Circulating levels of High-mobility group box 1 protein and nucleosomes are associated with outcomes after liver transplant.

BACKGROUND: Liver transplantation (LT) can be associated with early complications, such as allograft dysfunction and acute kidney injury, which contribute significantly to morbidity and mortality. High-mobility group box 1 protein (HMGB1) has been identified as mediator in ischemia-reperfusion injury. Nucleosomes are complexes formed by DNA and histone proteins, and histones contribute to organs failure and death during sepsis. METHODS: HMGB1 and nucleosome plasma levels were measured, by enzyme-linked immunosorbent assays, during LT and in the first 48 post-operative hours in 22 LT patients. The association between HMGB1 and nucleosome levels and the complications and survival within 6 months after LT were investigated. RESULTS: We observed peak HMGB1 and nucleosome levels after graft reperfusion. HMGB1 and nucleosome levels were associated with the occurrence of acute kidney injury, early allograft dysfunction, and early survival after LT. Nucleosome levels after graft reperfusion were associated with the occurrence of systemic inflammatory response syndrome. CONCLUSIONS: HMGB1 and nucleosome levels increased after liver reperfusion in human LT setting and were associated with early complications and survival. New studies are necessary to explore their role as early markers of hepatocellular injury in human LT and the risk of graft and organs dysfunction and death.

The Brucella abortus phosphoglycerate kinase mutant is highly attenuated and induces protection superior to that of vaccine strain 19 in immunocompromised and immunocompetent mice.

Brucella abortus is a facultative intracellular bacterial pathogen that causes abortion in domestic animals and undulant fever in humans. The mechanism of virulence of Brucella spp. is not yet fully understood. Therefore, it is crucial to identify new molecules that can function as virulence factors to better understand the host-pathogen interplay. Herein, we identified the gene encoding the phosphoglycerate kinase (PGK) of B. abortus strain 2308. To test the role of PGK in Brucella pathogenesis, a pgk deletion mutant was constructed. Replacement of the wild-type pgk by recombination was demonstrated by Southern and Western blot analyses. The B. abortus Delta pgk mutant strain exhibited extreme attenuation in bone marrow-derived macrophages and in vivo in BALB/c, C57BL/6, 129/Sv, and interferon regulatory factor-1 knockout (IRF-1 KO) mice. Additionally, at 24 h postinfection the Delta pgk mutant was not found within the same endoplasmic reticulum-derived compartment as the wild-type bacteria, but, instead, over 60% of Brucella-containing vacuoles (BCVs) retained the late endosomal/lysosomal marker LAMP1. Furthermore, the B. abortus Delta pgk deletion mutant was used as a live vaccine. Challenge experiments revealed that the Delta pgk mutant strain induced protective immunity in 129/Sv or IRF-1 KO mice that was superior to the protection conferred by commercial strain 19 or RB51. Finally, the results shown here demonstrated that Brucella PGK is critical for full bacterial virulence and that a Delta pgk mutant may serve as a potential vaccine candidate in future studies.