Search Results (916)

Background/Objectives: Alcohol and smoking during pregnancy may be associated with several complications, but the underlying mechanism is still unclear. The aim of this study was to evaluate the role of oxidative stress induced by smoking and alcohol during pregnancy and their effects on fetal and neonatal outcomes. Material and methods: We considered pregnant women at term. Validated questionnaires were used to investigate smoking and alcohol habits. Ultrasound was performed to evaluate fetal weight, amniotic fluid index, and maternal-fetal Doppler velocimetry. At the time of delivery, we collected a tuft of maternal hair, maternal venous blood, and cord blood. In these samplings we determined in phase I nicotine, cotinine, and ethyl glucuronide on the maternal keratin matrix with the gas chromatography-mass spectrometry technique. In phase II, the Free Oxygen Radicals Test (FORT) and Free Oxygen Radical Defense (FORD) test were used to assess circulating reactive oxygen species (ROS). Results: 119 pregnant patients were enrolled (n = 62 for smoking and n = 57 for alcohol). Twenty-six patients (42%) out of 62 were active smokers. Three patients (5%) out of 57 were alcoholic consumers. Mean neonatal weight and mean placental weight were significantly lower for active smokers (p = 0.0001). The neonatal weight was in the 1st–2nd percentile for all alcohol abusers. Considering two subgroups (n = 10 non-smokers and n = 10 smokers) for ROS determination, a statistically significant higher oxidative stress in the blood of smoking patients was evidenced (p < 0.0001). In cord blood the differences were not statistically significant (p = 0.2216). Conclusions: Fetal growth restriction was present in the group of active smokers and in patients with alcohol abuse. Oxidative stress was higher in smoking patients than in non-smokers. However, in cord blood, FORT was negative in all cases, suggesting a protective mechanism in utero. Given the limited sample size, the results obtained are preliminary and require future studies. Full article

Objective: To synthesize the current evidence on the cardiovascular effects of electronic cigarettes (ECs) in young adults (18–30 years), distinguishing between acute and chronic exposure, and comparing their effects to conventional tobacco (CT) use. Methods: A systematic review and meta-analysis (PROSPERO: CRD420251072847) was conducted following PRISMA guidelines. A total of 21 studies (12 RCTs, 8 case–control, 1 cohort) involving 17241 participants were included. Results: Acute EC use, particularly with nicotine, significantly increased systolic blood pressure (SBP: MD = 3.14 mmHg, 95% CI: 0.76 to 5.52), diastolic blood pressure (DBP: MD = 2.05 mmHg, 95% CI: 0.85 to 3.25), and heart rate (HR: MD = 4.23 bpm, 95% CI: 2.10 to 6.37), with effects most pronounced at 0 min post-exposure and dissipating within 1 h. Chronic EC use was associated with reduced endothelium-dependent vasodilation and early atherosclerotic changes. Nicotine-free ECs induced fewer cardiovascular alterations. Comparisons with CT revealed less severe cardiovascular damage with ECs, though still significant when compared to non-smokers. Conclusion: Nicotine-containing EC use in young individuals is associated with modest, predominantly acute and dose-dependent, cardiovascular effects, including transient increases in BP and HR. While initially less harmful than CT, the evidence is largely from cross-sectional studies and acute use, so ECs cannot be considered safe and their use warrants caution in youth. Full article

Marine sources contain compounds that act on a wide variety of systems, including ligand-gated ion channels. This review will focus on the effectors of nicotinic acetylcholine receptors (nAChRs), for which the diversity of ligands and modulators from marine sources is determined mainly by neurotoxic peptides (α-conotoxins) from mollusks of the Conus genus. These are very selective compounds that allow the study of the role of different nAChR subtypes in the cancer cells. They have analgesic or anti-inflammatory activities associated with cholinergic transmission and have shown analgesic effect in case of chemotherapy-induced neuropathic pain. Another class of marine compounds targeting nAChRs for which cytotoxicity for cancer cells was shown is represented by low molecular organic substances found mostly in dinoflagellates and marine sponges. Some of the compounds discussed in this review show promise for developing drugs that suppress cancer growth. Full article

