[Clinical, therapeutic and pathophysiological aspects of Darier's disease]. / Aspects physiopathologiques cliniques et thérapeutiques de la maladie de Darier.

Darier Disease is a rare autosomal dominant inherited skin disorder classified as an acantholytic dermatosis. It manifests around puberty as brownish keratotic papules of skin folds and seborrheic areas, associated with onychopathy and mucosal involvementand have a chronic relapsing-remitting course with frequent exacerbations triggered by sun exposure, heat, friction, or infections. Darier patients have an increased risk of neuropsychiatric disorders, type 1 diabetes and heart failure. Short-term management relies on antibiotics/antiviral, topical corticosteroids and/or retinoids. Moisturizers, sun protection and avoiding triggers are essential for long-term management. Conventional long-term treatment is not standardized and many topical treatments, physical and surgical measures and systemic treatments are described in the literature.

La maladie de Darier est une génodermatose rare à transmission autosomique dominante. Elle se manifeste autour de la puberté par des papules kératosiques brunâtres des plis et des zones séborrhéiques, associées à une onychopathie et une atteinte muqueuse, et évolue par poussées déclenchées par les UV, la chaleur, les frottements ou les infections. Les patients atteints présentent un risque accru de diabète de type 1, d'insuffisance cardiaque et de troubles neuropsychiatriques. La prise en charge à court terme consiste en des antibiotiques/antiviraux, des corticostéroïdes topiques et/ou des rétinoïdes. Celle à long terme repose sur les émollients et l'éviction des facteurs déclenchants. Le traitement à long terme n'étant pas codifié, de nombreux traitements locaux et sytémiques, mesures physiques et chirurgicales sont décrits dans la littérature.

Efficacy and Tolerability of Topical 0.1% Stabilized Bioactive Retinol for Photoaging: A Vehicle-Controlled Integrated Analysis.

INTRODUCTION: Chronic exposure to ultraviolet light photoages skin. Retinol, a precursor molecule to retinoic acid that causes less irritation, is available as a nonprescription, cosmetic retinoid and improves collagen production, skin elasticity, and signs of photoaging. Advances in formulation science have allowed the production of stabilized bioactive retinol formulations. This integrated analysis aims to build on previous studies and further examine the comprehensive efficacy and tolerability of topical 0.1% stabilized bioactive retinol. METHODS: This analysis included 6 vehicle-controlled studies of 0.1% stabilized bioactive retinol in women with mild-to-moderate signs of photodamage. Across all studies, the same dermatologist investigator assessed overall photodamage; wrinkles on the forehead, cheeks, and undereye area; crow’s feet wrinkles and fine lines; lack of even skin tone; and brown spots at baseline and weeks 4, 8, and 12 on a numerical scale. Tolerability was also assessed. RESULTS: Participants (retinol, N=237; vehicle, N=234) had a mean (SD) age of 47.4 (6.6) years. Retinol induced greater improvements from baseline in all signs of photoaging vs vehicle as early as week 4 and through 12 weeks of application. Few participants experienced irritation; all events were mild to moderate and transient. The most common signs of irritation were erythema (n=2) and skin scaling/peeling (n=5). CONCLUSIONS: This pooled analysis of 6 vehicle-controlled clinical studies provides new evidence for the efficacy of 0.1% stabilized bioactive retinol in improving signs of photoaging without causing major irritation. Topical 0.1% stabilized bioactive retinol was well tolerated with only a few reported cases of skin irritation. J Drugs Dermatol. 2024;23(4):     doi:10.36849/JDD.8124.

Human Clinical Trials Using Topical Bakuchiol Formulations for the Treatment of Skin Disorders: A Systematic Review.

