1.
Ortho Isomeric Mn(III) N-Alkyl- and Alkoxyalkylpyridylporphyrins-Enhancers of Hyaluronan Degradation Induced by Ascorbate and Cupric Ions.
Valachová, K, Rapta, P, Moura, NMM, Batinic-Haberle, I, Šoltés, L
International journal of molecular sciences. 2021;(16)
Abstract
High levels of hyaluronic acid (HA) in tumors correlate with poor outcomes with several types of cancers due to HA-driven support of adhesion, migration and proliferation of cells. In this study we explored how to enhance the degradation of HA into low-molecular fragments, which cannot prevent the immune system to fight tumor proliferation and metastases. The physiological solution of HA was exposed to oxidative degradation by ascorbate and cupric ions in the presence of either one of three ortho isomeric Mn(III) substituted N-alkyl- and alkoxyalkylpyridylporphyrins or para isomeric Mn(III) N-methylpyridyl analog, commonly known as mimics of superoxide dismutase. The changes in hyaluronan degradation kinetics by four Mn(III) porphyrins were monitored by measuring the alteration in the dynamic viscosity of the HA solution. The ortho compounds MnTE-2-PyP5+ (BMX-010, AEOL10113), MnTnBuOE-2-PyP5+ (BMX-001) and MnTnHex-2-PyP5+ are able to redox cycle with ascorbate whereby producing H2O2 which is subsequently coupled with Cu(I) to produce the •OH radical essential for HA degradation. Conversely, with the para analog, MnTM-4-PyP5+, no catalysis of HA degradation was demonstrated, due to its inertness towards redox cycling with ascorbate. The impact of different Mn(III)-porphyrins on the HA decay was further clarified by electron paramagnetic resonance spectrometry. The ability to catalyze the degradation of HA in a biological milieu, in the presence of cupric ions and ascorbate under the conditions of high tumor oxidative stress provides further insight into the anticancer potential of redox-active ortho isomeric Mn(III) porphyrins.
2.
Assessment of the efficacy of a new complex antisensitive skin cream.
Wang, Y, Viennet, C, Jeudy, A, Fanian, F, He, L, Humbert, P
Journal of cosmetic dermatology. 2018;(6):1101-1107
Abstract
BACKGROUND Sensitive skin is frequently complaint in dermatology consultation with cutaneous manifestations such as stinging, redness, dryness, and burning sensation that affect the quality of life. Its pathogenesis is mainly related to dysfunction of neurosensory, skin barrier, and also immune activity. The treatment is generally based on continuous and topical therapy by nonirritating complex. OBJECTIVE To evaluate the antisensitive function of a new complex cream composed by Yunnan Portulaca oleracea extract, Prinsepia utilis oil, beta-glucan, and sodium hyaluronate extracted from mushroom. METHODS A randomized double-blind and self-control study was conducted on 20 selected volunteers with sensitive skin. Subjects applied the test cream to 1 side of the face, and the control cream (tolerance-extreme cream) to the other side of the face, twice daily over 28 days. Evaluations were performed at baseline and at 28 days. Expert clinical grading of facial skin including dryness, roughness, desquamation, and erythema was assessed. Subject self-assessment questionnaires, digital photography and noninvasive bioinstrumentation of hydration, transepidermal water loss, lipid index, skin texture, and wettability were also included in the study. RESULTS Products were well tolerated. For all parameters studied, no significant difference was observed between test and control creams. Results showed that test cream provided a statistically significant improvement in clinical grading scores for dryness, roughness, and erythema at 28 days compared to baseline. In addition, statistically significant improvement of skin hydration and texture parameters (eg, smoothness and roughness) was demonstrated. Volunteers' questionnaire revealed self-perceived benefits consistent with expert visual grading. CONCLUSION This study confirmed the effectiveness and tolerance of the new complex cream in subjects with sensitive skin. The test cream could serve as a daily care moisturizer for face.
3.
Thymosin α1 Interacts with Hyaluronic Acid Electrostatically by Its Terminal Sequence LKEKK.
Mandaliti, W, Nepravishta, R, Pica, F, Vallebona, PS, Garaci, E, Paci, M
Molecules (Basel, Switzerland). 2017;(11)
Abstract
Thymosin α1 (Tα1), is a peptidic hormone, whose immune regulatory properties have been demonstrated both in vitro and in vivo and approved in different countries for treatment of several viral infections and cancers. Tα1 assumes a conformation in negative membranes upon insertion into the phosphatidylserine exposure as found in several pathologies and in apoptosis. These findings are in agreement with the pleiotropy of Tα1, which targets both normal and tumor cells, interacting with multiple cellular components, and have generated renewed interest in the topic. Hyaluronan (HA) occurs ubiquitously in the extracellular matrix and on cell surfaces and has been related to a variety of diseases, and developmental and physiological processes. Proteins binding HA, among them CD44 and the Receptor for HA-mediated motility (RHAMM) receptors, mediate its biological effects. NMR spectroscopy indicated preliminarily that an interaction of Tα1 with HA occurs specifically around lysine residues of the sequence LKEKK of Tα1 and is suggestive of a possible interference of Tα1 in the binding of HA with CD44 and RHAMM. Further studies are needed to deepen these observations because Tα1 is known to potentiate the T-cell immunity and anti-tumor effect. The binding inhibitory activity of Tα1 on HA-CD44 or HA-RHAMM interactions can suppress both T-cell reactivity and tumor progression.