...] Read more.
Background/Objectives: Thiamethoxam (TMX) is one of the most extensively utilized insecticides of the neonicotinoid family; however, its application is associated with notable toxic effects on multiple organs of mammals. Our purpose was to explore the potential hepatoprotective effect of taurine (TAU) and/or gallic acid (GA) against TMX-induced liver damage, with an emphasis on their role in regulating SIRT-1/PGC-1α, NF-κB/iNOS, and p53/Bax/caspase-3 pathways. Methods: Rats were assigned to seven groups (n = 6) and gavaged daily for 28 days with saline (control group), TAU at 50 mg/kg, GA at 20 mg/kg, TMX at 78.15 mg/kg, TMX + TAU, TMX + GA, and TMX + TAU + GA. Results: The findings revealed that TAU and/or GA attenuated TMX-induced liver injury, as demonstrated by the restoration of hepatic performance hallmarks and histological structure. TAU and GA mitigated TMX-mediated oxidative stress and boosted the antioxidant defense mechanism by upregulating the transcription levels of SIRT-1, PGC-1α, Nrf2, and HO-1. Moreover, TAU and GA suppressed TMX-associated inflammatory response by increasing IL-10 concentration and lowering the levels of NF-κB, IL-1β, and iNOS; the mRNA levels of NLRP3; and TNF-α immunoexpression. Both compounds, individually or concurrently, exerted an anti-apoptotic effect in TMX-treated rats, evidenced by increased Bcl-2 expression and reduced p53 mRNA level, Bax expression, and caspase-3 concentration. Conclusions: TAU and/or GA may be regarded as promising remedies that can alleviate TMX-induced hepatotoxicity by activating SIRT-1/PGC-1α signaling and abolishing inflammation and apoptosis. Full article
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18 pages, 3426 KiB  
Article
XPS on Co0.95R0.05Fe2O4 Nanoparticles with R = Gd or Ho
by Adam Szatmari, Rareș Bortnic, Tiberiu Dragoiu, Radu George Hategan, Lucian Barbu-Tudoran, Coriolan Tiusan, Raluca Lucacel-Ciceo, Roxana Dudric and Romulus Tetean
Appl. Sci. 2025, 15(15), 8313; https://doi.org/10.3390/app15158313 - 25 Jul 2025
Viewed by 135
Abstract
Co0.95R0.05Fe2O4 nanoparticles were synthesized using a sol-gel approach incorporating bio-based agents and were found to be single phases adopting a cubic Fd-3m structure. XPS shows the presence of Gd3+ and Ho3+ ions. The spin–orbit [...] Read more.
Co0.95R0.05Fe2O4 nanoparticles were synthesized using a sol-gel approach incorporating bio-based agents and were found to be single phases adopting a cubic Fd-3m structure. XPS shows the presence of Gd3+ and Ho3+ ions. The spin–orbit splitting of about 15.4 eV observed in Co 2p core-level spectra is an indication that Co is predominantly present as Co3+ state, while the satellite structures located at about 6 eV higher energies than the main lines confirm the existence of divalent Co in Co0.95R0.05Fe2O4. The positions of the Co 3s and Fe 3s main peaks obtained by curve fitting and the exchange splitting obtained values for Co 3s and Fe 3s levels point to the high Co3+/Co2+ and Fe3+/Fe2+ ratios in both samples. The saturation magnetizations are smaller for the doped samples compared to the pristine ones. For theoretical magnetization calculation, we have considered that the heavy rare earths are in octahedral sites and their magnetic moments are aligned antiparallelly with 3d transition magnetic moments. ZFC-FC curves shows that some nanoparticles remain superparamagnetic, while the rest are ferrimagnetic, ordered at room temperature, and showing interparticle interactions. The MS/Ms ratio at room temperature is below 0.5, indicating the predominance of magnetostatic interactions. Full article
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28 pages, 1775 KiB  
Review
Forensic Narcotics Drug Analysis: State-of-the-Art Developments and Future Trends
by Petar Ristivojević, Božidar Otašević, Petar Todorović and Nataša Radosavljević-Stevanović
Processes 2025, 13(8), 2371; https://doi.org/10.3390/pr13082371 - 25 Jul 2025
Viewed by 424
Abstract
Narcotics trafficking is a fundamental part of organized crime, posing significant and evolving challenges for forensic investigations. Addressing these challenges requires rapid, precise, and scientifically validated analytical methods for reliable identification of illicit substances. Over the past five years, forensic drug testing has [...] Read more.
