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Journal of the American Academy of... May 2024Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older.
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.
Topics: Adult; Adolescent; Humans; Acne Vulgaris; Benzoyl Peroxide; Anti-Bacterial Agents; Isotretinoin; Retinoids; Dermatologic Agents
PubMed: 38300170
DOI: 10.1016/j.jaad.2023.12.017 -
Biomolecules Nov 2023The skin is the most-extensive and -abundant tissue in the human body. Like many organs, as we age, human skin experiences gradual atrophy in both the epidermis and... (Review)
Review
The skin is the most-extensive and -abundant tissue in the human body. Like many organs, as we age, human skin experiences gradual atrophy in both the epidermis and dermis. This can be primarily attributed to the diminishing population of epidermal stem cells and the reduction in collagen, which is the primary structural protein in the human body. The alterations occurring in the epidermis and dermis due to the aging process result in disruptions to the structure and functionality of the skin. This creates a microenvironment conducive to age-related skin conditions such as a compromised skin barrier, slowed wound healing, and the onset of skin cancer. This review emphasizes the recent molecular discoveries related to skin aging and evaluates preventive approaches, such as the use of topical retinoids. Topical retinoids have demonstrated promise in enhancing skin texture, diminishing fine lines, and augmenting the thickness of both the epidermal and dermal layers.
Topics: Humans; Vitamin A; Skin Aging; Skin; Retinoids; Aging
PubMed: 38002296
DOI: 10.3390/biom13111614 -
Marine Drugs Sep 2023Astaxanthin (AX), a lipid-soluble pigment belonging to the xanthophyll carotenoids family, has recently garnered significant attention due to its unique physical... (Review)
Review
Astaxanthin (AX), a lipid-soluble pigment belonging to the xanthophyll carotenoids family, has recently garnered significant attention due to its unique physical properties, biochemical attributes, and physiological effects. Originally recognized primarily for its role in imparting the characteristic red-pink color to various organisms, AX is currently experiencing a surge in interest and research. The growing body of literature in this field predominantly focuses on AXs distinctive bioactivities and properties. However, the potential of algae-derived AX as a solution to various global environmental and societal challenges that threaten life on our planet has not received extensive attention. Furthermore, the historical context and the role of AX in nature, as well as its significance in diverse cultures and traditional health practices, have not been comprehensively explored in previous works. This review article embarks on a comprehensive journey through the history leading up to the present, offering insights into the discovery of AX, its chemical and physical attributes, distribution in organisms, and biosynthesis. Additionally, it delves into the intricate realm of health benefits, biofunctional characteristics, and the current market status of AX. By encompassing these multifaceted aspects, this review aims to provide readers with a more profound understanding and a robust foundation for future scientific endeavors directed at addressing societal needs for sustainable nutritional and medicinal solutions. An updated summary of AXs health benefits, its present market status, and potential future applications are also included for a well-rounded perspective.
Topics: Xanthophylls; Antioxidants
PubMed: 37888449
DOI: 10.3390/md21100514 -
Drug Design, Development and Therapy 2023In 1982, the Food and Drug Administration (FDA) of the United States of America approved isotretinoin (13-cis-retinoic acid), a retinoid derivative of vitamin A, to... (Review)
Review
In 1982, the Food and Drug Administration (FDA) of the United States of America approved isotretinoin (13-cis-retinoic acid), a retinoid derivative of vitamin A, to treat severe recalcitrant acne vulgaris. Apart from its prescribed use for severe acne, evidence suggests that isotretinoin is commonly used off-label to treat mild-to-moderate acne, inflammatory skin conditions, genodermatoses, skin cancer, and other skin disorders. This is due to its anti-inflammatory, immunomodulatory, and antineoplastic properties. Some "off-label" use is successful, while others are ineffective. Therefore, this information is essential to clinicians for deciding on the appropriate use of isotretinoin. In this article, we aim to review the most updated evidence-based data about the use of oral isotretinoin in dermatology.
