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Frontiers in Molecular Biosciences 2023Atopic dermatitis (AD) is a common, chronic and relapsing inflammatory skin disease with various clinical presentations and combinations of symptoms. The pathophysiology... (Review)
Review
Atopic dermatitis (AD) is a common, chronic and relapsing inflammatory skin disease with various clinical presentations and combinations of symptoms. The pathophysiology of AD is complex and multifactorial. There are several factors involved in the etiopathogenesis of AD including structural and immunological epidermal barrier defect, imbalance of the skin microbiome, genetic background and environmental factors. Alterations in structural proteins, lipids, proteases, and their inhibitors, lead to the impairment of the stratum corneum which is associated with the increased skin penetration and transepidermal water loss. The elevated serum immunoglobulin E levels and blood eosinophilia have been shown in the majority of AD patients. Type 2 T-helper cell immune pathway with increased expression of interleukin (IL)-4, IL-5, and IL-13, has an important role in the etiopathogenesis of AD. Both T cells and keratinocytes contribute to epidermal barrier impairment in AD via a dynamic interaction of cytokines and chemokines. The skin microbiome is another factor of relevance in the etiopathogenesis of AD. It has been shown that during AD flares, () colonization increased, while () decreased. On the contrary, and species of , Corynebacterium and Propionibacterium increased during the remision phases. However, it is not clear whether skin dysbiosis is one of the symptoms or one of the causes of AD. There are several therapeutic options, targeting these pathways which play a critical role in the etiopathogenesis of AD. Although topical steroids are the mainstay of the treatment of AD, new biological therapies including IL-4, IL-13, and IL-31 inhibitors, as well as Janus kinase inhibitors (JAKi), increasingly gain more importance with new advances in the therapy of AD. In this review, we summarize the role of immunological and structural epidermal barrier dysfunction, immune abnormalities, impairment of lipids, filaggrin mutation and skin microbiome in the etiopathogenesis of AD, as well as the therapeutic options for AD and their effects on these abnormalities in AD skin.
PubMed: 37654796
DOI: 10.3389/fmolb.2023.1159404 -
Acne vulgaris: A review of the pathophysiology, treatment, and recent nanotechnology based advances.Biochemistry and Biophysics Reports Dec 2023Globally, Acne Vulgaris is a widespread, chronic inflammatory condition of the pilosebaceous follicles. Acne is not fatal, but depending on its severity, it can leave... (Review)
Review
BACKGROUND
Globally, Acne Vulgaris is a widespread, chronic inflammatory condition of the pilosebaceous follicles. Acne is not fatal, but depending on its severity, it can leave the sufferer with scars, irritation, and significant psychological effects (including depression). In the current review, we have included various factors for acne and their treatment explained. It also narrated the current medicament and the new investigation dosage forms with clinical phases information provided.
MAIN BODY OF THE ABSTRACT
Acne's pathophysiology involves four important factors: excessive sebum production, hyperkeratinization of pilosebaceous follicles, hyperproliferation of propionibacterium acnes (P. acnes), and inflammation. Identifying both inflammatory (Papule, pustule, nodule, and cyst) and non-inflammatory (black heads, white heads) acne lesions is necessary for diagnosing and treating acne vulgaris.
SHORT CONCLUSION
In this review, traditional therapy approaches such as topical (i.e., retinoids and antibiotics), systemic (i.e., retinoids, antibiotics, and hormonal), and physical therapies are briefly discussed. In addition, we highlight the issues posed by P. acne's resistance to the antibiotics used in commercially available medications and the necessity for novel therapeutic techniques. Finally, we examined a few innovative acne therapies pending clinical trial approval and commercial acne medications.
PubMed: 38076662
DOI: 10.1016/j.bbrep.2023.101578 -
Dermatology and Therapy Jan 2024The skin microbiome consists of the microorganisms populating the human skin. Cutibacterium acnes (C. acnes, formerly named Propionibacterium acnes) is recognized as a... (Review)
Review
The skin microbiome consists of the microorganisms populating the human skin. Cutibacterium acnes (C. acnes, formerly named Propionibacterium acnes) is recognized as a key factor in acne development, regulating inflammatory and immune pathways. Dysbiosis has been described as the imbalance in skin microbiome homeostasis and may play a role in acne pathogenesis. Microbial interference has been shown to be a contributor to healthy skin homeostasis and staphylococcal strains may exclude acne-associated C. acnes phylotypes. In this review we present an update on the skin microbiome in acne and discuss how current acne treatments such as benzoyl peroxide, orally administered isotretinoin, and antibiotics may affect the skin microbiome homeostasis. We highlight the collateral damage of acne antibiotics on the skin microbiome, including the risk of antimicrobial resistance and the dysregulation of the microbiome equilibrium that may occur even with short-term antibiotic courses. Consequently, the interest is shifting towards new non-antibiotic pharmacological acne treatments. Orally administered spironolactone is an emerging off-label treatment for adult female patients and topical peroxisome proliferator-activated receptor gamma (PPARγ) modulation is being studied for patients with acne. The potential application of topical or oral probiotics, bacteriotherapy, and phage therapy for acne are further promising areas of future research.