BACKGROUND: Bakuchiol is a topical cosmeceutical marketed as a retinoid alternative. Human clinical trial data on bakuchiol’s efficacy for the treatment of dermatologic conditions has not been thoroughly evaluated. OBJECTIVE: To review human clinical trials using topical formulations containing bakuchiol in the treatment of facial skin disorders. MATERIALS AND METHODS: A comprehensive electronic search of Cochrane Library, PubMed, EMBASE, and Web of Science was conducted on August 28, 2022, using the search terms “bakuchiol” and “UP256.” Study characteristics, measured outcomes, significant results, and stated limitations were extracted.  Results: Fifteen human clinical trials were analyzed. Dermatologic conditions treated included aging, acne, and post-inflammatory hyperpigmentation. Twelve trials were unblinded, open-label trials without a control group. Ten trials used a combination therapy containing bakuchiol. Four trials did not specify the dose or concentration of bakuchiol in treatment regimens. The heterogeneity of treatments, study designs, and measured outcomes makes meta-analysis unfeasible.  Conclusion: Trials lack methodologic rigor, which introduces a high risk of bias in reported outcomes. The use of combination topical formulations containing bakuchiol limits the comparison of bakuchiol’s efficacy with retinoids. Continued research with an improved trial design is needed.J Drugs Dermatol. 2024;23(4): doi:10.36849/JDD.7763.

Treatment of plaque-psoriasis in HIV-positive patients.

Psoriasis is a chronic inflammatory disease that can often accompany human immunodeficiency virus (HIV) epidemics. Development of psoriasis in HIV patients is correlated with a decrease in CD4+ count. Significant variability in the clinical presentation of psoriasis makes it a challenging disease to diagnose. Furthermore, associated immunodeficiency complicates standard treatment with immunosuppressive and biological therapy. Articles that match the terms psoriasis and HIV were searched in MEDLINE and Embase and selected based on their relevance. Highly active antiretroviral therapy (HAART) is a medication regimen used to manage and treat HIV infection. In treating mild psoriasis in HIV-positive patients, topical agents combined with HAART are considered first-line therapy, followed by phototherapy. Second-line therapy includes oral retinoids, alone or combined. In treating challenging cases, apremilast has been used due to its lack of immunosuppressive effect. In case of progressive and refractory disease, limited data from studies suggest that immunosuppressive or biological therapy may be effective. Treatment of psoriasis in HIV patients remains a challenge, which is largely attributable to its complicated etiopathology and lack of an approved therapy option. In treating severe psoriasis, close collaboration with an infectious disease specialist is highly recommended. Further research is needed, preferably with an aim toward developing individualized therapy.

RAR Inhibitors Display Photo-Protective and Anti-Inflammatory Effects in A2E Stimulated RPE Cells In Vitro through Non-Specific Modulation of PPAR or RXR Transactivation.

N-retinylidene-N-retinylethanolamine (A2E) has been associated with age-related macular degeneration (AMD) physiopathology by inducing cell death, angiogenesis and inflammation in retinal pigmented epithelial (RPE) cells. It was previously thought that the A2E effects were solely mediated via the retinoic acid receptor (RAR)-α activation. However, this conclusion was based on experiments using the RAR "specific" antagonist RO-41-5253, which was found to also be a ligand and partial agonist of the peroxisome proliferator-activated receptor (PPAR)-γ. Moreover, we previously reported that inhibiting PPAR and retinoid X receptor (RXR) transactivation with norbixin also modulated inflammation and angiogenesis in RPE cells challenged in the presence of A2E. Here, using several RAR inhibitors, we deciphered the respective roles of RAR, PPAR and RXR transactivations in an in vitro model of AMD. We showed that BMS 195614 (a selective RAR-α antagonist) displayed photoprotective properties against toxic blue light exposure in the presence of A2E. BMS 195614 also significantly reduced the AP-1 transactivation and mRNA expression of the inflammatory interleukin (IL)-6 and vascular endothelial growth factor (VEGF) induced by A2E in RPE cells in vitro, suggesting a major role of RAR in these processes. Surprisingly, however, we showed that (1) Norbixin increased the RAR transactivation and (2) AGN 193109 (a high affinity pan-RAR antagonist) and BMS 493 (a pan-RAR inverse agonist), which are photoprotective against toxic blue light exposure in the presence of A2E, also inhibited PPARs transactivation and RXR transactivation, respectively. Therefore, in our in vitro model of AMD, several commercialized RAR inhibitors appear to be non-specific, and we propose that the phototoxicity and expression of IL-6 and VEGF induced by A2E in RPE cells operates through the activation of PPAR or RXR rather than by RAR transactivation.