Narcotics trafficking is a fundamental part of organized crime, posing significant and evolving challenges for forensic investigations. Addressing these challenges requires rapid, precise, and scientifically validated analytical methods for reliable identification of illicit substances. Over the past five years, forensic drug testing has advanced considerably, improving detection of traditional drugs—such as tetrahydrocannabinol, cocaine, heroin, amphetamine-type stimulants, and lysergic acid diethylamide—as well as emerging new psychoactive substances (NPS), including synthetic cannabinoids (e.g., 5F-MDMB-PICA), cathinones (e.g., α-PVP), potent opioids (e.g., carfentanil), designer psychedelics (e.g., 25I-NBOMe), benzodiazepines (e.g., flualprazolam), and dissociatives (e.g., 3-HO-PCP). Current technologies include colorimetric assays, ambient ionization mass spectrometry, and chromatographic methods coupled with various detectors, all enhancing accuracy and precision. Vibrational spectroscopy techniques, like Raman and Fourier transform infrared spectroscopy, have become essential for non-destructive identification. Additionally, new sensors with disposable electrodes and miniaturized transducers allow ultrasensitive on-site detection of drugs and metabolites. Advanced chemometric algorithms extract maximum information from complex data, enabling faster and more reliable identifications. An important emerging trend is the adoption of green analytical methods—including direct analysis, solvent-free extraction, miniaturized instruments, and eco-friendly chromatographic processes—that reduce environmental impact without sacrificing performance. This review provides a comprehensive overview of innovations over the last five years in forensic drug analysis based on the ScienceDirect database and highlights technological trends shaping the future of forensic toxicology. Full article
(This article belongs to the Special Issue Feature Review Papers in Section “Pharmaceutical Processes”)
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18 pages, 2182 KiB  
Article
Assessment of Hydroxyl Radical Reactivity in Sulfur-Containing Amino Acid Models Under Acidic pH
by Chryssostomos Chatgilialoglu, Piotr Filipiak, Tomasz Szreder, Ireneusz Janik, Gordon L. Hug, Magdalena Grzelak, Franciszek Kazmierczak, Jerzy Smorawinski, Krzysztof Bobrowski and Bronislaw Marciniak
Int. J. Mol. Sci. 2025, 26(15), 7203; https://doi.org/10.3390/ijms26157203 - 25 Jul 2025
Viewed by 148
Abstract
Methionine residues in proteins and peptides are frequently oxidized by losing one electron. The presence of nearby amide groups is crucial for this process, enabling methionine to participate in long-range electron transfer. Hydroxyl radical (HO) plays an important role being generated [...] Read more.
Methionine residues in proteins and peptides are frequently oxidized by losing one electron. The presence of nearby amide groups is crucial for this process, enabling methionine to participate in long-range electron transfer. Hydroxyl radical (HO) plays an important role being generated in aerobic organisms by cellular metabolisms as well as by exogenous sources such as ionizing radiations. The reaction of HO with methionine mainly affords the one-electron oxidation of the thioether moiety through two consecutive steps (HO addition to the sulfur followed by HO elimination). We recently investigated the reaction of HO with model peptides mimicking methionine and its cysteine-methylated counterpart, i.e., CH3C(O)NHCHXC(O)NHCH3, where X = CH2CH2SCH3 or CH2SCH3 at pH 7. The reaction mechanism varied depending on the distance between the sulfur atom and the peptide backbone, but, for a better understanding of various suggested equilibria, the analysis of the flux of protons is required. We extended the previous study to the present work at pH 4 using pulse radiolysis techniques with conductivity and optical detection of transient species, as well as analysis of final products by LC-MS and high-resolution MS/MS following γ-radiolysis. Comparing all the data provided a better understanding of how the presence of nearby amide groups influences the one-electron oxidation mechanism. Full article
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18 pages, 2205 KiB  
Article
Lupeol Attenuates Oxysterol-Induced Dendritic Cell Activation Through NRF2-Mediated Antioxidant and Anti-Inflammatory Effects
by Sarmistha Saha, Antonella Capozzi, Elisabetta Profumo, Cristiano Alessandri, Maurizio Sorice, Luciano Saso and Brigitta Buttari
Int. J. Mol. Sci. 2025, 26(15), 7179; https://doi.org/10.3390/ijms26157179 - 25 Jul 2025
Viewed by 164
Abstract
Oxysterols such as 7-ketocholesterol (7KCh) contribute to the pathogenesis of autoimmune and chronic inflammatory diseases by inducing oxidative stress and promoting pro-inflammatory immune cell activation. Dendritic cells (DCs) play a central role in maintaining immune tolerance, and their dysregulation is a key driver [...] Read more.
