Chronic obstructive pulmonary disease (COPD) currently lacks effective treatments to halt disease progression, making the search for preventive and therapeutic drugs a pressing issue. Natural products, with their accessibility, affordability, and low toxicity, offer promising avenues. Investigating the pharmacological effects and related signaling mechanisms of active components from natural products on COPD animal models induced by various triggers has become an important focus. In animal models induced by cigarette smoke, cigarette smoke combined with lipopolysaccharide (LPS), air pollution, elastase, bacterial or viral infections, the active compounds of natural products, such as flavonoids, terpenoids, and phenolics, can exert anti-inflammatory, antioxidant, mucus-regulating, and airway remodeling-inhibiting effects through key signaling pathways including nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB), and mitogen-activated protein kinase (MAPK). These findings not only provide a theoretical basis for the clinical diagnosis and treatment of COPD but also point to new directions for future scientific research.
Pulmonary Disease, Chronic Obstructive/etiology* ; Animals ; Disease Models, Animal ; Biological Products/pharmacology* ; Humans ; NF-kappa B/metabolism* ; Flavonoids/pharmacology* ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Heme Oxygenase-1/metabolism* ; Terpenes/pharmacology* ; Antioxidants/pharmacology* ; NF-E2-Related Factor 2/metabolism* ; Smoke/adverse effects* ; Phenols/therapeutic use*

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a major chronic respiratory condition with high morbidity and mortality, imposing a serious economic and public health burden. The World Health Organization ranks COPD among the top 4 chronic diseases worldwide. Zangsiwei Qingfei Mixture (ZSWQF), a novel Tibetan herbal formulation independently developed by our research team, has shown therapeutic potential for chronic respiratory diseases. This study aims to evaluate the effects of aerosolized ZSWQF on cigarette smoke-induced COPD in mice and explore its underlying mechanisms. METHODS: Thirty C57 mice were randomly divided into a Control group, a COPD group, and a ZSWQF group. The Control group received saline aerosol inhalation without cigarette smoke exposure; both the COPD group and the ZSWQF group were exposed to cigarette smoke, with the former receiving saline inhalation and the latter treated with ZSWQF aerosol. White blood cell (WBC) count was performed using a fully automatic blood cell analyzer. Serum, alanine transaminase (ALT), and serum creatinine (SCr), as well as interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α levels in serum and bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). BALF cell classification was determined using a hematology analyzer. Lung function was assessed with a small animal pulmonary function system, including airway resistance (RI) and cyclic dynamic compliance (CyDN). Lung tissues were stained with hematoxylin and eosin (HE), and mean linear intercept (MLI) and destruction index (DI) were calculated to evaluate morphological changes. Network pharmacology was applied to identify disease-related and ZSWQF-related targets, followed by intersection and protein-protein interaction (PPI) network analysis, and enrichment analysis of biological functions and pathways. Primary type II alveolar epithelial cell (AEC II) from SD rats were isolated and divided into a Control group, a lipopolysaccharide (LPS) group, a normal serum group, a water extract of ZSWQF (W-ZSWQF) group, a ZSWQF containing serum group, and a MLN-4760 [angiotensin-converting enzyme (ACE) 2 inhibitor]. Western blotting was performed to assess protein expression of ACE, p38 [a mitogen-activated protein kinase (MAPK)], phospho (p)-p38, extracellular signal-regulated kinases 1 and 2 (ERK1/2), p-ERK1/2, c-Jun N-terminal kinase (JNK), p-JNK, inhibitor of nuclear factor-kappa B alpha (IκBα), p-IκBα, and p-p65 subunit of nuclear factor-kappa B (NF-κBp65). RESULTS: WBC counts were significantly higher in the COPD group than in controls (P<0.01) and decreased following ZSWQF treatment (P<0.05). No significant intergroup differences were found in organ weights, ALT, or SCr (all P>0.05). Serum and BALF levels of IL-6, IL-8, and TNF-α, as well as total BALF cells, neutrophils, and macrophages, were elevated in the COPD group compared with controls and reduced by ZSWQF treatment (P<0.05). COPD mice exhibited increased RI, decreased CyDN, marked alveolar congestion, inflammatory infiltration, thickened septa, and higher MLI and DI values versus controls (P<0.05); ZSWQF treatment significantly reduced MLI and DI (P<0.05). Network pharmacology identified 151 potential therapeutic targets for ZSWQF against COPD, with key nodes including TNF, IL-6, protein kinase B (Akt) 1, albumin (ALB), tumor protein p53 (TP53), non-receptor tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT) 3, matrix metalloproteinase (MMP)-9, and beta-catenin (CTNNB1). Enrichment analysis indicates involvement of cancer-related, phosphatidylinositol 3-kinase (PI3K)/Akt, hypoxia-inducible factor (HIF)-1, calcium, and MAPK signaling pathways. Western blotting results showed that compared with the LPS group, AEC II treated with ZSWQF-containing serum exhibited decreased expression of ACE, p-p38/p38, p-ERK1/2/ERK1/2, p-JNK/JNK, p-IκBα/IκBα, and p-NF-κBp65, while ACE2 expression was upregulated, consistent with the MAPK/nuclear factor-kappa B (NF-κB) pathway regulation predicted by network pharmacology. CONCLUSIONS Aerosolized ZSWQF provides protective effects in COPD mice by reducing airway inflammation and remodeling.
Animals ; Pulmonary Disease, Chronic Obstructive/etiology* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Mice, Inbred C57BL ; Male ; Network Pharmacology ; Smoke/adverse effects* ; Bronchoalveolar Lavage Fluid ; Administration, Inhalation ; Inflammation/drug therapy* ; Tumor Necrosis Factor-alpha ; Lung/drug effects* ; Interleukin-6/blood*

