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19 pages, 5577 KB  
Article
Comparative Analysis of the Effects of Acidic and Alkaline Beverages on the Optical Properties, Surface Topography, and Bacterial Activity of Zirconia Materials
by Nasser M. Alahmari
J. Funct. Biomater. 2025, 16(9), 329; https://doi.org/10.3390/jfb16090329 - 5 Sep 2025
Abstract
This study aimed to evaluate how acidic and alkaline staining solutions affect the optical properties (mean color change, ΔE*), geometric characteristics (surface roughness, Ra), and bacterial adhesion of zirconia Ceramill Zolid PS computer-aided design/computer-aided manufacture (CAD/CAM) material after 21 days of immersion. Ninety-six [...] Read more.
This study aimed to evaluate how acidic and alkaline staining solutions affect the optical properties (mean color change, ΔE*), geometric characteristics (surface roughness, Ra), and bacterial adhesion of zirconia Ceramill Zolid PS computer-aided design/computer-aided manufacture (CAD/CAM) material after 21 days of immersion. Ninety-six zirconia CAD/CAM Ceramill Zolid multilayer PS specimens were prepared and allocated to eight groups based on the pH values of the immersion solutions; the acidic solutions included Mirinda Citrus, CodeRed, yerba mate tea, Saudi coffee, and Nescafe (A–E), and the alkaline solutions included artificial saliva, DZRT (tobacco-free nicotine pouches), and smokeless tobacco (F–H). The specimens were immersed for 21 days at 37 °C, with the solutions replaced every 12 h to ensure consistency. Color changes were measured using a VITA Easyshade V spectrophotometer, and Ra was evaluated via white-light interferometric microscopy. The bacterial adhesion of Streptococcus mutans was quantified by counting colony-forming units (CFUs, CFU/mm2). Statistical analyses included the Shapiro–Wilk test for normality, one-way ANOVA with Tukey’s HSD post hoc test for group comparisons, and paired t-tests, with significance set at <0.05. The recorded pH values of the staining materials ranged from acidic (Mirinda Citrus: 3.23) to alkaline (smokeless tobacco: 8.54). Smokeless tobacco caused the most unacceptable mean color change (ΔE* = 6.84), followed by DZRT (ΔE* = 6.46), whereas artificial saliva produced the least discoloration (ΔE* = 2.15), with statistically significant differences among the solutions (p < 0.001). The Ra measurements varied significantly (p < 0.001), with Nescafe demonstrating the lowest value (0.486 µm) and DZRT the highest (0.748 µm). S. mutans adhesion was the highest for CodeRed (546.75 CFU) and the lowest for smokeless tobacco (283.92 CFU), demonstrating significant variation across groups (ANOVA, p < 0.001). The acidic and alkaline solutions significantly altered the optical properties, Ra, and bacterial adhesion of zirconia Ceramill Zolid PS CAD/CAM, with acidic solutions leading to higher bacterial adhesion. Full article
(This article belongs to the Section Dental Biomaterials)
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44 pages, 3472 KB  
Article
An Optimal Control Theory-Based Study for Fractional Smoking Model Using Bernoulli Wavelet Method
by Sanowar Ahasan, Sunil Kumar and Shaher Momani
Fractal Fract. 2025, 9(9), 583; https://doi.org/10.3390/fractalfract9090583 - 2 Sep 2025
Viewed by 105
Abstract
This paper introduces a dynamic model that explores smoking and optimal control strategies. It shows how fractional-order (FO) analysis has uncovered hidden parts of complex systems and provides information about previously ignored elements. This paper uses the Bernoulli wavelet operational matrix method and [...] Read more.
