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INTRODUCTION: A three-pronged approach to acne treatment combining an antibiotic, antimicrobial, and retinoid may be more efficacious than single/double treatments while potentially reducing antibiotic resistance. This study evaluated the efficacy and safety of the first fixed-dose, triple-combination topical acne product, clindamycin 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB) using pooled phase 3 data. METHODS: In two identical phase 3 (N = 183; N = 180), double-blind, 12-week studies, participants aged ≥ 9 years with moderate-to-severe acne were randomized 2:1 to receive once-daily CAB or vehicle gel. Endpoints included ≥ 2-grade reduction from baseline in Evaluators Global Severity Score and clear/almost clear skin (treatment success) and least-squares mean percent change from baseline in acne lesion counts. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were evaluated. RESULTS: At week 12, 50.0% of participants achieved treatment success with CAB versus 22.6% with vehicle gel (P  70% reductions in inflammatory and noninflammatory lesions at week 12 (77.9% and 73.0%, respectively), which were significantly greater than vehicle (57.9% and 48.2%; P

Patients with BRAF‐mutated colorectal cancer (BRAFV600E CRC) are currently treated with a combination of BRAF inhibitor and anti‐EGFR antibody with or without MEK inhibitor. A fundamental problem in treating patients with BRAFV600E CRC is intrinsic and/or acquired resistance to this combination therapy. By screening 78 compounds, we identified tretinoin, a retinoid, as a compound that synergistically enhances the antiproliferative effect of a combination of BRAF inhibition and MEK inhibition with or without EGFR inhibition on BRAFV600E CRC cells. This synergistic effect was also exerted by other retinoids. Tretinoin, added to BRAF inhibitor and MEK inhibitor, upregulated PARP, BAK, and p‐H2AX. When either RARα or RXRα was silenced, the increase in cleaved PARP expression by the addition of TRE to ENC/BIN or ENC/BIN/CET was canceled. Our results suggest that the mechanism of the synergistic antiproliferative effect involves modulation of the Bcl‐2 family and the DNA damage response that affects apoptotic pathways, and this synergistic effect is induced by RARα‐ or RXRα‐mediated apoptosis. Tretinoin also enhanced the antitumor effect of a combination of the BRAF inhibitor and anti‐EGFR antibody with or without MEK inhibitor in a BRAFV600E CRC xenograft mouse model. Our data provide a rationale for developing retinoids as a new combination agent to overcome resistance to the combination therapy for patients with BRAFV600E CRC. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusions Many people are interested in addressing visible signs of aging with non‐invasive cosmetic treatments. Development of effective topical products will provide options to delay or support cosmetic procedures.This study assessed and compared the efficacy and tolerance of a topical product used over the course of 16 weeks to a single ablative laser treatment on women with moderate global photodamage on the face.Subjects in Cell 1 (Laser Cell) were treated over the entire face with a fractional CO2 laser system. Subjects in Cell 2 (Topical Serum Cell) were treated with a topical serum containing hydroxypinacolone retinoate and peptides over the entire face, twice per day for 16 weeks. The study was composed of 71 women, with 29 in the Laser Cell (mean age 56.2) and 42 in the Topical Serum Cell (mean age 55.0), between 40 and 65 years old. Expert grading was used to determine efficacy parameters.Participants in the Topical Serum Cell achieved more significant improvement (p < 0.05) in Marionette lines, fine lines (global face), wrinkles (global face), wrinkles (crow's feet), nasolabial folds, texture, smoothness (tactile), global hyperpigmentation, lift, and photodamage compared to participants in the Laser Cell. Participants in the Topical Serum Cell achieved parity in the look of fine lines (crow's feet), forehead lines, glabella, firmness/bounce (tactile), skin tone evenness, radiance.While no statistically significant differences in tolerability were observed, treatment with the topical cosmetic product achieved parity or statistically better improvement in parameters compared to laser treatment at 16 weeks. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease worldwide and is characterized by progressive muscle atrophy. There are currently two approved treatments, but they only relieve symptoms briefly and do not cure the disease. The main hindrance to research is the complex cause of ALS, with its pathogenesis not yet fully elucidated. Retinoids (vitamin A derivatives) appear to be essential in neuronal cells and have been implicated in ALS pathogenesis. This study explores 4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydroquinoxalin-2-yl)ethylnyl]benzoic acid (Ellorarxine, or DC645 or NVG0645), a leading synthetic retinoic acid, discussing its pharmacological mechanisms, neuroprotective properties, and relevance to ALS. The potential therapeutic effect of Ellorarxine was analyzed in vitro using the WT and SOD1G93A NSC-34 cell model of ALS at an administered concentration of 0.3–30 nM. Histological, functional, and biochemical analyses were performed. Elorarxine significantly increased MAP2 expression and neurite length, increased AMPA receptor GluA2 expression and raised intracellular Ca2+ baseline, increased level of excitability, and reduced Ca2+ spike during depolarization in neurites. Ellorarxine also displayed both antioxidant and anti-inflammatory effects. Overall, these results suggest Ellorarxine shows relevance and promise as a novel therapeutic strategy for treatment of ALS. [ABSTRACT FROM AUTHOR]

Post inflammatory hyperpigmentation (PIH) affects all skin types with a heightened predilection for darker skin tones. Its course is chronic once developed and treatment is often difficult. This systematic review aims to summarize the treatment outcomes for PIH with a focus on skin of colour (SOC) individuals. A literature search was conducted using MEDLINE (from 1946), Embase (from 1974), PubMed, and Cochrane in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline. Results from 48 studies summarized 1356 SOC individuals. The mean age was 29 years (n = 1036) and 78% were female (n = 786). The ethnic prevalence was 70% Black, 27% Asian, and 3% Latin. Overall, 20% were Fitzpatrick skin type (FST) III, 40% FST IV, 34% FST V, and 6% FST VI. Most cases were precipitated by inflammatory conditions (89%) and localized to the face (83%). The most frequently reported interventions were topical retinoids (22%) and laser therapy (17%). Partial improvement was seen in 85% and 66% of participants, respectively. Laser was the only intervention that offered complete resolution in a subgroup of patients (26%); however, there were reported cases of PIH exacerbation following treatment. Chemical peels (9%) and hydroquinone (7%) were among other treatments with less effective outcomes. PIH and its persistence is a prevalent issue, significantly affecting many affected individuals with darker skin tones. Our results show a lack of robust efficacy across all treatment modalities. There is considerable room for improvement in interventions for at-risk populations. [ABSTRACT FROM AUTHOR]