Oxysterols such as 7-ketocholesterol (7KCh) contribute to the pathogenesis of autoimmune and chronic inflammatory diseases by inducing oxidative stress and promoting pro-inflammatory immune cell activation. Dendritic cells (DCs) play a central role in maintaining immune tolerance, and their dysregulation is a key driver of autoimmunity. Targeting DCs by using natural compounds offers a promising strategy to restore redox balance and suppress aberrant immune responses. This study investigated the immunomodulatory and antioxidant properties of Lupeol, a natural triterpenoid, in human monocyte-derived DCs exposed to 7KCh. Flow cytometry and cytokine profiling demonstrated that Lupeol preserved the immature, tolerogenic phenotype of DCs by promoting a dose-dependent increase in the anti-inflammatory cytokine IL-10. Lupeol also inhibited the 7KCh-induced upregulation of maturation markers (CD83, CD86) and suppressed the release of pro-inflammatory cytokines IL-1β and IL-12p70. Functionally, Lupeol-treated DCs directed T cell polarization toward an anti-inflammatory and regulatory profile while dampening the inflammatory responses triggered by 7KCh. This immunoregulatory effect was further supported by the decreased secretion of the pro-inflammatory cytokines IL-1β and IL-12p70 in DC culture supernatants. Mechanistic analyses using immunofluorescence showed that Lupeol alone significantly increased nuclear NRF2 levels and upregulated HO-1 expression. Western blot analysis further confirmed Lupeol’s ability to activate the KEAP1-NRF2 signaling pathway, as evidenced by increased expression of NRF2 and its downstream target, NQO1. The use of ML385, a selective NRF2 inhibitor, in ROS and cytokine assays supported the involvement of NRF2 in mediating the Lupeol antioxidant and anti-inflammatory effects in DCs. Notably, the oxidative burden induced by 7KCh limited the full activation of NRF2 signaling triggered by Lupeol. Furthermore, docking and MM/PBSA analyses revealed the specific interactions of Lupeol with the kelch domain of KEAP1. These findings suggest that Lupeol may serve as a promising orally available immunomodulatory agent capable of promoting tolerogenic DCs, offering potential applications in autoimmune and other chronic inflammatory diseases. Full article
(This article belongs to the Special Issue Updates on Synthetic and Natural Antioxidants)
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24 pages, 4430 KiB  
Article
Early Bearing Fault Diagnosis in PMSMs Based on HO-VMD and Weighted Evidence Fusion of Current–Vibration Signals
by Xianwu He, Xuhui Liu, Cheng Lin, Minjie Fu, Jiajin Wang and Jian Zhang
Sensors 2025, 25(15), 4591; https://doi.org/10.3390/s25154591 - 24 Jul 2025
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Abstract
To address the challenges posed by weak early fault signal features, strong noise interference, low diagnostic accuracy, poor reliability when using single information sources, and the limited availability of high-quality samples in practical applications for permanent magnet synchronous motor (PMSM) bearings, this paper [...] Read more.
To address the challenges posed by weak early fault signal features, strong noise interference, low diagnostic accuracy, poor reliability when using single information sources, and the limited availability of high-quality samples in practical applications for permanent magnet synchronous motor (PMSM) bearings, this paper proposes an early bearing fault diagnosis method based on Hippopotamus Optimization Variational Mode Decomposition (HO-VMD) and weighted evidence fusion of current–vibration signals. The HO algorithm is employed to optimize the parameters of VMD for adaptive modal decomposition of current and vibration signals, resulting in the generation of intrinsic mode functions (IMFs). These IMFs are then selected and reconstructed based on their kurtosis to suppress noise and harmonic interference. Subsequently, the reconstructed signals are demodulated using the Teager–Kaiser Energy Operator (TKEO), and both time-domain and energy spectrum features are extracted. The reliability of these features is utilized to adaptively weight the basic probability assignment (BPA) functions. Finally, a weighted modified Dempster–Shafer evidence theory (WMDST) is applied to fuse multi-source feature information, enabling an accurate assessment of the PMSM bearing health status. The experimental results demonstrate that the proposed method significantly enhances the signal-to-noise ratio (SNR) and enables precise diagnosis of early bearing faults even in scenarios with limited sample sizes. Full article
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