This paper introduces a dynamic model that explores smoking and optimal control strategies. It shows how fractional-order (FO) analysis has uncovered hidden parts of complex systems and provides information about previously ignored elements. This paper uses the Bernoulli wavelet operational matrix method and the Adam–Bashforth–Moulton (ABM) method to analyse this model numerically. The mathematical model is segmented into five sub-classes: susceptible smokers, ingestion class, unusual smokers, regular smokers, and ex-smokers. It considers four optimal control measures: an anti-smoking education campaign, distribution of anti-smoking gum, administration of anti-nicotine drugs, and governmental restrictions on smoking in public areas. We show in this model how to control smoking in society strategically. Full article
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8 pages, 235 KB  
Article
The Relationship Between Chronic Low Back Pain and Cigarette Smoking Habits in Patients Treated with Conservative Therapy
by Fabiola Cappella, Alessandro Di Rienzo, Mario Chiapponi, Valentina Liverotti and Mauro Dobran
Rheumato 2025, 5(3), 13; https://doi.org/10.3390/rheumato5030013 - 2 Sep 2025
Viewed by 138
Abstract
Aim of the study: This paper focuses on the correlation of nicotine use with chronic lumbar back pain (CLBP). Methods: This is a cross-sectional observational study involving smoker and non-smoker patients with a diagnosis of chronic low back pain (CLBP), recruited [...] Read more.
Aim of the study: This paper focuses on the correlation of nicotine use with chronic lumbar back pain (CLBP). Methods: This is a cross-sectional observational study involving smoker and non-smoker patients with a diagnosis of chronic low back pain (CLBP), recruited during their initial neurosurgical consultation at the Neurosurgery Clinic over a period of 6 months. All patients were followed for a minimum of 3 months after the start of conservative therapy. Age, sex, smoking habits, and the presence of any comorbidities were noted. Pain severity and discomfort were evaluated using the Numeric Rating Scale (NRS), the DN4 questionnaire, and the Oswestry Disability Index (ODI). Based on imaging (MRI of the lumbosacral spine), diagnoses of disc herniation or vertebral lumbar stenosis were documented. Statistical analysis was performed using IBM SPSS Statistics software (Version 30). A p-value of less than 0.05 was considered statistically significant. Results: Improvement on the CLBP, NRS, and DN4 scales after the same conservative therapy was better in Patients with non-smoking habits improved more on the CLBP, NRS and DN4 scales when compared to smokers (NRS scale 0.001 and DN4 scale 0.027). Conclusions: Patients with smoking habitudes affected by lumbar disk her-niation and stenosis and undergoing conservative therapy had worse pain scores Full article
18 pages, 2660 KB  
Article
Impacts of PACAP 1-38 and BGP-15 on the Healing of Fasciocutaneous Groin Flaps Affected by Ischemia–Reperfusion in Rats
by Anna Orsolya Flasko, Laszlo Adam Fazekas, Gergo Kincses, Adam Varga, Adam Attila Matrai, Ildiko Czirjak, Noemi Dodity, Ildiko Katalin Bacskay, Agota Peto, Dora Reglodi, Csaba Filler, Tamas Juhasz and Norbert Nemeth
Biomedicines 2025, 13(9), 2129; https://doi.org/10.3390/biomedicines13092129 - 31 Aug 2025
Viewed by 306
Abstract
Background/Objectives: To prevent flap failure, adequate tissue perfusion and effective regenerative processes, undisturbed wound healing are essential, among others. To improve wound healing, various locally and systematically administered pharmacons can be used. This study investigated the effect of PACAP 1-38 (pituitary adenylate [...] Read more.
