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Biomedicine & Pharmacotherapy =... Jul 2024Atopic dermatitis (AD) is a globally increasing chronic inflammatory skin disease with limited and potentially side-effect-prone treatment options. Monotropein is the...
Atopic dermatitis (AD) is a globally increasing chronic inflammatory skin disease with limited and potentially side-effect-prone treatment options. Monotropein is the predominant iridoid glycoside in Morinda officinalis How roots, which has previously shown promise in alleviating AD symptoms. This study aimed to systematically investigate the pharmacological effects of monotropein on AD using a 2, 4-dinitrochlorobenzene (DNCB)/Dermatophagoides farinae extract (DFE)-induced AD mice and tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated keratinocytes. Oral administration of monotropein demonstrated a significant reduction in AD phenotypes, including scaling, erythema, and increased skin thickness in AD-induced mice. Histological analysis revealed a marked decrease in immune cell infiltration in skin lesions. Additionally, monotropein effectively downregulated inflammatory markers, encompassing pro-inflammatory cytokines, T helper (Th)1 and Th2 cytokines, and pro-inflammatory chemokines in skin tissues. Notably, monotropein also led to a considerable decrease in serum immunoglobulin (Ig)E and IgG2a levels. At a mechanistic level, monotropein exerted its anti-inflammatory effects by suppressing the phosphorylation of Janus kinase / signal transducer and activator of transcription proteins in both skin tissues of AD-induced mice and TNF-α/IFN-γ-stimulated keratinocytes. In conclusion, monotropein exhibited a pronounced alleviation of AD symptoms in the experimental models used. These findings underscore the potential application of monotropein as a therapeutic agent in the context of AD, providing a scientific basis for further exploration and development.
Topics: Animals; Dermatitis, Atopic; Signal Transduction; Mice; Janus Kinases; Skin; Keratinocytes; Cytokines; Mice, Inbred BALB C; STAT Transcription Factors; Humans; Dinitrochlorobenzene; Anti-Inflammatory Agents; Female; Disease Models, Animal; Inflammation; Immunoglobulin E; Dermatophagoides farinae; Iridoids
PubMed: 38861857
DOI: 10.1016/j.biopha.2024.116911 -
Acta Dermato-venereologica Jun 2024Atopic dermatitis is a prevalent skin condition that affects up to 17% of adult population. It can lead to itching, pain, and other symptoms such as sleep disturbance,...
Atopic dermatitis is a prevalent skin condition that affects up to 17% of adult population. It can lead to itching, pain, and other symptoms such as sleep disturbance, anxiety, and depression. Due to its high prevalence and limiting symptoms, atopic dermatitis often has a great impact on patients' quality of life but there is scarce information regarding how atopic dermatitis affects women's sexual health and reproductive desires. The purpose of this article was to assess the impact of atopic dermatitis on sexual function and reproductive wishes in women. A cross-sectional study was conducted from February to March 2022. A total of 102 women with atopic dermatitis were recruited through online questionnaires sent through the Spanish Atopic Dermatitis Association; 68.6% of the patients acknowledged impairment in sexual function, especially those with more severe disease and those with genital and gluteal involvement. In addition, 51% of the women considered that atopic dermatitis may have an influence on their gestational desire, particularly those with gluteal involvement. In conclusion, atopic dermatitis has a great impact on sexual function and reproductive desires in women.
Topics: Humans; Female; Dermatitis, Atopic; Adult; Cross-Sectional Studies; Quality of Life; Sexual Dysfunction, Physiological; Middle Aged; Young Adult; Sexual Dysfunctions, Psychological; Surveys and Questionnaires; Sexual Behavior; Libido; Severity of Illness Index; Sexual Health
PubMed: 38860625
DOI: 10.2340/actadv.v104.35107 -
Acta Dermato-venereologica Jun 2024Patients with atopic dermatitis (AD) are more likely than healthy individuals to harbour Staphylococcus aureus on their skin. Superantigens (SAgs) produced by specific...
