Psoriasin (S100A7) expression is altered during skin tumorigenesis

BACKGROUND: Psoriasin (S100A7) expression has previously been associated with psoriasiform hyperplasia as well as with tumor progression in breast cancer. Its expression profile for different stages of skin lesions is unknown. The aim of this study was to determine the relationship between psoriasin (S100A7) and tumor progression in skin. METHODS: Psoriasin was assessed by immunohistochemistry and levels of expression determined by semi-quantitative scoring in skin biopsies from 50 patients. The cohort included normal skin, actinic keratosis, squamous carcinoma in-situ, invasive squamous cell carcinoma, and basal cell carcinoma. RESULTS: In normal skin, psoriasin was rarely detected in epidermis but was expressed in underlying adnexae. In abnormal epidermis psoriasin was frequently expressed in abnormal keratinocytes in actinic keratosis, in-situ and invasive squamous cell carcinoma, but was rarely observed in the basal epidermal layer or in superficial or invasive basal cell carcinoma. The highest levels of expression were seen within squamous carcinoma in-situ. Significantly reduced levels of expression were observed in both unmatched (p = 0.0001) and matched (p < 0.004) invasive squamous cell carcinoma. Psoriasin expression within abnormal squamous lesions correlated with mitotic count (r = 0.54, p = 0.0036), however no significant relation was found with the intensity of dermal inflammatory cell infiltrates assessed within each pathology. CONCLUSION: These results suggest that altered psoriasin expression occurs in abnormal epidermis and that downregulation may be related to the onset of invasion in squamous cell carcinoma in skin

Expression analysis of the mouse S100A7/psoriasin gene in skin inflammation and mammary tumorigenesis

BACKGROUND: The human psoriasin (S100A7) gene has been implicated in inflammation and tumor progression. Implementation of a mouse model would facilitate further investigation of its function, however little is known of the murine psoriasin gene. In this study we have cloned the cDNA and characterized the expression of the potential murine ortholog of human S100A7/psoriasin in skin inflammation and mammary tumorigenesis. METHODS: On the basis of chromosomal location, phylogenetic analysis, amino acid sequence similarity, conservation of a putative Jab1-binding motif, and similarities of the patterns of mouse S100A7/psoriasin gene expression (measured by RT-PCR and in-situ hybridization) with those of human S100A7/psoriasin, we propose that mouse S100A7/psoriasin is the murine ortholog of human psoriasin/S100A7. RESULTS: Although mouse S100A7/psoriasin is poorly conserved relative to other S100 family members, its pattern of expression parallels that of the human psoriasin gene. In murine skin S100A7/psoriasin was significantly upregulated in relation to inflammation. In murine mammary gland expression is also upregulated in mammary tumors, where it is localized to areas of squamous differentiation. This mirrors the context of expression in human tumor types where both squamous and glandular differentiation occur, including cervical and lung carcinomas. Additionally, mouse S100A7/psoriasin possesses a putative Jab1 binding motif that mediates many downstream functions of the human S100A7 gene. CONCLUSION: These observations and results support the hypothesis that the mouse S100A7 gene is structurally and functionally similar to human S100A7 and may offer a relevant model system for studying its normal biological function and putative role in tumor progression

