Ozone/toxicity* ; Air Pollution/analysis* ; Air Pollutants/analysis* ; China/epidemiology* ; Environmental Exposure/analysis* ; Mortality ; Particulate Matter/analysis*

OBJECTIVES: Sepsis is a critical dysregulated host response with high mortality and current treatment is difficult to achieve optimal efficacy. Ozone therapy has been revealed to protect infection and inflammation-related diseases due to its role in antibiotic and immunoregulatory effect. Ozonated triglyceride is a key component of ozonated oil that is one of ozone therapy dosage form. However, the potential role of ozonated triglyceride in sepsis remains unclear. This study aims to explore the effect of ozonated triglyceride on septic mouse model and the molecular mechanism. METHODS: Intraperitoneal injection of lipopolysaccharide (LPS), cecal ligation and puncture (CLP) were applied to construct septic mouse model. The mouse serum was obtained for detection of cytokines, and lung tissues were collected for hematoxylin and eosin (HE) staining to evaluate the extent of lung injury in septic mouse with ozonated triglyceride treatment at different time and doses. The survival of septic mice was observed for 96 h and Kaplan-Meier analysis was used to analyze the survival rates. In addition, primary peritoneal macrophages and human acute monocytic-leukemia cell line (THP-1) were treated with inflammasome activators with or without ozonated triglyceride. The level of cytokines was detected by enzyme-linked immunosorbent assay (ELISA). The cleavage of caspase-1 and gasdermin-D (GSDMD) was detected by Western blotting. RESULTS: Ozonated triglyceride at different time and doses reduced the release of inflammasome-related cytokines [interleukin (IL)-1β and IL-18] (all P<0.05) but not pro-inflammatory cytokines such as IL-6 and tumor necrosis factor-α (TNF-α) in septic mice (all P>0.05). Ozonated triglyceride significantly improved the survival rate of septic mice and reduced sepsis-induced lung injury (all P<0.05). Ozonated triglyceride significantly suppressed the canonical and non-canonical activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome (all P<0.05) but not affected absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) inflammasomes in vitro (all P>0.05). Ozonated triglyceride reduced the cleavage of caspase-1 and the downstream GSDMD. CONCLUSIONS Ozonated triglyceride presents a protect effect on sepsis lethality via reducing cytokines release and sepsis-related organ injury. The mechanism is that ozonated triglyceride specifically suppresses the activation of NLRP3 inflammasome. Ozonated triglyceride is a promising candidate for sepsis treatment.
Animals ; Humans ; Mice ; Caspase 1 ; Cytokines ; Disease Models, Animal ; Inflammasomes ; Lung Injury ; NLR Family, Pyrin Domain-Containing 3 Protein ; Ozone/therapeutic use* ; Sepsis/drug therapy*

Humans ; Ozone ; Rhinitis, Allergic ; Rhinitis, Allergic, Perennial

OBJECTIVE: To investigate the roles of angiotensin-converting enzyme 2 (ACE2) in ozone-induced pulmonary inflammation and airway remodeling in mice. METHODS: Sixteen wild-type (WT) C57BL/6J mice and 16 ACE2 knock-out (KO) mice were exposed to either filtered air or ozone (0.8 ppm) for 3 h per day for 5 consecutive days. Masson's staining and HE staining were used to observe lung pathologies. Bronchoalveolar lavage fluid (BALF) was collected and the total cell count was determined. The total proteins and cytokines in BALF were determined by BCA and ELISA method. The transcription levels of airway remodeling-related indicators in the lung tissues were detected using real-time quantitative PCR. The airway resistance of the mice was measured using a small animal ventilator with methacholine stimulation. RESULTS: Following ozoneexposure ACE2 KO mice had significantly higher lung pathological scores than WT mice (P < 0.05). Masson staining results showed that compared with ozone-exposed WT mice, ozone-exposed ACE2 KO mice presented with significantly larger area of collagen deposition in the bronchi [(19.62±3.16)% vs (6.49±1.34)%, P < 0.05] and alveoli [(21.63±3.78)% vs (4.44±0.99)%, P < 0.05]. The total cell count and total protein contents in the BALF were both higher in ozone-exposed ACE2 KO mice than in WT mice, but these differences were not statistically significant (P > 0.05). The concentrations of IL-6, IL-1β, TNF-α, CXCL1/KC and MCP-1 in the BALF were all higher in ozone-exposed ACE2 KO mice than in ozone-exposed WT mice, but only the difference in IL-1β was statistically significant (P < 0.05). The transcription levels of MMP-9, MMP-13, TIMP 4, COL1A1, and TGF-β in the lung tissues were all significantly higher in ozone-exposed ACE2 KO mice (P < 0.01). No significant difference was found in airway resistance between ozone-exposed ACE KO mice and WT mice after challenge with 0, 10, 25, or 100 mg/mL of methacholine. CONCLUSION ACE2 participates in ozone-induced lung inflammation and airway remodeling in mice.
Airway Remodeling ; Angiotensin-Converting Enzyme 2 ; Animals ; Methacholine Chloride ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Ozone/adverse effects* ; Pneumonia

