Search Results (143)

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide, primarily driven by chronic airway inflammation due to cigarette smoke exposure. Despite its burden, however, current anti-inflammatory therapies offer limited efficacy in preventing disease progression. Plasminogen activator inhibitor-1 (PAI-1), as a key regulator of fibrinolysis, has recently been implicated in structural airway changes and persistent inflammation in patients with COPD. This study aimed to investigate the ability of the PAI-1 inhibitor TM5441 to attenuate airway inflammation and structural lung damage induced by a cigarette smoke extract (CSE) in a mouse model. Mice received intratracheal CSE or vehicle on days 1, 8, and 15, and were sacrificed on day 22. TM5441 (20 mg/kg) was administered orally from days 1 to 22. The CSE significantly increased the mean linear intercept, destructive index, airway resistance, and reductions in dynamic compliance. The CSE also increased the numbers of neutrophils and macrophages in the bronchoalveolar lavage fluid, systemic PAI-1 activity, and neutrophil elastase mRNA and protein expression in the lungs. TM5441 treatment significantly suppressed these changes without affecting coagulation time. These findings suggest that TM5441 may be a novel therapeutic agent for COPD by targeting PAI-1-mediated airway inflammation and emphysema. Full article

Chronic obstructive pulmonary disease (COPD), whose main risk factor is cigarette smoking, is among the most prevalent diseases worldwide. Previous studies have shown that cigarette smoke extract (CSE) can directly affect pulmonary artery function independently of hypoxia resulting from the airway obstruction. In addition, CSE also affects bronchial smooth muscle, leading to airway hyper-responsiveness. However, its specific impact on the contractile machinery of this compartment remains unclear. In this study, using in vitro experiments with human bronchial smooth muscle cells (hBSMCs), we found that CSE exposure disrupted calcium homeostasis, increased ROS and lipid peroxidation, and reduced cell antioxidant defenses. Furthermore, CSE exposure altered the cell contractile apparatus by decreasing key cytoskeletal proteins and impairing actin dynamics, potentially contributing to the dysregulated contractile response of cells. Notably, these effects were significantly attenuated by antioxidant drugs such as mitoTEMPO and N-acetylcysteine, as well as by the inhibition of the endoplasmic reticulum (ER) calcium channels with 2-aminoethoxydiphenyl borate (2-APB). More importantly, mitoTEMPO partially restored the contractile response of bronchus upon CSE challenge. Collectively, our findings give evidence that CSE-mediated increase in ROS and intracellular calcium contribute to cytoskeletal disruption and functional impairment in airway smooth muscle. Moreover, these results also point to potential therapeutical approaches for mitigating the harmful effects of cigarette smoke in the lung. Full article

Background: Naringenin has demonstrated potential therapeutic effects against cigarette smoke-induced lung injury; however, its underlying mechanisms of regulating matrix metalloproteinase-9 (MMP-9) in alveolar macrophages remain unclear. Methods: The regulatory mechanisms of naringenin in cigarette smoke extract (CSE)-induced alveolar macrophages were investigated using proteomics, and then, naringenin’s targets were further validated by Western blot, molecular docking, molecular dynamics (MD) simulations, cellular thermal shift assay (CETSA), and enzyme activity assay. Results: The proteomics revealed that the PI3K/AKT signaling pathway might play a crucial role in naringenin’s inhibition of MMP-9. Western blot analysis confirmed that naringenin significantly inhibited CSE-upregulated PI3K/AKT signaling pathway and reduced MMP-9 expression in MH-S cells. Notably, the PI3K activator 740Y-P reversed naringenin’s effects on MMP-9. Additionally, molecular docking, MD simulations, and CETSA identified PI3K p85alpha as the potential binding site for naringenin, and naringenin markedly inhibited CSE-induced PI3K activity. In in vitro experiments, naringenin inhibiting MMP-9 secretion in alveolar macrophages contributed to alleviating elastin and E-cadherin damage in alveolar epithelial cells. Furthermore, naringenin effectively suppressed CSE-induced MMP-9 secretion in primary mouse alveolar macrophages and human THP-1-differentiated macrophages. Conclusions: Our findings revealed that naringenin, a potential candidate for treating smoking-induced lung injury, directly targeted PI3K p85alpha, inhibiting PI3K activity and MMP-9 expression in CSE-induced alveolar macrophages via suppressing the PI3K/AKT signaling pathway. Full article