PubMed: 38183614
DOI: 10.1007/s13555-023-01079-8 -
Pharmaceutics Jul 2023Acne vulgaris is a common skin disease characterized by increased sebum production, inflammation, and (CA: formerly ) hyperproliferation in pilosebaceous follicles....
Acne vulgaris is a common skin disease characterized by increased sebum production, inflammation, and (CA: formerly ) hyperproliferation in pilosebaceous follicles. This study evaluated the efficacy of FRO, a formula composed of fermented Stokes and , against acne pathogenesis via antimicrobial assessment and an in vitro analysis. Stimulated model cells treated with hormones, CA, or lipopolysaccharide (LPS) were designed based on the characteristics of acne pathogenesis, including inflammation and sebum hypersecretion. High-performance liquid chromatography, disc diffusion, MTS, and western blotting assays were used to examine potential anti-acne effects. FRO was determined to contain phenolics such as gallic acid, fisetin, quercetin, and kaempferol. FRO exerted antimicrobial activity against CA and inhibited reactive oxygen species production that was otherwise increased by LPS or CA in HaCaT cells. Additionally, FRO exerted anti-inflammatory effects by inhibiting iNOS, TNF-α, IL-6, p-STAT-3, and p-NF-κB, which were previously upregulated by LPS or CA in THP-1 and HaCaT cells. FRO inhibited lipogenesis induced by steroid hormones and CA by decreasing FAS and SREBP-1 levels in sebocytes. Additionally, FRO down-regulated the androgen receptor, 5α-reductase, SREBP-1, and FAS levels, which were upregulated by steroid hormone in LNCaP cells. Taken together, our findings suggest that FRO alleviates acne by inhibiting the growth of CA, inflammation, and excess sebum and could be used for functional cosmetics or acne treatments.
PubMed: 37514071
DOI: 10.3390/pharmaceutics15071885 -
Nature Communications Dec 2023Acne is a dermatologic disease with a strong pathologic association with human commensal Cutibacterium acnes. Conspicuously, certain C. acnes phylotypes are associated...
Acne is a dermatologic disease with a strong pathologic association with human commensal Cutibacterium acnes. Conspicuously, certain C. acnes phylotypes are associated with acne, whereas others are associated with healthy skin. Here we investigate if the evolution of a C. acnes enzyme contributes to health or acne. Two hyaluronidase variants exclusively expressed by C. acnes strains, HylA and HylB, demonstrate remarkable clinical correlation with acne or health. We show that HylA is strongly pro-inflammatory, and HylB is modestly anti-inflammatory in a murine (female) acne model. Structural and phylogenic studies suggest that the enzymes evolved from a common hyaluronidase that acquired distinct enzymatic activity. Health-associated HylB degrades hyaluronic acid (HA) exclusively to HA disaccharides leading to reduced inflammation, whereas HylA generates large-sized HA fragments that drive robust TLR2-dependent pathology. Replacing an amino acid, Serine to Glycine near the HylA catalytic site enhances the enzymatic activity of HylA and produces an HA degradation pattern intermediate to HylA and HylB. Selective targeting of HylA using peptide vaccine or inhibitors alleviates acne pathology. We suggest that the functional divergence of HylA and HylB is a major driving force behind C. acnes health- and acne- phenotype and propose targeting of HylA as an approach for acne therapy.
Topics: Humans; Female; Animals; Mice; Hyaluronoglucosaminidase; Skin; Acne Vulgaris; Propionibacterium acnes; Amino Acids
PubMed: 38052825
DOI: 10.1038/s41467-023-43833-8 -
GeroScience Apr 2024Oral health plays a significant role in the quality of life and overall well-being of the aging population. However, age-related changes in oral health are not well...