OBJECTIVE: To analyze the effects of ozone (O₃) concentrations measured with different approaches across different seasons on the total number of childhood asthma-related clinical visits, as well as the differentiation of such effects across different groups of patients. METHODS: The outpatient data of three grade A tertiary hospitals in Lanzhou City spanning from 1 January 2014 to 31 December 2017, as well as air pollution and meteorological data during the same period were collected. Considering the nonlinear relationship between O₃ concentrations and the total number of childhood asthma-related clinical visits and meteorological factors, a generalized additive temporal sequence model was employed to analyze the short-term association between changes in O₃ concentrations and the total number of childhood asthma-related clinical visits. Taking into account of the variations in O₃ concentrations within 1 day, this study adopted different measurement approaches to address the three types of O₃ exposures, namely, the maximum 1 h daily concentration (O₃max1h), the maximum 8 h daily concentration (O₃8h) and the mean 24 h daily concentration (O₃24h) as the short term exposure indicators to O₃, followed by a model-based analysis. RESULTS: The increase in short-term exposure levels to O₃ in summer had a significant effect on the increase in the total number of childhood asthma-related clinical visits. With lag0 for the current day, every 10 μg/m³ increase in atmospheric concentration of O₃max1h was associated with an increase in the total number of childhood asthma-related clinical visits by 3.351% (95%CI: 1.231%-5.516%); for every 10 μg/m³ increase in O₃8h concentration, the total number of childhood asthma-related clinical visits increased by 3.320% (95%CI: 0.197%-3.829%); for every 10 μg/m³increase in O₃24h concentration, the total number of childhood asthma-related clinical visits in summer increased by 6.600% (95%CI: 0.914%-12.607%); moreover, an increase in exposure to O₃max1h also led to a significant rise in the total number of childhood asthma-related clinical visits among the males. CONCLUSION The increase in short-term exposure levels to O₃ in summer in Lanzhou City has a significant effect on the increase in the total number of childhood asthma-related clinical visits; O₃max1h is more closely correlated with the increase in the total number of childhood asthma-related clinical visits.
Air Pollutants/analysis* ; Air Pollution/analysis* ; Asthma/etiology* ; China/epidemiology* ; Humans ; Male ; Outpatients ; Ozone/analysis* ; Particulate Matter ; Seasons ; Tertiary Care Centers

