Protective effects of BML-111 on cerulein-induced acute pancreatitis-associated lung injury via activation of Nrf2/ARE signaling pathway.

The aim of this study was to investigate whether BML-111 can exert protective effects on cerulein-induced acute pancreatitis-associated lung injury (APALI) via activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant responsive element (ARE) signaling pathway. Severe acute pancreatitis (SAP) was established by intraperitoneal injection of cerulein (50 µg/kg) seven times at hourly intervals and Escherichia coli lipopolysaccharide (10 mg/kg) once after the last dose of cerulein immediately. BML-111 (1 mg/kg) was administered 1 h before the first injection of cerulein. Samples were taken at 3, 6, 12, and 24 h after the last injection. Pathologic lesions of the pancreas and lung tissues as well as the levels of serum amylase were analyzed; Myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase-1 (NQO1) of lung tissue were determined. The findings revealed that the injuries of pancreas and lung were typically induced by cerulein. The administration of BML-111 reduced the levels of serum amylase, lung MPO, lung MDA, the wet-to-dry weight ratio, and the pathology injury scores of the lung and pancreas, which increased in the SAP group. The expressions of Nrf2, HO-1, NQO1, and activity of SOD in lung tissue increased in the BML-111 group compared with those in the SAP group. This study indicates that BML-111 may play a critical protective role in APALI induced by cerulein. The underlying mechanisms of protective role may be attributable to its antioxidant effects through the activation of Nrf2/ARE pathway.

BML-111, a lipoxin receptor agonist, ameliorates 'two-hit'-induced acute pancreatitis-associated lung injury in mice by the upregulation of heme oxygenase-1.

The objective of this study is to investigate the effects of BML-111 on acute pancreatitis-associated lung injury (APALI) induced by cerulein with subsequent an LPS administration in mice and its possible mechanisms. One hundred and twenty-eight mice were randomly allocated to four groups, namely the APALI group, the BML-111 pretreatment group, the BM-111 control group, and the control group. The 'two-hit' mice APALI model was established by intraperitoneal injection of cerulein 7 times at hourly intervals and Escherichia coli lipopolysaccharide (LPS) once after the last dose of cerulein immediately. The samples were taken at 3, 6, 12, and 24 h after the last injection. Serum levels of amylase, TNF-a, IL-1ß and IL-10, were determined. Histological score of the pancreas and lung, the wet/dry weight ratio, and heme oxygenase-1 (HO-1) expression in the lung were also evaluated. BML-111 pretreatment significantly reduced the serum levels of amylase, TNF-α, IL-1ß, the wet/dry weight ratio of lung, and the pathology injury scores of pancreas and lung, and the serum levels of IL-10 were markedly increased. The severity of pancreatic and lung histology were also significantly improved by the administration of BML-111, and the expressions of HO-1 in lung tissues also increased in the BML-111 group compared with those in the APALI group. In conclusion, BML-111 exerts protective effects on APALI induced by cerulein and LPS. In addition to its anti-inflammatory effects, the beneficial effects may also be due to the upregulation of HO-1 expression in the lung tissues.

[Construction and characterization of a brucella suis S2 strain with a chloramphenicol resistance marker].

Vaccination has not been used widely because of the interference in the discrimination between infected and vaccinated animals in immune-screening procedures. In the present study, chloramphenicol resistance gene (Cm(r)) was cloned into the genomic DNA of brucella suis S2 strain by homologous recombination with knocking out the WbkC gene, and obtained the recombinant rS2-WbkC. Further study confirmed that rS2-WbkC was conversed into rough-phenotype form smooth-phenotype. The recombinant keeps the ability to chloramphenicol resistance after 25 passages in tryptic soy agar (TSA). Mice tests showed rS2-WbkC offered similar protection to S2 strain, but more safe than S2. Serum collected form rS2-WbkC immunized mice could be easily distinguished from antiserum produced by smooth-phenotype brucella abortus. In view of these result, rS2-WbkC is a promising candidate for vaccine strain.

[The application and research advances of Brucella vaccines].

Brucellosis is a crucial zoonosis caused by Brucella, which has some traits of wide hosts, great infectivity and difficulty in cure. Brucellosis caused great losses to farming and people's health. Vaccination is the main measure used to control Brucellosis, and some attenuated Brucella strains were often used as vaccines. To find more effective vaccines, Scientists are now constructing recombinant strains, DNA vaccines and subunit vaccines, as well as inducing new attenuated strains from isolations. The present applications of B. abortus strain 19 (S19) , B. melitensis Rev. 1 (Rev. 1), B. suis strain 2 (S2), B. abortus strain 45/20 (45/20) and rough strain B. abortus 51 (RB51) were discussed. And some recent research work on Brucella vaccines, such as Brucella recombinant vaccines, DNA vaccines and so on, were reviewed in this paper.