The histological and ultrastructural effects following 3 weeks' topical treatment with two agents (all-trans retinoic acid and a new synthetic retinoid-like substance, CD271) were evaluated on the epidermis and the epithelial wall of the pseudocomedones in rhino mouse skin. The comedolytic effects of these drugs were similar, and consisted of a reduction of the utricular diameter, with normalization of follicular units. Morphological examinations revealed a hyperplastic response with an increase in the number of cell layers of both epidermis and follicular epithelium, and modifications in keratinocyte differentiation. Ultrastructural changes in the epidermis and epithelial wall were observed mainly in the granular and horny layers, with increased desquamation, and a decrease in the cohesiveness of corneocytes. During the first week of treatment, some cutaneous toxic effects were noticed, but they normalized within two weeks. On the other hand, a fine granular material persisted in the intercellular spaces. It is confirmed that the skin of the rhino mouse is a good model for the evaluation of the comedolytic effects of drugs. Moreover, it reveals the specific effects of retinoids on epidermal differentiation. We have demonstrated that topically applied CD271 induces modifications similar to those obtained with all-trans retinoic acid. It is thus concluded that CD271 is a potentially effective anti-acne agent.
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Eur J Med Chem
December 2024
CERES BRAIN Therapeutics, Paris, France. Electronic address:
Dodecyl creatine ester (DCE) is a creatine prodrug currently developed for brain diseases, including creatine transporter deficiency (CTD), an incurable rare genetic disease. A dual strategy combining a prodrug to bypass the non-functional creatine transporter and its delivery via the nose-to-brain pathway has been proposed to replenish creatine levels in cerebral cells, particularly in neurons of CTD patients. In vitro and in vivo studies in various animal models, including wild-type non-human primates and creatine transporter deficient mice, show that formulated DCE, when administered intranasally, achieves significant cerebral distribution up to the target cells, the neurons, and modulates the expression of neuronal markers related to cognitive function at doses intended for patients.
View Article and Find Full Text PDFOcul Immunol Inflamm
December 2024
Department of Ophthalmology, Eye, Ear, Nose, and Throat Hospital of Fudan University, Shanghai, China.
Background: Increased reactive oxygen species (ROS) are involved in the pathological process of dry eye disease. Our previous results suggested that norepinephrine (NE) has a protective effect on dry eye.
Purpose: This study explored the potential therapeutic role and underlying mechanisms of NE in benzalkonium chloride (BAC)-induced dry eye disease.
J Control Release
December 2024
Department of Chemical Engineering, McMaster University, 1280 Main Street, West Hamilton, ON L8S 4L8, Canada. Electronic address:
While bipolar disorder patients can benefit from lithium therapy, high levels of lithium in the serum can induce undesirable systemic side effects. Intranasal (IN) lithium delivery offers a potential solution to this challenge given its potential to facilitate improved lithium transport to brain when delivered to the olfactory mucosa. Herein, a sprayable, in situ forming nanoparticle network hydrogel (NNH) based on Schiff base interactions between chelator-functionalized oxidized starch nanoparticles (SNPs) and carboxymethyl chitosan (CMCh) is reported that can be deployed within the nasal cavity to release ultra-small penetrative SNPs over time.
View Article and Find Full Text PDFPhysiol Behav
December 2024
Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington, USA. Electronic address:
Exposure to stressors has been shown to dysregulate motivated behaviors in a bidirectional manner over time. The relationship between stress and motivation is relevant to psychological disorders, including depression, binge eating, and substance abuse; however, this relationship is not well characterized, especially in females, despite their increased risk of these disorders. Social defeat stress is a common model to study stress-induced motivation changes, however, historically this model excluded females due to lack of female-to-female aggression and unreliable male-to-female aggression.
View Article and Find Full Text PDFCell Commun Signal
December 2024
Department of Otorhinolaryngology Head and Neck Surgery, Gongli Hospital of Shanghai Pudong New Area, 219 Miao Pu Road, Shanghai, 200135, China.
The development of nasal inverted papilloma (NIP) is closely related to human papillomavirus (HPV) infection. Previous studies indicated that HPV11 shows the highest expression in NIP tissues. However, the mechanisms following its integration into host DNA require further clarification.
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