Topics: United States; Humans; Isotretinoin; Dermatology; Acne Vulgaris; Retinoids; Skin Neoplasms
PubMed: 37649956
DOI: 10.2147/DDDT.S427530 -
Nature Nov 2023Decades of previous efforts to develop renal-sparing polyene antifungals were misguided by the classic membrane permeabilization model. Recently, the clinically vital...
Decades of previous efforts to develop renal-sparing polyene antifungals were misguided by the classic membrane permeabilization model. Recently, the clinically vital but also highly renal-toxic small-molecule natural product amphotericin B was instead found to kill fungi primarily by forming extramembraneous sponge-like aggregates that extract ergosterol from lipid bilayers. Here we show that rapid and selective extraction of fungal ergosterol can yield potent and renal-sparing polyene antifungals. Cholesterol extraction was found to drive the toxicity of amphotericin B to human renal cells. Our examination of high-resolution structures of amphotericin B sponges in sterol-free and sterol-bound states guided us to a promising structural derivative that does not bind cholesterol and is thus renal sparing. This derivative was also less potent because it extracts ergosterol more slowly. Selective acceleration of ergosterol extraction with a second structural modification yielded a new polyene, AM-2-19, that is renal sparing in mice and primary human renal cells, potent against hundreds of pathogenic fungal strains, resistance evasive following serial passage in vitro and highly efficacious in animal models of invasive fungal infections. Thus, rational tuning of the dynamics of interactions between small molecules may lead to better treatments for fungal infections that still kill millions of people annually and potentially other resistance-evasive antimicrobials, including those that have recently been shown to operate through supramolecular structures that target specific lipids.
Topics: Animals; Humans; Mice; Amphotericin B; Antifungal Agents; Cells, Cultured; Cholesterol; Drug Resistance, Fungal; Ergosterol; Kidney; Kinetics; Microbial Sensitivity Tests; Mycoses; Polyenes; Serial Passage; Sterols; Time Factors
PubMed: 37938782
DOI: 10.1038/s41586-023-06710-4 -
The Cochrane Database of Systematic... Sep 2023Age-related macular degeneration (AMD) is a degenerative condition of the back of the eye that occurs in people over the age of 50 years. Antioxidants may prevent... (Review)
Review
BACKGROUND
Age-related macular degeneration (AMD) is a degenerative condition of the back of the eye that occurs in people over the age of 50 years. Antioxidants may prevent cellular damage in the retina by reacting with free radicals that are produced in the process of light absorption. Higher dietary levels of antioxidant vitamins and minerals may reduce the risk of progression of AMD. This is the third update of the review.
OBJECTIVES
To assess the effects of antioxidant vitamin and mineral supplements on the progression of AMD in people with AMD.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, one other database, and three trials registers, most recently on 29 November 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared antioxidant vitamin or mineral supplementation to placebo or no intervention, in people with AMD.
DATA COLLECTION AND ANALYSIS
We used standard methods expected by Cochrane.
MAIN RESULTS
We included 26 studies conducted in the USA, Europe, China, and Australia. These studies enroled 11,952 people aged 65 to 75 years and included slightly more women (on average 56% women). We judged the studies that contributed data to the review to be at low or unclear risk of bias. Thirteen studies compared multivitamins with control in people with early and intermediate AMD. Most evidence came from the Age-Related Eye Disease Study (AREDS) in the USA. People taking antioxidant vitamins were less likely to progress to late AMD (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.58 to 0.90; 3 studies, 2445 participants; moderate-certainty evidence). In people with early AMD, who are at low risk of progression, this means there would be approximately four fewer cases of progression to late AMD for every 1000 people taking vitamins (one fewer to six fewer cases). In people with intermediate AMD at higher risk of progression, this corresponds to approximately 78 fewer cases of progression for every 1000 