Ethanol (EtOH) is a common trigger for gastric mucosal diseases, and mitigating oxidative stress is essential for attenuating gastric mucosal damage. Capsaicin (CAP) has been identified as a potential agent to counteract oxidative damage in the gastric mucosa; however, its precise mechanism remains unclear. This study demonstrates that CAP alleviates EtOH-induced gastric mucosal injuries through two primary pathways: by suppressing the chemokine receptor 4 (CCR4)/Src/p47phox axis, thereby reducing oxidative stress, and by inhibiting the phosphorylation and nuclear translocation of nuclear factor-κB p65 (NF-κB) p65, resulting in diminished inflammatory responses. These findings elucidate the mechanistic pathways of CAP and provide a theoretical foundation for its potential therapeutic application in the treatment of gastric mucosal injuries.
Ethanol/toxicity* ; Animals ; Gastric Mucosa/metabolism* ; Signal Transduction/drug effects* ; Oxidative Stress/drug effects* ; Capsaicin/pharmacology* ; Male ; NADPH Oxidases/genetics* ; Mice ; Humans ; src-Family Kinases/genetics*

Humans ; Electronic Nicotine Delivery Systems ; Prevalence ; Mental Disorders/epidemiology* ; Smoking/epidemiology* ; Perception

Nicotine addiction is a concern worldwide. Most mechanistic investigations are on nicotine substance dependence properties based on its pharmacological effects. However, no effective therapeutic treatment has been established. Nicotine addiction is reinforced by environments or habits. We demonstrate the neurobiological basis of the behavioural aspect of nicotine addiction. We utilized the conditioned place preference to establish nicotine-associated behavioural preferences (NABP) in rats. Brain-wide neuroimaging analysis revealed that the medial prefrontal cortex (mPFC) was activated and contributed to NABP. Chemogenetic manipulation of µ-opioid receptor positive (MOR⁺) neurons in the mPFC or the excitatory outflow to the nucleus accumbens shell (NAcShell) modulated the NABP. Electrophysiological recording confirmed that the MOR⁺ neurons directly regulate the mPFC-NAcShell circuit via GABA_A receptors. Thus, the MOR⁺ neurons in the mPFC modulate the formation of behavioural aspects of nicotine addiction via direct excitatory innervation to the NAcShell, which may provide new insight for the development of effective therapeutic strategies.
Animals ; Nucleus Accumbens/drug effects* ; Prefrontal Cortex/drug effects* ; Nicotine/pharmacology* ; Receptors, Opioid, mu/metabolism* ; Male ; Rats ; Rats, Sprague-Dawley ; Tobacco Use Disorder/metabolism* ; Neurons/drug effects* ; Neural Pathways/drug effects*

INTRODUCTION

Tobacco smoking is one of the most significant preventable lifestyle risk factors, causing a wide range of diseases and causing harm to millions of people worldwide. Nicotine replacement treatment (NRT) and behavioral counseling have long been used to help people quit smoking. However, because pharmacologic and behavioral therapy only have a 22% to 45% success rate in smoking cessation, a systematic review and meta-analysis was conducted to evaluate ear acupuncture’s usefulness as an adjunct to nicotine replacement therapy and behavioral counseling for smoking cessation.

This systematic review only included randomized controlled trials which involved current smokers aged 19 years or older, and who were in the contemplation stage according to the Transtheoretical Model of Intentional Behavior of Change. The RevMan 5 software was used in the analysis of data. The primary outcome that was measured is the rate of continuous abstinence based on participant/patient report at the end of treatment and secondary outcome of the study was reporting of nicotine withdrawal symptoms.

Of the 1,661 identified records, only 2 studies were included (both RCTs) in the meta- analysis. The studies were rated with low to unclear selection bias and high risk of performance bias. The pooled estimates of effect were statistically significant in favor of ear acupuncture plus counseling (standard therapy), RR= 2.28, 95% CI 1.27, 4.08, p= 0.006, I2= 0%. Nicotine withdrawal symptoms were noted to be less pronounced in those who received the intervention of ear acupuncture even after 3 months post-treatment. The evidence was graded as low quality, indicating that more research is needed and would extremely likely have a significant impact on confidence in the estimate of effect.

The results of this systematic review and meta-analysis suggest that ear acupuncture produces an additive benefit on counseling (standard of care) as a means of smoking cessation. Future research should be conducted using RCTs of a high quality in order to address the substantial risk of bias that was present in the studies that were included and to improve the quality of the evidence.

