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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 -
Journal of Cutaneous Medicine and... 2023Topical retinoids have an essential role in treatment of acne. Trifarotene, a topical retinoid selective for retinoic acid receptor (RAR) γ, is the most recent retinoid... (Review)
Review
Topical retinoids have an essential role in treatment of acne. Trifarotene, a topical retinoid selective for retinoic acid receptor (RAR) γ, is the most recent retinoid approved for treatment of acne. RAR-γ is the most common isoform of RARs in skin, and the strong selectivity of trifarotene for RAR-γ translates to efficacy in low concentration. Trifarotene, like other topical retinoids, acts by increasing keratinocyte differentiation and decreasing proliferation, which reduces hyperkeratinization. Retinoids have also been shown to inhibit inflammatory pathways via effects on leukocyte migration, toll-like receptors, and Activator Protein (AP)-1. Large-scale randomized, controlled clinical trials have demonstrated trifarotene to be safe, well tolerated, and efficacious in reducing both comedones and papules/pustules of acne. However, unlike all other retinoids, trifarotene is the first topical retinoid with rigorous clinical data on safety and efficacy in truncal acne. Data supporting use of trifarotene to manage acne are reviewed in this publication.
Topics: Humans; Dermatologic Agents; Administration, Cutaneous; Retinoids; Acne Vulgaris
PubMed: 36927117
DOI: 10.1177/12034754231163542 -
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 -
Cells Nov 2023This review on acne transcriptomics allows for deeper insights into the pathogenesis of acne and isotretinoin's mode of action. Puberty-induced insulin-like growth... (Review)
Review
This review on acne transcriptomics allows for deeper insights into the pathogenesis of acne and isotretinoin's mode of action. Puberty-induced insulin-like growth factor 1 (IGF-1), insulin and androgen signaling activate the kinase AKT and mechanistic target of rapamycin complex 1 (mTORC1). A Western diet (hyperglycemic carbohydrates and milk/dairy products) also co-stimulates AKT/mTORC1 signaling. The AKT-mediated phosphorylation of nuclear FoxO1 and FoxO3 results in their extrusion into the cytoplasm, a critical switch which enhances the transactivation of lipogenic and proinflammatory transcription factors, including androgen receptor (AR), sterol regulatory element-binding transcription factor 1 (SREBF1), peroxisome proliferator-activated receptor γ (PPARγ) and signal transducer and activator of transcription 3 (STAT3), but reduces the FoxO1-dependent expression of GATA binding protein 6 (GATA6), the key transcription factor for infundibular keratinocyte homeostasis. The AKT-mediated phosphorylation of the p53-binding protein MDM2 promotes the degradation of p53. In contrast, isotretinoin enhances the expression of p53, FoxO1 and FoxO3 in the sebaceous glands of acne patients. The overexpression of these proapoptotic transcription factors explains isotretinoin's desirable sebum-suppressive effect via the induction of sebocyte apoptosis and the depletion of BLIMP1(+) sebocyte progenitor cells; it also explains its adverse effects, including teratogenicity (neural crest cell apoptosis), a reduced ovarian reserve (granulosa cell apoptosis), the risk of depression (the apoptosis of hypothalamic neurons), VLDL hyperlipidemia, intracranial hypertension and dry skin.
Topics: Humans; Isotretinoin; Proto-Oncogene Proteins c-akt; Tumor Suppressor Protein p53; Transcriptome; Acne Vulgaris; Mechanistic Target of Rapamycin Complex 1; Transcription Factors
PubMed: 37998335
DOI: 10.3390/cells12222600 -
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 -
Annals of Family Medicine 2023Acne is an extremely common skin disease with an estimated global prevalence of 9.4%. We aim to provide comprehensive comparisons of the common pharmacological... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Acne is an extremely common skin disease with an estimated global prevalence of 9.4%. We aim to provide comprehensive comparisons of the common pharmacological treatments for acne.
METHODS
Randomized controlled trials comparing the efficacy of pharmacological therapies for acne vulgaris in patients of any age and sex and with a treatment duration of >2 weeks were included. PubMed and Embase databases were searched from inception until February 2022. Our prespecified primary end points were mean percentage reduction in total, inflammatory, and noninflammatory lesions. Treatment ranking was determined by values.