Isotretinoin is an oral medication commonly utilized to treat severe acne. It belongs to the class of retinoids and is a synthetic form of vitamin A. Possible changes in bone tissue associated with the systemic administration of Isotretinoin for long periods and in high doses, such as hypercalcemia, osteopenia, diffuse hyperostosis, or even skeletal deformities, are reported in scientific studies. The objective of this literature review was to analyze the available scientific literature on the systemic administration of Isotretinoin and its effects on bone tissue. To this end, articles that demonstrate effects of Isotretinoin on bone metabolism, bone mineral density, bone formation, and resorption, in addition to possible changes generated in this tissue were considered valid for inclusion in this literature review. The search for articles that fit the premise of this work was carried out in the PubMed/MEDLINE database. In a preliminary search, 85 articles were obtained; after in-depth investigation and checking of the inclusion and exclusion criteria, 21 articles were selected, with 17 articles reporting the effect of systemic administration of Isotretinoin in humans and four articles analyzing the effect generated by this substance systemically administrated in animals, more specifically in rats. After analyzing the selected articles, it was possible to observe several reports on hyperostosis or even changes in the formation of bone structures in human patients. Concerning animals, the largest number of studies addressed the changes caused in the formation or development of bone structures by the systemic administration of Isotretinoin. From the current analyses, and given the wide use of Isotretinoin, it is necessary to know its viability and influence on tissues. Its clinical efficacy seems to overcome any of the skeletal side effects observed; however, more studies are necessary to properly evaluate and prove the effects generated on bone tissues as well as other structures.

Abstract Introduction An expert panel of Canadian dermatologists was assembled to develop consensus statements regarding the current landscape of topical therapies for plaque psoriasis and the place in therapy of the recently approved fixed-dose combination halobetasol propionate (HP)/tazarotene (TAZ) lotion (HP/TAZ) in the treatment algorithm for plaque psoriasis. Method A modified nominal group technique, which combined both independent and group input from the expert panel, was used to develop the consensus statements. The expert panel completed surveys to elicit their independent views on the current landscape of topical therapies for plaque psoriasis in Canada. The first expert panel session was held to discuss the existing body of literature and develop draft consensus statements about topical therapies and the place in therapy of HP/TAZ. Independent feedback on the draft consensus statements was solicited from expert panel members prior to another expert panel session where the amended consensus statements were further discussed, edited and, finally, voted on. Results The expert panel reached consensus on 20 statements. Conclusion Expert panel members agreed, based on the existing body of literature, that there is a place in therapy for HP/TAZ to address several current unmet treatment needs of patients with plaque psoriasis. Studies have shown that HP/TAZ is an effective and safe first-line treatment for moderate-to-severe plaque psoriasis. Due to its cosmetically pleasing vehicle and once-daily administration, HP/TAZ may improve patient acceptance and treatment adherence.

Introduction: An expert panel of Canadian dermatologists was assembled to develop consensus statements regarding the current landscape of topical therapies for plaque psoriasis and the place in therapy of the recently approved fixed-dose combination halobetasol propionate (HP)/tazarotene (TAZ) lotion (HP/TAZ) in the treatment algorithm for plaque psoriasis. Method: A modified nominal group technique, which combined both independent and group input from the expert panel, was used to develop the consensus statements. The expert panel completed surveys to elicit their independent views on the current landscape of topical therapies for plaque psoriasis in Canada. The first expert panel session was held to discuss the existing body of literature and develop draft consensus statements about topical therapies and the place in therapy of HP/TAZ. Independent feedback on the draft consensus statements was solicited from expert panel members prior to another expert panel session where the amended consensus statements were further discussed, edited and, finally, voted on. Results: The expert panel reached consensus on 20 statements. Conclusion: Expert panel members agreed, based on the existing body of literature, that there is a place in therapy for HP/TAZ to address several current unmet treatment needs of patients with plaque psoriasis. Studies have shown that HP/TAZ is an effective and safe first-line treatment for moderate-to-severe plaque psoriasis. Due to its cosmetically pleasing vehicle and once-daily administration, HP/TAZ may improve patient acceptance and treatment adherence. [ABSTRACT FROM AUTHOR]

Acne scarring is common and can occur even with effective acne management. In addition, patients with acne scarring suffer from significant psychosocial morbidity, including depression and suicidality. Despite the availability and advancement of therapeutic modalities, treatment for acne scarring is not always optimized and often overlooked in patients with acne encounters. Using acne scarring assessment tools and identifying specific acne scar subtypes allows for a tailored therapeutic approach. Part I of this continuing medical education series covers the pathophysiology and morphology of textural and pigmented acne scars, scarring assessment tools, and medical treatment options. The principles reviewed will aid in approaching and initiating acne scar treatment in the outpatient setting. [ABSTRACT FROM AUTHOR]

Abstract Introduction A three-pronged approach to acne treatment combining an antibiotic, antimicrobial, and retinoid may be more efficacious than single/double treatments while potentially reducing antibiotic resistance. This study evaluated the efficacy and safety of the first fixed-dose, triple-combination topical acne product, clindamycin 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB) using pooled phase 3 data. Methods In two identical phase 3 (N = 183; N = 180), double-blind, 12-week studies, participants aged ≥ 9 years with moderate-to-severe acne were randomized 2:1 to receive once-daily CAB or vehicle gel. Endpoints included ≥ 2-grade reduction from baseline in Evaluator’s Global Severity Score and clear/almost clear skin (treatment success) and least-squares mean percent change from baseline in acne lesion counts. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were evaluated. Results At week 12, 50.0% of participants achieved treatment success with CAB versus 22.6% with vehicle gel (P 70% reductions in inflammatory and noninflammatory lesions at week 12 (77.9% and 73.0%, respectively), which were significantly greater than vehicle (57.9% and 48.2%; P

Isotretinoin is an oral medication commonly utilized to treat severe acne. It belongs to the class of retinoids and is a synthetic form of vitamin A. Possible changes in bone tissue associated with the systemic administration of Isotretinoin for long periods and in high doses, such as hypercalcemia, osteopenia, diffuse hyperostosis, or even skeletal deformities, are reported in scientific studies. The objective of this literature review was to analyze the available scientific literature on the systemic administration of Isotretinoin and its effects on bone tissue. To this end, articles that demonstrate effects of Isotretinoin on bone metabolism, bone mineral density, bone formation, and resorption, in addition to possible changes generated in this tissue were considered valid for inclusion in this literature review. The search for articles that fit the premise of this work was carried out in the PubMed/MEDLINE database. In a preliminary search, 85 articles were obtained; after in-depth investigation and checking of the inclusion and exclusion criteria, 21 articles were selected, with 17 articles reporting the effect of systemic administration of Isotretinoin in humans and four articles analyzing the effect generated by this substance systemically administrated in animals, more specifically in rats. After analyzing the selected articles, it was possible to observe several reports on hyperostosis or even changes in the formation of bone structures in human patients. Concerning animals, the largest number of studies addressed the changes caused in the formation or development of bone structures by the systemic administration of Isotretinoin. From the current analyses, and given the wide use of Isotretinoin, it is necessary to know its viability and influence on tissues. Its clinical efficacy seems to overcome any of the skeletal side effects observed; however, more studies are necessary to properly evaluate and prove the effects generated on bone tissues as well as other structures. [ABSTRACT FROM AUTHOR]