Silica Microparticles from Sugarcane By-Products as an Encapsulation System for Retinoids Aimed at Topical Sustained Release.

The encapsulation of retinol within silica microparticles has emerged as a promising opportunity in the realm of cosmetic and pharmaceutical formulations, driven by the need to reinforce the photoprotection and oxidation stability of retinol. This work examines the process of encapsulating retinol into silica microparticles. The association efficiency, microparticle size, molecular structure, morphology, oxidation, and release profile, as well as biocompatibility and skin sensitization, were evaluated. Results showed that 0.03% of retinol and 9% of emulsifier leads to an association efficiency higher than 99% and a particle size with an average of 5.2 µm. FTIR results indicate that there is an association of retinol with the silica microparticles, and some may be on the surface. Microscopy indicates that when association happens, there is less aggregation of the particles. Oxidation occurs in two different phases, the first related to the retinol on the surface and the second to the associated retinol. In addition, a burst release of up to 3 h (30% free retinol, 17% associated retinol) was observed, as well as a sustained release of 44% of retinol up to 24 h. Encapsulation allowed an increase in the minimal skin cytotoxic concentrations of retinol from 0.04 µg/mL to 1.25 mg/mL without skin sensitization. Overall, retinol is protected when associated with silica microparticles, being safe to use in cosmetics and dermatology.

Retinoid orphan receptor gamma t (rorγt) promotes inflammatory eosinophilia but is dispensable for innate immune-mediated colitis.

Inflammatory bowel diseases (IBD) result from uncontrolled inflammation in the intestinal mucosa leading to damage and loss of function. Both innate and adaptive immunity contribute to the inflammation of IBD and innate and adaptive immune cells reciprocally activate each other in a forward feedback loop. In order to better understand innate immune contributions to IBD, we developed a model of spontaneous 100% penetrant, early onset colitis that occurs in the absence of adaptive immunity by crossing villin-TNFAIP3 mice to RAG1-/- mice (TRAG mice). This model is driven by microbes and features increased levels of innate lymphoid cells in the intestinal mucosa. To investigate the role of type 3 innate lymphoid cells (ILC3) in the innate colitis of TRAG mice, we crossed them to retinoid orphan receptor gamma t deficient (Rorγt-/-) mice. Rorγt-/- x TRAG mice exhibited markedly reduced eosinophilia in the colonic mucosa, but colitis persisted in these mice. Colitis in Rorγt-/- x TRAG mice was characterized by increased infiltration of the intestinal mucosa by neutrophils, inflammatory monocytes, macrophages and other innate cells. RNA and cellular profiles of Rorγt-/- x TRAG mice were consistent with a lack of ILC3 and ILC3 derived cytokines, reduced antimicrobial factors, increased activation oof epithelial repair processes and reduced activation of epithelial cell STAT3. The colitis in Rorγt-/- x TRAG mice was ameliorated by antibiotic treatment indicating that microbes contribute to the ILC3-independent colitis of these mice. Together, these gene expression and cell signaling signatures reflect the double-edged sword of ILC3 in the intestine, inducing both proinflammatory and antimicrobial protective responses. Thus, Rorγt promotes eosinophilia but Rorγt and Rorγt-dependent ILC3 are dispensable for the innate colitis in TRAG mice.

LX-2 Stellate Cells Are a Model System for Investigating the Regulation of Hepatic Vitamin A Metabolism and Respond to Tumor Necrosis Factor α and Interleukin 1ß.