Background/Objectives: To prevent flap failure, adequate tissue perfusion and effective regenerative processes, undisturbed wound healing are essential, among others. To improve wound healing, various locally and systematically administered pharmacons can be used. This study investigated the effect of PACAP 1-38 (pituitary adenylate cyclase activating polypeptide) and BGP-15 (a nicotinic amidoxime derivative) on the healing of epigastric fasciocutaneous flaps exposed to ischemia–reperfusion (I/R). Methods: Wistar rats were randomly divided into control (no substance), PACAP 1-38, and BGP-15 groups. Groin flaps were prepared bilaterally. The left flap was exposed to 120 min of ischemia prior to suturing it back. We applied wound gels containing substances. Laboratory tests (hematology, erythrocyte deformability, and aggregation) were performed before surgery on the 1st, 3rd, and 7th postoperative days. Lastly, flap skin samples were taken for histological and tensile strength measurements. Results: Impaired erythrocyte deformability and enhanced aggregation were found because of flap I/R. The pharmacons were able to reduce the systemic micro-rheological impairment to varying degrees. The tensile strength increased in the areas of better perfusion. Conclusions: The anti-inflammatory effects of PACAP 1-38 and BPG-15, as well as the impact of PACAP 1-38 on collagen and elastic fiber composition, have been demonstrated. Full article
(This article belongs to the Section Cell Biology and Pathology)
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17 pages, 2407 KB  
Article
Urine Metabolomics of Gout Reveals the Dynamic Reprogramming and Non-Invasive Biomarkers of Disease Progression
by Guizhen Zhu, Yuan Luo, Nan Su, Xiangyi Zheng, Zhusong Mei, Qiao Ye, Jie Peng, Peiyu An, Yangqian Song, Weina Luo, Hongxia Li, Guangyun Wang and Haitao Zhang
Metabolites 2025, 15(9), 580; https://doi.org/10.3390/metabo15090580 - 29 Aug 2025
Viewed by 229
Abstract
Background/Objectives: Gout, a complex metabolic disorder of increasing global incidence, remains incompletely understood in its pathogenesis. Current diagnostic approaches exhibit significant limitations, including insufficient specificity and the requirement for invasive joint aspiration, highlighting the need for non-invasive, sensitive biomarkers for early detection. Methods: [...] Read more.
Background/Objectives: Gout, a complex metabolic disorder of increasing global incidence, remains incompletely understood in its pathogenesis. Current diagnostic approaches exhibit significant limitations, including insufficient specificity and the requirement for invasive joint aspiration, highlighting the need for non-invasive, sensitive biomarkers for early detection. Methods: Urine metabolites were extracted from 28 healthy controls, 13 asymptomatic hyperuricemia (HUA) patients, and 29 acute gouty arthritis (AGA) patients. The extracted metabolites were analyzed by UHPLC-MS/MS for untargeted metabolomics. Differential metabolites were screened by partial least squares discriminant analysis (PLS-DA) and volcano plot analysis. Pathway analysis determined the core disorder pathway of gout progression. Results: A total of 278 differential metabolites associated with gout progression were identified. The most pronounced metabolic alterations were observed between the AGA and control groups, indicative of substantial metabolic reprogramming during disease transition. Metabolic pathway analysis revealed four significantly dysregulated pathways: histidine metabolism, nicotinate and nicotinamide metabolism, phenylalanine metabolism, and tyrosine metabolism. Receiver operating characteristic (ROC) curve analysis revealed that three urine markers with high diagnostic efficacy—oxoamide, 3-methylindole, and palmitic acid—exhibited progressive alterations across the disease continuum. Conclusions: This metabolomics study identified core regulatory metabolites and newly discovered metabolic pathways underlying gout pathogenesis, along with novel urinary biomarkers capable of predicting HUA-to-AGA progression. The aberrant levels of key metabolites in the disordered pathway implicate neuroimmune dysregulation, energy metabolism disruption, and oxidative stress in gout pathogenesis. These findings provide new foundations and strategies for the daily monitoring and prevention of gout. Full article
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19 pages, 2480 KB  
Article
Application of Organic Nanofibers to Boost Specialized Metabolite Production and Antioxidant Potential in Stevia rebaudiana In Vitro Cultures
by Maria Geneva, Antoaneta Trendafilova, Kamelia Miladinova-Georgieva, Mariana Sichanova, Daniela Tsekova, Viktoria Ivanova, Elisaveta Kirova and Maria Petrova
Metabolites 2025, 15(9), 579; https://doi.org/10.3390/metabo15090579 - 29 Aug 2025
Viewed by 196
Abstract
Background: Potential advantages for improving plant growth, stress tolerance, and valuable metabolites generation are provided by the implementation of nanotechnology into plant biotechnology. A recently discovered technique with significant promise for agricultural practices is the use of biopolymer-based nanomaterials, like peptidomimetics, as insecticides, [...] Read more.