people taking vitamins (26 fewer to 126 fewer). AREDS also provided evidence of a lower risk of progression for both neovascular AMD (OR 0.62, 95% CI 0.47 to 0.82; moderate-certainty evidence) and geographic atrophy (OR 0.75, 95% CI 0.51 to 1.10; moderate-certainty evidence), and a lower risk of losing 3 or more lines of visual acuity (OR 0.77, 95% CI 0.62 to 0.96; moderate-certainty evidence). Low-certainty evidence from one study of 110 people suggested higher quality of life scores (measured with the Visual Function Questionnaire) in treated compared with non-treated people after 24 months (mean difference (MD) 12.30, 95% CI 4.24 to 20.36). In exploratory subgroup analyses in the follow-on study to AREDS (AREDS2), replacing beta-carotene with lutein/zeaxanthin gave hazard ratios (HR) of 0.82 (95% CI 0.69 to 0.96), 0.78 (95% CI 0.64 to 0.94), 0.94 (95% CI 0.70 to 1.26), and 0.88 (95% CI 0.75 to 1.03) for progression to late AMD, neovascular AMD, geographic atrophy, and vision loss, respectively. Six studies compared lutein (with or without zeaxanthin) with placebo and one study compared a multivitamin including lutein/zeaxanthin with multivitamin alone. The duration of supplementation and follow-up ranged from six months to five years. Most evidence came from the AREDS2 study in the USA; almost all participants in AREDS2 also took the original AREDS supplementation formula. People taking lutein/zeaxanthin may have similar or slightly reduced risk of progression to late AMD (RR 0.94, 95% CI 0.87 to 1.01), neovascular AMD (RR 0.92, 95% CI 0.84 to 1.02), and geographic atrophy (RR 0.92, 95% CI 0.80 to 1.05) compared with control (1 study, 4176 participants, 6891 eyes; low-certainty evidence). A similar risk of progression to visual loss of 15 or more letters was seen in the lutein/zeaxanthin and control groups (RR 0.98, 95% CI 0.91 to 1.05; 6656 eyes; low-certainty evidence). Quality of life (Visual Function Questionnaire) was similar between groups (MD 1.21, 95% CI -2.59 to 5.01; 2 studies, 308 participants; moderate-certainty evidence). One study in Australia randomised 1204 people to vitamin E or placebo with four years of follow-up; 19% of participants had AMD. The number of late AMD events was low (N = 7) and the estimate of effect was uncertain (RR 1.36, 95% CI 0.31 to 6.05; very low-certainty evidence). There was no evidence of any effect of treatment on visual loss (RR 1.04, 95% CI 0.74 to 1.47; low-certainty evidence). There were no data on neovascular AMD, geographic atrophy, or quality of life. Five studies compared zinc with placebo. Evidence largely drawn from the largest study (AREDS) found a lower progression to late AMD over six years (OR 0.83, 95% CI 0.70 to 0.98; 3 studies, 3790 participants; moderate-certainty evidence), neovascular AMD (OR 0.76, 95% CI 0.62 to 0.93; moderate-certainty evidence), geographic atrophy (OR 0.84, 95% CI 0.64 to 1.10; moderate-certainty evidence), or visual loss (OR 0.87, 95% CI 0.75 to 1.00; 2 studies, 3791 participants; moderate-certainty evidence). There were no data on quality of life. Gastrointestinal symptoms were the main reported adverse effect. In AREDS, zinc was associated with a higher risk of genitourinary problems in men, but no difference was seen between high- and low-dose zinc groups in AREDS2. Most studies were too small to detect rare adverse effects. Data from larger studies (AREDS/AREDS2) suggested there may be little or no effect on mortality with multivitamin (HR 0.87, 95% CI 0.60 to 1.25; low-certainty evidence) or lutein/zeaxanthin supplementation (HR 1.06, 95% CI 0.87 to 1.31; very low-certainty evidence), but confirmed the increased risk of lung cancer with beta-carotene, mostly in former smokers.
AUTHORS' CONCLUSIONS
Moderate-certainty evidence suggests that antioxidant vitamin and mineral supplementation (AREDS: vitamin C, E, beta-carotene, and zinc) probably slows down progression to late AMD. People with intermediate AMD have a higher chance of benefiting from antioxidant supplements because their risk of progression is higher than people with early AMD. Although low-certainty evidence suggested little effect with lutein/zeaxanthin alone compared with placebo, exploratory subgroup analyses from one large American study support the view that lutein/zeaxanthin may be a suitable replacement for the beta-carotene used in the original AREDS formula.