OBJECTIVES: To evaluate the protective effect of Bufei Yishen Formula (BYF) against cigarette smoke extract (CSE)-induced injuries in human bronchial epithelial BEAS-2B cells and explore the underlying mechanism. METHODS: BEAS-2B cells exposed to CSE were treated with normal rat serum, BYF-medicated rat serum at low or high doses, pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor), PDTC combined with high-dose BYF-medicated serum, or S-carbomethyloysteine (S-CMC, as the positive control). CCK-8 assay was used to determine the optimal concentration and treatment time of CSE, BYF-medicated serum and S-CMC. The treated cells were examined for inflammatory factor levels in the supernatant and cellular expressions of MUC5AC and MUC5B using ELISA, cell ultrastructural changes with transmission electron microscopy, and cell apoptosis rate using flow cytometry. The expression levels of TLR4/NF‑κB pathway-associated mRNAs and proteins were determined by qRT-PCR and Western blotting. RESULTS: CSE exposure significantly increased secretions of IL-1β, IL-6 and TNF-α, mRNA and protein expressions of MUC5AC and MUC5B, and early and total apoptosis rates in BEAS-2B cells, where the presence of apoptotic bodies was detected. CSE also significantly enhanced the mRNA and protein expressions of TLR4, I-κB, and NF-κB and reduced mRNA and protein expressions of AQP5. Treatments of the CSE-exposed cells with BYF-medicated serum, PDTC and S-CMC all significantly lowered inflammatory factor levels, MUC5AC and MUC5B expressions, and early and total cell apoptosis rates, and partly reversed the changes in cellular ultrastructure and mRNA and protein expressions of the TLR4/NF-κB pathway, and the effects were the most conspicuous following the combined treatment with high-dose BYF-medicated serum and PDTC. CONCLUSIONS BYF can inhibit cell apoptosis, inflammation and mucus hypersecretion in CSE-induced BEAS-2B cells by inhibiting the TLR4/NF-κB signaling pathway.
Humans ; Epithelial Cells/cytology* ; Drugs, Chinese Herbal/pharmacology* ; NF-kappa B/metabolism* ; Bronchi/cytology* ; Smoke/adverse effects* ; Apoptosis/drug effects* ; Mucin 5AC/metabolism* ; Cell Line ; Toll-Like Receptor 4/metabolism* ; Mucin-5B/metabolism* ; Signal Transduction/drug effects* ; Nicotiana ; Rats ; Thiocarbamates/pharmacology* ; Animals