Patients with atopic dermatitis (AD) are more likely than healthy individuals to harbour Staphylococcus aureus on their skin. Superantigens (SAgs) produced by specific S. aureus strains may contribute to AD-associated skin inflammation. The present study compared the prevalence and types of SAg-encoding genes between S. aureus isolated from patients with AD and from controls, and within the AD group between isolates from different sampling sites (lesional skin, non-lesional skin, and nares). This retrospective case-control study extracted data from 2 previous studies that examined S. aureus using whole-genome sequencing. The 138 S. aureus isolates obtained from 71 AD patients contained 349 SAg-encoding genes; 22 (6.3%) were found in isolates from nares (0.4 ± 0.6 genes per isolate), 99 (28.4%) in isolates from non-lesional skin (3.7 ± 3.9), and 228 (65.3%) in isolates from lesional skin (4.2 ± 4.5). S. aureus (n = 101) from the control group contained 594 SAg-encoding genes (5.9 ± 4.2). Of the S. aureus isolated from lesional AD skin, 69% carried at least 1 gene encoding SAg compared with 33% of AD nasal isolates. SAg could be a factor in the pathogenesis of a subset of AD patients.
Topics: Humans; Dermatitis, Atopic; Superantigens; Staphylococcus aureus; Retrospective Studies; Skin; Male; Female; Case-Control Studies; Adult; Staphylococcal Skin Infections; Middle Aged; Young Adult
PubMed: 38860624
DOI: 10.2340/actadv.v104.34882 -
International Journal of Women's... Jun 2024Atopic dermatitis (AD) is one of the most common inflammatory dermatoses in adults. Women are disproportionately impacted by AD and report significant impacts on quality...
BACKGROUND
Atopic dermatitis (AD) is one of the most common inflammatory dermatoses in adults. Women are disproportionately impacted by AD and report significant impacts on quality of life compared to men.
OBJECTIVE
Given the absence of formal guidelines for the treatment of AD in women of childbearing age, we will review special considerations for treating women of childbearing age with AD to ensure consistent care and optimal outcomes for these patients.
METHODS
PubMed and Google Scholar databases were searched for relevant articles from database inception through May of 2023.
RESULTS
There are several treatments including topical therapies, systemic therapies, and phototherapy that are considered safe during preconception, pregnancy and breastfeeding. Given the negative consequences of uncontrolled AD for both the mother and the unborn baby, the risks and benefits of potential therapies should be reviewed with all women of childbearing age suffering from AD.
LIMITATIONS
The gold standard in recommending therapies is randomized controlled trials; however, pregnant and lactating women are often excluded from these trials.
CONCLUSION
Through shared decision-making between the dermatologist, obstetrician, and patient, the risks and benefits of any therapy should be thoroughly discussed and considered with all women of childbearing age, to optimize care and outcomes for this unique population.
PubMed: 38860232
DOI: 10.1097/JW9.0000000000000151 -
JID Innovations : Skin Science From... Jul 2024Loss-of-function variants in the gene have been identified as the strongest cause of susceptibility to atopic dermatitis (AD) in Europeans and Asians. However, very...
Loss-of-function variants in the gene have been identified as the strongest cause of susceptibility to atopic dermatitis (AD) in Europeans and Asians. However, very little is known about the genetic etiology behind AD in African populations, where the prevalence of AD is notably high. We sought to investigate the genetic origins of AD by performing whole-genome sequencing in an Ethiopian family with 12 individuals and several affected in different generations. We identified 2 variants within (p.D13Y) and (p.A918S) genes cosegregating with AD in the affected individuals. Further genotyping analyses in both Ethiopian and Swedish AD cases and controls revealed a significant association with the variant (p.D13Y, < .0013) only in the Ethiopian cohort. However, the variant (p.A918S) did not show any association in our Ethiopian cohort. Instead, 2 previously recognized variants (p.A849V, < .0085 and p.G908R, < .0036) were significantly associated with AD in our Ethiopian cohort. Our study indicates that the and genes might be important in the etiology of AD in Ethiopians. Additional genetic and functional studies are needed to confirm the role of these genes and the associated variants into the development of AD.
PubMed: 38859976
DOI: 10.1016/j.xjidi.2024.100284 -
Journal of the American Academy of... Jun 2024
Effectiveness of abrocitinib for the treatment of moderate-to-severe atopic dermatitis in patients switched from dupilumab and/or tralokinumab: A real-world retrospective study.
PubMed: 38857764
DOI: 10.1016/j.jaad.2024.05.081 -
Biomedical Optics Express May 2024The therapeutic application of blue light (380 - 500nm) has garnered considerable attention in recent years as it offers a non-invasive approach for the management of...