Background: Potential advantages for improving plant growth, stress tolerance, and valuable metabolites generation are provided by the implementation of nanotechnology into plant biotechnology. A recently discovered technique with significant promise for agricultural practices is the use of biopolymer-based nanomaterials, like peptidomimetics, as insecticides, growth regulators, and nutrient carriers. This study explores the impact of biopolymer-based organic nanofibers—specifically peptidomimetics formed through the self-assembly of L-valine and nicotinic acid (NA) (denoted as M6) on Stevia rebaudiana in vitro propagation and specialized metabolite production. The central hypothesis was that such nanofibers, particularly when used as hormone carriers, can beneficially influence plant morphology, physiology, and biochemistry, thereby promoting the synthesis of antioxidant compounds with therapeutic potential. Methods: The nanofibers were tested either alone (M6) or as carriers of the plant hormone indole-3-acetic acid (IAA) (M6+IAA), supplemented to the cultivation MS medium at variable concentrations (0, 1, 10, and 50 mg L−1). Results: The results revealed that treatment with 10 mg L−1 M6 significantly enhanced shoot growth parameters, including the highest fresh weight (0.249 g), mean shoot height (9.538 cm), shoot number (1.95), and micropropagation rate. Plants treated with M6 alone outperformed those treated with M6+IAA in terms of shoot growth, total soluble sugars, and steviol glycoside content. Conversely, M6+IAA treatment more effectively promoted root initiation, the increased accumulation of mono- and dicaffeoylquinic acids, and boosted antioxidant enzyme activity. Conclusions: These findings highlight the potential of organic nanofibers, both with and without hormone loading, as novel tools for optimizing micropropagation and metabolite enhancement in Stevia rebaudiana. Full article
(This article belongs to the Special Issue Bioactive Metabolites from Natural Sources (2nd Edition))
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27 pages, 355 KB  
Article
Smoking Abstinence Self-Efficacy, Decisional Balance, and Quitting Desire Among Adult Smokers in Saudi Arabia: Gender-Based Cross-Sectional Study
by Samiha Hamdi Sayed, Olfat Abdulgafoor Gushgari, Fadiyah Abdullah Alshwail, Hanan Abd Elwahab Elsayed, Hanem Awad Mekhamier and Ebtesam Abbas Elsayed
Healthcare 2025, 13(17), 2158; https://doi.org/10.3390/healthcare13172158 - 29 Aug 2025
Viewed by 233
Abstract
Background: Smoking is a major public health concern in Saudi Arabia, with significant gender differences influencing smoking behavior and cessation. Aim: This study aimed to investigate smoking abstinence self-efficacy (ASE), decisional balance (DB), quitting desire, and their predictors among adult male and female [...] Read more.
Background: Smoking is a major public health concern in Saudi Arabia, with significant gender differences influencing smoking behavior and cessation. Aim: This study aimed to investigate smoking abstinence self-efficacy (ASE), decisional balance (DB), quitting desire, and their predictors among adult male and female smokers in Saudi Arabia. Methods: A cross-sectional study was conducted using a convenience sample of 375 male and 220 female adult smokers recruited via social media. Data were collected through an online survey assessing personal health, smoking behavior, desire to quit, ASE, and DB. Logistic regression was used to identify predictors of earnest quitting desire, high ASE, and negative DB. Results: Males were more likely to smoke for 10 or more years (70.7% vs. 29.1%), maintain regular smoking patterns (86.9% vs. 54.1%), and exhibit high nicotine dependence (29.3% vs. 6.4%) compared to females. A higher proportion of females (76.8%) than males (66.9%) expressed a strong desire to quit. ASE was generally higher in males, with 49.6% showing average levels, while 46.4% of females had low ASE, particularly in social and positive mood contexts. Females displayed a higher prevalence of negative DB (73.6% vs. 58.1%), indicating greater awareness of smoking’s drawbacks. Both genders acknowledged the cons of smoking, though males perceived fewer pros. Conclusions: A complex interplay of factors influences smoking behavior and cessation among adult smokers. Gender differences also play a crucial role in smoking cessation factors among Saudi adults. Tailored cessation strategies addressing self-efficacy and motivation are recommended to enhance quitting success. Full article
42 pages, 981 KB  
Review
E-Cigarette Use Among University Students: A Structured Literature Review of Health Risks, Behavioral and Social Determinants, and Nursing Implications
by Luis-Rodrigo Rocha-Ávila, María-Ángeles Núñez-Baila and José Rafael González-López
Healthcare 2025, 13(17), 2150; https://doi.org/10.3390/healthcare13172150 - 28 Aug 2025
Viewed by 393
Abstract
Background/Objectives: E-cigarette use has increased substantially among university students in recent years, coinciding with a broader shift in nicotine consumption patterns globally. Despite initial perceptions of e-cigarettes as harm-reduction tools, growing evidence indicates significant health risks, misinformation, and limited awareness—especially within higher [...] Read more.
