1.Study on the risk of infection with SARS-coronavirus in health care workers in the designated hospital exclusively for SARS
Jinjun CHEN ; Sizhao LIAO ; Jiafan CHEN
Medical Journal of Chinese People's Liberation Army 2001;0(09):-
Objective To investigate the risk rate of infection with SARS coronavirus in health care workers in an designated hospital, and to assess the effectiveness of the isolation system in prevention of nosocomial transmission of SARS. Methods Questionnaire was submitted to all health care workers related with SARS patients, and ELISA assay was performed to detect IgG antibody against SARS coronavirus for all of them. Results 450 health care workers were submitted the same questionnaire, 445 questionnaires were returned, and 441 blood samples were collected. It was confirmed that all health care workers involved had complied with the isolation guidelines as formulated by the authority of the hospital. Two hundred and sixty persons out of 441 were classified into the group who had close contact with SARS patients and/or SARS materials. Among these 260 workers, IgG antibody against SARS Coronavirus was detected in 5 of them, who had either worked in the SARS ward, CCU (where 3 SARS probable cases had stayed for a short term), paediatric ward, center for sample transference, or laundry. Therefore, there was no statistically significant difference in the risk rate between the group of workers who had close contact with SARS patients and/or SARS materials and the group without contact. Conclusion The current isolation system against SARS was effective, though might not perfect.
2.The protective effects of different doses of fasudil on hepatic ischemia/reperfusion injury in rats with cirrhosis
Xiaopeng HONG ; Genglong ZHU ; Jian LI ; Borun ZHUANG ; Jiafan CHEN ; Baimeng ZHANG
Chinese Journal of General Surgery 2016;31(12):1038-1041
Objective To investigate the protective effects of different doses of fasudil on hepatic ischemia/reperfussion (I/R) injury in rats with liver cirrhosis.Methods Cirrhosis was induced in rats by subcutaneous injection of 60% carbon tetrachloride (CC14) corn oil solution (0.4 ml/100 g) twice a week for twelve weeks.Five percent of alcohol was given intermittently in drinking water.Then 40 cirrhotic rats were randomized into 4 groups.In sham group,sham operation was performed.In I/R group A and B,whole rat livers were subjected to warm ischemia by clamping the hepatic artery and portal vein for 30 min.In group A,the selected rats were pretreated with low-dose fasudil 1 mg/kg (intraperitoneal injection) 30 min before the induction of ischemia,and in group B,with high-dose 10 mg/kg.The serum levels of alanine aminotransferase (ALT) and endothelin-1 (ET-1),and the liver tissue superoxide dismutase (SOD)activity,malondialdehyde (MDA) content,the expression of HIF-1a (hypoxia-inducible fador-1a) were measured after reperfusion for 6 hours.Hepatic pathologic changes were observed under microscope.Results Compared with I/R group,the serum ALT,AST,ET-1 levels,MDA content and the expression of HIF-1 a were markedly decreased in group B,while the SOD activity significantly increased (P < 0.05).And the pathologic changes were less severe in group B.Conclusion The high-dose fasudil markedly lessened the expression of HIF-1a,up-regulated the concentration of SOD,and lowered the levels of MDA and ET-1,protecting against heoatic ischemia/reperfusion injury in rats with liver cirrhosis.
3.Phylogeny and virulence gene profile of Francisella salimarina
Xiaowei CHEN ; Qiwei LI ; Yan CHEN ; Shunguang LI ; Jiafan CHEN ; Chao YANG ; Cha CHEN ; Pinghua QU ; Renxin CAI
Chinese Journal of Microbiology and Immunology 2023;43(8):612-618
Objective:To study the molecular phylogeny and virulence gene profile of Francisella salimarina. Methods:Phylogenetic analysis of Francisella salimarina was performed based on the global genome data of related Francisella species on GenBank database. The consistency in phylogenetic analysis based on single marker genes (such as 16S rRNA gene, rpoB gene and mdh gene) and the core genome as compared. Virulence genes and antibiotic resistance genes were annotated using the virulence factor database (VFDB) and the Comprehensive Antibiotic Resistance Database (CARD), respectively. The virulence of Francisella salimarina was analyzed with a Galleria mellonella (greater wax moth) infection model using Francisella philomiragia ATCC 25015 T as reference strain. Results:The phylogenetic analysis revealed that Francisella salimarina was closely related to Francisella philomiragia. The phylogenetic tree based on mdh gene was highly similar to that based on the core genome. Francisella salimarina could be differentiated from other related species by 16S rRNA gene or mdh gene, with the latter being more accurate. Eight Francisella salimarina strains carried multiple virulence genes, mainly involved in secretion, adhesion, immune regulation, motility and stress survival. Moreover, beta-lactam resistance gene blaFPH was identified in all eight strains. Francisella salimarina showed high lethality in the Galleria mellonella infection model, which was similar to Francisella philomiragia ATCC 25015 T. Conclusions:Francisella salimarina was a rare pathogen with similar pathogenicity to Francisella philomiragia. The mdh gene could be used as a molecular target for rapid identification of Francisella salimarina.
4.Characterization of the depsidone gene cluster reveals etherification, decarboxylation and multiple halogenations as tailoring steps in depsidone assembly.
Jiafan YANG ; Zhenbin ZHOU ; Yingying CHEN ; Yongxiang SONG ; Jianhua JU
Acta Pharmaceutica Sinica B 2023;13(9):3919-3929
Depsides and depsidones have attracted attention for biosynthetic studies due to their broad biological activities and structural diversity. Previous structure‒activity relationships indicated that triple halogenated depsidones display the best anti-pathogenic activity. However, the gene cluster and the tailoring steps responsible for halogenated depsidone nornidulin ( 3) remain enigmatic. In this study, we disclosed the complete biosynthetic pathway of the halogenated depsidone through in vivo gene disruption, heterologous expression and in vitro biochemical experiments. We demonstrated an unusual depside skeleton biosynthesis process mediated by both highly-reducing polyketide synthase and non-reducing polyketide synthase, which is distinct from the common depside skeleton biosynthesis. This skeleton was subsequently modified by two in-cluster enzymes DepG and DepF for the ether bond formation and decarboxylation, respectively. In addition, the decarboxylase DepF exhibited substrate promiscuity for different scaffold substrates. Finally, and interestingly, we discovered a halogenase encoded remotely from the biosynthetic gene cluster, which catalyzes triple-halogenation to produce the active end product nornidulin ( 3). These discoveries provide new insights for further understanding the biosynthesis of depsidones and their derivatives.