Humans ; Nicotine ; Non-alcoholic Fatty Liver Disease ; Bacteroides

Objective: To investigate the effects of nicotine on the morphology, structure of offspring's dental germ, enamel organ and other dental tissues and the further potential epigenetic mechanisms by establishing prenatal nicotine exposure mouse model. Methods: Ten C57BL/6 pregnant mice were randomly divided into control group (physiological saline subcutaneous injection) and prenatal nicotine exposure (PNE) group (nicotine subcutaneous injection) by using a random number table. Postnatal day 0 (P0), postnatal day 14 (P14) and postnatal day 25 (P25) offspring mice were collected for subsequent experiments. The offspring mice were divided into offspring control group and offspring PNE group according to the maternal group respectively. Weights of P0 and P25 offspring mice were recorded. Micro-CT, scanning electron microscope (SEM) and Vickers hardness test were performed to analyze the related parameters of hard tissues including alveolar bones and mandibular incisors. Total RNAs were extracted from mandible tissues and the third generation of dental epithelial stem cells (DESC) in P25 mice. The relative expression levels of osteogenic and ameloblastic differentiation related genes were measured by real-time quantitative PCR (RT-qPCR). Immunohistochemical stainings of paraffin sections were then performed to observe the distribution and expression level of proliferating cell nuclear antigen (Pcna), amelogenin (Amelx), histone H3 trimethylated at lysine 27 (H3K27me3) and enhancer of zeste homolog 2 (Ezh2). Cell counting kit-8 (CCK-8) assays were used to detect the cell viabilities of DESCs after administrations of different concentrations of nicotine (0.01, 0.1, 1 mmol/L) and GSK126 (an inhibitor of histone methyltransferase Ezh2). Results: Compared with the control group, pregnant mice in PNE group were more likely to have adverse pregnancy outcomes, such as significantly lower offspring body weight [P0: offspring control (1.20±0.04) g, offspring PNE (0.99±0.02) g, P<0.001; P25: offspring control (15.26±1.70) g, offspring PNE (9.65±1.32) g, P<0.001] and increased stillbirths rate [offspring control (0), offspring PNE (46.40±9.30) %, P<0.001]. At P14 and P25, the distance parameters between the enamel mineralized deposits of mandibular incisors and the mesial surface of the first molar in offspring PNE group [P14: (-1 349±45) μm; P25: (-1 192±147) μm] was significantly decreased compared with the control group [P14: (-506±380) μm, P25: (504±198) μm] (P<0.05, P<0.001). The enamel column and enamel column stroma of incisors in offspring PNE group were blurred, arranged loosely and disorderly than those in the control group, while the microhardness of incisor enamel in offspring PNE group [(245.7±18.4) MPa] was significantly lower compared to the control group [(371.9±28.7) MPa] (P<0.001). HE staining showed disordered pre-ameloblast (Pre-Am) arrangement and delayed mineralization deposition point in offspring PNE group compared with the control group, while the length of transit-amplifying cell (TA) and Pre-Am region were prolonged as well. Immunohistochemical staining results displayed that the overall Pcna (P<0.05), H3K27me3 (P<0.01), Ezh2 (P<0.01) expression of labial cervical loop (LaCL) in PNE group were increased, while the positive signal of Amelx in ameloblast cytoplasm was impaired. In vitro, the addition of 1 mmol/L nicotine could significantly upregulate the expression level of Pcna (P<0.01) and downregulate the expression levels of B lymphoma Mo-MLV insertion region 1 (P<0.05), leucine rich repeats and immunoglobulin like domains 1 (P<0.05), Amelx (P<0.01). In addition, 1 mmol/L nicotine could also significantly enhance the proliferation activity of DESCs (P<0.001). Addition of 10 μmol/L GSK126, could rescue the proliferation activation effect of 1 mmol/L nicotine on DESCs. Conclusions: PNE may delay the process of enamel formation and lineage differentiation, leading to the abnormal proliferation of DESCs and changes of epigenetic modification state in H3K27me3, which affect the development of enamel in offspring mice,suggesting PNE might be one of risk environmental factor for tooth development.
Pregnancy ; Female ; Mice ; Animals ; Nicotine/toxicity* ; Proliferating Cell Nuclear Antigen ; Histones ; Mice, Inbred C57BL ; Dental Enamel