The most common and widespread type of cutaneous T-cell lymphoma is mycosis fungoides (MF), and it has a multiphasic clinical and biological course, with early stages being indolent for many years and later stages being faster and more aggressive. The clinical stage has a significant impact on the management and course of treatment: in the early stages, skin-directed therapies (SDT) plus/or biologic response modifiers (BRM); in the later stages, radiotherapy and/or systemic therapies. Even though national and international societies and groups periodically update their clinical recommendations, there is still no universally accepted approach. This paper reviews and discusses the various SDT and BRM options, either separately or in combination. [ABSTRACT FROM AUTHOR]

Tamibarotene-based therapy is a novel targeted approach for the treatment of relapsed/refractory (R/R) acute myeloid leukemia (AML) with retinoic acid receptor alpha (RARA) gene overexpression. Approximately, 50% of higher-risk myelodysplastic syndrome (MDS) patients and approximately 30% of AML patients are positive for RARA overexpression using a blood-based biomarker test that measures RARA expression in peripheral blasts. A phase 2 study investigating the activity of tamibarotene in patients with RARA overexpression was conducted in patients with AML and MDS (NCT02807558). In 28 patients with R/R AML and RARA overexpression treated with tamibarotene in combination with azacitidine, the median overall survival was 5.9 months. In 21 response-evaluable patients, the complete remission/complete remission with incomplete hematologic recovery (CR/CRi) rate was 19%, and median time to initial CR/CRi was 1.2 months. The favorable safety profile and preliminary clinical activity support the development of combination therapies with tamibarotene in myeloid malignancies with RARA overexpression. [ABSTRACT FROM AUTHOR]

The most common and widespread type of cutaneous T-cell lymphoma is mycosis fungoides (MF), and it has a multiphasic clinical and biological course, with early stages being indolent for many years and later stages being faster and more aggressive. The clinical stage has a significant impact on the management and course of treatment: in the early stages, skin-directed therapies (SDT) plus/or biologic response modifiers (BRM); in the later stages, radiotherapy and/or systemic therapies. Even though national and international societies and groups periodically update their clinical recommendations, there is still no universally accepted approach. This paper reviews and discusses the various SDT and BRM options, either separately or in combination.

Abstract Introduction Plants are a source of natural ingredients with retinol-like properties that can deliver anti-aging benefits without the side effects typically associated with retinoid use. We hypothesized that by combining two such analogs, bakuchiol (BAK) and Vigna aconitifolia extract (VAE), with the potent retinoid retinal (RAL), the anti-photoaging potential of RAL could be enhanced without compromising its skin irritation profile. The purpose of this study was to demonstrate that BAK and VAE potentiate the anti-photoaging activity of RAL. Methods Gene expression profiling of full-thickness reconstructed skin was first used to examine the impact of BAK or VAE in combination with RAL on skin biology. Next, the irritative potential of this combination, and its capacity to reverse key signs of photoaging in an ex vivo model was assessed. Finally, a proof-of-concept open label clinical study was performed to evaluate the anti-photoaging capacity and skin compatibility of a cosmetic formulation (tri-retinoid complex; 3RC) containing this complex in combination with other well characterized anti-photoaging ingredients. Results In vitro profiling suggested that combining 0.1% RAL with BAK or VAE potentiates the effect of RAL on keratinocyte differentiation and skin barrier function without affecting its skin irritation profile. When formulated with other anti-photoaging ingredients, such as niacinamide and melatonin, 3RC reversed ultraviolet radiation-induced deficits in structural components of the dermal extracellular matrix, including hyaluronic acid and collagen. In vivo, it led to a reversal of clinical signs of age and photodamage, with statistically significant improvement to skin firmness (+5.6%), skin elasticity (+13.9%), wrinkle count (−43.2%), and skin tone homogeneity (+7.0%), observed within 28 days of once nightly use. Notably, the number of crow’s feet wrinkles was reduced in 100% of subjects. Furthermore, 3RC was very well tolerated. Conclusion These data suggest that 3RC is a highly effective and well-tolerated treatment for photoaging.

Pseudomyxoma peritonei (PMP) refers to a growth disorder characterized by glycoprotein neoplasm in the peritoneum, where mucin oversecretion occurs. The tumors of the appendix region are well associated with PMP; however, ovarian, colon, stomach, pancreas, and urachus tumors have also been linked to PMP. Other mucinous tumors in the pelvis, paracolic gutters, greater omentum, retrohepatic space, and Treitz ligament can be the reason for PMP. Despite being rare and having a slow growth rate, PMP can be lethal without treatment. It is treated with neoadjuvant chemotherapy with the option of cytoreductive surgery and intraperitoneal chemotherapy. In the current study, we hypothesize that there may be novel gentle ways to inhibit or eliminate the mucin. Dr. David Morris has used mucolytics—such as bromelain and N-acetyl cysteine to solubilize mucin. In the present review, we aimed to study the regulation of mucin expression by promoter methylation, and drugs that can inhibit mucin, such as boldine, amiloride, naltrexone, dexamethasone, and retinoid acid receptors antagonist. This review also explored some possible pathways, such as inhibition of Na + , Ca2+ channels and induction of DNA methyltransferase along with inhibition of ten-eleven translocation enzymes, which can be good targets to control mucin. Mucins are strong adhesive molecules that play great roles in clinging to cells or cell to cell. Besides, they have been greatly involved in metastasis and also act as disease markers for cancers. Diagnostic markers may have exclusive roles in disease initiation and progression. Therefore, the present review explores various drugs to control and target mucin in various diseases, specifically cancers.

Abstract is missing (Short communication)

Background Excessive sebum production is a factor in acne development. Tazarotene 0.045% lotion has demonstrated reductions in acne lesions and acne-induced sequelae. Objective Evaluate efficacy, changes in skin oiliness, and safety with tazarotene 0.045% lotion in participants with moderate-to-severe acne and oily skin. Methods In two phase 3, double-blind, 12-week studies (NCT03168321; NCT03168334), participants aged ≥ 9 years with moderate-to-severe acne were randomized 1:1 to once-daily tazarotene 0.045% lotion or vehicle lotion (N = 1614). This pooled, post hoc analysis included only participants self-categorized with oily skin at baseline on the Acne-Specific Quality of Life questionnaire item 19 (scores: 0 [extremely oily] to 6 [not at all oily]). Inflammatory/noninflammatory lesion counts, treatment success, skin oiliness, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability were evaluated. Results In all participants with oily skin (n = 793), tazarotene provided greater reductions in inflammatory/noninflammatory lesions (p