Hepatic stellate cells (HSCs) are the major site of vitamin A (retinol) esterification and subsequent storage as retinyl esters within lipid droplets. However, retinyl esters become depleted in many pathophysiological states, including acute and chronic liver injuries. Recently, using a liver slice culture system as a model of acute liver injury and fibrogenesis, a time-dependent increase and decrease in the apparent formation of the bioactive retinoid all-trans-retinoic acid (atRA) and retinyl palmitate was measured, respectively. This coincided with temporal changes in the gene expression of retinoid-metabolizing enzymes and binding proteins, that preceded HSC activation. However, the underlying mechanisms that promote early changes in retinoid metabolism remain unresolved. We hypothesized that LX-2 cells could be applied to investigate differences in quiescent and activated HSC retinoid metabolism. We demonstrate that the hypermetabolic state of activated stellate cells relative to quiescent stellate cells may be attributed to induction of STRA6, RBP4, and CYP26A1, thereby reducing intracellular concentrations of atRA. We further hypothesized that paracrine and autocrine cytokine signaling regulates HSC vitamin A metabolism in both quiescent and activated cells. In quiescent cells, tumor necrosis factor α dose-dependently downregulated LRAT and CRBP1 mRNA, with EC50 values of 30-50 pg/mL. Likewise, interleukin-1ß decreased LRAT and CRBP1 gene expression but with less potency. In activated stellate cells, multiple enzymes were downregulated, suggesting that the full effects of altered hepatic vitamin A metabolism in chronic conditions require both paracrine and autocrine signaling events. Further, this study suggests the potential for cell type-specific autocrine effects in hepatic retinoid signaling. SIGNIFICANCE STATEMENT: HSCs are the major site of vitamin A storage and important determinants of retinol metabolism during liver fibrogenesis. Here, two LX-2 culture methods were applied as models of hepatic retinoid metabolism to demonstrate the effects of activation status and dose-dependent cytokine exposure on the expression of genes involved in retinoid metabolism. This study suggests that compared to quiescent cells, activated HSCs are hypermetabolic and have reduced apparent formation of retinoic acid, which may alter downstream retinoic acid signaling.

Microsomal triglyceride transfer protein is necessary to maintain lipid homeostasis and retinal function.

Lipid processing by the retinal pigment epithelium (RPE) is necessary to maintain retinal health and function. Dysregulation of retinal lipid homeostasis due to normal aging or age-related disease triggers lipid accumulation within the RPE, on Bruch's membrane (BrM), and in the subretinal space. In its role as a hub for lipid trafficking into and out of the neural retina, the RPE packages a significant amount of lipid into lipid droplets for storage and into apolipoprotein B (APOB)-containing lipoproteins (Blps) for export. Microsomal triglyceride transfer protein (MTP), encoded by the MTTP gene, is essential for Blp assembly. Herein we test the hypothesis that MTP expression in the RPE is essential to maintain lipid balance and retinal function using the newly generated RPEΔMttp mouse model. Using non-invasive ocular imaging, electroretinography, and histochemical and biochemical analyses we show that genetic depletion of Mttp from the RPE results in intracellular lipid accumulation, increased photoreceptor-associated cholesterol deposits, and photoreceptor cell death, and loss of rod but not cone function. RPE-specific reduction in Mttp had no significant effect on plasma lipids and lipoproteins. While APOB was decreased in the RPE, most ocular retinoids remained unchanged, with the exception of the storage form of retinoid, retinyl ester. Thus suggesting that RPE MTP is critical for Blp synthesis and assembly but is not directly involved in plasma lipoprotein metabolism. These studies demonstrate that RPE-specific MTP expression is necessary to establish and maintain retinal lipid homeostasis and visual function.

Evaluation of an advanced antioxidant and double-conjugated retinoid/AHA cream in participants with FST IV-V.