Background/Objectives: E-cigarette use has increased substantially among university students in recent years, coinciding with a broader shift in nicotine consumption patterns globally. Despite initial perceptions of e-cigarettes as harm-reduction tools, growing evidence indicates significant health risks, misinformation, and limited awareness—especially within higher education environments. This structured literature review aims to synthesize peer-reviewed evidence on the health impacts, behavioral determinants, and the role of nursing in addressing e-cigarette use among university students. Methods: A literature search was conducted across five databases (PubMed, CINAHL, Scopus, Embase, Dialnet) between February and March 2025. Eligible studies were published between January 2020 and January 2025 in English or Spanish. A total of 43 studies were included. Data were synthesized narratively, and methodological quality was assessed using Joanna Briggs Institute checklists and The Scale for the Assessment of Narrative Reviews Articles. Results: E-cigarette use among university students showed wide variability in prevalence, with higher rates among males, students in non-health disciplines, and users of disposable devices. Key behavioral and social determinants included peer influence, curiosity, stress management, and social media exposure. Despite documented health risks—such as nicotine dependence, respiratory and cardiovascular impairment, and mental health concerns—misconceptions about safety and cessation efficacy were common, even among health science students. Nursing-led interventions hold great potential for prevention but remain underdeveloped within university settings. Conclusions: The findings underscore the urgent need for evidence-based prevention strategies—particularly those led by nurses—to reduce e-cigarette use, bridge knowledge gaps, and mitigate associated health risks in higher education. Future efforts should prioritize institutional policy reinforcement, improved health communication, and the integration of vaping-related education into nursing curricula and public health campaigns targeting emerging adults. Full article
(This article belongs to the Section Nursing)
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12 pages, 2157 KB  
Article
Novel Biosynthetic Pathway for Nicotinamide Mononucleotide Production from Cytidine in Escherichia coli
by Jiaxiang Yuan, Rongchen Feng, Mingming Liu, Xin Wang, Kequan Chen and Sheng Xu
Catalysts 2025, 15(9), 816; https://doi.org/10.3390/catal15090816 - 27 Aug 2025
Viewed by 351
Abstract
Nicotinamide mononucleotide, known as NMN, is an important nicotinamide adenine dinucleotide (NAD+) precursor. It is integral in cellular metabolism, energy generation, and processes associated with aging. Since NMN provides healthy value, it becomes a major focus for the biotechnological industry. This [...] Read more.
Nicotinamide mononucleotide, known as NMN, is an important nicotinamide adenine dinucleotide (NAD+) precursor. It is integral in cellular metabolism, energy generation, and processes associated with aging. Since NMN provides healthy value, it becomes a major focus for the biotechnological industry. This study presents a new biosynthetic pathway for producing NMN without limits on intracellular PRPP (5′-phosphoribosyl pyrophosphate) metabolic flux. The route started by converting cytidine into 1-phosphoribose via pyrimidine-nucleoside phosphorylase (PyNP), after transforming into nicotinamide riboside (NR) through either purine-nucleoside phosphorylase (XapA) or nicotinate riboside kinase (NRK). NR was phosphorylated by NRK in the presence of nicotinamide (NAM) to produce NMN. We established an in vitro enzyme activity verification system for the feasibility check. The optimization of multienzyme cascade reactions was figured out for the NMN biosynthesis. Finally, the enzymes of PyNP and NRK were expressed in the cytidine-producing strain; we established a de novo biosynthesis pathway from glucose to NMN, achieving a production titer of 33.71 mg/L at a shake-flask scale. Full article
(This article belongs to the Section Biocatalysis)
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16 pages, 272 KB  
Review
Ketamine’s Therapeutic Role in Substance Use Disorders: A Narrative Review
by Alexander Thomas and R. Andrew Chambers
NeuroSci 2025, 6(3), 83; https://doi.org/10.3390/neurosci6030083 - 27 Aug 2025
Viewed by 436
Abstract
Interest in ketamine as a novel treatment for substance use disorders (SUDs) has been increasing due to its N-methyl-D-aspartate (NMDA) glutamate receptor antagonism and mounting evidence that glutamate neurotransmission is involved in the pathogenesis of both depression and addictions. This narrative review provides [...] Read more.