Pulmonary fibrosis (PF) is a chronic pulmonary disease characterized by excessive extracellular matrix (ECM) deposition, with cigarette smoking being a major risk factor and no effective treatment at present. Transforming growth factor beta 1 (TGF-β1) plays a key role in PF and regulating oxidative stress. This study investigated the effects and mechanisms of Artemisia rupestris L. ethanol extract (ER) on cigarette smoke (CS)-induced PF. We used pull-down and LC–MS analyses to screen and identify compounds that bind to TGF-β1 in ER. We demonstrated that ER inhibits CS-induced PF, lung inflammation, and oxidative stress, thereby improving pulmonary structural injury. The ER inhibits fibroblast activation and fibroblast-to-myofibroblast transition (FMT), reducing collagen deposition for the treatment of PF. We identified the active ingredient in ER that binds to TGF-β1, namely, Luteolin 7-glucuronide (LG). LG inhibits the TGF-β1 signaling pathway through targeted binding to TGF-β1, downregulates the expression of downstream proteins (including collagen I, α-SMA, MMP-2, and MMP-9), and inhibits fibronectin expression. It also inhibits fibroblast activation and FMT, enhances E-cadherin expression to promote fibroblast adhesion, and suppresses collagen deposition, alleviating PF. Based on these findings, we propose that LG might be a promising therapeutic drug candidate for treating PF. Full article

Background: Nrf2 plays a key role in regulating the antioxidant response against oxidative stress. Therefore, it is imperative to examine the advantages of Nrf2 activation by new small molecules capable of inhibiting the Nrf2-Keap1 protein interaction that do not present electrophilic sites, since electrophilic compounds have intrinsic toxicity. The bixin pigment has been used as a form of treatment and prevention of several pathological conditions in animal models since it was described as an Nrf2 activator without electrophilic sites. This study aims to synthetize a soluble derivate KBx (potassium bixinate) and evaluate its ability to activate Nrf2/ARE in a model of exposure to cigarette smoke extract (CSE; in vitro) and intranasal LPS administration (in vivo). Methods: In the in vivo study, C57BL/6 mice were pretreated with 200 mg/kg of KBx (gavage) during 5 consecutive days and then challenged with 60 µg of LPS i.n. for 16 h. Bronchoalveolar lavage was collected to examine cytokines dosage. In the in vitro study, RAW 264.7 macrophages were exposed to CSE and post-treated with KBx to evaluate their ability to revert the redox imbalance caused by the stressor. Results: KBx was characterized using mass spectrometry (433.1778 m/z). KC levels were increased in the LPS group (p = 0.021), and KBx inhibited this (p = 0.001). IL-10 levels were decreased (p = 0.055) in the LPS group that was prevented when pretreated with KBx (p = 0.037). The in vitro study showed KBx to be a more potent derivate of bixin through its ability to intercept ROS formation with three-fold more potency, and it showed an anti-inflammatory propriety by reducing the nuclear translocation of p65 (p < 0.001). Conclusions: In conclusion, these data suggest that KBx was able to activate the Nrf2/ARE pathway and intercept ROS formation induced by CSE and LPS in both in vivo and in vitro studies. Full article

Electronic cigarettes (e-cigarettes) are devices designed to vaporize a liquid solution, offering an alternative to traditional tobacco consumption. The identification, detection, and analysis of the compounds present in these devices are crucial for understanding their impacts on health and the environment. Numerous studies have identified a diverse range of compounds emitted by e-cigarettes, including well-known substances such as nicotine, thermal degradation products, and other toxicants that may be harmful or carcinogenic. Although e-cigarettes are often considered an alternative to conventional smoking, they are not without risks. Recent research has increasingly focused on assessing the health impacts of e-cigarettes, integrating findings from various scientific disciplines. Two primary analytical approaches are used for the sample preparation, identification, and quantification of these compounds. The first approach focuses on aerosol analysis, utilizing techniques such as headspace static extraction and gas chromatography coupled with mass spectrometry (GC-MS). The second approach is directed towards liquid analysis, employing liquid–liquid extraction techniques and liquid chromatography (LC) systems. Given the constant publication of new research in this area, a comprehensive review that consolidates information on identified compounds, sample preparation methods, and extraction and analysis techniques is necessary to integrate current knowledge and address emerging findings. Full article