Vaping tetrahydrocannabinol (THC), a cannabis derivative, using electronic cigarettes (e-cigarettes) could deregulate oral health and lead to oral candidiasis. This study aimed to investigate the effects of vaped THC on Candida albicans growth, metabolic activity, biofilm formation, and the expression of virulence genes. Exposure to e-cigarette aerosol with or without nicotine and with or without 10% or 15% THC increased C. albicans growth and metabolic activity; the effects were more pronounced when THC was present in the e-cigarette aerosol. Biofilm analyses showed that e-cigarette aerosol with THC significantly promoted C. albicans biofilm formation, with the higher THC concentration (15%) having the greater effect. Consistently, e-cigarette aerosol with THC increased the expression of the virulence genes EAP1, SAP2, SAP4, and SAP9. These findings suggested that exposure to vaped THC could contribute to the pathogenesis of oral candidiasis, which may lead to oral health problems. Full article

Considering the increased risk of cognitive deficits and mood disorders programming associated with bisphenol exposure, we used a preclinical model to identify short- and long-term effects of early exposure to Bisphenol A (BPA) and its replacement, Bisphenol S (BPS), on the central cholinergic and serotonergic systems. Wistar female and male rats born to dams exposed to BPA or BPS (both at 10 μg/kg/day or 50 μg/kg/day) during pregnancy and lactation were euthanized at weaning or adulthood. Cholinergic and serotonergic biomarkers were assessed in the frontal cortex and pons + medulla oblongata. BPA and BPS disrupted these systems, with outcomes depending on the specific bisphenol, biomarker, and time point. Effects also varied across brain regions and between sexes. The nicotinic cholinergic receptor showed more pronounced alterations than the presynaptic choline transporter. Both serotonergic receptors—5-HT1AR and 5-HT2R—were affected; however, the serotonergic transporter remained unchanged. Increased binding was the predominant effect for both systems. Maternal exposure to BPA, even at low doses, induces sex-dependent short- and long-term changes in the cholinergic and serotonergic systems of the progeny. BPS affects these same neurotransmitter systems, although leading to compound-specific outcomes. These results pose both BPA and BPS as neurotoxicants that compromise neurodevelopment and program disorders later in life. Full article

Bethanechol chloride, a nonselective muscarinic agonist, is the most frequently employed drug in dogs and cats to induce detrusor smooth muscle contraction under conditions characterized by poor or absent bladder emptying. Although this drug has minimal or absent nicotinic activity, at higher doses, weak stimulation of neuronal nicotinic receptors may occur, causing the release of noradrenaline, which induces contraction of the urethral smooth muscle by activating α-adrenergic receptors. In the presence of total or partial suprasacral lesions, the elaboration and initiation phase of the urination process is absent due to an interruption of afferent signals from the bladder to the brainstem. In such cases, hypertonicity of the urethral sphincters is expected, and bethanechol is contraindicated. Bethanechol is also not indicated for reflex dyssynergia. In the presence of complete injuries involving the sacral segments, cauda equina, or pelvic nerve, both reflex and voluntary micturition are abolished, and bethanechol is usually ineffective. However, in cases of partial injuries, bethanechol is likely to be effective, as partial integrity of the micturition reflex is required to produce sustained bladder contraction. Bethanechol may benefit patients with myopathic decompensated bladder, although its effectiveness depends on the severity of detrusor damage. Full article