Interest in ketamine as a novel treatment for substance use disorders (SUDs) has been increasing due to its N-methyl-D-aspartate (NMDA) glutamate receptor antagonism and mounting evidence that glutamate neurotransmission is involved in the pathogenesis of both depression and addictions. This narrative review provides an outline of clinical evidence reported in the literature from the 1970s to 2025 that examines the efficacy of ketamine for the treatment of SUDs, focusing primarily on randomized blinded controlled trials (RBCTs). Key cohort studies, retrospective studies, secondary analyses, case reports, and relevant basic neuroscience studies are reviewed to complement the more rigorous human controlled trial data. Thus far, ketamine has been tested in nine RBCTs targeting cocaine (three studies), alcohol (three studies), opioid use disorder (two studies), and nicotine (one study), suggesting efficacy for addiction in combination with psychotherapies, and often when doses produce subjectively reported mystical or psychedelic experiences. This review highlights promising preliminary evidence, and the need for more rigorous studies to elucidate the scope of drug addictions ketamine may target, its optimal dosing or route of administration, the importance of concurrent psychotherapies, professional supervision and safety monitoring, and which psychiatric comorbidities or contexts may contraindicate its use for SUDs. Full article
11 pages, 1320 KB  
Article
Fenmezoditiaz Inhibited the Acquisition and Transmission of Southern Rice Black-Streaked Dwarf Virus by Sogatella furcifera
by Yuting Chen, Lixin Mao, Xiulan Ding, Hengchien Liu, Devendra J. Vyas and Dongsheng Jia
Insects 2025, 16(9), 875; https://doi.org/10.3390/insects16090875 - 23 Aug 2025
Viewed by 420
Abstract
Rice planthoppers are the most destructive pests of rice production and the vectors of rice viruses. Fenmezoditiaz as a novel mesoionic insecticide is used for rice planthopper management by targeting the insect’s neural nicotinic acetylcholine receptor. This study aimed to evaluate the effects [...] Read more.
Rice planthoppers are the most destructive pests of rice production and the vectors of rice viruses. Fenmezoditiaz as a novel mesoionic insecticide is used for rice planthopper management by targeting the insect’s neural nicotinic acetylcholine receptor. This study aimed to evaluate the effects of fenmezoditiaz on the acquisition, propagation, and transmission of southern rice black-streaked dwarf virus (SRBSDV) by the white-backed planthopper, Sogatella furcifera (Hemiptera: Delphacida). The results revealed that sublethal concentrations of fenmezoditiaz significantly impaired SRBSDV acquisition and viral replication in S. furcifera. Fenmezoditiaz-treated viruliferous S. furcifera exhibited a lower transmission efficiency of SRBSDV to un-infected rice seedlings. Electrical penetration graph (EPG) recordings revealed prolonged non-probing (NP), salivary secretion (N2/N3), and xylem feeding (N5) durations, alongside shortened phloem contact behavior (N4a/N4b), of fenmezoditiaz-treated individuals, indicating disrupted feeding behaviors, which are critical for reducing viral infection. By reducing viral titers and interfering with phloem ingestion, fenmezoditiaz significantly suppresses SRBSDV transmission. These findings revealed fenmezoditiaz’s dual role in pest control and viral transmission blockage, providing a foundation for incorporation into integrated management of vector-borne plant viruses. Full article
(This article belongs to the Section Insect Pest and Vector Management)
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26 pages, 2295 KB  
Article
Retrospective Urine Metabolomics of Clinical Toxicology Samples Reveals Features Associated with Cocaine Exposure
by Rachel K. Vanderschelden, Reya Kundu, Delaney Morrow, Simmi Patel and Kenichi Tamama
Metabolites 2025, 15(9), 563; https://doi.org/10.3390/metabo15090563 - 22 Aug 2025
Viewed by 414
Abstract
Background/Objectives: Cocaine is a widely used illicit stimulant with significant toxicity. Despite its clinical relevance, the broader metabolic alterations associated with cocaine use remain incompletely characterized. This study aims to identify novel biomarkers for cocaine exposure by applying untargeted metabolomics to retrospective urine [...] Read more.
