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Articles by L Shan
Total Records ( 2 ) for L Shan
  X Li , Y Li , L Shan , E Shen and T. Peng
  Aims

Lipopolysaccharide (LPS) induces cardiomyocyte caspase-3 activation and proinflammatory factors, in particular tumour necrosis factor-alpha (TNF-) production, both of which contribute to myocardial dysfunction during sepsis. The present study was to investigate the roles of calpain/calpastatin system in cardiomyocyte caspase-3 activation, TNF- expression, and myocardial dysfunction during LPS stimulation.

Methods and results

In cultured adult rat cardiomyocytes, LPS (1 µg/mL) induced calpain and caspase-3 activity, and up-regulated TNF- expression. These effects of LPS were abrogated by over-expression of calpastatin, an endogenous calpain inhibitor, transfection of calpain-1 siRNA, or various pharmacological calpain inhibitors. Furthermore, blocking gp91phox-NADPH oxidase prevented calpain and caspase-3 activation and decreased TNF- expression in LPS-stimulated cardiomyocytes. To investigate the role of calpastatin in endotoxaemia, transgenic mice with calpastatin over-expression (CAST-Tg) and wild-type mice were treated with LPS (4 mg/kg, i.p.) or saline in the presence of calpain inhibitor-III (10 mg/kg, i.p.) for 4 h, and their heart function was measured with a Langendorff system. Over-expression of calpastatin significantly attenuated myocardial dysfunction (P < 0.05). Consistently, calpain activity, caspase-3 activity, and TNF- expression were also reduced in CAST-Tg and calpain inhibitor-III compared with wild-type and vehicle-treated hearts, respectively.

Conclusion

gp91phox-NADPH oxidase-mediated calpain-1 activation induces caspase-3 activation and TNF- expression in cardiomyocytes during LPS stimulation. Over-expression of calpastatin inhibits calpain activation and improves myocardial function in endotoxaemia. The present study suggests that targeting calpain/calpastatin system may be a potential therapeutic intervention for septic hearts.

  L Shan and H. Zhu
 

Generation of adequate test cases is difficult and expensive, especially for testing software systems whose input is structurally complex. This paper presents an approach called data mutation to generating a large number of test data from a few seed test cases. It is inspired by mutation testing methods, but differs from them in the aim and the way that mutation operators are defined and used. While mutation testing is a method for measuring test adequacy, data mutation is a method of test case generation. In traditional mutation testing, mutation operators are used to transform the program under test. In contrast, mutation operators in our approach are applied on input data to generate test cases, hence called data mutation operators. The paper reports a case study with the method on testing an automated modelling tool to illustrate the applicability of the proposed method. Experiment data clearly demonstrate that the method is adequate and cost effective, and able to detect a large proportion of faults.

 
 
 
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