Introduction: Plants are a source of natural ingredients with retinol-like properties that can deliver anti-aging benefits without the side effects typically associated with retinoid use. We hypothesized that by combining two such analogs, bakuchiol (BAK) and Vigna aconitifolia extract (VAE), with the potent retinoid retinal (RAL), the anti-photoaging potential of RAL could be enhanced without compromising its skin irritation profile. The purpose of this study was to demonstrate that BAK and VAE potentiate the anti-photoaging activity of RAL. Methods: Gene expression profiling of full-thickness reconstructed skin was first used to examine the impact of BAK or VAE in combination with RAL on skin biology. Next, the irritative potential of this combination, and its capacity to reverse key signs of photoaging in an ex vivo model was assessed. Finally, a proof-of-concept open label clinical study was performed to evaluate the anti-photoaging capacity and skin compatibility of a cosmetic formulation (tri-retinoid complex; 3RC) containing this complex in combination with other well characterized anti-photoaging ingredients. Results: In vitro profiling suggested that combining 0.1% RAL with BAK or VAE potentiates the effect of RAL on keratinocyte differentiation and skin barrier function without affecting its skin irritation profile. When formulated with other anti-photoaging ingredients, such as niacinamide and melatonin, 3RC reversed ultraviolet radiation-induced deficits in structural components of the dermal extracellular matrix, including hyaluronic acid and collagen. In vivo, it led to a reversal of clinical signs of age and photodamage, with statistically significant improvement to skin firmness (+5.6%), skin elasticity (+13.9%), wrinkle count (−43.2%), and skin tone homogeneity (+7.0%), observed within 28 days of once nightly use. Notably, the number of crow's feet wrinkles was reduced in 100% of subjects. Furthermore, 3RC was very well tolerated. Conclusion: These data suggest that 3RC is a highly effective and well-tolerated treatment for photoaging. [ABSTRACT FROM AUTHOR]

Benzoyl peroxide and tretinoin are commonly prescribed acne treatments. Historically, they have been difficult to combine in a single formulation due to chemical instability, and both medications are potentially irritating. Microencapsulation helps overcome these challenges. Examine efficacy, safety, and tolerability of encapsulated BPO/encapsulated tretinoin (E-BPO/T) cream, 3%/0.1%. Subjects ≥9 years old with moderate to severe acne were enrolled in 2 multicenter, double-blind, vehicle-controlled, parallel trials and randomized (2:1) to 12 weeks of once-daily E-BPO/T (n = 571) or vehicle cream (n = 287). E-BPO/T was significantly superior to vehicle in both studies, with more subjects achieving IGA success with E-BPO/T (38.5%/25.4%) versus vehicle (11.5%/14.7%; P <.001/ P =.017). The change from baseline in inflammatory lesion count for E-BPO/T was −21.6 versus −14.8 for vehicle (P <.001) in study 1 and −16.2 versus −14.1 (P =.018) in study 2. The changes from baseline in noninflammatory lesions for E-BPO/T were −29.7 versus −19.8 for vehicle (P <.001) and −24.2 and −17.4 (P <.001) in studies 1 and 2, respectively. E-BPO/T was well tolerated in both studies. Long-term data are not available. E-BPO/T provided statistically significant and clinically relevant improvements in IGA and inflammatory and noninflammatory lesion counts and was well tolerated in subjects with moderate to severe acne. [ABSTRACT FROM AUTHOR]

Cytochrome P450 monooxygenases CYP120As are the unique non-membrane P450s, which are extensively involved in retinoid biodegradation. As the O-functionalized 1,3,3-trimethylcyclohex-1-ene moiety exists in many bioactive compounds which could only be catalyzed by Class II P450s, exploration of the catalytic repertoire of CYP120As is therefore highly attractive. However, up to date, only one bacteriogenic candidate (CYP120A1) was demonstrated for the hydroxylation of C16 and C17 of retinoic acid, by utilizing the integral membrane protein cytochrome P450 reductase redox partner for the electron transfer. Herein, we provided an efficient prokaryotic functional expression system of CYP120As in E. coli by expression of the CYP120A1 coupled with several reductase partners. Fusion redox partners to the C-terminal of the heme-domain are also working on other CYP120A members. Among them, the fusion protein of CYP120A29 and FAD/FMN reductase from Bacillus megaterium P450BM3 (CYP101A2) showed the highest expression level. Based on the available translational fusion systems, the regioselectivity and the substrate scope of the CYP120As have also been explored. This work represents a good starting point for further expanding the catalytic potential of CYP120 family. Key Points: • Characterization of CYP120As in E. coli is firstly achieved by constructing fusion proteins. • The feasibility of three P450 reductase domains to CYP120As was evaluated. • Hydroxylated products of retinoic acid by six CYP120As were sorted and analyzed. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The condition of the skin can vary due to weather fluctuations. Therefore, this post-hoc analysis evaluated efficacy and safety of tazarotene 0.045% lotion in warmer versus colder months. METHODS: In two Phase III, double-blind, 12-week studies, participants aged nine years or older with moderate-to- severe acne were randomized 1:1 to once-daily tazarotene or vehicle lotion. The pooled population (N=1,614) was stratified by randomization date (warmer=May to September; colder=October to April). Evaluations included inflammatory/noninflammatory lesion counts, treatment success, adverse events, and safety/tolerability. RESULTS: Tazarotene 0.045% lotion was similarly efficacious over colder and warmer months. Compared with vehicle, tazarotene demonstrated significantly greater least-squares mean absolute reductions from baseline to Week 12 in inflammatory (colder/warmer tazarotene vs. vehicle: -16.6/-15.8 vs. -13.2/-12.9) and noninflammatory lesions (-23.2/-22.6 vs. -17.5/-15.1); treatment success rates were also significantly higher (30.1/30.8% vs. 18.2/17.6%) (P<0.001, all). No strong seasonal trends in safety were observed, though tazarotene led to slightly more discontinuations (3.4% vs. 1.9%) and related adverse events (12.0% vs. 10.3%) in colder versus warmer months. Transient increases in scaling, erythema, and itching at Weeks 2 to 8 of tazarotene treatment were slightly higher in colder versus warmer months but returned to baseline/improved by Week 12. LIMITATIONS: Geographical variation across study sites can lead to varying temperatures and humidity within the same months. CONCLUSION: Tazarotene 0.045% lotion was efficacious and well tolerated for acne treatment, regardless of season. Year-round tolerability of tazarotene 0.045% lotion may be due to its lower tazarotene concentration and polymeric emulsion technology, which simultaneously delivers moisturizers/humectants/emollients to skin. [ABSTRACT FROM AUTHOR]

Longitudinal growth and puberty are the result of a complex interaction of genetic, hormonal, nutritional, and environmental factors. Acne vulgaris is a chronic disease of the pilosebaceous unit that affects 85% of adolescents worldwide. Isotretinoin is a synthetic vitamin A derivative drug effective and is widely employed for the treatment of moderate and severe acne vulgaris. Premature epiphyseal closure has been reported in patients with neuroblastoma treated with high doses of isotretinoin as well as in patients with acne receiving lower doses. Although the mechanisms for these effects are not clear, it has been suggested that isotretinoin may have a negative impact on the GH-IGF-I axis, leading to a reduction in IGF-I and IGFBP3 serum levels. Although many of the isotretinoin adverse effects in pediatric patients are transient, premature epiphyseal closure and bone abnormalities can lead to transient abnormalities and permanent deformities with a negative impact on longitudinal growth and final height. The aim of this study was to review the potential effects of oral isotretinoin on the growth plate and growth during childhood and adolescence.