Role of atrial natriuretic factor in experimental high-output heart failure

It has been hypothesized that the pathophysiology of chronic heart failure (CHF) may be due to a relative deficiency of atrial natriuretic factor (ANF) and/or blunted responsiveness to ANF in this state. The work presented in this thesis evaluates the role of ANF in rats with chronic moderate high-output heart failure by (1) characterizing plasma and tissue ANF levels, hemodynamics and renal function at different stages of the development of heart failure; (2) assessing the contribution of the atria and ventricles to plasma ANF levels; and (3) investigating the role of ANF and renin-angiotensin systems (RAS) in rats with aorto-caval (A-C) shunts.Chronically increased cardiac filling pressure stimulated not only ANF release but also ANF synthesis in each cardiac chamber. This in turn contributed to elevated plasma ANF levels in A-C shunt rats. An attenuated renal response to endogenous ANF and sodium and water retention were apparent in A-C shunt rats. Under inhibition of RAS, plasma ANF may exert its actions more effectively. Thus, chronic ACE inhibition and ANG II receptor antagonism improved hemodynamic conditions, diminished water retention, reversed cardiac hypertrophy, and restored plasma and tissue ANF to more "normal" levels in rats with moderate high-output heart failure.Taken together, elevated plasma ANF levels may play an important role in maintaining hemodynamic and body fluid homeostasis by opposing the neurohormonal vasoconstrictor systems in A-C shunt rats. However, a relative deficiency of plasma ANF and/or an attenuated response to endogenous ANF, mediated by activated neurohormonal vasoconstrictor systems, may contribute to the pathophysiology and development of heart failure at different stages. (Abstract shortened by UMI.

Quantum Dots-Loaded Self-Healing Gels for Versatile Fluorescent Assembly

From the perspective of applied science, methods that allow the simple construction of versatile quantum dots (QDs)-loaded gels are highly desirable. In this work, we report the self-healing assembly methods for various fluorescent QDs-loaded gels. Firstly, we employed horizontal frontal polymerization (FP) to fabricate self-healing gels within several minutes using a rapid and energy-saving means of preparation. The as-prepared gels showed pH sensitivity, satisfactory mechanical properties and excellent self-healing properties and the healing efficiency reached 90%. The integration of the QDs with the gels allowed the generation of fluorescent composites, which were successfully applied to an LED device. In addition, by using the self-healing QDs-loaded gels as building blocks, the self-healing assembly method was used to construct complex structures with different fluorescence, which could then be used for sensing and encoding. This work offers a new perspective on constructing various fluorescent assemblies by self-healing assembly, and it might stimulate the future application of self-healing gels in a self-healing assembly fashion.</jats:p

Quantum Dots-Loaded Self-Healing Gels for Versatile Fluorescent Assembly

From the perspective of applied science, methods that allow the simple construction of versatile quantum dots (QDs)-loaded gels are highly desirable. In this work, we report the self-healing assembly methods for various fluorescent QDs-loaded gels. Firstly, we employed horizontal frontal polymerization (FP) to fabricate self-healing gels within several minutes using a rapid and energy-saving means of preparation. The as-prepared gels showed pH sensitivity, satisfactory mechanical properties and excellent self-healing properties and the healing efficiency reached 90%. The integration of the QDs with the gels allowed the generation of fluorescent composites, which were successfully applied to an LED device. In addition, by using the self-healing QDs-loaded gels as building blocks, the self-healing assembly method was used to construct complex structures with different fluorescence, which could then be used for sensing and encoding. This work offers a new perspective on constructing various fluorescent assemblies by self-healing assembly, and it might stimulate the future application of self-healing gels in a self-healing assembly fashion

Sustained suppression of IL-18 by employing a vaccine ameliorates intestinal inflammation in TNBS-induced murine colitis

Aim: To develop IL-18 peptide-based virus-like particle vaccines that elicit autoantibodies against IL-18 and to evaluate the in vivo effects of the vaccines in murine colitis. Methods: Recombinant IL-18 vaccines were constructed, and the effects of the vaccines were evaluated in trinitrobenzene sulfonic acid-induced acute and chronic colitis in mice. Results: Two murine IL-18 peptide-based vaccines (A and D) were developed, which induced relative long-lasting specific antibodies against IL-18. Vaccine-immunized mouse antisera could partially block IL-18-induced IFN-γ production in vitro. Mice receiving vaccine D, not vaccine A, had a significant decrease in intestinal inflammation, collagen deposition and pro-inflammatory cytokine levels in colon tissue. Conclusion: IL-18 vaccine may provide a potential therapeutic approach in the treatment of Crohn’s disease. </jats:p