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Cell Host & Microbe Jun 2024Cutibacterium acnes is the most abundant bacterium of the human skin microbiome since adolescence, participating in both skin homeostasis and diseases. Here, we...
Cutibacterium acnes is the most abundant bacterium of the human skin microbiome since adolescence, participating in both skin homeostasis and diseases. Here, we demonstrate individual and niche heterogeneity of C. acnes from 1,234 isolate genomes. Skin disease (atopic dermatitis and acne) and body site shape genomic differences of C. acnes, stemming from horizontal gene transfer and selection pressure. C. acnes harbors characteristic metabolic functions, fewer antibiotic resistance genes and virulence factors, and a more stable genome compared with Staphylococcus epidermidis. Integrated genome, transcriptome, and metabolome analysis at the strain level unveils the functional characteristics of C. acnes. Consistent with the transcriptome signature, C. acnes in a sebum-rich environment induces toxic and pro-inflammatory effects on keratinocytes. L-carnosine, an anti-oxidative stress metabolite, is up-regulated in the C. acnes metabolome from atopic dermatitis and attenuates skin inflammation. Collectively, our study reveals the joint impact of genes and the microenvironment on C. acnes function.
PubMed: 38936370
DOI: 10.1016/j.chom.2024.06.002 -
Archives of Dermatological Research Jun 2024
Review
Topics: Humans; Hidradenitis Suppurativa; Trisomy 13 Syndrome
PubMed: 38935334
DOI: 10.1007/s00403-024-03196-6 -
Pharmaceutics Jun 2024The high prevalence of acne, which affects nearly 85% of adolescents and young adults, underscores the importance of exploring new therapeutic solutions. The aim of the...
The high prevalence of acne, which affects nearly 85% of adolescents and young adults, underscores the importance of exploring new therapeutic solutions. The aim of the present study was to design a stable hydrogel formulation containing tetracycline hydrochloride (TC) in the presence of ethanol at various concentration levels. The antibiotic stability was assessed over a period of 84 days using the HPLC method. The rheological properties of the formulations and their microbiological activity were also evaluated. Hydrogels without ethanol and those containing 5% and 25% alcohol showed similar rheological properties and high stability of the antibiotic throughout the observation period. The formulation with the highest ethanol content of 50% differed significantly from the others in terms of rheological properties. Although the flow and viscosity curves were like those of the other formulations, the viscosity values were significantly lower. The stability of tetracycline in this formulation was also significantly lower, and by the 84th day of observation, the concentration of the drug had decreased to almost 45% of its initial content. The formulations containing the highest concentration of ethanol displayed the highest activity against the biofilm of the acne-causing agent, . The study demonstrated the possibility of developing stable and antimicrobial effective hydrogel formulations with tetracycline and ethanol as a substance enhancing drug penetration into the hair follicles.
PubMed: 38931950
DOI: 10.3390/pharmaceutics16060830 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Acne vulgaris is a common disease, which occurs in adolescents as well as adults and has a significant influence on the patient's quality of life (QoL) in every aspect.... (Review)
Review
Acne vulgaris is a common disease, which occurs in adolescents as well as adults and has a significant influence on the patient's quality of life (QoL) in every aspect. Due to resistance to standard therapies, it has become necessary to prospect for new treatment strategies. It is important to highlight that the diagnosis and treatment of the underlying cause of acne such as metabolic and hormonal disorders may significantly improve the effectiveness of acne treatment. The correlation between Insulin Resistance (IR) and acne has been proven. Both disorders share many common occurrence factors and activation pathways. Metformin, an antihyperglycemic agent, seems to be a possible therapy option, not only because of its insulin sensitizing ability but also via plenty of additional effects of this medicine. While the efficiency of metformin therapy in patients with acne and Polycystic Ovary Syndrome (PCOS) is well explored, it is still necessary to evaluate it in patients without any endocrinopathies. This meta-analysis aimed to estimate the effectiveness of oral metformin as a monotherapy in acne patients without PCOS or other endocrinopathies. Study selection was performed with included criteria such as no PCOS and other endocrinopathies diagnosed, oral administration of metformin, and metformin in monotherapy. Selected studies contained comparisons in the Global Acne Grading System (GAGS) before and after metformin therapy. Statistical analysis detected significant improvement in skin condition after treatment with metformin.
