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Effects of Topical Retinoids on Acne and Post-inflammatory Hyperpigmentation in Patients with Skin of Color: A Clinical Review and Implications for Practice.
Callender, VD, Baldwin, H, Cook-Bolden, FE, Alexis, AF, Stein Gold, L, Guenin, E
American journal of clinical dermatology. 2022;(1):69-81
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Abstract
Acne is a common cause for post-inflammatory hyperpigmentation (PIH), particularly in patients with skin of color (SOC), and PIH is often more distressing to patients than the acne itself. Topical retinoids are approved for the treatment of acne and for pigmentation disorders such as melasma or mottled hyperpigmentation associated with photodamage; moreover, they have been shown to reduce hyperpigmentation in patients with SOC. Therefore, treatment with topical retinoids should be started as early as possible unless contraindicated. Use of novel formulations or application of commonly recommended moisturizers may help reduce irritation. Combining retinoids with other topical agents and procedures such as superficial chemical peels can help to improve hyperpigmentation. Primary acne lesions are likely to improve weeks before PIH resolves and helping patients manage their expectations may reduce frustration. Providing clinicians and researchers with more education about the presentation and management of dermatologic conditions in patients with SOC is also recommended.
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The Transcriptional Role of Vitamin A and the Retinoid Axis in Brown Fat Function.
Herz, CT, Kiefer, FW
Frontiers in endocrinology. 2020;:608
Abstract
In recent years, brown adipose tissue (BAT) has gained significance as a metabolic organ dissipating energy through heat production. Promotion of a thermogenic program in fat holds great promise as potential therapeutic tool to counteract weight gain and related sequelae. Current research efforts are aimed at identifying novel pathways regulating brown fat function and the transformation of white adipocytes into BAT-like cells, a process called "browning." Besides numerous genetic factors some circulating molecules can act as mediators of adipose tissue thermogenesis. Vitamin A metabolites, the retinoids, are potent regulators of gene transcription through nuclear receptor signaling and are thus involved in a plethora of metabolic processes. Accumulating evidence links retinoid action to brown fat function and browning of WAT mainly via orchestrating a transcriptional BAT program in adipocytes including expression of key thermogenic genes such as uncoupling protein 1. Here we summarize the current understanding how retinoids play a role in adipose tissue thermogenesis through transcriptional control of thermogenic gene cassettes and potential non-genomic mechanisms.
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Protagonist or antagonist? The complex roles of retinoids in the regulation of hematopoietic stem cells and their specification from pluripotent stem cells.
Grace, CS, Mikkola, HKA, Dou, DR, Calvanese, V, Ronn, RE, Purton, LE
Experimental hematology. 2018;:1-16
Abstract
Hematopoietic stem cells (HSCs) are multipotent cells responsible for the maintenance of the hematopoietic system throughout life. Dysregulation of the balance in HSC self-renewal, death, and differentiation can have serious consequences such as myelodysplastic syndromes or leukemia. All-trans retinoic acid (ATRA), the biologically active metabolite of vitamin A/RA, has been shown to have pleiotropic effects on hematopoietic cells, enhancing HSC self-renewal while also increasing differentiation of more mature progenitors. Furthermore, ATRA has been shown to have key roles in regulating the specification and formation of hematopoietic cells from pluripotent stem cells including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Here, we summarize the known roles of vitamin A and RA receptors in the regulation of hematopoiesis from HSCs, ES, and iPSCs.
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New Treatment Modalities for Geographic Atrophy.
Kandasamy, R, Wickremasinghe, S, Guymer, R
Asia-Pacific journal of ophthalmology (Philadelphia, Pa.). 2017;(6):508-513
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Abstract
Age‑related macular degeneration (AMD) is a significant cause of global visual morbidity and is projected to affect 288 million people by the year 2040. The advent of treatment with anti‒vascular endothelial growth factor (anti‑VEGF) drugs has revolutionized the treatment of neovascular AMD (nAMD) but there have been no similar breakthroughs for the treatment of geographic atrophy (GA) to retard its progression. The advancements in imaging and new understanding of disease mechanisms, based on molecular and genetic models, have paved the way for the development of novel experimental treatment options for GA that aim to cater to a thus far largely unmet need. This review paper focuses on the recent clinical trials of new treatment options for slowing GA progression rates with emphasis on the agents that are currently undergoing, or have already undergone, significant clinical trial testing. Several new groups of drugs, including those targeting the complement cascade and agents considered as neuroprotective, have shown some promising results and could potentially pave the way forward in the treatment of this devastating disease.
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Retinoids and motor neuron disease: Potential role in amyotrophic lateral sclerosis.