Topical and systemic retinoids have long been used in the treatment of ichthyoses and other disorders of cornification. Due to the need for long-term use of retinoids for these disorders, often beginning in childhood, numerous clinical concerns must be considered. Systemic retinoids have known side effects involving bone and eye. Additionally, potential psychiatric and cardiovascular effects need to be considered. Contraceptive concerns, as well as the additive cardiovascular and bone effects of systemic retinoid use with hormonal contraception must also be deliberated for patients of childbearing potential. The Pediatric Dermatology Research Alliance (PeDRA) Use of Retinoids in Ichthyosis Work Group was formed to address these issues and to establish best practices regarding the use of retinoids in ichthyoses based on available evidence and expert opinion.

Background: Acne often worsens in transmasculine patients who are on prolonged testosterone therapy. Isotretinoin is an oral retinoid used in the treatment of severe or refractory cases of acne, but it has the potential to cause delayed wound healing. Transmasculine patients may potentially be prescribed treatment for acne with isotretinoin while also planning to undergo chest masculinization surgery. Objective: This scoping review aims to determine whether isotretinoin has a negative impact on postoperative healing in transmasculine patients undergoing chest masculinization surgery. Methods: A scoping review was performed using the PubMed and Ovid databases. A total of 16 publications were selected for inclusion. Results: Acne tends to peak in transmasculine patients six months after initiation of testosterone treatment. Severe cases can be treated with isotretinoin; however, acne may recur once treatment is discontinued, given ongoing hormone therapy. There is little-to-no evidence in the medical literature regarding perioperative use of isotretinoin specifically among transmasculine patients undergoing chest masculinization surgery. In general, however, recent studies have found no evidence of increased hypertrophic scars or keloids in patients taking isotretinoin. Conclusion: Further studies are required to strengthen the current evidence that suggests that isotretinoin does not need to be discontinued before or after incisional or excisional surgeries, including chest masculinization surgery in transmasculine patients. [ABSTRACT FROM AUTHOR]

Purpose: Fenretinide (4-HPR) is a synthetic retinoid that induces cytotoxicity through dihydroceramide production. Safingol, a stereochemical-variant dihydroceramide precursor, exhibits synergistic effects when administered with fenretinide in preclinical studies. We conducted a phase 1 dose-escalation clinical trial of this combination. Methods: Fenretinide was administered as a 600 mg/m2 24-h infusion on Day 1 of a 21-day cycle followed by 900 mg/m2/day on Days 2 and 3. Safingol was concurrently administered as a 48-h infusion on Day 1 and 2 using 3 + 3 dose escalation. Primary endpoints were safety and maximum tolerated dose (MTD). Secondary endpoints included pharmacokinetics and efficacy. Results: A total of 16 patients were enrolled (mean age 63 years, 50% female, median three prior lines of therapy), including 15 patients with refractory solid tumors and one with non-Hodgkin lymphoma. The median number of treatment cycles received was 2 (range 2–6). The most common adverse event (AE) was hypertriglyceridemia (88%; 38% ≥ Grade 3), attributed to the fenretinide intralipid infusion vehicle. Other treatment-related AEs occurring in ≥ 20% of patients included anemia, hypocalcemia, hypoalbuminemia, and hyponatremia. At safingol dose 420 mg/m2, one patient had a dose-limiting toxicity of grade 3 troponinemia and grade 4 myocarditis. Due to limited safingol supply, enrollment was halted at this dose level. Fenretinide and safingol pharmacokinetic profiles resembled those observed in monotherapy trials. Best radiographic response was stable disease (n = 2). Conclusion: Combination fenretinide plus safingol commonly causes hypertriglyceridemia and may be associated with cardiac events at higher safingol levels. Minimal activity in refractory solid tumors was observed. Trial registration number: NCT01553071 (3.13.2012). [ABSTRACT FROM AUTHOR]

Background: Acitretin has been linked to the development of psychiatric disturbance. Objectives: The aim of this study was to assess the psychiatric hazards in patients with psoriasis prescribed acitretin compared with those prescribed disease-modifying antirheumatic drugs (DMARDs). Methods: This is a nationwide matched cohort study. From Taiwan's National Health Insurance Research Database, adult patients with psoriasis between 1997 and 2013 were screened. Patients prescribed acitretin for at least 30 days per year on average (acitretin cohort) were matched 1:2 with those prescribed DMARDs for at least 30 days per year on average (reference cohort), by means of age, gender, and psoriasis duration. Patients prescribed medication of the corresponding cohort for more than 7 days during the observation period were excluded. Cumulative incidences of psychiatric disorders in both cohorts were plotted with the Kaplan-Meier method. The modified Cox regression models were constructed to estimate hazard ratios (HRs). Results: In total, 1,152 and 2,304 patients in the acitretin and the reference cohorts, respectively, were included. The 4-year cumulative incidence of overall psychiatric disorders (19.62% vs. 12.06%; p < 0.001), mood disorders (12.81% vs. 7.67%; p < 0.001), and psychosis (7.21% vs. 4.63%; p < 0.001) in the acitretin cohort was significantly higher than that in the reference cohort. Acitretin was independently associated with psychiatric disorders (HR 1.51, 95% confidence interval [CI] 1.23–1.85). The risk is more accentuated in the subgroups of comorbid chronic liver disease (HR 2.60, 95% CI: 1.56–4.33) or psoriatic arthritis (HR 3.23, 95% CI: 1.75–5.97). Other independent risk factors included insomnia, acute coronary syndrome, females, and age. Conclusions: Compared with DMARDs, acitretin was associated with higher hazards of psychiatric disorders among psoriasis patients. [ABSTRACT FROM AUTHOR]