Objective: To understand the relationship between secondhand smoke exposure and dyslipidemia among adults in Beijing and to provide a scientific basis for relevant intervention. Methods: Data were from Beijing Adult Non-communicable and Chronic Diseases and Risk Factors Surveillance Program in 2017. A total of 13 240 respondents were selected by multistage cluster stratified sampling method. The monitoring contents include a questionnaire survey, physical measurement, collection of fasting venous blood, and determination of related biochemical indicators. SPSS 20.0 software was used for the chi-square test and multivariate logistic regression analysis. Results: The prevalence of total dyslipidemia (39.27%), hypertriglyceridemia (22.61%), and high LDL-C (6.03%) were the highest among those exposed to daily secondhand smoke. Among the male respondents, the prevalence of total dyslipidemia (44.42%) and hypertriglyceridemia (26.12%) were the highest among those exposed to secondhand smoke daily. Multivariate logistic regression analysis after adjustment for confounding factors showed that compared with no exposure to secondhand smoke, the population with an average exposure frequency of 1-3 days per week had the highest risk of total dyslipidemia (OR=1.276, 95%CI: 1.023-1.591). Among the patients with hypertriglyceridemia, those exposed to secondhand smoke daily had the highest risk (OR=1.356, 95%CI: 1.107-1.661). Among the male respondents, those exposed to secondhand smoke for 1-3 days per week had a higher risk of total dyslipidemia (OR=1.366, 95%CI: 1.019-1.831), and the highest risk of hypertriglyceridemia (OR=1.377, 95%CI: 1.058-1.793). There was no significant correlation between the frequency of secondhand smoke exposure and the risk of dyslipidemia among female respondents. Conclusions: Secondhand smoke exposure in Beijing adults, especially men, will increase the risk of total dyslipidemia, especially hyperlipidemia. Improving personal health awareness and minimizing or avoiding exposure to secondhand smoke is necessary.
Adult ; Humans ; Female ; Male ; Tobacco Smoke Pollution/adverse effects* ; Beijing ; Dyslipidemias/epidemiology* ; Hypertriglyceridemia/epidemiology* ; Fasting

OBJECTIVE: To observe the effects of moxa smoke through olfactory pathway on learning and memory ability in rapid aging (SAMP8) mice, and to explore the action pathway of moxa smoke. METHODS: Forty-eight six-month-old male SAMP8 mice were randomly divided into a model group, an olfactory dysfunction group, a moxa smoke group and an olfactory dysfunction + moxa smoke group, with 12 mice in each group. Twelve age-matched male SAMR1 mice were used as the blank group. The olfactory dysfunction model was induced in the olfactory dysfunction group and the olfactory dysfunction + moxa smoke group by intraperitoneal injection of 3-methylindole (3-MI) with 300 mg/kg, and the moxa smoke group and the olfactory dysfunction + moxa smoke group were intervened with moxa smoke at a concentration of 10-15 mg/m³ for 30 min per day, with a total of 6 interventions per week. After 6 weeks, the emotion and cognitive function of mice was tested by open field test and Morris water maze test, and the neuronal morphology in the CAI area of the hippocampus was observed by HE staining. The contents of neurotransmitters (glutamic acid [Glu], gamma-aminobutyric acid [GABA], dopamine [DA], and 5-hydroxytryptamine [5-HT]) in hippocampal tissue of mice were detected by ELISA. RESULTS: The mice in the blank group, the model group and the moxa smoke group could find the buried food pellets within 300 s, while the mice in the olfactory dysfunction group and the olfactory dysfunction + moxa smoke group took more than 300 s to find them. Compared with the blank group, the model group had increased vertical and horizontal movements (P<0.05) and reduced central area residence time (P<0.05) in the open field test, prolonged mean escape latency on days 1-4 (P<0.05), and decreased search time, swimming distance and swimming distance ratio in the target quadrant of the Morris water maze test, and decreased GABA, DA and 5-HT contents (P<0.05, P<0.01) and increased Glu content (P<0.05) in hippocampal tissue. Compared with the model group, the olfactory dysfunction group had increased vertical movements (P<0.05), reduced central area residence time (P<0.05), and increased DA content in hippocampal tissue (P<0.05); the olfactory dysfunction + moxa smoke group had shortened mean escape latency on days 3 and 4 of the Morris water maze test (P<0.05) and increased DA content in hippocampal tissue (P<0.05); the moxa smoke group had prolonged search time in the target quadrant (P<0.05) and increased swimming distance ratio, and increased DA and 5-HT contents in hippocampal tissue (P<0.05, P<0.01) and decreased Glu content in hippocampal tissue (P<0.05). Compared with the olfactory dysfunction group, the olfactory dysfunction + moxa smoke group showed a shortened mean escape latency on day 4 of the Morris water maze test (P<0.05). Compared with the moxa smoke group, the olfactory dysfunction + moxa smoke group had a decreased 5-HT content in the hippocampus (P<0.05). Compared with the blank group, the model group showed a reduced number of neurons in the CA1 area of the hippocampus with a disordered arrangement; the olfactory dysfunction group had similar neuronal morphology in the CA1 area of the hippocampus to the model group. Compared with the model group, the moxa smoke group had an increased number of neurons in the CA1 area of the hippocampus that were more densely packed. Compared with the moxa smoke group, the olfactory dysfunction + moxa smoke group had a reduced number of neurons in the CA1 area of the hippocampus, with the extent between that of the moxa smoke group and the olfactory dysfunction group. CONCLUSION The moxa smoke could regulate the contents of neurotransmitters Glu, DA and 5-HT in hippocampal tissue through olfactory pathway to improve the learning and memory ability of SAMP8 mice, and the olfactory is not the only effective pathway.
Male ; Animals ; Mice ; Olfactory Pathways ; Smoke/adverse effects* ; Serotonin ; Aging ; Dopamine ; Olfaction Disorders/etiology*

