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Simona Martinotti, Mauro Patrone, Elia Ranzato DiSIT – Dipartimento di Scienze e Innovazione Tecnologica, University of Piemonte Orientale, Alessandria, Italy Abstract: High-mobility group box 1 (HMGB1) protein is a member of the highly conserved non-histone DNA binding protein family. First identified in 1973, as one of a group of chromatin-associated proteins with high acidic and basic amino acid content, it was so named for its characteristic rapid mobility in polyacrylamide gel electrophoresis. HMGB1 was later discovered to have another function. It is released from a variety of cells into the extracellular milieu to act on specific cell-surface receptors. In this latter role, HMGB1 is a proinflammatory cytokine that may contribute to many inflammatory diseases, including sepsis. Therefore, HMGB1 regulates intracellular cascades influencing immune cell functions, including chemotaxis and immune modulation. The bioactivity of the HMGB1 is determined by specific posttranslational modifications that regulate its role in inflammation and immunity. During tumor development, HMGB1 has been reported to play paradoxical roles in promoting both cell survival and death by regulating multiple signaling pathways. In this review, we focus on the role of HMGB1 in physiological and pathological responses, as well as the mechanisms by which it contributes to immunity, inflammation, and cancer progression. Keywords: alarmin, DNA replication, HMGB1, posttranslational modifications, wound repair

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The recurrent or chronic "non specific pharyngitis" is one of the most common complaints of adults treated in an outpatient setting and it is a disease without a certain aetiology, but with many probable causes which can be of bacterial or viral nature, but incidence of atypical microorganism infection, such as Chlamydia trachomatis (Ct), Mycoplasma hoininis (Mh) and Ureaplasina urealyticum (Uu) is believed to be on the rise. The increase is correlated above all to sexual behavior and to diffusion of new microbiological diagnostic methods, such as PCR. From 840 patients affected by recurrent episodes of chronic pharyngeal phlogosis and examined from 2006 to 2008, we selected 67 patients, 37 women and 30 men. On the basis of molecular and cultural analysis, 85.07% of patients were positive to Ct, and 89.55% were positive to Mollicutes (Mh+Uu), showing a vast overlapping of co-infections of Uu and Mh. Our data indicated a higher rate of infection by atypical microorganism in selected patients affected by chronic pharyngitis. It is important to suspect this aetiology during recurrent chronic pharingitis because patients with these oropharingeal infections, must be considered as carriers and the correct treatment, only possible after exact diagnosis, is above all necessary to prevent fearful complications in other body areas. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To perform a longitudinal evaluation of high-sensitivity C-reactive protein (hs-CRP) in young people with type 1 diabetes in relation to the development of microalbuminuria (MA). RESEARCH DESIGN AND METHODS: hs-CRP was measured in 329 blood samples collected from 49 subjects with type 1 diabetes with MA and 49 normoalbuminuric subjects matched for age, sex, and duration of diabetes. RESULTS: In subjects developing MA, a progressive rise in hs-CRP was detected with levels significantly higher in the years after the onset of MA when compared with levels before MA onset (P = 0.003; age-adjusted P = 0.06). After the onset of MA, hs-CRP levels were significantly higher in subjects with MA when compared with normoalbuminuric subjects (median 1.9 mg/l [range 0.2-9.8] vs. 1.1 mg/l [0.2-6.4]; P = 0.02; adjusted P = 0.036). CONCLUSIONS: In this population of young subjects with type 1 diabetes, there was a significant increase in hs-CRP levels after the onset of MA, likely reflecting a general state of inflammation. [ABSTRACT FROM AUTHOR]

Royal jelly (RJ) has successfully been used as a remedy in wound healing. RJ has multiple effects, including antibacterial, anti-inflammatory and immunomodulatory activities, in various cell types. However, no component(s) (other than antibacterial) have been identified in RJ-accelerated wound healing. In this study, we demonstrate that keratinocytes are responsible for the elevated production of matrix metalloproteinase-9 (MMP-9) after incubation with a water extract of RJ. Furthermore, the keratinocyte migration and wound closure rates were significantly increased in the presence of RJ extract. MMP-9 production was reduced significantly following proteinase K treatment but remained stable after heat treatment, indicating that active component(s) have a proteinous character. To identify the component responsible for inducing MMP-9 production, RJ extract was fractionated using C18 RP-HPLC. In fractions exhibiting stimulatory activity, we immunochemically detected the bee-derived antibacterial peptide, defensin-1. Defensin-1 was cloned, and recombinant peptide was produced in a baculoviral expression system. Defensin-1 stimulated MMP-9 secretion from keratinocytes and increased keratinocyte migration and wound closure in vitro. In addition, defensin-1 promoted re-epithelisation and wound closure in uninfected excision wounds. These data indisputably demonstrate that defensin-1, a regular but concentration variable factor found in honey and RJ, contributes to cutaneous wound closure by enhancing keratinocyte migration and MMP-9 secretion. [ABSTRACT FROM AUTHOR]