Simple Summary: In the realm of cancer treatment and prevention, the application of retinoids has led to unparalleled successes and humbling disappointments; all-trans retinoic acid (ATRA) has transformed APL (acute promyelocytic leukemia) into an eminently curable disease but has demonstrated little efficacy in acute myeloid leukemia (AML) more broadly. As a cancer prevention strategy, vitamin A supplementation was ineffective and appeared to increase lung cancer incidence, underscoring the complex relationship between retinoic acid signaling and carcinogenesis. This review aims to provide a survey of our current understanding of retinoic acid homeostasis and signaling, to reflect on prior successes and failures to deploy retinoids in the treatment and prevention of cancer, and to explore the unfulfilled potential of retinoids in cancer. New biological insights relating to the regulation of retinoid homeostasis and the discovery of biomarkers of retinoid sensitivity in subsets of non-APL AML have revived enthusiasm for the therapeutic potential of synthetic retinoids, and thus warrant a reacquaintance with retinoid biology. Since the introduction of all-trans retinoic acid (ATRA), acute promyelocytic leukemia (APL) has become a highly curable malignancy, especially in combination with arsenic trioxide (ATO). ATRA's success has deepened our understanding of the role of the RARα pathway in normal hematopoiesis and leukemogenesis, and it has influenced a generation of cancer drug development. Retinoids have also demonstrated some efficacy in a handful of other disease entities, including as a maintenance therapy for neuroblastoma and in the treatment of cutaneous T-cell lymphomas; nevertheless, the promise of retinoids as a differentiating therapy in acute myeloid leukemia (AML) more broadly, and as a cancer preventative, have largely gone unfulfilled. Recent research into the mechanisms of ATRA resistance and the biomarkers of RARα pathway dysregulation in AML have reinvigorated efforts to successfully deploy retinoid therapy in a broader subset of myeloid malignancies. Recent studies have demonstrated that the bone marrow environment is highly protected from exogenous ATRA via local homeostasis controlled by stromal cells expressing CYP26, a key enzyme responsible for ATRA inactivation. Synthetic CYP26-resistant retinoids such as tamibarotene bypass this stromal protection and have shown superior anti-leukemic effects. Furthermore, recent super-enhancer (SE) analysis has identified a novel AML subgroup characterized by high expression of RARα through strong SE levels in the gene locus and increased sensitivity to tamibarotene. Combined with a hypomethylating agent, synthetic retinoids have shown synergistic anti-leukemic effects in non-APL AML preclinical models and are now being studied in phase II and III clinical trials. [ABSTRACT FROM AUTHOR]

Background: Aging is responsible for the majority of skin and soft tissue remolding in humans. Retinol and its derivatives or retinoids effectively intervene skin aging process. Nevertheless, retinoids usually induce skin intolerance, especially among the Chinese, and thus, their application to prevent skin aging is yet to be well accepted. The study of optimal composition and concentration of retinoids is necessary to offer strong antiaging efficacies with minimum irritations. Therefore, a better understanding of retinol and its derivatives is acutely needed to develop strategies to combat skin aging. Objective: In this study, we aimed to determine the optimal ratio of two retinol derivatives—hydroxypinacolone retinoate (HPR) and retinyl propionate (RP) in terms of dermal remodeling and skin aging prevention—and to investigate their synergistic antiaging effects both in vitro and in vivo. Methods: An in vitro human foreskin fibroblast (HFF‐1) cell model was established to evaluate the cell viability of HPR and/or RP treatment. In addition, the antiaging and retinol receptor genes expressions in HFF‐1 cells cotreated with HPR and RP were quantified. The in vivo adverse reaction evaluation of skincare serums containing various levels of retinol or the optimal HPR and RP combination termed Gravi‐A was performed by 24 h patch tests in 33 subjects prior to the clinical research. Last but not the least, clinical research with 42 Chinese urban women was conducted to assess the in vivo antiaging efficacy of the skincare serum containing this optimal retinoid combination. Results: The combination of HPR and RP at the weight ratio of 5:9 was shown to achieve the optimal in vitro antiaging performance. Coadministration of 5 μg/mL HPR and 9 μg/mL RP to HFF‐1 cells promoted their proliferation at 24 h and synergistically enhanced the expressions of type IV collagen, CRBP‐I, and RARB genes. In addition, the skincare serum containing HPR and RP combination at 5:9 weight ratio demonstrated superior in vivo anti‐wrinkle and skin elasticity improvement benefits without any adverse reactions, while retinol in the same concentration exerted much higher adverse effect. Skin wrinkles, skin smoothness, TEWL, skin elasticity R2 and R5 were improved by 8.3%, 11.9%, 25.7%, 14.5%, and 22.6%, respectively, after 8‐week use. Conclusion: Our results indicated the advanced antiaging effect of HPR and RP combination both in vitro and in vivo. In addition, little adverse effect was observed in this study, in comparison with retinol. This combination named as Gravi‐A is a potential therapeutic strategy to prevent skin aging, especially for Chinese women. [ABSTRACT FROM AUTHOR]

Limited molecular knowledge of Merkel cell polyomavirus (MCPyV)‐positive and ‐negative Merkel cell carcinoma (MCC) subsets (MCCP/MCCN) has prevented so far the identification of the MCC origin cell type and, therefore, the development of effective therapies. The retinoic gene signature was investigated in various MCCP, MCCN, and control fibroblast/epithelial cell lines to elucidate the heterogeneous nature of MCC. Hierarchical clustering and principal component analysis indicated that MCCP and MCCN cells were clusterizable from each other and control cells, according to their retinoic gene signature. MCCP versus MCCN differentially expressed genes (n = 43) were identified. Protein–protein interaction network indicated SOX2, ISL1, PAX6, FGF8, ASCL1, OLIG2, SHH, and GLI1 as upregulated hub genes and JAG1 and MYC as downregulated hub genes in MCCP compared to MCCN. Numerous MCCP‐associated hub genes were DNA‐binding/‐transcription factors involved in neurological and Merkel cell development and stemness. Enrichment analyses indicated that MCCP versus MCCN differentially expressed genes predominantly encode for to DNA‐binding/‐transcription factors involved in development, stemness, invasiveness, and cancer. Our findings suggest the neuroendocrine origin of MCCP, by which neuronal precursor cells could undergo an MCPyV‐driven transformation. These overarching results might open the way to novel retinoid‐based MCC therapies. [ABSTRACT FROM AUTHOR]

Dietary deficiencies in zinc (Zn) and vitamin A (VA) are among the leading micronutrient deficiencies globally and previous research has proposed a notable interaction between Zn and VA physiological status. This study aimed to assess the effects of zinc and vitamin A (isolated and combined) on intestinal functionality and morphology, and the gut microbiome (Gallus gallus). The study included nine treatment groups (n~11)—no-injection (NI); H2O; 0.5% oil; normal zinc (40 mg/kg ZnSO4) (ZN); low zinc (20 mg/kg) (ZL); normal retinoid (1500 IU/kg retinyl palmitate) (RN); low retinoid (100 IU/kg) (RL); normal zinc and retinoid (40 mg/kg; 1500 IU/kg) (ZNRN); low zinc and retinoid (ZLRL) (20 mg/kg; 100 IU/kg). Samples were injected into the amniotic fluid of the fertile broiler eggs. Tissue samples were collected upon hatch to target biomarkers. ZLRL reduced ZIP4 gene expression and upregulated ZnT1 gene expression (p < 0.05). Duodenal surface area increased the greatest in RL compared to RN (p < 0.01), and ZLRL compared to ZNRN (p < 0.05). All nutrient treatments yielded shorter crypt depths (p < 0.01). Compared to the oil control, ZLRL and ZNRN reduced (p < 0.05) the cecal abundance of Bifidobacterium and Clostridium genera (p < 0.05). These results suggest a potentially improved intestinal epithelium proceeding with Zn and VA intra-amniotic administration. Intestinal functionality and gut bacteria were modulated. Further research should characterize long-term responses and the microbiome profile. [ABSTRACT FROM AUTHOR]

