Plasminogen is a master regulator and a potential drug candidate for the healing of radiation wounds.

Around 95% of cancer patients undergoing radiotherapy experience cutaneous side effects, and some develop radiation wounds or fibrosis. Currently, there is no effective treatment for these indications. We show here that plasminogen administration enhanced the healing of radiation wounds via pleiotropic effects on gene expression. Using RNA sequencing, we found that plasminogen downregulated the expression of genes in the TLR, TNF, WNT, MAPK, and TGF-ß signaling pathways, and enhanced the anti-inflammatory effect of arachidonic acid, leading to significantly decreased inflammation and improved remodeling of granulation tissue compared with placebo treatment. In addition, plasminogen induced metabolic changes, including decreased glycolysis. Importantly, many of the factors downregulated by plasminogen are pro-fibrotic. Therefore, in radiation wounds with excessive inflammation, plasminogen is able to enhance and redirect the healing process, such that it more closely resembles physiological healing with significantly reduced risk for developing fibrosis. This makes plasminogen an attractive drug candidate for the treatment of radiation wounds in cancer patients.

Plasminogen activation is required for the development of radiation-induced dermatitis.

Skin damage caused by radiation therapy (radiodermatitis) is a severe side effect of radiotherapy in cancer patients, and there is currently a lack of effective strategies to prevent or treat such skin damage. In this work, we show with several lines of evidence that plasminogen, a pro-inflammatory factor, is key for the development of radiodermatitis. After skin irradiation in wild-type (plg+/+) mice, the plasminogen level increased in the irradiated area, leading to severe skin damage such as ulcer formation. However, plasminogen-deficient (plg-/-) mice and mice lacking plasminogen activators were mostly resistant to radiodermatitis. Moreover, treatment with a plasminogen inhibitor, tranexamic acid, decreased radiodermatitis in plg+/+ mice and prevented radiodermatitis in plg+/- mice. Together with studies at the molecular level, we report that plasmin is required for the induction of inflammation after irradiation that leads to radiodermatitis, and we propose that inhibition of plasminogen activation can be a novel treatment strategy to reduce and prevent the occurrence of radiodermatitis in patients.

Microbiology of hidradenitis suppurativa (acne inversa): a histological study of 27 patients.

Hidradenitis suppurativa (acne inverse) (HS) is a chronic skin disease primarily affecting hair follicles. The aetiology of HS is unknown, but infection is believed to play some role. This retrospective study investigated the microbial colonization directly in skin appendices in HS skin samples. Archival samples from 27 patients with HS were screened by immunofluorescence labelling with monoclonal and polyclonal antibodies against Gram-positive bacteria, Propionibacterium acnes and Propionibacterium granulosum. Fluorescence in situ hybridization was used for further species identification of Staphylococcus spp. Overall, 17 patients (63%) were found positive for bacterial colonization. Of these, 15 showed colonization in hair follicles and/or sinus tracts. The most commonly identified bacteria were DAPI labelled coccoids that were seen in 71% of the positive patients in the form of biofilms and microcolonies. P. acnes was found as biofilms in hair follicles of two patients. Staphylococcus aureus and coagulase-negative staphylococci were not detected in any sample. The results of this study indicate a common bacterial presence in HS skin lesions. Bacterial biofilms are not uncommon and their pathogenic role needs further evaluation.

Microbiology of folliculitis: a histological study of 39 cases.

Folliculitis is a common inflammatory skin syndrome. Several microbial organisms have been put forward as causative agents, but few studies visualized microbes directly in inflamed hair follicles. This retrospective study investigated bacterial and fungal colonization of inflamed hair follicles in patients with clinically diagnosed non-infectious folliculitis. Skin biopsies from 39 folliculitis patients and 27 controls were screened by fluorescence in situ hybridization (FISH) using broad-range bacterial and fungal probes and by immunofluorescence microscopy using a monoclonal antibody towards Gram-positive bacteria. Specific monoclonal and polyclonal antibodies towards Staphylococcus spp. and Propionibacterium acnes were applied for further species identification. Inflamed follicles were associated with bacterial colonization in 10 samples (26%) and fungal colonization in three samples (8%). Staphylococcus spp. were observed in inflamed follicles in seven samples (18%). Two samples were positive for P. acnes, which were identified as either type II or type IB/type III. Both Staphylococcus spp. and P. acnes were seen in macrocolonies/biofilm structures. In conclusion, one-third of patients with clinically diagnosed, non-infectious folliculitis exhibited microbial colonization with predominance of Staphylococcus spp.

Non-invasive identification of melanoma with near-infrared and skin impedance spectroscopy.

BACKGROUND/PURPOSE: An early diagnosis of cutaneous malignant melanoma is of high importance for good prognosis. An objective, non-invasive instrument could improve the diagnostic accuracy of melanoma and decrease unnecessary biopsies. The aim of this study was to investigate the use of Near-infrared and skin impedance spectroscopy in combination as a tool to distinguish between malignant and benign skin tumours. METHODS: Near-infrared and skin impedance spectra were collected in vivo on 50 naevi or suspect melanomas prior to excision. Received data were analysed using multivariate techniques and the results were compared to histopathology analyses of the tumours. A total of 12 cutaneous malignant melanomas, 19 dysplastic naevi and 19 benign naevi were included in the study. RESULTS: The observed sensitivity and specificity of the proposed method were 83% and 95%, respectively, for malignant melanoma. CONCLUSION: The results indicate that the combination of near-infrared and skin impedance spectroscopy is a promising tool for non-invasive diagnosis of suspect cutaneous malignant melanomas.

No link between rosacea and Propionibacterium acnes.

Rosacea is a common skin disease in adults affecting mainly the facial skin. Although inflammation appears to play a pathogenic role in rosacea, initiating factors are largely unknown. Microbial involvement in the development of rosacea has been suggested previously. We aimed to visualize Propionibacterium acnes in the skin compartments of rosacea patients. Facial skin biopsies from 82 rosacea patients and 25 controls were stained with a P. acnes-specific monoclonal antibody (QUBPa3). Seven of 82 patients (8.5%) tested positive for P. acnes which was present either as a biofilm (57% of positive) or a microcolony (43%) in colonized patients. Our results suggest that P. acnes does not play a major role in the pathogenesis of rosacea.

Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation.

Helicobacter pylori adherence in the human gastric mucosa involves specific bacterial adhesins and cognate host receptors. Here, we identify sialyl-dimeric-Lewis x glycosphingolipid as a receptor for H. pylori and show that H. pylori infection induced formation of sialyl-Lewis x antigens in gastric epithelium in humans and in a Rhesus monkey. The corresponding sialic acid-binding adhesin (SabA) was isolated with the "retagging" method, and the underlying sabA gene (JHP662/HP0725) was identified. The ability of many H. pylori strains to adhere to sialylated glycoconjugates expressed during chronic inflammation might thus contribute to virulence and the extraordinary chronicity of H. pylori infection.