Topics: Male; Female; Humans; Antioxidants; Vitamins; Geographic Atrophy; beta Carotene; Lutein; Zeaxanthins; Minerals; Dietary Supplements; Macular Degeneration; Vitamin A; Vitamin K; Zinc; Malnutrition
PubMed: 37702300
DOI: 10.1002/14651858.CD000254.pub5 -
Cancer Research Jul 2023Ferroptosis is an iron-dependent form of regulated cell death induced by the lethal overload of lipid peroxides in cellular membranes. In recent years, modulating...
UNLABELLED
Ferroptosis is an iron-dependent form of regulated cell death induced by the lethal overload of lipid peroxides in cellular membranes. In recent years, modulating ferroptosis has gained attention as a potential therapeutic approach for tumor suppression. In the current study, retinol saturase (RETSAT) was identified as a significant ferroptosis mediator using a publicly accessible CRISPR/Cas9 screening dataset. RETSAT depletion protected tumor cells from lipid peroxidation and subsequent cell death triggered by various ferroptosis inducers. Furthermore, exogenous supplementation with retinoids, including retinol (the substrate of RETSAT) and its derivatives retinal and retinoic acid, also suppressed ferroptosis, whereas the product of RETSAT, 13, 14-dihydroretinol, failed to do so. As effective radical-trapping antioxidant, retinoids protected the lipid membrane from autoxidation and subsequent fragmentation, thus terminating the cascade of ferroptosis. Pseudotargeted lipidomic analysis identified an association between retinoid regulation of ferroptosis and lipid metabolism. Retinoic acid, but not 13, 14-dihydroretinoic acid, interacted with its nuclear receptor and activated transcription of stearoyl-CoA desaturase, which introduces the first double bond into saturated fatty acid and thus catalyzes the generation of monounsaturated fatty acid, a known ferroptosis suppressor. Therefore, RETSAT promotes ferroptosis by transforming retinol to 13, 14-dihydroretinol, thereby turning a strong anti-ferroptosis regulator into a relatively weak one.
SIGNIFICANCE
Retinoids have ferroptosis-protective properties and can be metabolized by RETSAT to promote ferroptosis, suggesting the possibility of targeting retinoid metabolism in cancer as a treatment strategy to trigger ferroptosis.
Topics: Humans; Vitamin A; Retinoids; Tretinoin; Ferroptosis; Lipid Metabolism; Neoplasms
PubMed: 37184371
DOI: 10.1158/0008-5472.CAN-22-3977 -
Journal of Nanobiotechnology Aug 2023Gene therapy holds great promise for treating a multitude of inherited and acquired diseases by delivering functional genes, comprising DNA or RNA, into targeted cells... (Review)
Review
Gene therapy holds great promise for treating a multitude of inherited and acquired diseases by delivering functional genes, comprising DNA or RNA, into targeted cells or tissues to elicit manipulation of gene expression. However, the clinical implementation of gene therapy remains substantially impeded by the lack of safe and efficient gene delivery vehicles. This review comprehensively outlines the novel fastest-growing and efficient non-viral gene delivery vectors, which include liposomes and lipid nanoparticles (LNPs), highly branched poly(β-amino ester) (HPAE), single-chain cyclic polymer (SCKP), poly(amidoamine) (PAMAM) dendrimers, and polyethyleneimine (PEI). Particularly, we discuss the research progress, potential development directions, and remaining challenges. Additionally, we provide a comprehensive overview of the currently approved non-viral gene therapeutics, as well as ongoing clinical trials. With advances in biomedicine, molecular biology, materials science, non-viral gene vectors play an ever-expanding and noteworthy role in clinical gene therapy.
Topics: Genetic Therapy; Esters; Polyethyleneimine; Polymers; RNA
PubMed: 37592351
DOI: 10.1186/s12951-023-02044-5 -
Biomedicine & Pharmacotherapy =... Aug 2023Vitamin A (retinol) is a lipid-soluble vitamin that acts as a precursor for several bioactive compounds, such as retinaldehyde (retinal) and isomers of retinoic acid....
