Rejuvenation of photoaged aged mouse skin using high-intensity focused ultrasound.

BACKGROUND: High-intensity focused ultrasound (HIFU) therapy has emerged as an option for skin rejuvenation. However, the application against photo-damaged skin remains obscure. This study evaluates the effect of HIFU against photoaged skin using a mouse model. METHODS: A total of 60 mice were used and divided into 3 groups; group 1: natural aging control group (n = 20), group 2: UVB irradiation group (n = 20), and group 3: UVB irradiation followed by HIFU treatment (n = 20). The evaluation was made grossly by analyzing wrinkles and histologically by performing H&E, Toluidine Blue, Masson's Trichrome, and immunohistochemistry for TGF-ß and MMP3. Imaging software was used to quantify the findings. RESULTS: Gross findings showed HIFU treated group 3 with similar findings with the control group supporting the rejuvenation effect for photo-aged skin. Histology findings with H&E show a significant reduction in skin thickness after HIFU treatment (60.115 units (group 2) vs. 40.853 units (group 3), p<0.05). Toluidine Blue and Masson's Trichrome showed improved collagen array and significantly increased distribution for group 3 over group 2 (272,879.88 units (group 2) vs. 533,805.78 units (group 3), p<0.05). Immunohistochemistry for TGF-ß showed a significantly higher value for group 3 (2.45450 units) over group 2 (0.58880 units) and MMP3 with a significantly lower value for group 3 (99,180 units) over group 2 (559,830 units) (p<0.05). CONCLUSIONS: The treatment of HIFU supports the rejuvenation effect for photoaged skin. Findings show that HIFU provides benefits of collagen formation and rearrangement by enhancing TGF-ß and inhibiting MMP3 activity. This study is the first animal study to show the direct effect of HIFU on photo-aged skin further supporting the use of HIFU in aging skin aiming to reverse the morphological effects of aging.

IL-17 Receptor Signaling through IL-17A or IL-17F Is Sufficient to Maintain Innate Response and Control of Helicobacter pylori Immunopathogenesis.

IL-17R signaling is required for control of extracellular pathogens and is also implicated in development of chronic inflammatory processes. The response to the human pathogen Helicobacter pylori results in Th1 and Th17 cell activation and a chronic inflammatory process that can lead to adverse outcomes, such as gastric cancer. Previously, we identified IL-17RA as a requirement for the recruitment of neutrophils and control of H. pylori colonization in the gastric mucosa. Unexpectedly, H. pylori-infected Il17ra -/- mice had significantly more chronic inflammation than H. pylori-infected wild-type mice. In this study, human epithelial cell lines and murine models were used to investigate differential roles for IL-17A, IL-17F, and IL-17A/F during H. pylori infection. Moreover, the hypothesis that IL-17RA signaling, specifically in lymphocytes, provides an autocrine feedback loop that downregulates Th17 cytokine production was investigated. The data indicate that epithelial cells exhibit a stronger response to IL-17A and IL-17A/F than IL-17F, and that IL-17A and IL-17A/F can synergize with TNF and IL-22 to induce antimicrobial genes of gastric epithelial cells. In vivo deficiencies of IL-17A or IL-17F alone did not significantly change the immunopathological response to H. pylori, but if both cytokines were absent, a hyperinflammatory lymphocytic response developed. Using a cre/flox targeting approach for IL-17RA combined with infection, our findings demonstrate that increased chronic inflammation in Il17ra -/- mice was not attributed to a T cell-intrinsic defect. These data imply that IL-17A and IL-17F may have overlapping roles in maintenance of the gastric mucosal response to infection.

Clinical significance of tryptophan metabolism in the nontumoral hemisphere in patients with malignant glioma.

UNLABELLED: α-(11)C-methyl-L-tryptophan (AMT) PET allows evaluation of brain serotonin synthesis and can also track upregulation of the immunosuppressive kynurenine pathway in tumor tissue. Increased AMT uptake is a hallmark of World Health Organization grade III-IV gliomas. Our recent study also suggested decreased frontal cortical AMT uptake in glioma patients contralateral to the tumor. The clinical significance of extratumoral tryptophan metabolism has not been established. In the present study, we investigated clinical correlates of tryptophan metabolic abnormalities in the nontumoral hemisphere of glioma patients. METHODS: Standardized AMT uptake values (SUVs) and the uptake rate constant of AMT (K [mL/g/min], a measure proportional to serotonin synthesis in nontumoral gray matter) were quantified in the frontal and temporal cortex and thalamus in the nontumoral hemisphere in 77 AMT PET scans of 66 patients (41 men, 25 women; mean age ± SD, 55 ± 15 y) with grade III-IV gliomas. These AMT values were determined before treatment in 35 and after treatment in 42 patients and were correlated with clinical variables and survival. RESULTS: AMT uptake in the thalamus showed a moderate age-related increase before treatment (SUV, r = 0.39, P = 0.02) but decrease after treatment (K, r = -0.33, P = 0.057). Women had higher thalamic SUVs before treatment (P = 0.037) and higher thalamic (P = 0.013) and frontal cortical K values (P = 0.023) after treatment. In the posttreatment glioma group, high thalamic SUVs and high thalamocortical SUV ratios were associated with short survival in Cox regression analysis. The thalamocortical ratio remained strongly prognostic (P < 0.01) when clinical predictors, including age, glioma grade, and time since radiotherapy, were entered in the regression model. Long interval between radiotherapy and posttreatment AMT PET as well as high radiation dose affecting the thalamus were associated with lower contralateral thalamic or cortical AMT uptake values. CONCLUSION: These observations provide evidence for altered tryptophan uptake in contralateral cortical and thalamic brain regions in glioma patients after initial therapy, suggesting treatment effects on the serotonergic system. Low thalamic tryptophan uptake appears to be a strong, independent predictor of long survival in patients with previous glioma treatment.