Objective: To explore the influencing factors of electronic cigarette use among adolescent students in China. Methods: We searched CNKI, Database of Chinese sci-tech periodicals (VIP), Wan-fang database, PubMed, Web of Science and ScienceDirect for potentially relevant articles published from the inception to March 20th, 2023. The Metagen package in R was used for Meta-analysis. Results: A total of 19 publications with a sample size of 5 336 017 were identified. The results showed that electronic cigarette use among Chinese adolescent students was associated with gender (OR=2.41, 95%CI: 2.03-2.86), close friends smoking (OR=3.02, 95%CI: 2.08-4.39), current smoking (OR=11.26, 95%CI: 4.35-29.18), friends using electronic cigarettes (OR=5.19, 95%CI: 2.01-13.38), thinking smoking makes young people look more attractive (OR=2.00, 95%CI: 1.35-2.97), type of school (OR=2.10, 95%CI: 1.59-2.78), thinking smoking makes people feel more comfortable in social situations (OR=3.58, 95%CI: 2.99-4.28), other tobacco use (OR=5.53, 95%CI: 3.33-9.20), and ever experimented with cigarette use (OR=9.32, 95%CI: 4.38-19.80). Conclusion: The influencing factors for electronic cigarette use among adolescent students in China include gender, close friends smoking, current smoking, friends using electronic cigarettes, thinking smoking makes young people look more attractive, type of school, thinking smoking makes people feel more comfortable in social situations, other tobacco use, and ever experimented with cigarette use.
Adolescent ; Humans ; Cross-Sectional Studies ; East Asian People ; Electronic Nicotine Delivery Systems ; Students ; Vaping

To evaluate e-cigarette vaping-induced respiratory toxicity and the interventional effects of air cleaners. A randomized controlled trial study of toxic vaping by the respiratory tract were conducted at the Key Laboratory of Environmental Medical Engineering, Ministry of Education, the School of Public Health, Southeast University from January to December 2022. 8-week-old male C57BL/6JGpt mice selected with a random number table method were used to establish a vaping-exposure model at different periods (0 d, 3 d, 7 d or 14 d), or exposed to clean air as a control group. Mice were exposed to regular heated vaping (200 ℃) and high-temperature heated vaping (280 ℃). Total lung RNA was extracted from control and e-cigarette exposed mice for transcriptome sequencing analysis. Reactive Oxygen Species (ROS) generation and mitochondrial membrane potential (MMP) were detected by flow cytometry. Total superoxide dismutase (SOD) and superoxide (O^2-) were evaluated using a microplate reader. Real-Time Quantitative PCR (RT-qPCR) was used to detect gene expression. Air filter and ionizer were used to intervene the toxicity of vaping. Data were expressed as (x¯±s), differences between multiple groups were compared using one-way or two-way ANOVA. The results showed that, RNA sequencing assays suggested that the differential genes between the control and vaping exposure groups were significantly enriched in the oxidative stress (Fold Enrichment=3.18) and mitochondrial oxidative phosphorylation (OXPHOS) (Fold Enrichment=5.74) pathways. Both types of heated vaping exposure caused significantly increased the score of alveolitis (F=10.8, P<0.001), increased endogenous ROS generation (F=16.8, P<0.001), decreased MMP (F=13.6, P<0.01), and gene expression of mitochondrial complex I dysfunction. The toxic effects of high-temperature heated vaping were stronger compared to regular heated vaping (F=2.9, P<0.05). The filter demonstrated better protective effects against vaping than the ionizer by reducing pulmonary alveolitis (F=7.4, P<0.01). Air cleaners could partially alleviate oxidative stress and mitochondrial dysfunction. In conclusion, this study demonstrate that vaping brings potential health risks. Air cleaners could partially reverse mitochondrial dysfunction, but cannot completely prevent the toxic effects, effective interventions remain to be investigated.
Humans ; Male ; Animals ; Mice ; Mice, Inbred C57BL ; Electronic Nicotine Delivery Systems ; Reactive Oxygen Species ; Vaping ; Mitochondrial Diseases