BACKGROUND: Topical antioxidants and retinoids are foundational components of an effective skincare regimen. Pyrroloquinoline quinone (PQQ) is a potent free radical scavenger that supports efficient mitochondrial energy creation. An advanced antioxidant combines topical allyl PQQ with existing WEL antioxidant technology (TAP) to comprehensively address extrinsic and intrinsic skin aging. In conjunction with TAP, a double-conjugated retinoid/alpha hydroxy acid (AHA-Ret) designed to minimize irritation and optimize delivery was used over 12 weeks to improve the appearance of photodamaged skin. PATIENTS/METHODS: Twice-daily application of TAP and nightly application of AHA-Ret was evaluated in female participants aged 40-65 years with FST IV-V and mild (3) to moderate (6) facial photodamage using a 10-point grading scale. Visible improvements from baseline in lines/wrinkles, skin texture, skin tone, skin dullness and erythema were assessed using a six-point grading scale (0 = None to 5 = Severe). Adverse Events (AEs) were captured throughout the study period. RESULTS: Participants (N = 21; mean age, 56 years) equally represented mild and moderate photodamage, and FST IV and V (41%, Hispanic; 36%, African American; and 32%, Caucasian). Significant mean improvements from baseline occurred in skin dullness, skin texture, and skin tone (all, p < 0.0001), and significant mean reductions from baseline were demonstrated in erythema and melanin at Week 12. Mild, transient AEs were reported. No participant discontinued study participation due to an AE. CONCLUSIONS: A skincare regimen comprised of an advanced antioxidant and AHA-Ret cream, in conjunction with daily use of a broad-spectrum sunscreen (SPF 56), led to significant improvements at 12 weeks in the appearance of photodamaged skin in females with FST IV and V.

Guidelines of care for the management of acne vulgaris.

BACKGROUND: Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older. OBJECTIVE: The objective of this study was to provide evidence-based recommendations for the management of acne. METHODS: A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements. LIMITATIONS: Analysis is based on the best available evidence at the time of the systematic review. CONCLUSIONS: These guidelines provide evidence-based recommendations for the management of acne vulgaris.

Unraveling the mystery of ocular retinoid turnover: Insights from albino mice and the role of STRA6.

A delicate balance between photon absorption for vision and the protection of photoreceptors from light damage is pivotal for ocular health. This equilibrium is governed by the light-absorbing 11-cis-retinylidene chromophore of visual pigments, which, upon bleaching, transforms into all-trans-retinal and undergoes regeneration through an enzymatic pathway, named the visual cycle. Chemical side reactions of retinaldehyde during the recycling process can generate by-products that may result in a depletion of retinoids. In our study, we have clarified the crucial roles played by melanin pigmentation and the retinoid transporter STRA6 in preventing this loss and preserving the integrity of the visual cycle. Our experiments initially confirmed that consecutive green and blue light bleaching of isolated bovine rhodopsin produced 9-cis and 13-cis retinal. The same unusual retinoids were found in the retinas of mice exposed to intense light, with elevated concentrations observed in albino mice. Examining the metabolic fate of these visual cycle byproducts revealed that 9-cis-retinal, but not 13-cis-retinal, was recycled back to all-trans-retinal through an intermediate called isorhodopsin. However, investigations in Stra6 knockout mice unveiled that the generation of these visual cycle byproducts correlated with a light-induced loss of ocular retinoids and visual impairment. Collectively, our findings uncover important novel aspects of visual cycle dynamics, with implications for ocular health and photoreceptor integrity.

Effect of a retinoic acid analogue on BMP-driven pluripotent stem cell chondrogenesis.