Oral health plays a significant role in the quality of life and overall well-being of the aging population. However, age-related changes in oral health are not well understood due to challenges with current animal models. In this study, we analyzed the oral health and microbiota of a short-lived non-human primate (i.e., marmoset), as a step towards establishing a surrogate for studying the changes that occur in oral health during human aging. We investigated the oral health of marmosets using cadaveric tissues in three different cohorts: young (aged ≤6 years), middle-aged, and older (>10 years) and assessed the gingival bacterial community using analyses of the V3-V4 variable region of 16S rRNA gene. The oldest cohort had a significantly higher number of dental caries, increased dental attrition/erosion, and deeper periodontal pocket depth scores. Oral microbiome analyses showed that older marmosets had a significantly greater abundance of Escherichia-Shigella and Propionibacterium, and a lower abundance of Agrobacterium/Rhizobium at the genus level. Alpha diversity of the microbiome between the three groups showed no significant differences; however, principal coordinate analysis and non-metric multidimensional scaling analysis revealed that samples from middle-aged and older marmosets were more closely clustered than the youngest cohort. In addition, linear discriminant analysis effect size (LEFSe) identified a higher abundance of Esherichia-Shigella as a potential pathogenic biomarker in older animals. Our findings confirm that changes in the oral microbiome are associated with a decline in oral health in aging marmosets. The current study suggests that the marmoset model recapitulates some of the changes in oral health associated with human aging and may provide opportunities for developing new preventive strategies or interventions which target these disease conditions.
Topics: Humans; Animals; Aged; Middle Aged; Callithrix; Oral Health; RNA, Ribosomal, 16S; Dental Caries; Quality of Life; Aging
PubMed: 37775702
DOI: 10.1007/s11357-023-00939-7 -
Frontiers in Endocrinology 2023This study was designed to explore the composition of the intestinal microbiota and its longitudinal variation between the second trimester (T2) and the third trimester... (Observational Study)
Observational Study
Composition of the intestinal microbiota and its variations between the second and third trimesters in women with gestational diabetes mellitus and without gestational diabetes mellitus.
OBJECTIVE
This study was designed to explore the composition of the intestinal microbiota and its longitudinal variation between the second trimester (T2) and the third trimester (T3) in women with gestational diabetes mellitus (GDM) and pregnant women with normal glucose tolerance.
METHODS
This observational study was conducted at Peking Union Medical College Hospital (PUMCH). Women with GDM and pregnant women with normal glucose tolerance were enrolled in the study, and fecal samples were collected during T2 (weeks 24~28) and T3 (weeks 34~38). Fecal samples were analyzed from 49 women with GDM and 42 pregnant women with normal glucose tolerance. The 16S rRNA gene amplicon libraries were sequenced to analyze the microbiota and QIIME2 was used to analyze microbiome bioinformatics.
RESULTS
The four dominant phyla that , , and which accomplish about 99% of the total relative abundance did not significantly change between the T2 and T3 in the GDM and healthy groups. At the genus level, the relative abundance of (0 vs. 0.25%, P = 0.041) and (0 vs. 0.29%, P = 0.041) increased significantly in the control group, but not in the GDM group. At the phylum level, the relative abundance of and was significantly different between women with GDM and pregnant women with normal glucose tolerance in both T2 and T3. In T2 and T3, the relative abundances of , , and were significantly higher in the GDM group than in the control group (P<0.05). The relative abundance of in the GDM group was lower than in the control group in both T2 and T3.
CONCLUSIONS
The intestinal microbiota composition was stable from T2 to T3 in the GDM and control groups; however, the intestinal microbiota composition was different between the two groups.
Topics: Pregnancy; Female; Humans; Diabetes, Gestational; Pregnancy Trimester, Third; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Blood Glucose; Glucose; Bacteria; Actinobacteria
PubMed: 37522117
DOI: 10.3389/fendo.2023.1126572 -
Postepy Dermatologii I Alergologii Dec 2023Azelaic acid (AZA) is a naturally occurring saturated dicarboxylic acid whose topical application has found multiple uses in dermatology. Its anti-inflammatory,... (Review)
Review
Azelaic acid (AZA) is a naturally occurring saturated dicarboxylic acid whose topical application has found multiple uses in dermatology. Its anti-inflammatory, antioxidant and antimicrobial properties against Propionibacterium acne are currently used in the treatment of various types of acne such as rosacea and acne vulgaris. AZA is an inhibitor of tyrosinase, mitochondrial respiratory chain enzymes and DNA synthesis, and is a scavenger of harmful free radicals and inhibits the production of reactive oxygen species by neutrophils. Interestingly, AZA also has anti-proliferative and cytotoxic effects on various cancer cells. To date, its inhibitory effect on melanocytes has been mainly used, making it widely used in the treatment of hyperpigmentation disorders such as melasma and post-inflammatory hyperpigmentation. Commercially available topical formulations with cosmetic and drug status contain 5% to 20% AZA in the form of gels and creams. The use of liposomal technology allows greater control over the pharmacokinetics and pharmacodynamics of the formulations. When applied topically, AZA is well tolerated, and side effects are limited to generally mild and transient local skin irritation. Importantly, liposomal technology has enabled the drug to penetrate all layers of the skin while maintaining a very high accumulation of the active ingredient. This solution could be revolutionary for the treatment of skin cancer, where until now the main obstacle was poor absorption through the skin, making the treatment require multiple applications to maintain long-term activity levels. In this review, we will present the mechanism of action and pharmacokinetics of AZA. We will summarize its use in the treatment of dermatoses and its potential in skin cancer therapy. We will provide an overview of the preparations available on the market, taking into consideration technologies used.