Objective: To investigate the effect of sugammadex on postoperative nausea and vomiting(PONV) after intracranial aneurysm surgery. Methods: Data from intracranial aneurysms patients who met the inclusion and exclusion criteria and underwent interventional surgery in the Department of Neurosurgery, Peking University International Hospital from January 2020 to March 2021 were prospectively included. According to the random number table method, the patients were divided by 1∶1 into the neostigmine+atropine group (group N) and the sugammadex group (group S). Use an acceleration muscle relaxation monitor for muscle relaxation monitoring, and administer neostigmine+atropine and sugammadex to block residual muscle relaxation drugs after surgery. The incidence rates of PONV and severity, the appearance of anesthesia, and the correlation between PONV and postoperative complications were recorded in both groups during five periods after surgery: 0-0.5 hours (T1),>0.5-2.0 hours(T2),>2.0-6.0 hours (T3),>6.0-12.0 hours (T4) and >12.0-24.0 hours (T5). Group comparisons of quantitative data were performed by the independent sample t-test, and categorical data was performed by the χ² or rank sum test. Results: A total of 66 patients were included in the study, including 37 males and 29 female, aged (59.3±15.4) years (range: 18 to 77 years). The incidence rates of PONV of 33 patients in group S at different time periods of T1, T2, T3, T4, and T5 after surgery were respectively 27.3%(9/33),30.3%(10/33),12.1%(4/33),3.0%(1/33),0(0/33),and the incidence rates of PONV of 33 patients in the group N at different time periods of T1, T2, T3, T4 and T5 after surgery were respectively 36.4%(12/33),36.4%(12/33),33.3%(11/33),6.1%(2/33) and 0(0/33).The incidence of PONV was lower in the group S only in the T3 period after reversal than in the group N (χ²=4.227, P=0.040).However, there was no statistically significant difference in the incidence of PONV between the two groups of patients in other periods (all P>0.05). The recovery time for spontaneous breathing in patients in group S was (7.7±1.4) minutes, the extubation time was (12.4±5.3) minutes, and the safe exit time for anesthesia recovery was (12.3±3.4) minutes; the N groups were (13.9±2.0) minutes, (18.2±6.0) minutes, and (18.6±5.2) minutes, respectively; three time periods in group S were shorter than those in group N, and the differences were statistically significant (all P<0.05). The results regarding the occurrence of complications in patients with different levels of PONV at different time intervals after surgery in the two groups were as follows: in the T3 time period of group N, a significant difference was observed only in the occurrence of postoperative complications among patients with different levels of PONV (χ²=24.786, P<0.01). However, in the T4 time period, significant differences were found in the occurrence of postoperative complications among both the same level and different level PONV patients (χ²=15.435, 15.435, both P<0.01). Significant differences were also observed in the occurrence of postoperative complications among the same level and different level PONV patients in both the T3 and T4 time periods of group S (all P<0.01). Conclusion: Sugammadex can be used to reverse muscle relaxation in patients undergoing intracranial aneurysm intervention surgery,and it does not have a significant impact on the incidence of PONV, it can also optimize the quality of anesthesia recovery and reduce the incidence of complications after intracranial aneurysm embolization surgery.
Male ; Humans ; Female ; Sugammadex ; Postoperative Nausea and Vomiting/chemically induced* ; Neostigmine/adverse effects* ; Intracranial Aneurysm/surgery* ; gamma-Cyclodextrins/adverse effects* ; Atropine

OBJECTIVES: To establish the GC-MS qualitative and quantitative analysis methods for the synthetic cannabinoids, its main matrix and additives in suspicious electronic cigarette (e-cigarette) oil samples. METHODS: The e-cigarette oil samples were analyzed by GC-MS after diluted with methanol. Synthetic cannabinoids, its main matrix and additives in e-cigarette oil samples were qualitatively analyzed by the characteristic fragment ions and retention time. The synthetic cannabinoids were quantitatively analyzed by using the selective ion monitoring mode. RESULTS: The linear range of each compound in GC-MS quantitative method was 0.025-1 mg/mL, the matrix recovery rate was 94%-103%, the intra-day precision relative standard deviations (RSD) was less than 2.5%, and inter-day precision RSD was less than 4.0%. Five indoles or indazole amide synthetic cannabinoids were detected in 25 e-cigarette samples. The main matrixes of e-cigarette samples were propylene glycol and glycerol. Additives such as N,2,3-trimethyl-2-isopropyl butanamide (WS-23), glycerol triacetate and nicotine were detected in some samples. The content range of synthetic cannabinoids in 25 e-cigarette samples was 0.05%-2.74%. CONCLUSIONS The GC-MS method for synthesizing cannabinoid, matrix and additive in e-cigarette oil samples has good selectivity, high resolution, low detection limit, and can be used for simultaneous qualitative and quantitative analysis of multiple components; The explored fragment ion fragmentation mechanism of the electron bombardment ion source of indole or indoxamide compounds helps to identify such substances or other compounds with similar structures in cases.
Gas Chromatography-Mass Spectrometry/methods* ; Electronic Nicotine Delivery Systems ; Illicit Drugs/analysis* ; Indazoles/chemistry* ; Glycerol/analysis* ; Cannabinoids ; Indoles/chemistry* ; Ions