Background/Objectives: The differential diagnosis between primary polycythemia vera (PV) and secondary polycythemia (SP) presents significant clinical challenges owing to substantial phenotypic overlap. This investigation utilized untargeted metabolomic approaches to elucidate disease-specific metabolic perturbations and evaluate the metabolic consequences of cytoreductive therapeutic interventions. Methods: Plasma specimens obtained from PV patients (n = 40) and SP patients (n = 25) underwent comprehensive metabolomic profiling utilizing liquid chromatography–mass spectrometry (LC-MS) platforms. Multivariate statistical analyses, including principal component analysis (PCA), were employed in conjunction with pathway enrichment analyses to characterize disease-associated metabolic dysregulation. Additionally, receiving treatment (tPV) (n = 25) and not receiving treatment (ntPV) (n = 15) PV patients were compared to assess therapeutic metabolic effects. Results: Comprehensive metabolomic analysis identified 67 significantly altered metabolites between PV and SP patients, with 36 upregulated and 31 downregulated in PV. Key upregulated metabolites in PV included thyrotropin-releasing hormone, 3-sulfinoalanine, nicotinic acid adenine dinucleotide, and protoporphyrin IX, while 4-hydroxyretinoic acid and deoxyuridine were notably downregulated. Pathway enrichment analysis revealed disruptions in taurine, glutamate, nicotinate, and cysteine metabolism in PV. ntPV patients exhibited higher glucose and octanoyl-CoA levels compared to treated patients, indicating the normalization of glucose and fatty acid metabolism with cytoreductive therapy. ntPV was also associated with altered B-vitamin metabolism, including decreased nicotinic acid adenine dinucleotide and increased nicotinamide ribotide levels. Cross-comparison analysis revealed overlapping pathway enrichment in glutamate metabolism, nicotinate and nicotinamide metabolism, and cysteine metabolism between both comparisons. Conclusions: This study demonstrates that PV and SP exhibit fundamentally distinct metabolic signatures, providing novel insights into disease pathogenesis and potential diagnostic biomarkers. The identification of oxidative stress signatures, disrupted energy metabolism, and altered B-vitamin cofactor pathways distinguishes PV from SP at the molecular level. Cytoreductive therapy significantly normalizes metabolic dysregulation, particularly glucose and nucleotide metabolism, validating current therapeutic approaches while revealing broader systemic treatment effects. The metabolic signatures identified, particularly the combination of deoxyuridine, thyrotropin-releasing hormone, and oxidative stress metabolites, may serve as complementary diagnostic tools to traditional morphological and molecular approaches. These findings advance our understanding of myeloproliferative neoplasm pathophysiology and provide a foundation for developing metabolically targeted therapeutic strategies and precision medicine approaches in PV management. Full article

Substance use disorders (SUDs) remain a major global health challenge with limited treatment options and high relapse rates. Vaccines that induce drug-sequestering antibodies have shown promise, but their efficacy is hindered by the poor immunogenicity of small-molecule haptens. Adjuvants, substances that enhance immune responses, are critical for overcoming this limitation and improving vaccine efficacy. This review synthesizes over two decades of preclinical and clinical research to guide rational adjuvant design for SUD vaccines. Five major adjuvant classes are examined: aluminum-salt adjuvants, emulsion adjuvants, toll-like receptor (TLR) agonists, protein immunopotentiators, and cytokine modulators. Their physicochemical properties, innate immune activation profiles, and applications in nicotine, stimulant, and opioid vaccines are discussed. Comparative analyses reveal pronounced drug-specific and carrier-specific variability. Case studies illustrate the superior performance of a complementary TLR-agonist pair in a nicotine nanovaccine versus its limited effect in oxycodone vaccines. They also reveal the differential efficacy of an oil-in-water emulsion adjuvant across antigen types. Four principles emerge: (i) no adjuvant is universally optimal; (ii) drug pharmacology influences immune signaling; (iii) adjuvant-carrier compatibility is important; (iv) complementary adjuvant pairings often outperform single agents. These insights support a precision-vaccinology paradigm that tailors adjuvant strategies to each drug class and the delivery vehicle, advancing the development of next-generation SUD vaccines. Full article