Background/Objectives: Cocaine is a widely used illicit stimulant with significant toxicity. Despite its clinical relevance, the broader metabolic alterations associated with cocaine use remain incompletely characterized. This study aims to identify novel biomarkers for cocaine exposure by applying untargeted metabolomics to retrospective urine drug screening data. Methods: We conducted a retrospective analysis of a raw mass spectrometry (MS) dataset from urine comprehensive drug screening (UCDS) from 363 patients at the University of Pittsburgh Medical Center Clinical Toxicology Laboratory. The liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-qToF-MS) data were preprocessed with MS-DIAL and subjected to multiple statistical analyses to identify features significantly associated with cocaine-enzyme immunoassay (EIA) results. Significant features were further evaluated using MS-FINDER for feature annotation. Results: Among 14,883 features, 262 were significantly associated with cocaine-EIA results. A subset of 37 more significant features, including known cocaine metabolites and impurities, nicotine metabolites, norfentanyl, and a tryptophan-related metabolite (3-hydroxy-tryptophan), was annotated. Cluster analysis revealed co-varying features, including parent compounds, metabolites, and related ion species. Conclusions: Features associated with cocaine exposure, including previously underrecognized cocaine metabolites and impurities, co-exposure markers, and alterations in an endogenous metabolic pathway, were identified. Notably, norfentanyl was found to be significantly associated with cocaine -EIA, reflecting current trends in illicit drug use. This study highlights the potential of repurposing real-world clinical toxicology data for biomarker discovery, providing a valuable approach to identifying exposure biomarkers and expanding our understanding of drug-induced metabolic disturbances in clinical toxicology. Further validation and exploration using complementary analytical platforms are warranted. Full article
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21 pages, 1126 KB  
Article
Reversed-Phase (RP) and Hydrophilic Interaction (HILIC) Separation Mechanisms for the Assay of Nicotine and E-Cigarette Liquids
by Răzvan Moisi, Mircea-Alexandru Comănescu and Andrei-Valentin Medvedovici
Molecules 2025, 30(16), 3443; https://doi.org/10.3390/molecules30163443 - 21 Aug 2025
Viewed by 551
Abstract
Nicotine is a highly used addictive substance that has recently also become available through electronic cigarettes. Here we present a study of nicotine from e-cigarette liquids through reversed-phase (RP) and hydrophilic interaction (HILIC) liquid chromatography. Multiple aqueous mobile-phase additives are considered for the [...] Read more.
Nicotine is a highly used addictive substance that has recently also become available through electronic cigarettes. Here we present a study of nicotine from e-cigarette liquids through reversed-phase (RP) and hydrophilic interaction (HILIC) liquid chromatography. Multiple aqueous mobile-phase additives are considered for the RP mechanism, focusing on chaotropic agents, mobile-phase concentrations and mixing ratios, and column temperature. Sample preparation was conducted by toluene liquid–liquid extraction of e-cigarette liquids diluted with aqueous 25 mM NaHCO3/Na2CO3. Optimal RP results for retention and peak symmetry were obtained using aqueous 0.1% formic acid and 20 mM ammonium hexafluorophosphate with 0.1% formic acid in acetonitrile, using a gradient profile with a C18 column, exploited at 40 °C and a 1.5 mL/min flow rate. A dilute-and-shoot alternative with automated flow reversal after isocratic elution is presented. For HILIC, aqueous 100 mM ammonium formate and 0.1% formic acid in acetonitrile were used as mobile-phase components, using a gradient profile, on a Thermo Scientific™ Acclaim™ Mixed-Mode HILIC-1 column, operated at 25 °C with a 1 mL/min flow rate. UV detection was at 260 nm. Absolute limits of quantitation in the 1 μg/mL range were obtained for all tested alternatives, with 1 μL injection volumes. Full article
(This article belongs to the Special Issue Chromatography—The Ultimate Analytical Tool, 3rd Edition)
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10 pages, 975 KB  
Article
Neuromuscular System of Nematodes Is a Target of Synergistic Pharmacological Effects of Carvacrol and Geraniol
by Maja Stojković, Djordje S. Marjanović, Dragana Medić, Claude L. Charvet and Saša M. Trailović
Pharmaceuticals 2025, 18(8), 1232; https://doi.org/10.3390/ph18081232 - 20 Aug 2025
Viewed by 439
Abstract
Background: The active ingredients of essential plant oils appear as potentially effective antinematodal drugs or substances that can potentiate the action of already-existing anthelmintics. So far, we have verified that, aside from the direct effect on the neuromuscular system of nematodes, some of [...] Read more.
