Aims To provide the first systematic analysis of the burden and underlying causes of heart failure (HF) in 195 countries and territories from 1990 to 2017. Methods and results We collected detailed information on prevalence, years lived with disability (YLDs), and underlying causes of HF from the Global Burden of Disease study 2017. Numbers and age-standardized rates of HF prevalence and YLDs were compared by age, sex, socio-demographic index (SDI), and location. The proportions of HF age-standardized prevalence rates due to 23 underlying causes were also presented. Globally, the age-standardized prevalence and YLD rates of HF in 2017 were 831.0 and 128.2 per 100 000 people, a decrease of −7.2% and −0.9% from 1990, respectively. Nevertheless, the absolute numbers of HF prevalent cases and YLDs have increased by 91.9% and 106.0% from 1990, respectively. There is significant geographic and socio-demographic variation in the levels and trends of HF burden from 1990 to 2017. Among all causes of HF, ischaemic heart disease accounted for the highest proportion (26.5%) of age-standardized prevalence rate of HF in 2017, followed by hypertensive heart disease (26.2%), chronic obstructive pulmonary disease (23.4%). Conclusion HF remains a serious public health problem worldwide, with increasing age-standardized prevalence and YLD rates in countries with relatively low SDI. More geo-specific strategies aimed at preventing underlying causes and improving medical care for HF are warranted to reduce the future burden of this condition.

Allergic asthma has a global prevalence, morbidity, and mortality. Many environmental factors, such as pollutants and allergens, are highly relevant to allergic asthma. The most important pathological symptom of allergic asthma is airway inflammation. Accordingly, the unique role of reactive oxygen species It is well known that reactive oxygen species (ROS), endogenous nitric oxide (NO) and NO derived reactive nitrogen species (RNS) have been reported to mediate oxidative stress and airway inflammation and pathogenesis. However, ROS are more common in allergic asthma development (6,7). Hence, in our review, we mainly focus on the relationship between ROS and allergic asthma. ROS, such as hydrogen peroxide, may be directly or indirectly involved in epithelial cell apoptosis and inactivation of antioxidant enzymes and contribute to allergic asthma (8-11). ROS are derived from endogenous or exogenous oxidants. Endogenous ROS are composed of mitochondria, NADPH, and the xanthine/xanthine oxidase (XO) system. Exogenous sources of ROS production have been linked to strong oxidizing gases, such as ozone (O 3 ), sulfur dioxide (SO 2 ), nitrogen dioxide (NO 2 ) and particulate matter (PM), which are a major component of air pollution (12,13). The oxygen stress level in asthma is increased because of inflammatory cells in vivo, and cigarette smoke (CS) or PM produces ROS in vitro. For example, compared with normal subjects, the level of H 2 O 2 and superoxide that are produced by eosinophils and neutrophils are significantly increased in asthma patients (14). Increased levels of ROS can cause harmful pathophysiological disorders of allergic asthma. Studies have reported that excessive ROS can damage DNA, carbohydrates, proteins, and lipids, ultimately leading to an increased inflammatory response in allergic asthma (15,16). In this review, we will discuss the updated pathophysiological and mechanisms of oxidative stress relating to allergic asthma. Exogenous oxidants and allergic asthmaPatients' exposure to the environmental atmosphere is the main way that exogenous oxidative stress is induced (17). CS is a complex mixture including more than 4,000 different compounds. It has been demonstrated that inhaled CS can increase ROS levels. Most of these compounds have ability to generate ROS during their metabolism. The mechanism of CS induced inflammation is incorporated with oxidative stress leading to cell death and oxidative DNA damage via apoptosis and/or necrosis (7). It was reported that antioxidants have the ability to protect cells from cigarette smoke extract (CSE) induced apoptosis (18). Isolated human airway smooth muscle (hASM) cells were used to determine Ca 2+ responses and hASM proliferation, as well as ROS level and cytokine generation, by incubating these cells in the presence or absence of CSE. The results revealed that Ca 2+ regulatory proteins alter airway remolding and function in smoking-related airway disease, especially allergic asthma (19). CSE can damage bronchial epithelial cells from asthm...

Here we show that FTO as an N6-methyladenosine (m6A) RNA demethylase is degraded by selective autophagy, which is impaired by low-level arsenic exposure to promote tumorigenesis. We found that in arsenic-associated human skin lesions, FTO is upregulated, while m6A RNA methylation is downregulated. In keratinocytes, chronic relevant low-level arsenic exposure upregulated FTO, downregulated m6A RNA methylation, and induced malignant transformation and tumorigenesis. FTO deletion inhibited arsenic-induced tumorigenesis. Moreover, in mice, epidermis-specific FTO deletion prevented skin tumorigenesis induced by arsenic and UVB irradiation. Targeting FTO genetically or pharmacologically inhibits the tumorigenicity of arsenic-transformed tumor cells. We identified NEDD4L as the m6A-modified gene target of FTO. Finally, arsenic stabilizes FTO protein through inhibiting p62-mediated selective autophagy. FTO upregulation can in turn inhibit autophagy, leading to a positive feedback loop to maintain FTO accumulation. Our study reveals FTO-mediated dysregulation of mRNA m6A methylation as an epitranscriptomic mechanism to promote arsenic tumorigenicity.

Altered expression of microRNA (miRNA) is associated with lung carcinogenesis and metastasis. Our previous study of lung cancer miRNAs using the gene chip assay demonstrated altered miR-33b expression in lung adenocarcinoma. The present study further investigated miR-33b expression, function, and gene regulation in lung cancer cells in vitro and in nude mouse xenografts. Our data showed that the level of miR-33b expression was dramatically decreased in lung adenocarcinoma cell lines and tissues and that the reduced miR-33b expression was associated with tumor lymph node metastasis. Furthermore, restoration of miR-33b expression inhibited lung adenocarcinoma cell proliferation, migration, and invasion and tumor cell epithelial-mesenchymal transition (EMT) in vitro. Luciferase assay revealed that miR-33b bound to ZEB1 3'-UTR region and inhibited ZEB1 expression, while expression of ZEB1 mRNA and miR-33b was inversely associated with lung adenocarcinoma cell lines and tissues. Subsequently, we found that miR-33b suppressed the activity of WNT/β-catenin signaling in lung adenocarcinoma cells and in turn suppressed tumor cell growth and EMT in vitro and in vivo nude mouse xenografts. In conclusion, the present study provided novel insight into the molecular mechanism of lung adenocarcinoma progression. MicroRNA-33b should be further investigated as a potential therapeutic target in human lung adenocarcinoma.