Objective: This article aims to observe the changes in long noncoding RNA (lncRNA) expression profiles in rat hearts after ozone sub-chronic exposure. To provide scientific data to explore the role and mechanism of differentially expressed lncRNA in damaged hearts caused by ozone sub-chronic exposure. Methods: Eighteen Wistar rats were randomly divided into filtered air and ozone exposure groups, with nine rats in each group. The rats in filtered air group were exposed to filtered air, while the rats in ozone exposure group were exposed to ozone at 0.5 ppm(0.980 mg/m³)for 90 days at a frequency of 6 hours per day. After ozone exposure, cardiac tissues were collected and the total RNA was extracted. The expression level of lncRNA in the hearts of two groups was detected by microarray and qRT-PCR method and the potential functions of the differentially expressed lncRNA were analyzed by bioinformatics. Results: Compared with the filtered air group, lncRNA's expression profile was significantly altered in the rat hearts of ozone exposure group. A total of 167 lncRNA were up-regulated significantly and 64 lncRNA were down-regulated significantly. GO analysis indicated that the up-regulated lncRNA might involve in the process of regulating growth and development, and the down-regulated lncRNA might participate in nutrient catabolic. KEGG results showed that the up-regulated lncRNA might be involved in regulating the PI3K-Akt signaling pathway. The down-regulated lncRNA might regulate the metabolic processes of various vitamins and main energy-supplying substances. Conclusion: Ozone sub-chronic exposure can cause changes in the expression profile of lncRNA in rat hearts, which may regulate the effects of ozone sub-chronic exposure on the heart through the metabolism of energy and nutrients.
Animals ; Computational Biology ; Ozone/adverse effects* ; Phosphatidylinositol 3-Kinases ; RNA, Long Noncoding/genetics* ; Rats ; Rats, Wistar

OBJECTIVE: To compare the effects of medical ozone oil and urea ointment for prevention and treatment of hand-foot skin reaction (HFSR) caused by sorafenib in patients with hepatocellular carcinoma (HCC). METHODS: A total of 99 patients diagnosed with advanced HCC according to National Comprehensive Cancer Network (NCCN) who were scheduled to receive sorafenib treatment for the first time were enrolled in this study between April, 2018 and January, 2020. The patients were randomized into medical ozone oil group ( RESULTS: Eight patients were excluded for poor compliance or protocol violations, leaving a total of 91 patients for analysis, including 44 in medical ozone oil group and 47 in urea ointment group. Sixteen (36.4%) of patients in ozone oil group developed HFSR, a rate significantly lower than that in urea ointment group (57.4%; CONCLUSIONS Medical ozone oil can significantly reduce the incidence and severity of HFSR to improve the quality of life of HCC patients receiving sorafenib treatment.
Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Hand-Foot Syndrome/prevention & control* ; Humans ; Liver Neoplasms/drug therapy* ; Niacinamide/therapeutic use* ; Ozone/therapeutic use* ; Phenylurea Compounds/adverse effects* ; Quality of Life ; Sorafenib/therapeutic use*

OBJECTIVE: To assess the associations of different monitoring metrics for short-term exposure to ambient ozone (O₃) with pulmonary function and airway inflammation in healthy young adults. METHODS: A total of 97 healthy young college students were recruited and followed in a panel study conducted from December 2017 to June 2018. Each participant underwent 3 follow-up visits, and lung function and fractional exhaled nitric oxide (FeNO) were measured at each visit. Ambient air pollutant concentrations were obtained from the environment monitoring station of Beijing closest to the participant residences, and meteorological data were collected from China Meteorological Data Service Center. Linear mixed-effect models were applied to assess the associations between different monitoring metrics for ambient O₃ short-term exposure with pulmonary function or airway inflammation in the healthy young adults. RESULTS: During the study period, the P₅₀ (P₂₅, P₇₅) values for ambient O₃ concentration expressed as daily 1-hour maximum (O₃-1 h max), daily maximum 8-hour average (O₃-8 h max) and 24-hour average (O₃-24 h avg) were 102.5 (76.8, 163.0) μg/m³, 91.1 (68.3, 154.3) μg/m³ and 61.6 (36.9, 81.7) μg/m³, respectively. The different monitoring metrics for short-term exposure to ambient O₃ were significantly associated with reduced forced expiratory volume in the first second (FEV₁) and increased FeNO. An interquartile range (IQR) increase in 6-d moving average of O₃-1 h max (IQR=71.5 μg/m³) was associated with a 6.2% (95%CI: －11.8%, －0.5%) decrease in FEV₁ and a 63.3% (95%CI: 13.8%, 134.3%) increase in FeNO. An IQR increase in 7-d moving average of O₃-8 h max (IQR=62.0 μg/m³) was associated with a 6.2% (95%CI: －11.6%, －0.7%) decrease in FEV₁and a 75.5% (95%CI: 19.3%, 158.0%) increase in FeNO. An IQR increase in 5-d moving average of O₃-24 h avg (IQR=32.9 μg/m³) was associated with a 3.7% (95%CI: －7.1%, －0.2%) decrease in FEV₁and a 25.3% (95%CI: 3.6%, 51.6%) increase in FeNO. There was no significant association between the three monitoring metrics for O₃ exposure and peak expiratory flow (PEF). CONCLUSION Short-term exposure to ambient O₃ was associated with decreased lung function and increased airway inflammation among the healthy young adults, and daily 1-hour maximum was more sensitively to the respiratory effects of O₃.
Air Pollutants ; Air Pollution ; Benchmarking ; China ; Environmental Exposure ; Humans ; Inflammation ; Ozone ; Particulate Matter ; Young Adult