Vitamin A (retinol) is a lipid-soluble vitamin that acts as a precursor for several bioactive compounds, such as retinaldehyde (retinal) and isomers of retinoic acid. Retinol and all-trans-retinoic acid (atRA) penetrate the blood-brain barrier and are reported to be neuroprotective in several animal models. We characterised the impact of retinol and its metabolites, all-trans-retinal (atRAL) and atRA, on ferroptosis-a programmed cell death caused by iron-dependent phospholipid peroxidation. Ferroptosis was induced by erastin, buthionine sulfoximine or RSL3 in neuronal and non-neuronal cell lines. We found that retinol, atRAL and atRA inhibited ferroptosis with a potency superior to α-tocopherol, the canonical anti-ferroptotic vitamin. In contrast, we found that antagonism of endogenous retinol with anhydroretinol sensitises ferroptosis induced in neuronal and non-neuronal cell lines. Retinol and its metabolites atRAL and atRA directly interdict lipid radicals in ferroptosis since these compounds displayed radical trapping properties in a cell-free assay. Vitamin A, therefore, complements other anti-ferroptotic vitamins, E and K; metabolites of vitamin A, or agents that alter their levels, may be potential therapeutics for diseases where ferroptosis is implicated.
Topics: Animals; Vitamin A; Ferroptosis; Lipid Peroxidation; Tretinoin; Vitamins; Retinaldehyde; Lipids
PubMed: 37236031
DOI: 10.1016/j.biopha.2023.114930 -
Pharmacology & Therapeutics Aug 2023Vitamin A (VA, retinol) and its metabolites (commonly called retinoids) are required for the proper development of the kidney during embryogenesis, but retinoids also... (Review)
Review
Vitamin A (VA, retinol) and its metabolites (commonly called retinoids) are required for the proper development of the kidney during embryogenesis, but retinoids also play key roles in the function and repair of the kidney in adults. Kidneys filter 180-200 liters of blood per day and each kidney contains approximately 1 million nephrons, which are often referred to as the 'functional units' of the kidney. Each nephron consists of a glomerulus and a series of tubules (proximal tubule, loop of Henle, distal tubule, and collecting duct) surrounded by a network of capillaries. VA is stored in the liver and converted to active metabolites, most notably retinoic acid (RA), which acts as an agonist for the retinoic acid receptors ((RARs α, β, and γ) to regulate gene transcription. In this review we discuss some of the actions of retinoids in the kidney after injury. For example, in an ischemia-reperfusion model in mice, injury-associated loss of proximal tubule (PT) differentiation markers occurs, followed by re-expression of these differentiation markers during PT repair. Notably, healthy proximal tubules express ALDH1a2, the enzyme that metabolizes retinaldehyde to RA, but transiently lose ALDH1a2 expression after injury, while nearby myofibroblasts transiently acquire RA-producing capabilities after injury. These results indicate that RA is important for renal tubular injury repair and that compensatory mechanisms exist for the generation of endogenous RA by other cell types upon proximal tubule injury. ALDH1a2 levels also increase in podocytes, epithelial cells of the glomeruli, after injury, and RA promotes podocyte differentiation. We also review the ability of exogenous, pharmacological doses of RA and receptor selective retinoids to treat numerous kidney diseases, including kidney cancer and diabetic kidney disease, and the emerging genetic evidence for the importance of retinoids and their receptors in maintaining or restoring kidney function after injury. In general, RA has a protective effect on the kidney after various types of injuries (eg. ischemia, cytotoxic actions of chemicals, hyperglycemia related to diabetes). As more research into the actions of each of the three RARs in the kidney is carried out, a greater understanding of the actions of vitamin A is likely to lead to new insights into the pathology of kidney disorders and the development of new therapies for kidney diseases.
Topics: Vitamin A; Kidney; Retinoids; Receptors, Retinoic Acid; Tretinoin; Kidney Diseases
PubMed: 37331524
DOI: 10.1016/j.pharmthera.2023.108481