Osteoarthritis is the most common degenerative joint condition, leading to articular cartilage (AC) degradation, chronic pain and immobility. The lack of appropriate therapies that provide tissue restoration combined with the limited lifespan of joint-replacement implants indicate the need for alternative AC regeneration strategies. Differentiation of human pluripotent stem cells (hPSCs) into AC progenitors may provide a long-term regenerative solution but is still limited due to the continued reliance upon growth factors to recapitulate developmental signalling processes. Recently, TTNPB, a small molecule activator of retinoic acid receptors (RARs), has been shown to be sufficient to guide mesodermal specification and early chondrogenesis of hPSCs. Here, we modified our previous differentiation protocol, by supplementing cells with TTNPB and administering BMP2 at specific times to enhance early development (referred to as the RAPID-E protocol). Transcriptomic analyses indicated that activation of RAR signalling significantly upregulated genes related to limb and embryonic skeletal development in the early stages of the protocol and upregulated genes related to AC development in later stages. Chondroprogenitors obtained from RAPID-E could generate cartilaginous pellets that expressed AC-related matrix proteins such as Lubricin, Aggrecan, and Collagen II, but additionally expressed Collagen X, indicative of hypertrophy. This protocol could lay the foundations for cell therapy strategies for osteoarthritis and improve the understanding of AC development in humans.

A retinoid analogue, TTNPB, promotes clonal expansion of human pluripotent stem cells by upregulating CLDN2 and HoxA1.

Enzymatic dissociation of human pluripotent stem cells (hPSCs) into single cells during routine passage leads to massive cell death. Although the Rho-associated protein kinase inhibitor, Y-27632 can enhance hPSC survival and proliferation at high seeding density, dissociated single cells undergo apoptosis at clonal density. This presents a major hurdle when deriving genetically modified hPSC lines since transfection and genome editing efficiencies are not satisfactory. As a result, colonies tend to contain heterogeneous mixtures of both modified and unmodified cells, making it difficult to isolate the desired clone buried within the colony. In this study, we report improved clonal expansion of hPSCs using a retinoic acid analogue, TTNPB. When combined with Y-27632, TTNPB synergistically increased hPSC cloning efficiency by more than 2 orders of magnitude (0.2% to 20%), whereas TTNPB itself increased more than double cell number expansion compared to Y-27632. Furthermore, TTNPB-treated cells showed two times higher aggregate formation and cell proliferation compared to Y-27632 in suspension culture. TTNPB-treated cells displayed a normal karyotype, pluripotency and were able to stochastically differentiate into all three germ layers both in vitro and in vivo. TTNBP acts, in part, by promoting cellular adhesion and self-renewal through the upregulation of Claudin 2 and HoxA1. By promoting clonal expansion, TTNPB provides a new approach for isolating and expanding pure hPSCs for future cell therapy applications.

Induction of Meiotic Initiation in Long-Term Mouse Spermatogonial Stem Cells Under Retinoid Acid and Nutrient Restriction Conditions.

Spermatogonial stem cells (SSCs) produce haploid sperm via mitosis and meiosis in vivo. Although the technique to culture mouse SSCs has been well established, induction of meiosis in vitro has remained a challenge. Retinoic acid (RA) is required for meiosis in vivo; however, RA alone is not sufficient to induce meiosis in vitro. Here, we describe a method in which nutrient restriction and RA synergistically induce meiotic initiation into meiotic prophase I in cultured mouse SSCs.

Dual role for microbial short-chain fatty acids in modifying SIV disease trajectory following anti-α4ß7 antibody administration.

BACKGROUND: Human Immunodeficiency Virus (HIV)/Simian Immunodeficiency Virus (SIV) infection is associated with significant gut damage, similar to that observed in patients with inflammatory bowel disease (IBD). This pathology includes loss of epithelial integrity, microbial translocation, dysbiosis, and resultant chronic immune activation. Additionally, the levels of all-trans-retinoic acid (atRA) are dramatically attenuated. Data on the therapeutic use of anti-α4ß7 antibodies has shown promise in patients with ulcerative colitis and Crohn's disease. Recent evidence has suggested that the microbiome and short-chain fatty acid (SCFA) metabolites it generates may be critical for anti-α4ß7 efficacy and maintaining intestinal homeostasis. MATERIALS AND METHODS: To determine whether the microbiome contributes to gut homeostasis after anti-α4ß7 antibody administered to SIV-infected rhesus macaques, faecal SCFA concentrations were determined, 16S rRNA sequencing was performed, plasma viral loads were determined, plasma retinoids were measured longitudinally, and gut retinoid synthesis/response gene expression was quantified. RESULTS: Our results suggest that anti-α4ß7 antibody facilitates the return of retinoid metabolism to baseline levels after SIV infection. Furthermore, faecal SCFAs were shown to be associated with retinoid synthesis gene expression and rebound viral loads after therapy interruption. CONCLUSIONS: Taken together, these data demonstrate the therapeutic advantages of anti-α4ß7 antibody administration during HIV/SIV infection and that the efficacy of anti-α4ß7 antibody may depend on microbiome composition and SCFA generation.