Longitudinal growth and puberty are the result of a complex interaction of genetic, hormonal, nutritional, and environmental factors. Acne vulgaris is a chronic disease of the pilosebaceous unit that affects 85% of adolescents worldwide. Isotretinoin is a synthetic vitamin A derivative drug effective and is widely employed for the treatment of moderate and severe acne vulgaris. Premature epiphyseal closure has been reported in patients with neuroblastoma treated with high doses of isotretinoin as well as in patients with acne receiving lower doses. Although the mechanisms for these effects are not clear, it has been suggested that isotretinoin may have a negative impact on the GH-IGF-I axis, leading to a reduction in IGF-I and IGFBP3 serum levels. Although many of the isotretinoin adverse effects in pediatric patients are transient, premature epiphyseal closure and bone abnormalities can lead to transient abnormalities and permanent deformities with a negative impact on longitudinal growth and final height. The aim of this study was to review the potential effects of oral isotretinoin on the growth plate and growth during childhood and adolescence. [ABSTRACT FROM AUTHOR]

The effects of topical non‐antibiotic acne treatment on skin microbiota have rarely been demonstrated. In the study, we randomized 45 mild acne vulgaris participants into three treatment groups, including a cream‐gel dermocosmetic containing Aqua Posae Filiformis, lipohydroxy acid, salicylic acid, linoleic acid, niacinamide and piroctone olamine (DC), retinoic acid 0.025% cream (VAA) and benzoyl peroxide 2.5% gel (BP). At months 0, 1 and 3, skin specimens were swabbed from the cheek and forehead and sequenced by targeting V3‐V4 regions of the 16 S rRNA gene. QIIME2 was used to characterize bacterial communities. Acne severity, sebum level and tolerability were assessed concomitantly in each visit. We found that both VAA and BP could significantly reduce the bacterial diversity at month 1 (p‐value = 0.010 and 0.004 respectively), while no significant reduction was observed in DC group. The microbiota compositions also significantly altered for beta diversity in all treatments (all p‐value = 0.001). An increased Cutibacterium with decreased Staphylococcus relative abundance was observed at months 1 and 3 in DC group, while an opposite trend was demonstrated in VAA and BP groups. These findings suggest a potential impact of DC, VAA and BP on the diversity and composition profiles of the skin microbiota in mild acne participants. [ABSTRACT FROM AUTHOR]

Chemotherapy with targeted drugs is the first line therapy option for acute and chronic myeloid leukemia. However, hematopoietic stem cell transplantation may be used in high‐risk patients or patients with failed responses to chemo drugs. Discovery and development of more effective new agents with lower side effects is the main aim of leukemia treatment. In this study, a novel retinoid compound with tetrahydronaphthalene ring was synthesized and evaluated for anticancer activity in human chronic and acute myeloid leukemia cell lines K562 and HL‐60. Novel N‐(1H‐indol‐1‐yl)‐5,5,8,8‐tetramethyl‐5,6,7,8‐tetrahydronaphthalene‐2‐carboxamide was synthesized based on molecular hybridization of the two different bioactive structures retinoid head and indole. The effects of the synthesized carboxamide compound, which was referred to as compound 5, were determined in K562 chronic myeloid leukemia and HL‐60 acute myeloid leukemia cell lines and L929 fibroblast cell line, which served as a control. Colorimetric MTT and caspase3 activity tests, flow cytometry, western blot, and microscopic examinations were used to evaluate biological activity. Compound 5 more effectively induced cell death in HL60 cells in comparison to K562 cells and L929 fibroblast cells. Therefore, further mechanism of cell death was investigated in HL60 cell line. It was found that compound 5 induced remarkable cytotoxicity, caspase3 activation, and PARP fragmentation in HL60 cells. Flow cytometric staining showed that the percentage of cells arrested in G0/G1 was also increased with compound 5 treatment. Important modulator proteins of cell proliferation p‐ERK, p‐AKT, and p‐m‐TOR were also found to be inhibited with compound 5 treatment. Collectively, our results reveal compound 5, which is a novel indole retinoid compound as a potential active agent for the treatment of acute promyelocytic leukemia. [ABSTRACT FROM AUTHOR]

Retinoids are defined as molecules that bind to and activate retinoic acid receptors to influence the proliferation and differentiation of cells. Topical retinoids have evolved over the past several decades, being used in multiple dermatological conditions. This review aims to differentiate between synthetic and natural retinoids, discuss the pharmacology behind topical retinoids, highlight clinical applications, and categorize all the commercially available agents, including combination products. Understanding retinoid afinities for unique receptor subtypes can impact clinical decisions, resulting in optimizing treatment and enhancing patient adherence. [ABSTRACT FROM AUTHOR]

Darier's disease (DD) is a rare autosomal dominantly inherited disorder. DD patients usually present with widespread keratotic eruptions with itching in the seborrheic regions that are exacerbated by various factors, including heat, sweat, and physical trauma. The SARS‐CoV‐2 (COVID‐19) pandemic has stirred confusion among the medical community, including dermatologists, as this infection has been implicated in various skin conditions. Only a handful of reports have documented DD associated with COVID‐19. Here, we report a 30‐year‐old male with Darier's disease whose symptoms were exacerbated following both COVID‐19 vaccination and COVID‐19 infection. The patient had noticed slight eruptions 7 years prior, but was not particularly concerned. After COVID‐19 vaccination and infection, he had erythematous maculopapular lesions in large areas of the trunk and extremities. The previously reported pathogenic variant c.2255_2257del (p.(Ile752_Tyr753delinsAsn)) in ATP2A2 was detected in the present patient. Oral etretinate greatly improved his DD manifestations. As far as we know, the present patient is the first genetically confirmed DD case who showed both COVID‐19 infection‐ and vaccination‐related DD exacerbations independently. We think that the further accumulation of DD cases exacerbated by COVID‐19 infection/vaccination is needed to clarify the mechanisms of DD aggravation. [ABSTRACT FROM AUTHOR]