Smoking has been associated, among other factors, with musculoskeletal disorders. Although there is no consensus about the effects of smoking on osteoarthritis (OA), the increase in TNF-alpha in smokers has been considered an important factor in OA induction or progression. However, studies on the effects of smoking on chondrocytes are lacking. Here we aimed to study the effects of cigarette smoke extract (CSE) associated with a TNF-alpha inhibitor on cell death of primary human chondrocytes derived from osteoarthritic patients. CSE at 10% led to cell death by apoptosis after 48 h of incubation, together with caspase 3/7 activation, decrease in mitochondrial transmembrane potential, ROS production, and improvement in syndercan-1, perlecan, and RUNX2 gene expression. All these effects promoted by CSE were reversed by TNF-alpha inhibitor. Collagen II, F-actin, and SOX9 were also analyzed, and CSE promoted alteration in the expression of these proteins. In conclusion, our results support the clinical impact of smoking on OA development by showing the detrimental action of CSE on osteoarthritis-derived chondrocytes and the protective effects of TNF-alpha inhibitors, reinforcing the importance of this cytokine in the cartilage injury process. Full article

Background and Objectives: Pneumothorax is a medical condition characterized by the accumulation of air in the pleural cavity, leading to lung collapse. While cigarette smoking is a well-known risk factor, the role of electronic cigarettes is less understood. This systematic review aimed to evaluate the outcomes of vaping-associated pneumothorax, in addition to its clinical features and management strategies, by compiling published case reports and case series. Materials and Methods: The choice to use case reports and case series was due to the limited availability of other types of studies on this emerging condition, as vaping-associated pneumothorax is relatively rare and primarily reported in isolated cases. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic search of six databases for case reports and case series. Data extraction and quality assessment were performed independently by multiple reviewers. Results: Seven case reports and four case series with a total number of 16 patients were included. Most patients were young, underweight men who presented with chest pain and shortness of breath. Conventional cigarette and cannabis use were commonly reported alongside vaping. The main treatment was the insertion of a chest tube, with surgical interventions reserved for severe cases. Patients who were treated non-surgically exhibited a higher recurrence rate. Additionally, specific symptoms such as chest pain radiating to the ipsilateral shoulder were associated with a higher recurrence rate. Conclusions: Clinicians should be vigilant for pneumothorax in at-risk individuals, consider targeted screening for symptomatic vapers, and prioritize early surgical intervention in recurrent cases to reduce complications. Further research is needed to understand the pathophysiology of vaping-associated spontaneous pneumothorax and optimal management strategies. Full article

Background/Objectives: Exposure to fine particulate matter (PM_2.5) causes significant respiratory and gastrointestinal health problems. In our prior research, we identified Lactobacillus acidophilus TW01 as a promising strain for mitigating oxidative damage, enhancing wound healing in intestinal epithelial cells, and protecting bronchial cells from cigarette smoke extract. Building upon these findings, this study examines the protective effects of this strain on lung damage induced by particulate matter (PM) through the gut–lung axis in mouse models. Methods: This study evaluated the protective effects of L. acidophilus TW01 against PM_2.5-induced lung injury using two in vivo mouse models (OVA sensitization combined with PM_2.5 exposure and DSS-induced colitis). Results: L. acidophilus TW01 exhibited significant protective effects in two in-vivo models, reducing pro-inflammatory cytokines (TNF-α, IL-6, and IL-5), modulating the immune response (IgG subtypes), and improving gut barrier integrity. Importantly, L. acidophilus TW01 increased the abundance of beneficial gut bacteria (Bifidobacterium and Lactobacillus). Conclusions: These findings highlight the significant protective/therapeutic potential of L. acidophilus TW01 in mitigating the adverse health effects of PM_2.5 exposure, emphasizing the interplay between the gut and lung microbiomes in overall health. The multi-faceted protective effects of this probiotic suggest a novel, multi-pronged therapeutic strategy for addressing the widespread health consequences of air pollution. Full article

