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4 result(s) for "Shershakova, Nadezda"
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Aqueous Dispersion of Unmodified Fullerene C60: Stimulation of Hair Growth and Study of a New Molecular Target for Interaction
Hair loss (alopecia) is a common disorder caused by an interruption in the body’s cycle of hair production. This pathology negatively affects the psychoemotional state of patients and significantly reduces their quality of life. The currently available medical treatments (including minoxidil therapy) are effective in arresting the progression of the disease; however, they allow only partial regrowth of hair at best. A significant clinical result occurs only with regular drug use. There is still great interest in finding new drugs for the treatment of alopecia. In this study, we aimed to examine the effect of an aqueous dispersion of unmodified fullerene C60 (ADF) on hair growth. ADF, produced by a unique technology, is biocompatible and non-toxic. Nu/nu mice were subcutaneously injected (2 μg/animal) every two days for a period of 11 days with ADF and, for control purposes, with phosphate-buffered saline (PBS). It was shown that ADF stimulated hair growth. Histological analysis of the nu/nu mice skin areas showed that animals treated with ADF had significantly more (about twice as many) hair follicles in the anagen phase compared to mice treated with PBS. The effect on hair growth persisted even after discontinuation of ADF administration. Analysis of gene expression demonstrated that ADF affected the Wnt-signaling pathway, increased the expression of the Wnt10b (wingless-type Mouse Mammary Tumor Virus integration site family, member 10B) factor, angiogenetic factors, and downregulated tumor necrosis factor-alpha levels. We propose that the mechanism of ADF action is likely related to its ability to attract macrophages to the hair follicle microenvironment and promote their polarization to the M2 phenotype. In addition, using molecular modeling, we tried to substantiate our hypothesis about the interaction of ADF with the adenosine A2A receptor, which may cause a decrease in tumor necrosis factor-alpha production. Thus, ADF may become a promising drug for the development of new approaches to the treatment of alopecia associated with immune disorders.
Allergen-Specific Immunotherapy with Monomeric Allergoid in a Mouse Model of Atopic Dermatitis
Atopic dermatitis (AD) is a widespread and difficult to treat allergic skin disease and is a tough challenge for healthcare. In this study, we investigated whether allergen-specific immunotherapy (ASIT) with a monomeric allergoid obtained by succinylation of ovalbumin (sOVA) is effective in a mouse model of atopic dermatitis. An experimental model of AD was reproduced by epicutaneous sensitization with ovalbumin (OVA). ASIT was performed with subcutaneous (SC) administration of increasing doses of OVA or sOVA. The levels of anti-OVA antibodies, as well as cytokines, were detected by ELISA. Skin samples from patch areas were taken for histologic examination. ASIT with either OVA or sOVA resulted in a reduction of both the anti-OVA IgE level and the IgG1/IgG2a ratio. Moreover, ASIT with sOVA increased the IFN-γ level in supernatants after splenocyte stimulation with OVA. Histologic analysis of skin samples from the sites of allergen application showed that ASIT improved the histologic picture by decreasing allergic inflammation in comparison with untreated mice. These data suggest that ASIT with a succinylated allergen represents promising approach for the treatment of AD.
Anti-inflammatory effect of fullerene C60 in a mice model of atopic dermatitis
Background Water-soluble form of fullerene C 60 is a promising tool for the control of ROS-dependent inflammation including allergic diseases. Anti-inflammatory effects of C 60 (nC 60 ) aqueous dispersion were evaluated in the mouse models of atopic dermatitis using subcutaneous (SC) and epicutaneous (EC) applications during 50 days period. A highly stable nC 60 was prepared by exhaustive dialysis of water-organic C 60 solution against water, where the size and ζ-potential of fullerene nanoparticles are about 100 nm and −30 mV, respectively. Results To induce skin inflammation, female BALB/c mice were EC sensitized with ovalbumin three times during one-weekly exposures. The nC 60 solution was administrated in mice subcutaneously (SC) (0.1 mg/kg) and epicutaneously (EC) (1 mg/kg). Significant suppression of IgE and Th2 cytokines production and a concomitant rise in concentrations of Th1 cytokines were observed in nC 60 -treated groups. In addition, a significant increase in the levels of Foxp3 + and filaggrin mRNA expression was observed at EC application. Histological examination of skin samples indicated that therapeutic effect was achieved by both EC and SC treatment, but it was more effective with EC. Pronounced reduction of the eosinophil and leukocyte infiltration in treated skin samples was observed. Conclusions We suppose that nC60 treatment shifts immune response from Th2 to Th1 and restores to some extent the function of the skin barrier. This approach can be a good alternative to the treatment of allergic and other inflammatory diseases.
Allergen-Specific Immunotherapy with Monomeric Allergoid in a Mouse Model of Atopic Dermatitis: e0135070
Atopic dermatitis (AD) is a widespread and difficult to treat allergic skin disease and is a tough challenge for healthcare. In this study, we investigated whether allergen-specific immunotherapy (ASIT) with a monomeric allergoid obtained by succinylation of ovalbumin (sOVA) is effective in a mouse model of atopic dermatitis. An experimental model of AD was reproduced by epicutaneous sensitization with ovalbumin (OVA). ASIT was performed with subcutaneous (SC) administration of increasing doses of OVA or sOVA. The levels of anti-OVA antibodies, as well as cytokines, were detected by ELISA. Skin samples from patch areas were taken for histologic examination. ASIT with either OVA or sOVA resulted in a reduction of both the anti-OVA IgE level and the IgG1/IgG2a ratio. Moreover, ASIT with sOVA increased the IFN- gamma level in supernatants after splenocyte stimulation with OVA. Histologic analysis of skin samples from the sites of allergen application showed that ASIT improved the histologic picture by decreasing allergic inflammation in comparison with untreated mice. These data suggest that ASIT with a succinylated allergen represents promising approach for the treatment of AD.