RESULTS
There were 210 articles describing 221 trials and 37 interventions included in the analysis. Our primary analysis of percentage reduction in total lesion count had 65,601 patients enrolled. Across all trials, the mean age was 20.4 years. The median duration of treatment was 12 weeks. The median total, inflammatory, and noninflammatory lesion counts were 72, 27, and 44, respectively. The most effective treatment was oral isotretinoin (mean difference [MD] = 48.41; = 1.00), followed by triple therapy containing a topical antibiotic, a topical retinoid, and benzoyl peroxide (BPO) (MD = 38.15; = .95) and by triple therapy containing an oral antibiotic, a topical retinoid, and BPO (MD = 34.83; = .90). For monotherapies, oral or topical antibiotics or topical retinoids have comparable efficacy for inflammatory lesions, while oral or topical antibiotics have less effect on noninflammatory lesions.
CONCLUSION
The most effective treatment for acne is oral isotretinoin, followed by triple therapies containing a topical retinoid, BPO, and an antibiotic. We present detailed comparisons of each intervention to serve as a practical database.
Topics: Humans; Young Adult; Adult; Dermatologic Agents; Isotretinoin; Network Meta-Analysis; Randomized Controlled Trials as Topic; Acne Vulgaris; Anti-Bacterial Agents; Retinoids; Treatment Outcome
PubMed: 37487721
DOI: 10.1370/afm.2995 -
Journal of Advanced Research Jul 2023Environmental microparticle is becoming a global pollutant and the entire population is increasingly exposed to the microparticles from artificial materials. The...
INTRODUCTION
Environmental microparticle is becoming a global pollutant and the entire population is increasingly exposed to the microparticles from artificial materials. The accumulation of microparticles including microplastics and its subsequent effects need to be investigated timely to keep sustainable development of human society.
OBJECTIVES
This study aimed to explore the accumulation of environmental particles in thrombus, the pathological structure in the blood circulation system.
METHODS
Patients receiving cardiovascular surgical operations were screened and twenty-six thrombi were collected, digested and filtered. Non-soluble microparticles were enriched on the filter membrane and then were analyzed and identified with Raman Spectrometer. The associations of particle status (presence or absence) or particle number in the thrombus and clinical indicators were examined. One strict quality control-particle detection system was designed to eliminate environmental contaminations.
RESULTS
Among twenty-six thrombi, sixteen contained eighty-seven identified particles ranging from 2.1 to 26.0 μm in size. The number of microparticles in each thrombus ranged from one to fifteen with the median reaching five. All the particles found in thrombi were irregularly block-shaped. Totally, twenty-one phthalocyanine particles, one Hostasol-Green particle, and one low-density polyethylene microplastic, which were from synthetic materials, were identified in thrombi. The rest microparticles included iron compounds and metallic oxides. After the adjustment for potential confounders, a significantly positive association between microparticle number and blood platelet levels was detected (P < 0.01).
CONCLUSION
This study provides the first photograph and Raman spectrum evidence of microparticles in thrombi. A large number of non-soluble particles including synthetic material microparticles could accumulate in arteries, suggesting that the risk of microparticle exposure was under-estimated and the re-evaluation of its health effects is urgently needed. There will be a series of reports on assessing the health effects of microparticle exposure in humans in the future and this research provided clues for the subsequent research.
Topics: Humans; Microplastics; Plastics; Thrombosis; Blood Platelets; Polyethylene
PubMed: 36116710
DOI: 10.1016/j.jare.2022.09.004 -
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 -
Danish Medical Journal Jun 2023Lipids are essential in human physiology, triglycerides for energy and cholesterol as a structural component in cells and as a precurser for hormones and vitamins....
Lipids are essential in human physiology, triglycerides for energy and cholesterol as a structural component in cells and as a precurser for hormones and vitamins. However, high blood levels of cholesterol cause atherosclerosis, leading to cardiovascular disease, which is the number one cause of death globally. Genetic evidence suggests that lipoprotein(a) and remnant cholesterol, cholesterol in very low-density and intermediate-density lipoproteins, are causally involved in the development of cardiovascular disease together with low-density lipoproteins and this has spurred the development of drugs potently lowering these.
Topics: Humans; Cardiovascular Diseases; Lipoproteins; Atherosclerosis; Triglycerides; Vitamin A
PubMed: 37381868
DOI: No ID Found