Riancho, J, Berciano, MT, Ruiz-Soto, M, Berciano, J, Landreth, G, Lafarga, M
Journal of the neurological sciences. 2016;:115-20
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Abstract
Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons (MN). This fatal disease is characterized by progressive muscular atrophy and unfortunately it does not have an effective treatment. Although a small proportion of ALS cases have a familiar origin, the vast majority of them are thought to have a sporadic origin. Although the pathogenesis of ALS has not been fully elucidated, various disorders in different cellular functions such as gene expression, protein metabolism, axonal transport and glial cell disorders have been linked to MN degeneration. Among them, proteostasis is one of the best studied. Retinoids are vitamin A-derived substances that play a crucial role in embryogenesis, development, programmed cell death and other cellular functions. Retinoid agonists behave as transcription factors throughout the activation of the nuclear retinoid receptors. Several reports in the literature suggest that retinoids are involved in proteostasis regulation, by modulating its two major pathways, the ubiquitin-proteasome system and the autophagy-lysosome response. Additionally, there are some evidences for a role of retinoids themselves, in ALS pathogenesis. In this review, we discuss the importance of proteostasis disruption as a trigger for MN degeneration and the capability of retinoids to modulate it, as well as the potential therapeutic role of retinoids as a new therapy in ALS.
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Pathogenesis of Endometriosis: Roles of Retinoids and Inflammatory Pathways.
Taylor, RN, Kane, MA, Sidell, N
Seminars in reproductive medicine. 2015;(4):246-56
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Abstract
Endometriosis is a nonmalignant, but potentially metastatic, gynecological condition manifested by the extrauterine growth of inflammatory endometrial implants. Ten percent of reproductive-age women are affected and commonly suffer pelvic pain and/or infertility. The theories of endometriosis histogenesis remain controversial, but retrograde menstruation and metaplasia each infer mechanisms that explain the immune cell responses observed around the ectopic lesions. Recent findings from our laboratories and others suggest that retinoic acid metabolism and action are fundamentally flawed in endometriotic tissues and even generically in women with endometriosis. The focus of our ongoing research is to develop medical therapies as adjuvants or alternatives to the surgical excision of these lesions. On the basis of concepts put forward in this review, we predict that the pharmacological actions and anticipated low side-effect profiles of retinoid supplementation might provide a new treatment option for the long-term management of this chronic and debilitating gynecological disease.
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The Role of Systemic Retinoids in the Treatment of Cutaneous T-Cell Lymphoma.
Huen, AO, Kim, EJ
Dermatologic clinics. 2015;(4):715-29
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Abstract
Retinoids are natural and synthetic vitamin A analogs with effects on cell proliferation, differentiation, and apoptosis. They have significant activity in hematologic malignancies and have been studied extensively in cutaneous T-cell lymphoma. Retinoids bind to nuclear receptors and exert their effects through moderation of gene expression. Retinoic acid receptor and retinoic X receptor exert regulatory activity in vivo, binding to distinct ligands. Studies investigating systemic retinoids as monotherapy and in combination with other agents active against cutaneous lymphoma are reviewed. Side effects associated with retinoids include teratogenicity, dyslipidemias, and hypothyroidism, which should be carefully monitored in patients receiving treatment.
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Oral lichen planus: a narrative review.
Di Stasio, D, Guida, A, Salerno, C, Contaldo, M, Esposito, V, Laino, L, Serpico, R, Lucchese, A
Frontiers in bioscience (Elite edition). 2014;(2):370-6
Abstract
Oral Lichen Planus (OLP) is a common disease of unknown aetiology affecting oral mucosae by T-cell mediated chronic inflammation. OLP diagnosis is made by evaluating both clinical and histological criteria. Pharmacological treatment is useful in symptomatic cases. Life-long clinical follow-up is essential, due to low-risk of malignant transformation. In vivo Reflectance Confocal Microscopy (RCM) offers a real-time virtual biopsy of the being tissues and does not require surgical excision nor histopathological processing. RCM was used to capture OLP lesions in order to clinically differentiate them from other clinical entities.
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The use of cultured human fetal retinal pigment epithelium in studies of the classical retinoid visual cycle and retinoid-based disease processes.
Hu, J, Bok, D
Experimental eye research. 2014;:46-50
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Abstract
Human fetal retinal pigment epithelium (hfRPE), when harvested by mechanical dissection and cultured initially under low calcium conditions, will proliferate and tolerate cryopreservation for future use. Cryopreserved cells can be subsequently thawed and cultured in standard calcium and in the presence of appropriate nutrients to a high state of differentiation, allowing recapitulation of multiple in vivo functions. In this review we briefly discuss some of our previous studies of the classical retinoid visual cycle and introduce current studies in our laboratory that involve two new areas of investigation; the dynamic response of the receptor for retinol binding protein, STRA6 to the addition of holo-retinol binding protein to the culture medium and the protective complement-based response of hfRPE to the ingestion of toxic byproducts of the visual cycle. This response is studied in the context of genotyped hfRPE expressing either predisposing or protective variants of complement factor H.
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Rethinking A2E.
Smith, RT, Bernstein, PS, Curcio, CA
Investigative ophthalmology & visual science. 2013;(8):5543