PubMed: 38931395
DOI: 10.3390/ph17060728 -
Pharmaceuticals (Basel, Switzerland) May 2024The aim of this review is to present the potential application of camphor-a bicyclic monoterpene ketone-in the prevention of skin infections. Skin diseases represent a... (Review)
Review
The aim of this review is to present the potential application of camphor-a bicyclic monoterpene ketone-in the prevention of skin infections. Skin diseases represent a heterogeneous group of disorders characterized by prolonged symptoms that significantly diminish the quality of life. They affect the dermis, the epidermis, and even subcutaneous tissue. They very often have a bacterial or fungal background. Therapy for dermatological skin disorders is difficult and long-term. Therefore, it is important to find a compound, preferably of natural origin, that (i) prevents the initiation of this infection and (ii) supports the skin's repair process. Based on its documented anti-inflammatory, antibacterial, antifungal, anti-acne, anesthetic, strengthening, and warming properties, camphor can be used as a preventative measure in dermatological infectious diseases and as a component in medical and cosmetic products. This work discusses the structure and physicochemical properties of camphor, its occurrence, and methods of obtaining it from natural sources as well as through chemical synthesis. The use of camphor in industrial preparations is also presented. Additionally, after a detailed review of the literature, the metabolism of camphor, its interactions with other medicinal substances, and its antimicrobial properties against bacteria and fungi involved in skin diseases are discussed with regard to their resistance.
PubMed: 38931382
DOI: 10.3390/ph17060715 -
Life (Basel, Switzerland) May 2024The imbalance of skin microbiota in acne can induce changes leading to induction or to aggravation of chronic inflammatory lesions; complex mechanisms are involved. (...
BACKGROUND
The imbalance of skin microbiota in acne can induce changes leading to induction or to aggravation of chronic inflammatory lesions; complex mechanisms are involved. ( ribotypes RT4 and RT5 express more biofilm and are associated with inflammatory acne lesions. RT6 is a non-acne ribotype, beneficial for the skin.
OBJECTIVES
In an open clinical trial, acne adults were included and assessed clinically at baseline and at month 2 using the Investigator Global Assessment of Acne (IGA) score. A topical emulsion was applied twice daily for 2 months (M2) in each included patient. In the same series of acne patients, skin swab samples were collected from acne patients at baseline and M2 from lesional and non-lesional skin; skin swabs were collected for the metagenomic long-read analysis of microbiota.
MATERIALS AND METHODS
Acne patients with a gravity score IGA of >1<3 were included in this pilot study. An emulsion of O/W formulated with vegetal extract of associated with a polysaccharide at 1% was applied twice daily for 2 months. At baseline and M2 clinical assessments were made; skin swab samples were also taken for microbiota analysis from lesional and non-lesional skin in each included patient. Extractions of genomic DNA (gDNA) from swab samples from baseline and from M2 were made, followed by full-length (V1-V9) amplification of the 16S rDNA and sequencing of amplicon libraries for strain-level bacterial community profiling.
RESULTS
In a series of 32 adult acne patients, the mean initial IGA scale was 3.1; at M2 the IGA scale was 1.5 ( < 0.001). The mean decrease in acne lesions was by 63%. Microbiome metagenomic long-read analysis in these series was mainly dominated by followed by (. The density of ribotypes RT6 (non-acne strain) was increased at M2 compared to baseline and the density of ribotypes RT1 to RT5 was decreased at M2, compared to baseline ( < 0.0001). ribotypes (1 to 36) were non significantly increased at M2, compared to baseline ( < 0.1).
CONCLUSIONS
In a series of 32 acne patients that applied an emulsion based on vegetal extract of and a polysaccharide at 1% twice daily, a significant clinical improvement in IGA scale for acne lesions was seen at M2, compared to baseline ( < 0.0001). The clinical improvement was correlated with an improvement in skin microbiome at M2 compared to baseline, indicated by the increase in the relative abundance of non-acne strain of ribotype 6 and of the decrease in the relative abundance of acne strains ribotypes RT1 to RT5.