Introduction/Background: Acitretin is a second-generation systemic retinoid. Its clinical applications are virtually exclusively limited to dermatology. It has anti-inflammatory, antiproliferative, and antikeratinizing effects. However, there is a lack of articles summarizing the relevant literature in a systemic way. Methods: A PubMed search was performed using keywords such as “retinoids,” “acitretin,” “etretinate,” and “retinoid embryopathy” to identify relevant original articles, case series, and case reports. Results: The most commonly used application of acitretin, a second-generation systemic retinoid is in the treatment of psoriasis. It has been used in various other dermatological disorders (keratoderma, ichthyosis, pityriasis rubra pilaris, and lichen planus) as a stand-alone therapy or may be combined with other topical and systemic agents. As the drug is not an immunosuppressive agent, hence can be given safely to patients suffering from human immunodeficiency virus and taking highly active antiretroviral therapy. The drug can be given safely in the pediatric as well as the adult population. Although adverse effects are common usually minor and self-limiting and can be managed easily without stopping the drug. The main side effects of the drug include teratogenicity, hepatotoxicity, and hyperlipidemia which should be monitored regularly. It should be avoided or used cautiously in patients taking methotrexate, cyclosporine, and corticosteroids. Conclusions: This article has discussed various uses of acitretin in dermatology, its side effect profile, indication, contraindication, and drug interactions. The drug can be administered safely and successfully with the right patient selection, progressive dose increase, careful monitoring, and appropriate patient counseling.

OBJECTIVE: The fixed-dose corticosteroid/retinoid combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) is approved for topical treatment of plaque psoriasis in adults. In addition to its current indication for plaque psoriasis, a growing body of clinical data suggests that HP/TAZ may be a beneficial therapy for palmoplantar and scalp psoriasis. Here, we discuss the efficacy and safety of HP/TAZ in various psoriatic phenotypes and related conditions. METHODS: Three studies (one post-hoc analysis, two open-label reports) of HP/TAZ were identified for this discussion. RESULTS: A post-hoc analysis demonstrated that once-daily HP/TAZ was associated with sustained efficacy and clinically meaningful quality-of-life improvements in participants with psoriatic disease who had low quality of life and 3% to 5% affected body surface area at baseline. In open-label reports, HP/TAZ was associated with improvement in scalp psoriasis measures, as well as quality of life. Additionally, HP/TAZ was efficacious in patients with palmoplantar psoriasis and in one report of a patient with palmoplantar pustulosis. LIMITATIONS: Limitations include the small sample sizes of open-label reports of HP/TAZ; larger studies are needed to confirm findings. CONCLUSION: Taken together, this evidence suggests that HP/TAZ may address unmet needs in psoriatic disease as a therapy for patients with all levels of psoriasis severity who experience daily challenges associated with their disease and that it may be a candidate for treating a variety of forms of psoriasis. [ABSTRACT FROM AUTHOR]

The variable composition of the chromophore-binding pocket in visual receptors is essential for vision. The visual phototransduction starts with the cis-trans isomerization of the retinal chromophore upon absorption of photons. Despite sharing the common 11-cis-retinal chromophore, rod and cone photoreceptors possess distinct photochemical properties. Thus, a detailed molecular characterization of the chromophore-binding pocket of these receptors is critical to understanding the differences in the photochemistry of vision between rods and cones. Unlike for rhodopsin (Rh), the crystal structures of cone opsins remain to be determined. To obtain insights into the specific chromophore-protein interactions that govern spectral tuning in human visual pigments, here we harnessed the unique binding properties of 11-cis-6-membered-ring-retinal (11-cis-6mr-retinal) with human blue, green, and red cone opsins. To unravel the specificity of the chromophore-binding pocket of cone opsins, we applied 11-cis-6mr-retinal analog-binding analyses to human blue, green, and red cone opsins. Our results revealed that among the three cone opsins, only blue cone opsin can accommodate the 11-cis-6mr-retinal in its chromophore-binding pocket, resulting in the formation of a synthetic blue pigment (B6mr) that absorbs visible light. A combination of primary sequence alignment, molecular modeling, and mutagenesis experiments revealed the specific amino acid residue 6.48 (Tyr-262 in blue cone opsins and Trp-281 in green and red cone opsins) as a selectivity filter in human cone opsins. Altogether, the results of our study uncover the molecular basis underlying the binding selectivity of 11-cis-6mr-retinal to the cone opsins.

Excessive sebum production is a factor in acne development. Tazarotene 0.045% lotion has demonstrated reductions in acne lesions and acne-induced sequelae. Evaluate efficacy, changes in skin oiliness, and safety with tazarotene 0.045% lotion in participants with moderate-to-severe acne and oily skin. In two phase 3, double-blind, 12-week studies (NCT03168321; NCT03168334), participants aged ≥ 9 years with moderate-to-severe acne were randomized 1:1 to once-daily tazarotene 0.045% lotion or vehicle lotion (N = 1614). This pooled, post hoc analysis included only participants self-categorized with oily skin at baseline on the Acne-Specific Quality of Life questionnaire item 19 (scores: 0 [extremely oily] to 6 [not at all oily]). Inflammatory/noninflammatory lesion counts, treatment success, skin oiliness, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability were evaluated. In all participants with oily skin (n = 793), tazarotene provided greater reductions in inflammatory/noninflammatory lesions (p < 0.001, both) and greater treatment success rates versus vehicle (p < 0.01) at week 12. Over two-thirds of polymeric lotion-treated participants had subjective skin oiliness reductions by week 12, with around a third reporting 'low/not' oily skin. Tazarotene TEAE rates were similar to the overall population. Once-daily treatment with tazarotene 0.045% polymeric emulsion lotion may help improve patient-perceived skin oiliness in those with moderate-to-severe acne. [ABSTRACT FROM AUTHOR]

Introduction/Background: Acitretin is a second-generation systemic retinoid. Its clinical applications are virtually exclusively limited to dermatology. It has anti-inflammatory, antiproliferative, and antikeratinizing effects. However, there is a lack of articles summarizing the relevant literature in a systemic way. Methods: A PubMed search was performed using keywords such as "retinoids," "acitretin," "etretinate," and "retinoid embryopathy" to identify relevant original articles, case series, and case reports. Results: The most commonly used application of acitretin, a second-generation systemic retinoid is in the treatment of psoriasis. It has been used in various other dermatological disorders (keratoderma, ichthyosis, pityriasis rubra pilaris, and lichen planus) as a stand-alone therapy or may be combined with other topical and systemic agents. As the drug is not an immunosuppressive agent, hence can be given safely to patients suffering from human immunodeficiency virus and taking highly active antiretroviral therapy. The drug can be given safely in the pediatric as well as the adult population. Although adverse effects are common usually minor and self-limiting and can be managed easily without stopping the drug. The main side effects of the drug include teratogenicity, hepatotoxicity, and hyperlipidemia which should be monitored regularly. It should be avoided or used cautiously in patients taking methotrexate, cyclosporine, and corticosteroids. Conclusions: This article has discussed various uses of acitretin in dermatology, its side effect profile, indication, contraindication, and drug interactions. The drug can be administered safely and successfully with the right patient selection, progressive dose increase, careful monitoring, and appropriate patient counseling. [ABSTRACT FROM AUTHOR]