Background: The active ingredients of essential plant oils appear as potentially effective antinematodal drugs or substances that can potentiate the action of already-existing anthelmintics. So far, we have verified that, aside from the direct effect on the neuromuscular system of nematodes, some of them can potentiate the effects of drugs that are agonists or antagonists of nematode cholinergic receptors. Methods: In this study, the antinematodal effects of geraniol and carvacrol were compared, as well as their interaction in the experimental model Caenorhabditis elegans, on the contractile properties of Ascaris suum neuromuscular preparations and on the ACR-16 nicotinic acetylcholine receptor (nAChR) of A. suum expressed in Xenopus leavis oocytes. Results: The combination of geraniol and carvacrol showed a synergistic nematocidal effect in the tests on C. elegans, reducing the value of individual LC50 by almost 10-times. This combination also exerted a synergistic inhibitory effect on the contractions of A. suum, significantly increased the EC50 of ACh and reduced the maximal contractile effect. The synergistic interaction of these two monoterpenes on Asu-ACR-16 nAChR expressed in Xenopus oocytes resulted in a significant decrease in the maximum current, while the ACh EC50 value remained unchanged. Conclusions: Our findings provide a better understanding of the mode of action of monoterpene plant compounds. The possible antiparasitic application of active ingredients of essential plant oils that exhibit a synergistic anthelmintic effect represents an important basis for the development of new drugs and new therapeutic procedures. Full article
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24 pages, 393 KB  
Review
The Health Effects of Heated Tobacco Product Use—A Narrative Review
by Małgorzata Znyk and Dorota Kaleta
Healthcare 2025, 13(16), 2042; https://doi.org/10.3390/healthcare13162042 - 18 Aug 2025
Viewed by 1787
Abstract
One of the most popular currently available tobacco products is the heated tobacco product (HTP), which heats nicotine and other chemical substances into a vapor for inhalation. The aim of the present review was to clarify the effects of exposure to HTP, which [...] Read more.
One of the most popular currently available tobacco products is the heated tobacco product (HTP), which heats nicotine and other chemical substances into a vapor for inhalation. The aim of the present review was to clarify the effects of exposure to HTP, which currently remain unclear. A literature search of Web of Science, Scopus, ClinicalKey, and PubMed was conducted. The search identified 55 studies on humans and human cells in vitro (mostly independent, i.e., not funded by the tobacco sector) published from February 2021 to May 2025. Studies evaluating the effects of HTP use on the cardiovascular system indicate an increase in blood pressure, heart rate, platelet clot formation, and an enhanced inflammatory response, which is often followed by endothelial dysfunction. Increases in white blood cell counts, pro-inflammatory cytokines, leukocytes, eosinophils, platelets, IL-6, IL-2, IL-8, total NNAL, and 2,3-d-TXB2 were also observed. The studies suggest a positive correlation between HTP use and the occurrence of respiratory diseases, with particular negative effects observed on lung physiology, human bronchial epithelial cells, acute eosinophilic pneumonia, allergies, and asthma. Our findings indicate that the use of HTP is associated with possible adverse effects on the reproductive system. The review also identified new studies on the health effects of HTP use during pregnancy on the fetus, newborn, and mothers. Further research is needed to determine the short-term and long-term health effects of using HTP products. Full article
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