Recent advances in the study of Nrf2 and inflammatory respiratory diseases / 药学学报

Nuclear factor-erythroid 2 related factor 2 (Nrf2) is an ubiquitous and important transcription factor. It regulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. A large body of research showed that Nrf2-Keap1 (Kelch-like ECH-associated protein 1, Keap 1)-ARE signaling pathway is involved in the endogenous antioxidant defense mechanisms. Nrf2 increases the expression of a number of cytoprotective genes, protects cells and tissues from the injury of a variety of toxicants and carcinogens. As a result, Nrf2 enhances the expression of glutathione and antioxidants such as superoxide dismutase and glutathione S-transferase, and subsequently scavenging free radicals. Air pollution especially from PM2.5 particles, is associated with an increasing morbidity of inflammatory pulmonary diseases and their deterioration. More and more studies demonstrated that Nrf2 was a novel signaling molecule in the modulation of inflammatory responses in these inflammatory respiratory diseases, such as asthma, acute lung injury (ALI) and COPD. Therefore, Nrf2 targeting might be a therapeutic target, which will provide clinical benefit by reducing both oxidative stress and inflammation in asthma, acute lung injury (ALI) and COPD. This review focused on the relationship between Nrf2 and inflammatory respiratory diseases and oxidative stress.

Effect of WS070117M1 on chronic obstructive pulmonary disease in mice and the underling mechanisms of anti-inflammation / 药学学报

The aim of this study is to investigate the anti-inflammatory effect of the adenosine derivative N6-(3-hydroxylaniline) adenosine (WS070117M1) on cigarette smoke plus LPS (lipopolysaccharide)-induced chronic obstructive pulmonary disease (COPD) in mice and its mechanism. COPD model was established by exposing male BALB/c mice to cigarette smoke and challenged with LPS inhalation. Supernatants of bronchoalveolar lavage fluid (BALF) were harvested and IL-1β, IL-6, IL-8 and TGF-β1 levels were measured by ELISA (enzyme-linked immunesorbent assay). The number of total white blood cells and neutrophils in bronchoalveolar lavage fluid was counted separately. Lung tissue was stained with Mayer 's hematoxylin and eosin for histopathologic examination. pAMPKa protein expression and distribution of lung tissue were analyzed by immunohistochemistry method. In vitro, levels of AMPKα phosphorylation in phorbol-12- myristate-13-acetate (PMA) differentiated THP-1 cells was detected by immunohistochemistry, IL-8 level in supernatants of cigarette smoke condensate stimulating PMA differentiated THP-1 cells was measured by ELISA. The results showed that WS070117M1 treatment significantly activated AMPKa in the lung tissue. It also resulted in down regulation of IL-1β, IL-6, IL-8 and TGF-β1 levels in bronchoalveolar lavage fluid and IL-8 level in cigarette smoke condensate stimulating PMA differentiated THP-1 cells. In addition, WS070117M1 could inhibit the recruitment of total white blood cells and neutrophils. These results suggest that WS070117M1 may alleviate the airway inflammation by activating AMPK in the lung tissue.

Study on Exhale CO_2 Recovery and Resting Energy Expenditure in Patients with Cirrhosis / 中国医师杂志

Objective To explore the recovery rate of exhale CO 2 and energy expenditure in the patients with cirrhosis.Methods The recovery rate of exhale CO 2 and energy expenditure in fourteen patients with cirrhosis and eleven healthy subjects were measured by using NaH 13 CO 3 as tracer.After overnight fast,all subjects were intravenously given NaH 13 CO 3 at a primed constant rate of infusion for two hours after a saturating dose infusion.Amount of 13 CO 2 in exhale air was measured using stable isotope mass spectrometry analysis,and the recovery rate of exhale CO 2 and energy expenditure were calculated.Results The recovery rate of exhale CO 2 in patients with Cirrhosis was (80 7?0 26)%,and in healthy control subjects was (78 3?0 84)%,which showed a significantly different between the two groups(P0 05)[(30 2?2 4)Kcal?kg -1 ?d -1 and (28 4?3 5)Kcal?kg -1 ?d -1 ,respectively].Conclusions The results provide theoretical basic to calculate meals for nutritional therapy in the patients with cirrhosis.