PURPOSE: The effects of air pollution on health can vary regionally. Our goal was to comprehensively review previous epidemiological studies on air pollution and health conducted in Korea to identify future areas of potential study. MATERIALS AND METHODS: We systematically searched all published epidemiologic studies examining the association between air pollution and occurrence of death, diseases, or symptoms in Korea. After classifying health outcomes into mortality, morbidity, and health impact, we summarized the relationship between individual air pollutants and health outcomes. RESULTS: We analyzed a total of 27 studies that provided 104 estimates of the quantitative association between risk of mortality and exposure to air pollutants, including particulate matter with aerodynamic diameter less than 10 µm, particulate matter with aerodynamic diameter less than 2.5 µm, sulfur dioxide, nitrogen dioxide, ozone, and carbon monoxide in Korea between January 1999 and July 2018. Regarding the association with morbidity, there were 38 studies, with 98 estimates, conducted during the same period. Most studies examined the short-term effects of air pollution using a time series or case-crossover study design; only three cohort studies that examined long-term effects were found. There were four health impact studies that calculated the attributable number of deaths or disability-adjusted life years due to air pollution. CONCLUSION: There have been many epidemiologic studies in Korea regarding air pollution and health. However, the present review shows that additional studies, especially cohort and experimental studies, are needed to provide more robust and accurate evidence that can be used to promote evidence-based policymaking.
Air Pollutants ; Air Pollution ; Carbon Monoxide ; Cohort Studies ; Environmental Medicine ; Epidemiologic Studies ; Korea ; Mortality ; Nitrogen Dioxide ; Ozone ; Particulate Matter ; Sulfur Dioxide

ozone on health are being reported by a number of studies. The effects of these air pollutants are likely to be stronger in the elderly population, but studies in this regard are scarce. The purpose of this study was to study the effects of PM ≤ 2.5 μm and ozone on chronic health effects of the elderly population.METHODS: In order to analyze the health status of the elderly population, National Statistical Office Mortality records were used. In this study, we calculated the number of deaths in Seoul of people who were 60 years or older between 2002 and 2012. The current study analyzed each disorder separately and the lag effect. PM and ozone were analyzed using the single exposure model, as well as the adjusted multi exposure model.RESULTS: In the single exposure analysis with PM2.5 as the exposure variable, with the increase of 10 μg/m³, the number of deaths increased by 1.0039 fold, and vascular disease 1.0053 fold. In the multi exposure model adjusting for ozone, the number of deaths increased by 1.0037 fold, and vascular disease 1.0049 fold. In the single exposure analysis with ozone as the exposure variable, with the increase of 10 ppb, the number of deaths increased by 1.0038 fold, and in the multi exposure model adjusting for PM2.5, the number of deaths increased by 1.0027 fold. These results differed depending on the period or season. There was a 5-day lag effect between PM2.5 and deaths in the multi exposure model, and 1.0028 fold when adjusted for ozone. There was a 1-day lag effect in single exposure models with ozone as the main variable, and 1.0027 fold increase in deaths.CONCLUSION: In our study, an increase in the number of deaths in the elderly population in accordance with the increase in the PM2.5 and ozone was found. The association found in our study could also influence socioeconomic burden. Future studies need to be performed in regards to younger population, as well as other air pollutants.]]>
Aged ; Air Pollutants ; Humans ; Mortality ; Ozone ; Particulate Matter ; Seasons ; Seoul ; Vascular Diseases