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Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody--induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that may be responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody--induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family, which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody--induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms, some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody--induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody--induced nephritis and lupus., Introduction Immune-mediated nephritis is an important pathogenic determinant in SLE and Goodpasture syndrome (anti--glomerular basement membrane [anti-GBM] disease). In spontaneous lupus nephritis, both Ab-mediated and Ab-independent mechanisms lead to renal [...]

Background: The emergence and rapid spreading of multidrug-resistant Acinetobacter baumannii strains has become a major health threat worldwide. To better understand the genetic recombination related with the acquisition of drug-resistant elements during bacterial infection, we performed complete genome analysis on three newly isolated multidrug-resistant A. baumannii strains from Beijing using next-generation sequencing technology. Methodologies/Principal Findings: Whole genome comparison revealed that all 3 strains share some common drug resistant elements including carbapenem-resistant blaOXA-23 and tetracycline (tet) resistance islands, but the genome structures are diversified among strains. Various genomic islands intersperse on the genome with transposons and insertions, reflecting the recombination flexibility during the acquisition of the resistant elements. The blood-isolated BJAB07104 and ascites-isolated BJAB0868 exhibit high similarity on their genome structure with most of the global clone II strains, suggesting these two strains belong to the dominant outbreak strains prevalent worldwide. A large resistance island (RI) of about 121-kb, carrying a cluster of resistance-related genes, was inserted into the ATPase gene on BJAB07104 and BJAB0868 genomes. A 78-kb insertion element carrying tra-locus and blaOXA-23 island, can be either inserted into one of the tniB gene in the 121-kb RI on the chromosome, or transformed to conjugative plasmid in the two BJAB strains. The third strains of this study, BJAB0715, which was isolated from spinal fluid, exhibit much more divergence compared with above two strains. It harbors multiple drug-resistance elements including a truncated AbaR-22-like RI on its genome. One of the unique features of this strain is that it carries both blaOXA-23 and blaOXA-58 genes on its genome. Besides, an Acinetobacter lwoffii adeABC efflux element was found inserted into the ATPase position in BJAB0715. Conclusions: Our comparative analysis on currently completed Acinetobacter baumannii genomes revealed extensive and dynamic genome organizations, which may facilitate the bacteria to acquire drug-resistance elements into their genomes. [ABSTRACT FROM AUTHOR]

The aim of the present study is to investigate the clinical value of Ilizarov transverse tibial bone transport and microcirculation reconstruction in the treatment of chronic ischemic diseases in lower limbs. A total of 90 patients with chronic ischemic diseases in lower limbs were selected and randomly divided into two groups: The observation group (n=45) and the control group (n=45). Those patients were treated with Ilizarov transverse tibial bone transport and microcirculation reconstruction, and percutaneous balloon angioplasty (PTBA), respectively. Changes in the diameter, blood flow of lower limb arteries in the paretic side, wound healing time, disappearance time of pains, dorsal foot skin temperature, and the expression area of vascular endothelial growth factors (VEGFs) were detected in both groups. Compared with control group, the diameters and blood flows of lower limb arteries were significantly larger (P<0.05), and the dorsal foot skin temperature was significantly higher at 1 day, 1 week and 1 month after operation, respectively. Meantime, the expression area of VEGFs in the observation group was significantly larger than that in the control group at 1 day, 1 week and 1 month, respectively. Furthermore, compared with control group, wound healing time and disappearance time of pains of patients were earlier in the observation group (P<0.05). At 1 month after operation, the intermittent claudication, rest pain and lower limb ulcer or gangrene among clinical symptoms of patients in the observation group improved significantly more than those in the control group (P<0.05). In conclusion, the application of Ilizarov transverse tibial bone transport and microcirculation reconstruction could achieve better outcomes in the treatment of chronic ischemic diseases in lower limbs.

Objective: To obtain peptide mimicking epitopes of Schistosoma japonicum (S. japonicum) through screening of a phage peptide library and to test their potential for induction of protection., Methods: S. japonicum infected sera from Microtus fortis (IMFS) and normal sera from Microtus fortis (NMFS) were used respectively to screen a 12-mers random peptide library by testing the reactivity of anti-S. japonicum serum with the phagotopes. After three rounds of biopanning, the pooled phages were used to immunize mice, after which challenge infection was performed., Results: Of 12 randomly picked clones, 10 clones selected using IMFS and 7 clones selected using NMFS were shown to be antigenic. Significant reduction in adult worms (22.6%) and a high reduction (68.9%) in liver eggs were achieved following immunization with phages screened with IMFS. However, no protection was elicited by those selected with NMFS., Conclusion: The results show that the phagotopes are both antigenic and immunogenic, suggesting a potential use of phage displayed peptide as novel vaccines against S. japonicum.