A Murine Model for Measuring Sebum Production That Can Be Used to Test Therapeutic Agents for the Management of Acne Vulgaris.

Acne vulgaris (acne) effects nearly 90% of all Western teenagers, and the only pharmaceutical class of agents to treat severe forms of this skin condition are the retinoids, which are well-described teratogens. Yet about 50% of the patients receiving this class of therapeutics are women of child-bearing age, in their peak years of reproductive potential. On this basis, there is a significant unmet medical need for agents to treat severe forms of acne that do not carry this liability. As a means to assess potential agents of this type, here we describe methods for estimating the relative amount of sebum that a mouse produces based on the water retention on fur following a thorough wetting procedure. We have shown that a compound that is clinically effective in reducing sebum production demonstrates activity in this model. The method is therefore useful for evaluating therapeutic candidates for reducing sebum production, which would in turn be useful for treating acne. We have broken the entire procedure down into two phases/two protocols, as listed below. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Pre-wash wet weight measurement Basic Protocol 2: Post-wash wet-weight measurement.

The antimicrobial potential of adarotene derivatives against Staphylococcus aureus strains.

Multidrug-resistant (MDR) pathogens are severely impacting our ability to successfully treat common infections. Here we report the synthesis of a panel of adarotene-related retinoids showing potent antimicrobial activity on Staphylococcus aureus strains (including multidrug-resistant ones). Fluorescence and molecular dynamic studies confirmed that the adarotene analogues were able to induce conformational changes and disfunctions to the cell membrane, perturbing the permeability of the phospholipid bilayer. Since the major obstacle for developing retinoids is their potential cytotoxicity, a selected candidate was further investigated to evaluate its activity on a panel of human cell lines. The compound was found to be well tolerated, with IC50 5-15-fold higher than the MIC on S. aureus strains. Furthermore, the adarotene analogue had a good pharmacokinetic profile, reaching a plasma concentration of about 6 µM after 0.5 h after administration (150 mg/kg), at least twice the MIC observed against various bacterial strains. Moreover, it was demonstrated that the compound potentiated the growth-inhibitory effect of the poorly bioavailable rifaximin, when used in combination. Overall, the collected data pave the way for the development of synthetic retinoids as potential therapeutics for hard-to-treat infectious diseases caused by antibiotic-resistant Gram-positive pathogens.

Modern techniques in addressing facial acne scars: A thorough analysis.

BACKGROUND: Facial acne scars are a prevalent concern, leading to the development of various treatment modalities. OBJECTIVES: This review aims to explore the latest advancements in the treatment of facial acne scars, focusing on both surgical and non-surgical methods. METHODS: The non-surgical treatments reviewed include topical medications (such as retinoids and alpha hydroxy acids) and non-invasive procedures (like microdermabrasion and chemical peels). Surgical options discussed are punch excision, subcision, and fractional laser treatments. RESULTS: Combination therapy, integrating both surgical and non-surgical approaches, is frequently utilized to achieve optimal results in scar improvement. CONCLUSION: Recent advancements in the treatment of facial acne scars provide promising options for individuals seeking improvement. However, these treatments have associated risks and potential adverse effects, highlighting the importance of consulting a dermatologist before beginning any treatment regimen.