(1) Introduction: Arab American (ArA) men have higher smoking rates than the general population, driven by cultural norms. Culturally tailored interventions that incorporate ArA cultural, linguistic, and social contexts are essential for addressing tobacco use and promoting health equity. This study aimed to evaluate a culturally tailored smoking cessation intervention for ArA men living in North Carolina. (2) Methods: This pilot study employed a one-group pre- and post-test design to evaluate program effectiveness within financial and time constraints. The participants completed questionnaires and Carbon monoxide measurements and were provided with Nicotine Replacement therapy. (3) Results: The study found that participants experienced anxiety and stress when delaying their first morning cigarette, which hindered cessation. Although smoking was reduced, relapse was common, highlighting the need for personalized support, especially for those with higher nicotine dependence. While telephone Motivational Interviewing helped reduce anxiety, it was insufficient for complete cessation, underscoring the need for tailored approaches addressing both psychological and physical factors. (4) Conclusions: The study suggests that culturally tailored telephone counseling did not show promise as a smoking cessation strategy for Arab Americans in North Carolina due to low participation. The sample size is really too small to test the efficacy of the intervention itself. It seems to have been more successful in another state. Future efforts should address cultural factors, emerging nicotine products, and expanded research. The project is significant for addressing health disparities among Arab Americans by integrating culturally relevant smoking cessation strategies with evidence-based methods like Nicotine Replacement Therapy. Full article

Keloids are characterized by excessive extracellular matrix (ECM) accumulation and persistent inflammation, leading to disfiguring scars and poor therapeutic outcomes. The α7 nicotinic acetylcholine receptor (α7nAChR) has emerged as a key modulator of inflammatory and fibrotic signaling. This study evaluated the antifibrotic effects of tropisetron, a clinically available α7nAChR agonist, in keloid fibroblasts (KFs) and a rat incisional scar model. In vitro, KFs exhibited reduced α7nAChR expression, which was restored by tropisetron in a dose-dependent manner. Tropisetron treatment significantly decreased KF viability, downregulated pro-fibrotic genes (COL1A1, COL3A1, α-SMA), and upregulated matrix metalloproteinases (MMP1 and MMP3). Additionally, it suppressed phosphorylation of Smad2/3 and reduced expression of NF-κB and TNF-α, indicating inhibition of both TGF-β and inflammatory pathways. In vivo, tropisetron-treated rats showed a ~40% reduction in scar area, improved collagen organization, and increased α7nAChR expression in scar tissue. Western blot analysis confirmed decreased levels of collagen I, p-Smad2/3, α-SMA, NF-κB, and TNF-α. These results indicate that tropisetron exerts dual antifibrotic and anti-inflammatory effects through α7nAChR-mediated signaling and enhanced ECM remodeling. This study provides the first evidence supporting α7nAChR activation as a promising therapeutic strategy for managing keloids and other fibrotic skin disorders. Full article

Smoking has a well-established impact on cardiovascular health, notably through elevated resting heart rate and impaired autonomic regulation—both key risk factors. While nicotine’s acute effects are well documented, the influence of smoking-related genetic variants on heart rate (HR) responses remains unclear. This study investigated the association between selected smoking-related single nucleotide polymorphisms (SNPs) and HR dynamics following physical exertion. A total of 661 Hungarian adults completed the YMCA 3 min step test, with HR measured at rest, immediately post-exercise, and during recovery at 5 and 10 min. Key indices included post-exercise HR (HR_aft), HR change (ΔHR), maximum HR percentage (HR_max%), and heart rate recovery coefficient (HRR). Genetic analysis focused on nine SNPs previously linked to smoking behaviours, with a composite genetic risk score derived from the three most influential variants (rs2235186, rs4142041, and rs578776). Associations were examined using adjusted linear regression. No significant relationship was found between any individual SNP and resting HR. However, rs2235186, rs4142041, and rs578776 were consistently associated with elevated HR_aft, increased ΔHR, higher HR_max%, and slower HRR. The genetic risk score showed significant correlations with all post-exercise HR measures, suggesting a cumulative genetic effect. These findings indicate that smoking-related genetic predisposition may influence autonomic cardiovascular responses to physical activity. Although resting HR remains unaffected, specific SNPs are linked to post-exercise HR dynamics and recovery, highlighting the potential value of genetic screening in personalised cardiovascular risk assessment among smokers. Full article