PubMed: 38282869
DOI: 10.5114/ada.2023.133955 -
Dermatology (Basel, Switzerland) 2024Darier disease is a rare inherited disease with dominant skin manifestations including keratotic papules and plaques on sebaceous and flexural areas. Secondary infection...
INTRODUCTION
Darier disease is a rare inherited disease with dominant skin manifestations including keratotic papules and plaques on sebaceous and flexural areas. Secondary infection of skin lesions is common, and Staphylococcus aureus commonly colonizes these lesions. The aim of the study was to characterize the bacterial microbiome of cutaneous Darier lesions compared to normal-looking skin and disease severity.
METHODS
All patients with a history of Darier followed up at Emek Medical Center were invited to participate in the study. Patients that did not use antibiotics in the past month and signed informed consent had four skin sites sampled with swabs: scalp, chest, axilla, and palm. All samples were analyzed for bacterial microbiome using 16S rDNA sequencing.
RESULTS
Two hundred and eighty microbiome samples obtained from lesional and non-lesional skin of the scalp, chest, axilla, and palm of 42 Darier patients were included in the analysis. The most abundant bacterial genera across all skin sites were Propionibacterium, Corynebacterium, Paracoccus, Micrococcus, and Anaerococcus. Scalp and chest lesions featured a distinct microbiome configuration that was mainly driven by an overabundance of Staphylococci species. Patients with more severe disease exhibited microbiome alterations in the chest, axilla, and palm compared with patients with only mild disease, driven by Peptoniphilus and Moryella genera in scalp and palmar lesions, respectively.
CONCLUSION
Staphylococci were significantly associated with Darier lesions and drove Darier-associated dysbiosis. Severity of the disease was associated with two other bacterial genera. Whether these associations also hold a causative role and may serve as a therapeutic target remains to be determined and requires further investigation.
Topics: Humans; Darier Disease; Male; Female; Dysbiosis; Adult; Middle Aged; Microbiota; Axilla; Skin; Corynebacterium; Young Adult; Propionibacterium; Micrococcus; Severity of Illness Index; Hand; Thorax; Scalp; Aged; Adolescent
PubMed: 38330926
DOI: 10.1159/000537714 -
The Journal of Investigative Dermatology Jan 2024Cutibacterium acnes is a commensal bacterium on the skin that is generally well-tolerated, but different strain types have been hypothesized to contribute to the disease...
Cutibacterium acnes is a commensal bacterium on the skin that is generally well-tolerated, but different strain types have been hypothesized to contribute to the disease acne vulgaris. To understand how some strain types might contribute to skin inflammation, we generated a repository of C. acnes isolates from skin swabs of healthy subjects and subjects with acne and assessed their strain-level identity and capacity to stimulate cytokine release. Phylotype II K-type strains were more frequent on healthy and nonlesional skin of subjects with acne than those isolated from lesions. Phylotype IA-1 C-type strains were increased on lesional skin compared with those on healthy skin. The capacity to induce cytokines from cultured monocyte-derived dendritic cells was opposite to this action on sebocytes and keratinocytes and did not correlate with the strain types associated with the disease. Whole-genome sequencing revealed a linear plasmid in high-inflammatory isolates within similar strain types that had different proinflammatory responses. Single-cell RNA sequencing of mouse skin after intradermal injection showed that strains containing this plasmid induced a higher inflammatory response in dermal fibroblasts. These findings revealed that C. acnes strain type is insufficient to predict inflammation and that carriage of a plasmid could contribute to disease.
Topics: Animals; Mice; Humans; Skin; Acne Vulgaris; Dermatitis; Propionibacterium acnes; Plasmids; Inflammation; Cytokines
PubMed: 37478901
DOI: 10.1016/j.jid.2023.05.029