PubMed: 38929671
DOI: 10.3390/life14060688 -
International Journal of Molecular... Jun 2024All- retinoic acid (ATRA), the major active metabolite of all- retinol (vitamin A), is a key hormonal signaling molecule. In the adult organism, ATRA has a widespread... (Review)
Review
All- retinoic acid (ATRA), the major active metabolite of all- retinol (vitamin A), is a key hormonal signaling molecule. In the adult organism, ATRA has a widespread influence on processes that are crucial to the growth and differentiation of cells and, in turn, the acquisition of mature cell functions. Therefore, there is considerable potential in the use of retinoids to treat diseases. ATRA binds to the retinoic acid receptors (RAR) which, as activated by ATRA, selectively regulate gene expression. There are three main RAR isoforms, RARα, RARβ, and RARγ. They each have a distinct role, for example, RARα and RARγ regulate myeloid progenitor cell differentiation and hematopoietic stem cell maintenance, respectively. Hence, targeting an isoform is crucial to developing retinoid-based therapeutics. In principle, this is exemplified when ATRA is used to treat acute promyelocytic leukemia (PML) and target RARα within PML-RARα oncogenic fusion protein. ATRA with arsenic trioxide has provided a cure for the once highly fatal leukemia. Recent in vitro and in vivo studies of RARγ have revealed the potential use of agonists and antagonists to treat diseases as diverse as cancer, heterotopic ossification, psoriasis, and acne. During the final drug development there may be a need to design newer compounds with added modifications to improve solubility, pharmacokinetics, or potency. At the same time, it is important to retain isotype specificity and activity. Examination of the molecular interactions between RARγ agonists and the ligand binding domain of RARγ has revealed aspects to ligand binding that are crucial to RARγ selectivity and compound activity and key to designing newer compounds.
Topics: Humans; Retinoic Acid Receptor gamma; Receptors, Retinoic Acid; Animals; Tretinoin; Protein Binding; Leukemia, Promyelocytic, Acute; Antineoplastic Agents
PubMed: 38928275
DOI: 10.3390/ijms25126568 -
Biomolecules Jun 2024Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor expressed in many tissues, including skin, where it is essential for maintaining skin... (Review)
Review
Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor expressed in many tissues, including skin, where it is essential for maintaining skin barrier permeability, regulating cell proliferation/differentiation, and modulating antioxidant and inflammatory responses upon ligand binding. Therefore, PPARγ activation has important implications for skin homeostasis. Over the past 20 years, with increasing interest in the role of PPARs in skin physiopathology, considerable effort has been devoted to the development of PPARγ ligands as a therapeutic option for skin inflammatory disorders. In addition, PPARγ also regulates sebocyte differentiation and lipid production, making it a potential target for inflammatory sebaceous disorders such as acne. A large number of studies suggest that PPARγ also acts as a skin tumor suppressor in both melanoma and non-melanoma skin cancers, but its role in tumorigenesis remains controversial. In this review, we have summarized the current state of research into the role of PPARγ in skin health and disease and how this may provide a starting point for the development of more potent and selective PPARγ ligands with a low toxicity profile, thereby reducing unwanted side effects.
Topics: PPAR gamma; Humans; Animals; Skin; Skin Neoplasms; Skin Diseases; Ligands; Cell Differentiation
PubMed: 38927131
DOI: 10.3390/biom14060728 -
Journal of the American Academy of... Jun 2024
PubMed: 38925435
DOI: 10.1016/j.jaad.2024.05.092 -
The Australasian Journal of Dermatology Jun 2024Caucasian and Asian patients with hidradenitis suppurativa demonstrate significant differences with regard to age, gender and body mass index. Demographic...
Response to adalimumab in Caucasian and Asian patients with hidradenitis suppurativa: A retrospective cohort study of an Australian cohort stratified by patient-reported ethnicity.
BACKGROUND/OBJECTIVES
Caucasian and Asian patients with hidradenitis suppurativa demonstrate significant differences with regard to age, gender and body mass index. Demographic characteristics are known to influence the efficacy and drug survival of hidradenitis suppurativa therapeutics including biologic therapies. What remains unknown is the impact of ethnicity upon the efficacy of therapeutics once demographic and disease characteristics have been taken into account. This is an important question given the expansion of biologic therapies for HS into the global patient community.
METHODS
We assessed 170 patients from a single HS specialist centre in Australia stratified by patient-identified ethnicity including those identifying as either Caucasian or Asian.
RESULTS
Asian patients demonstrated lower BMI, higher rates of smoking and greater odds of Hurley stage 3 disease with tunnels than Caucasian patients in line with the reported literature. There was no significant difference between percentage of individuals achieving HiSCR50 or IHS4-55 at Week 16. Significant differences were seen in median time to secondary loss of response, and Kaplan-Meier curve analysis showed a significant difference between curves when stratified by patient-reported ethnicity. Cox regression analysis demonstrated after accounting for age, gender, BMI, smoking and Hurley stage, the significance of ethnicity in influencing time to secondary loss of response disappears.
CONCLUSIONS
Caucasian or Asian ethnicity does not influence response to adalimumab treatment on patients with hidradenitis suppurativa.
PubMed: 38924541
DOI: 10.1111/ajd.14343