The current study began with the following question: Is smoking a balanced factor between human body systems? One of the particular features of the oral cavity is its localization at the gateway of respiratory and digestive. Morphologically, the oral cavity encompasses a complex association of soft tissues, hard tissues, salivary glands, and taste receptors. The main purpose of this study was to analyze the tobacco residues (TAR) deposited on dental materials and the alterations of artificial saliva that comes into contact with tobacco smoke, by obtaining a solution of cigarette smoke extracts (CSE) after 5, 10, 15, and 20 tobacco cigarettes. According to LC-MS analysis and FT-IR spectra, carbonyl compounds, phenols, and carboxylic acids are present in CSE, which could explain the pH decrease and acid characteristic. Moreover, the CSE solution was added to the culture medium of Mesenchymal Stem Cells (MSCs) to evaluate the cytotoxicity. The MTT study revealed decreased MSC viability; morphological changes and cell death were more intense at higher doses of CSE added to the culture medium. Scanning Electron Microscopy (SEM) indicated cellular ruffling and irregular cell surface under higher concentrations of CSE-15 and CSE-20 in culture media, which is a characteristic feature demonstrating the membrane stress. In conclusion, the present study, with its limitations, showed the negative cellular effects of tobacco cigarette smoking and the impact of this habit on the oral cavity homeostasis. Full article

Background: The extracellular matrix (ECM) plays a critical role in the proper regeneration of skeletal muscle. ECM remodeling has been reported in the skeletal muscle of chronic obstructive pulmonary disease (COPD), while the mechanisms remain poorly understood. Methods: In this study, we examined the dynamic interplay between ECM components and ECM enzymes in COPD skeletal muscle and cigarette smoke (CS) extract-treated C2C12 cells. C2C12 cells were further used to evaluate the role of a disintegrin and metalloproteinase with thrombospondin motif 4 (ADAMTS4) in ECM remodeling and myogenesis. Results: Chronic CS exposure induced the development of COPD and comorbid sarcopenia in C57BL/6J mice. Muscle fibrosis was observed in the gastrocnemius muscle of CS-exposed mice, accompanied by an upregulation of protein expression but a downregulation of mRNA levels of fibronectin and versican. We found that the discrepancy of mRNA and protein expression was attributed to the aberrant secretion of some ECM enzymes belonging to matrix metalloproteinases and ADAMTS proteases, especially ADAMTS4. CS exposure reduced ADAMTS4 expression in gastrocnemius muscles and C2C12 cells, and Adamts4 knockdown induced fibronectin and versican accumulation and impeded myogenic process. Conclusions: Considering that recent studies have indicated an impaired skeletal muscle regeneration in COPD, we suggested that the restrained production of ADAMTS4 in response to CS could be involved in the damaged muscle regeneration through regulating skeletal muscle ECM in COPD. Targeting ECM enzymes may benefit the rehabilitation of COPD-related sarcopenia. Full article

Asthma is a chronic inflammatory respiratory disease that affects millions globally and poses a serious public health challenge. Current therapeutic strategies, including corticosteroids, are constrained by variable patient responses and adverse effects. In this study, a polyphenolic extract derived from the Tibetan medicinal plant Spenceria ramalana Trimen (SRT) was employed and shown to improve experimentally (ovalbumin + cigarette smoke, OVA + CS) induced asthma in rats. Initially, the potential therapeutic mechanism of the polyphenolic components in SRT on OVA + CS-induced asthma was predicated by network pharmacology analysis. Subsequently, in vivo experiments identified that SRT polyphenols exhibit significant anti-asthmatic activities, primarily mediated by lowering inflammatory cell counts such as the WBC (white blood cell), eosinophils, and neutrophils, decreasing the expression of inflammatory cytokines (IL-4, IL-5, IL-13, and TNF-α), alleviating lung histological damage (reduced inflammation, collagen deposition, and mucus secretion), and enhancing the epithelial barrier integrity (upregulation of ZO-1, occludin, and claudin-1). Additionally, SRT polyphenols downregulated the PI3K/Akt (Phosphoinositide 3-kinase/protein kinase B) signaling pathway, improved gut microbiota disruption, and regulated fecal metabolites (glucose-6-glutamate, PS (16:0/0:0), 8-aminocaprylic acid, galactonic acid, Ascr#10, 2,3,4,5,6,7-hexahydroxyheptanoic acid, phosphodimethylethanolamine, muramic acid, 9-oxohexadeca-10e-enoic acid, and sedoheptulose) in asthmatic rats. In conclusion, SRT polyphenols exerted multifaceted protective effects against OVA + CS-induced asthma in rats, highlighting their potential value in preventing asthma via the PI3K/Akt signaling pathway. Full article

