Search

Malaria is an infectious disease caused by a Plasmodium genus parasite that remains the most widespread parasitosis. The spread of Plasmodium clones that are increasingly resistant to antimalarial molecules is a serious public health problem for underdeveloped countries. Therefore, the search for new therapeutic approaches is necessary. For example, one strategy could consist of studying the redox process involved in the development of the parasite. Regarding potential drug candidates, ellagic acid is widely studied due to its antioxidant and parasite-inhibiting properties. However, its low oral bioavailability remains a concern and has led to pharmacomodulation and the synthesis of new polyphenolic compounds to improve antimalarial activity. This work aimed at investigating the modulatory effect of ellagic acid and its analogues on the redox activity of neutrophils and myeloperoxidase involved in malaria. Overall, the compounds show an inhibitory effect on free radicals as well as on the enzyme horseradish peroxidase- and myeloperoxidase (HRP/MPO)-catalyzed oxidation of substrates (L-012 and Amplex Red). Similar results are obtained with reactive oxygen species (ROS) produced by phorbol 12-mystate acetate (PMA)-activated neutrophils. The efficiency of ellagic acid analogues will be discussed in terms of structure–activity relationships. [ABSTRACT FROM AUTHOR]

Aging is associated with progressive skin fragility, characterized in part by extracellular matrix (ECM) fragmentation. This degradation produces matrikines which have an impact on ECM rremodeling. Our group previously designed and characterized a trifunctional peptide (TFP), constituted of i) an elastokine motif (VGVAPG) 3 , able to increase the expression of matrix constituent through the stimulation of the elastin-binding protein receptor, ii) a tripeptide inhibiting matrix metalloproteinase-1 activity (GIL), and iii) a linker domain acting as a competitive substrate for urokinase (RVRL). TFP was shown to activate the production of matrix constituents while inhibiting Matrix MetalloProtease MMP-1 in vitro on fibroblasts and ex vivo on skin explants., Objective: In the present study, TFP properties were evaluated in a clinical assay., Methods: Twenty-two volunteers applied a TFP-based cream on one hemi-face and a placebo-based cream on the other hemi-face, twice a day during 28 days, before undergoing a surgical lifting. Cutometry and skin relief measurements were performed at days 0 and 28, and skin explants from lifting surgery were used for histological analyses., Results: Cutometry and skin relief measurements reveal TFP firming properties and wrinkle depth decrease in 28 days on TFP- as compared to placebo-treated hemi-faces. These results are confirmed by histological analyses showing an increase of the ratio between basal lamina and stratum corneum. Furthermore, immunostaining of collagen reveals a modification of the ratio between type I and III collagens., Conclusion: The combined analysis of phenotypic and histologic parameters demonstrates a reorganization of the ECM towards a regenerative profile upon TFP treatment., Competing Interests: JDA and AV are Regentis Pharma employees. WH and DR are consulting experts for Regentis Pharma. Other authors have no conflict of interest to declare., (AJTR Copyright © 2023.)

On the basis of the activity of 1,2,4-benzothiadiazine 1,1-dioxides as positive allosteric modulators of AMPA receptors, thiochroman 1,1-dioxides were designed applying the isosteric replacement concept. The new compounds expressed strong modulatory activity on AMPA receptors in vitro , although lower than their corresponding benzothiadiazine analogues. The pharmacokinetic profile of three thiochroman 1,1-dioxides ( 12a , 12b , 12e ) was examined in vivo after oral administration, showing that these compounds freely cross the blood-brain barrier. Structural analysis was achieved using X-ray crystallography after cocrystallization of the racemic compound 12b in complex with the ligand-binding domain of GluA2 (L504Y/N775S). Interestingly, both enantiomers of 12b were found to interact with the GluA2 dimer interface, almost identically to its benzothiadiazine analogue, BPAM344 ( 4 ). The interactions of the two enantiomers in the cocrystal were further analyzed (mapping Hirshfeld surfaces and 2D fingerprint) and compared to those of 4 . Taken together, these data explain the lower affinity on AMPA receptors of thiochroman 1,1-dioxides compared to their corresponding 1,2,4-benzothiadiazine 1,1-dioxides.

Unlabelled: Reconstruction after total amputation of the upper and lower eyelids with preserved globe is rare. The primary goal is immediate corneal protection. The second goal is to restore mobility, occlusion, and facial symmetry. Two women had full-thickness excision of both upper and lower eyelids to treat a melanoma. The reconstruction method required four steps over a period of 5 months. A buccal mucosal graft was used to recreate the conjunctival lining, and an oblique forehead flap was used to recreate the skin. Resection of the flap and replacement by a full-thickness skin graft made it possible to recreate a thin and mobile upper eyelid. Visual acuity remained unchanged, and the eyelids remained functional despite a degree of ptosis and lower eyelid retraction., Clinical Question/level of Evidence: Therapeutic, V.