OBJECTIVE: To analyze the association between exposure to second-hand smoke (SHS) and 23 diseases, categorized into four classifications, among the Chinese population. METHODS: We searched the literature up to June 30, 2021, and eligible studies were identified according to the PECOS format: Participants and Competitors (Chinese population), Exposure (SHS), Outcomes (Disease or Death), and Study design (Case-control or Cohort). RESULTS: In total, 53 studies were selected. The odds ratio (OR) for all types of cancer was 1.79 (1.56-2.05), and for individual cancers was 1.92 (1.42-2.59) for lung cancer, 1.57 (1.40-1.76) for breast cancer, 1.52 (1.12-2.05) for bladder cancer, and 1.37 (1.08-1.73) for liver cancer. The OR for circulatory system diseases was 1.92 (1.29-2.85), with a value of 2.29 (1.26-4.159) for stroke. The OR of respiratory system diseases was 1.76 (1.13-2.74), with a value of 1.82 (1.07-3.11) for childhood asthma. The original ORs were also shown for other diseases. Subgroup analyses were performed for lung and breast cancer. The ORs varied according to time period and were significant during exposure in the household; For lung cancer, the OR was significant in women. CONCLUSION The effect of SHS exposure in China was similar to that in Western countries, but its definition and characterization require further clarification. Studies on the association between SHS exposure and certain diseases with high incidence rates are insufficient.
Child ; Female ; Humans ; Asthma/epidemiology* ; Breast Neoplasms ; East Asian People ; Lung Neoplasms/etiology* ; Tobacco Smoke Pollution/adverse effects* ; China

Humans ; Pulmonary Disease, Chronic Obstructive ; Smoke/adverse effects* ; Tobacco ; Tobacco Smoke Pollution

OBJECTIVE: To observe the effect of long-term moxa smoke exposure of different concentrations on olfactory function in rats, and provide experimental basis of safety study of moxa smoke produced by moxibustion. METHODS: Forty SD rats were randomly divided into a normal control group, a low-concentration moxa smoke group, a moderate-concentration moxa smoke group and a high-concentration moxa smoke group, 10 rats in each one. The rats in the moxa smoke groups were put into three plexiglass moxibustion boxes with different moxa smoke concentrations, 4 hours per times, twice a day for 90 days. The general state of rats was evaluated before and during the experiment. After the intervention, the olfactory function was evaluated by two-bottle experiment (TBE); the morphology of nasal mucosa was observed by HE staining; the apoptosis of olfactory epithelial cells in nasal mucosa was detected by TUNEL method; the serum levels of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by ELISA method. RESULTS: In the late stage of moxa smoke exposure (45-90 days into intervention), the behavioral activity of rats in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was weaker than that in the normal control group, and their response to stimulation was strong, and their mental state was worse. After intervention, the drinking rate of vinegar-water mixture in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was higher than that in the normal control group and the low-concentration moxa smoke group ( CONCLUSION The long-term exposure to low, moderate and high concentrations of moxa smoke could cause pathological changes in nasal mucosa and increase the serum levels of IL-1, IL-6 and TNF-α; the moderate and high concentrations of moxa smoke exposure could cause a series of damage to olfactory function and reduce olfactory sensitivity in rats.
Animals ; Interleukin-1 ; Interleukin-6 ; Rats ; Rats, Sprague-Dawley ; Smoke/adverse effects* ; Tumor Necrosis Factor-alpha