Background/Objective: Cardiometabolic syndrome (CMS) is a complex clinical condition that encompasses metabolic dysregulation, cardiovascular disease, and diabetes risk factors. Worldwide, CMS is underdiagnosed, and its occurrence significantly increases cardiovascular morbimortality. Despite available pharmacological treatments, the approach is fragmented, and the associated clinical conditions are treated independently. This approach may be partially due to limited preclinical models to mimic the clinical conditions of CMS. Therefore, our study aims to present an innovative animal model of cardiometabolic syndrome and evaluate the effects of Baccharis dracunculifolia on the set of clinical alterations associated with the condition. Methods: Female Wistar rats were induced to develop diabetes, fed a cholesterol-enriched diet, and exposed to the smoke of 9 cigarettes/day for 6 weeks. During the last 2 weeks, the rats were treated with vehicle, B. dracunculifolia (30, 100, and 300 mg/kg), or a combination of simvastatin and insulin. At the end of the treatment, plasma lipid levels were measured, and the liver was analyzed histologically for hepatic lipid quantification and oxidative stress assessment. Results: Phytochemical analysis revealed seven phenolic acids and six flavonoids in the extract. B. dracunculifolia showed significant hepatoprotective effects, reducing AST and ALT levels and lowering both plasma and hepatic lipid levels. The extract also reversed hepatic steatosis and demonstrated antioxidant properties. Conclusions: These findings suggest that B. dracunculifolia may be a therapeutic option for the metabolic dysregulation present in CMS. Full article

Background: This systematic review assesses the current literature (2020–2024) evaluating the impact of smoking on dental implant failure rates. Methods: A non-funded Pubmed database review was conducted according to PRISMA guidelines, and the results were tabulated to extract the study design, patient characteristics, follow-up time, comparison, outcome, and strengths and weaknesses, including risk of bias. This review included 33 studies with 29,519 implants placed in over 18,301 patients. We included prospective and retrospective clinical studies, randomized and non-randomized controlled trials, cohort studies, and observational studies that examined smoking’s effects on implant failure rates. Studies had to classify individuals into two groups, smokers and non-smokers, with at least ten implants. Exclusions included reviews, case reports, experimental studies, guidelines, non-English publications, studies lacking comparative data on failure rates, those excluding smokers, and studies focusing on head and neck cancer patients or specialized implants. Results: Our findings indicate a significant correlation in 25 out of 33 studies between smoking and increased implant failure rates, affecting both early and late stages of implant integration and survival as well as revealing a dose–response relationship, with higher daily cigarette consumption significantly increasing the risk of implant failure. Conclusions: This review highlights the importance of smoking cessation efforts, patient education, and tailored patient care in dental implantology. Future research should explore the effects of smoking frequency and alternative tobacco products, such as e-cigarettes, aiming to improve success rates among smokers. Full article

Electronic cigarette (e-cig) use in pregnancy is common, but potential effects on fetal development are largely unknown. This study’s goal was to examine the association between e-cig exposure and fetal growth. Data were extracted from medical charts in this single-site retrospective study. The sample, excluding those with known tobacco, alcohol, illicit drug, opioid, and benzodiazepine use, contained women who used e-cigs throughout pregnancy and non-e-cig user controls. Fetal size measurements from second- and third-trimester ultrasounds and at birth were expressed as percentiles for gestational age. Following adjustment for confounding factors, in the second trimester, only femur length was significant, with an adjusted deficit of 11.5 percentile points for e-cig exposure compared to controls. By the third trimester, the femur length difference was 28.5 points, with the fetal weight difference also significant (17.2 points). At birth, all three size parameter differences between groups were significant. Significant size deficits were predicted by prenatal e-cig exposure, becoming larger and impacting more parameters with increasing gestation. While additional studies are warranted to confirm and expand upon these findings, this study adds to emerging data pointing to specific harms following e-cig exposure in pregnancy and suggests that e-cigs may not be a “safer” alternative to combustible cigarette smoking in pregnancy. Full article