Background: Epilepsy is a chronic, non-communicable brain disorder characterized by recurrent seizures. Some derivatives of 1,2,3,4-tetrahydroisoquinolines have demonstrated anticonvulsant effects. This study aims to investigate the effects of 33 derivatives of 1-aryl-1,2,3,4-tetrahydroisoquinoline on seizures induced by nicotine and strychnine. Methods: The anticonvulsant effects of 1-aryl-1,2,3,4-tetrahydroisoquinoline derivatives were evaluated in white male mice. Convulsant agents were administered subcutaneously at doses of 10.0 mg/kg for nicotine and 1.5 mg/kg for strychnine, 60 min after the oral administration of the test compounds at doses ranging from 0.1 to 10 mg/kg. The onset time, duration of tremors and seizures, and survival rate of the animals were recorded. The docking studies were conducted for 32 tested compounds targeting the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (PDB ID: 1FTL). Furthermore, a predictive ADMET study was conducted to evaluate the pharmacokinetic and toxicity profiles of the compounds. Results: Compounds 20 and 25 exhibited the highest activity against strychnine-induced seizures. When evaluating the effects of 1-aryl-1,2,3,4-tetrahydroisoquinolines and reference drugs on the tremorogenic and convulsive actions of nicotine at doses of 0.1–5 mg/kg, compounds 3, 6, 8, 14, 16, 25, 27, 29, 30, 31, and 34 demonstrated comparable activity to the reference drugs. The docking results targeting AMPA (PDB ID: 1FTL) revealed comparable binding interactions for most of the compounds, with a (−)C-Docker interaction energy range of 33.82–45.41 Kcal/mol, compared to that of the ligand (41.60 Kcal/mol). The structural requirements of the studied scaffold were analyzed to identify the essential pharmacophoric features for anticonvulsant activity. Furthermore, a predictive ADMET study was conducted to evaluate the pharmacokinetic and toxicity profiles of the compounds. Conclusions: Certain derivatives of 1,2,3,4-tetrahydroisoquinolines may serve as potential anticonvulsant agents for epilepsy. Full article

Background: Heated tobacco products (HTPs) are marketed as reduced-harm alternatives to conventional cigarettes (CCs) and are increasingly used by young adults and occasional smokers. However, their acute nicotine delivery and user experience remain insufficiently studied in occasional smokers without established cigarette or nicotine dependence. Additives such as menthol—known to reduce sensory irritation and facilitate inhalation—may further influence initiation and product appeal, particularly in naïve users. Methods: In a crossover study with three separate study days, n = 15 occasional smokers without established cigarette or nicotine dependence consumed a mentholated HTP (mHTP), a non-mentholated HTP (nmHTP), and a conventional cigarette (CC) under ad libitum conditions during a 30 min observation. We measured plasma nicotine concentrations, smoking topography, cardiovascular parameters, and subjective effects (mCEQ). Results: Nicotine pharmacokinetics (Cmax, AUC) were comparable across products (Cmax 7.8–8.5 ng/mL; AUC 2.3–2.8 ng·min/mL [geometric means]; no significant differences), even though participants had no prior experience with HTPs. Compared to CCs, HTPs were associated with longer puff durations (2.09 s mHTP/2.00 s nmHTP vs. 1.78 s CC), higher puff volumes (mean: 68.06/68.16 vs. 43.76 mL; total: 949.80/897.73 vs. 522.41 mL), and greater flow rates (mean 37.49/38.25 vs. 27.68 mL/s; peak 63.24/63.69 vs. 44.38 mL/s). Subjective effects did not differ significantly between products (mCEQ subscale examples: satisfaction 3.00–3.33/7; reward 2.81–3.31/7; craving reduction 5.07–5.60/7). Cardiovascular parameters such as heart rate or systolic blood pressure showed with no between-product differences (HR p = 0.518; SBP p = 0.109) and no differences in their change over time between products (HR p = 0.807; SBP p = 0.734). No differences were observed between mHTP and nmHTP. Conclusion: HTPs can deliver nicotine and evoke user experiences similar to CCs, even in non-dependent users. The more intensive inhalation behavior observed with HTPs may reflect compensatory use and merits further investigation. Although no menthol-specific effects were observed, methodological constraints may have limited their detectability. Full article

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

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