BACKGROUND: Health and education are closely linked. However, few studies have explored the correlates of children's academic performance in Japan. We aimed to investigate comprehensively the associations of low academic performance among school children with lifestyles, parental smoke, and socioeconomic status. METHODS: In 2016, children aged 6 to 13 years from the Super Diet Education School Project were surveyed using questionnaires. The survey explored the lifestyles and subjective academic performance of 1663 children and asked their parents about parental smoke and subjective socioeconomic status. Academic performance and socioeconomic status were divided into three levels. Then, we defined subjective academic performance in the lower two levels as low academic performance. The odds ratios (OR) were analyzed by logistic regression analysis. RESULTS: Among all participants, 299 (18.0%) children reported low academic performance. In general, low academic performance was significantly associated with late wakeup time (OR = 1.36 for 6:30 to < 7 a.m. and OR = 2.48 for ≥ 7 a.m.), screen time ≥ 2 h (OR = 1.35), studying at home < 1 h (OR = 1.82), paternal smoke (OR = 1.47), maternal smoke (OR = 1.87), and low socioeconomic status (OR = 1.48). Analyses stratified by grade showed stronger associations between academic performance and socioeconomic status in senior (OR = 1.62 for middle, OR = 1.52 for low in grades 4 to 6) than in junior children (OR = 1.15 for middle, OR = 1.38 for low in grades 1 to 3). CONCLUSIONS Children's lifestyles, parental smoke, and socioeconomic status were significantly associated with low academic performance among Japanese children. Parents and health care providers should take these findings into consideration to prevent children from having low academic performance.
Academic Performance ; statistics & numerical data ; Adolescent ; Child ; Cross-Sectional Studies ; Female ; Health Surveys ; Humans ; Japan ; Life Style ; Male ; Parents ; Risk Factors ; School Health Services ; statistics & numerical data ; Smoke ; adverse effects ; Social Class

BACKGROUND: We aimed to examine the association of exposure to environmental tobacco smoke with dental caries among preschool children. Exposure to environmental tobacco smoke was assessed in terms of urinary cotinine concentrations and pack-years of exposure to smoking by parents and other family members at home. METHODS: This cross-sectional study included 405 preschool children aged 3-6 years from two preschools in Japan in 2006. Information on the smoking habits of family members living with the child was obtained from parent-administered questionnaires. Dental examination was conducted to assess dental caries, that is, decayed and/or filled teeth. Urinary cotinine levels were measured using first-void morning urine samples. RESULTS: Overall, 31.1% of the children had dental caries, and 29.5% had decayed teeth. Exposure to current maternal and paternal smoking was positively associated with the presence of dental caries after controlling for covariates. More than three pack-years of exposure to maternal smoking and more than five pack-years of exposure to smoking by all family members were significantly associated with the presence of dental caries as compared with no exposure (odds ratio [OR] = 5.55, 95% confidence interval [CI] = 2.17-14.22, P for trend < 0.001 and OR = 2.00, 95% CI = 1.12-3.58, P for trend = 0.004, respectively). These exposure variables were similarly associated with the presence of decayed teeth (OR = 2.92, 95% CI = 1.23-6.96, P for trend = 0.01 and OR = 1.75, 95% CI = 0.96-3.20, P for trend = 0.03, respectively). As compared with lowest tertile of the urinary cotinine level, the highest tertile of the urinary cotinine level was significantly associated with the presence of dental caries as well as decayed teeth; the ORs for the highest vs. lowest tertile of urinary cotinine levels were 3.10 (95% CI = 1.71-5.63, P for trend = 0.012) and 2.02 (95% CI = 1.10-3.70, P for trend = 0.10), respectively. CONCLUSIONS These data suggest that exposure to tobacco smoke may have a dose-dependent influence on the development of caries.
Child ; Child, Preschool ; Cotinine ; urine ; Cross-Sectional Studies ; Dental Caries ; epidemiology ; etiology ; Female ; Humans ; Japan ; epidemiology ; Logistic Models ; Male ; Maternal Exposure ; adverse effects ; Parents ; Paternal Exposure ; adverse effects ; Risk Factors ; Surveys and Questionnaires ; Tobacco Smoke Pollution ; adverse effects ; Tobacco Smoking ; adverse effects ; epidemiology