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The risk factors promoting acute kidney injury (AKI) to chronic kidney disease (CKD) progression remain largely unknown. The aim of the present study was to investigate whether hyperhomocysteinemia (Hhcy) accelerates the development of renal fibrosis after AKI.Hhcy aggravated ischemia-reperfusion-induced AKI and the subsequent development of renal fibrotic lesions characterized by excessive extracellular matrix deposition. Mechanistically, the RNA binding protein human antigen R (HuR) bound to the 3'-untranslated region (3'-UTR) of heme oxygenase-1 (HO-1) messenger RNA (mRNA). Homocysteine (Hcy) downregulated HuR expression, reduced the binding of HuR to the 3'-UTR of HO-1, and thereafter decreased HO-1 expression. Administration of the HO-1 inducer cobalt protoporphyrin-IX significantly hindered Hhcy-augmented reactive oxygen species production and renal fibrotic lesions. Innovation and Conclusion: These data indicate that Hhcy might be a novel risk factor that promotes AKI to CKD progression. Lowering Hcy level or HO-1 induction might be a potential therapeutic strategy to improve the outcome of AKI.

We analyzed extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (226) and Klebsiella pneumoniae (53) collected from urine specimens during 2005-2009 for the presence of ESBL genes, class 1 integrons, and characterization of gene cassettes. TEM and CTX-M β-lactamase genes were the most prevalent. One hundred and forty-four E. coli and 35 K. pneumoniae were positive for the class 1 integrase gene; among them, 99 E. coli and 14 K. pneumoniae detected gene cassettes. Gene cassette regions were identified by restriction fragment length polymorphism and DNA sequencing analysis. Eleven distinct gene cassette arrays were found in E. coli isolates, and seven distinct gene cassette arrays were found in K. pneumoniae isolates. The cassette array aacA4-catB8-aadA1 was first found in E. coli and dfrA1-orfC was first reported in K. pneumoniae. Most of the gene cassettes found in this class 1 integrons were for aminoglycoside resistance. Enterobacterial repetitive intergenic consensus-polymerase chain reaction fingerprint patterns revealed the isolates carrying gene cassettes were genetically unrelated. In conclusion, we studied the class 1 integrons among urinary isolates of ESBL-producing E. coli and K. pneumoniae in Southern China during the past 5 years and found that class 1 integrons were widely disseminated and played a major role in antibiotic resistance.