The therapeutic application of blue light (380 - 500nm) has garnered considerable attention in recent years as it offers a non-invasive approach for the management of prevalent skin conditions including acne vulgaris and atopic dermatitis. These conditions are often characterised by an imbalance in the microbial communities that colonise our skin, termed the skin microbiome. In conditions including acne vulgaris, blue light is thought to address this imbalance through the selective photoexcitation of microbial species expressing wavelength-specific chromophores, differentially affecting skin commensals and thus altering the relative species composition. However, the abundance and diversity of these chromophores across the skin microbiota remains poorly understood. Similarly, devices utilised for studies are often bulky and poorly characterised which if translated to therapy could result in reduced patient compliance. Here, we present a clinically viable micro-LED illumination platform with peak emission 450 nm (17 nm FWHM) and adjustable irradiance output to a maximum 0.55 ± 0.01 W/cm, dependent upon the concentration of titanium dioxide nanoparticles applied to an accompanying flexible light extraction substrate. Utilising spectrometry approaches, we characterised the abundance of prospective blue light chromophores across skin commensal bacteria isolated from healthy volunteers. Of the strains surveyed 62.5% exhibited absorption peaks within the blue light spectrum, evidencing expression of carotenoid pigments (18.8%, 420-483 nm; , spp.), porphyrins (12.5%, 402-413 nm; spp.) and potential flavins (31.2%, 420-425 nm; and spp.). We also present evidence of the capacity of these species to diminish irradiance output when combined with the micro-LED platform and in turn how exposure to low-dose blue light causes shifts in observed absorbance spectra peaks. Collectively these findings highlight a crucial deficit in understanding how microbial chromophores might shape response to blue light and in turn evidence of a micro-LED illumination platform with potential for clinical applications.
PubMed: 38855662
DOI: 10.1364/BOE.522867 -
Archives of Dermatological Research Jun 2024The objective was to study a large, international, ethnically diverse population of patients with atopic dermatitis (AD) to support the creation of patient-centric...
The objective was to study a large, international, ethnically diverse population of patients with atopic dermatitis (AD) to support the creation of patient-centric recommendations for AD management. Qualitative data were generated from 45-min, 1:1 telephone interviews conducted across 15 countries in each patient's native language. Interviews explored the impact of AD on patients' lives, patients' most important symptoms, treatment expectations, and treatment decision-making. Participants were also questioned on their current knowledge of AD scoring systems and what was most important to include in these tools. In total, 88 adult patients (≥ 18 years old) receiving treatment for AD were recruited through a market research database, clinician referrals, and local advertising. All patients were screened to ensure a balanced and diverse sample in terms of age, gender, educational level, employment status, geographic location, and AD severity. Patients involved in market research or activities supporting advocacy groups within the previous 6 months or affiliated with or employed by pharmaceutical companies were excluded. AD had a substantial impact on patients' lives. Itch, skin redness, and dry/flaky skin were the most frequently reported symptoms, with > 75% of patients experiencing these symptoms every 1-3 days. Mental health issues were common and resulted in the greatest negative impact on patients' daily lives. Patients perceived clinicians to underestimate the burden of their AD. Patients had little awareness of AD scoring systems and indicated a preference for these to be more clearly incorporated in clinical practice. For an ideal scoring system, patients favored using a combination of patient-reported and clinician-reported outcomes to reflect disease burden and ensure consistency across all settings. This global study generated diverse patient perspectives on the disease burden of AD, their expectations of treatment, and their views on AD scoring methods. These data provide evidence to support the development of patient-centric recommendations for AD management.
Topics: Humans; Dermatitis, Atopic; Female; Male; Adult; Middle Aged; Qualitative Research; Patient Reported Outcome Measures; Severity of Illness Index; Cost of Illness; Young Adult; Quality of Life; Aged; Adolescent
PubMed: 38850461
DOI: 10.1007/s00403-024-03130-w -
Journal of Dermatological Science Mar 2024Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is a serine protease inhibitor consisting of multiple domains. A loss of function mutation is described in...
BACKGROUND
Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is a serine protease inhibitor consisting of multiple domains. A loss of function mutation is described in Netherton patients that show severe symptoms of atopic lesions and itch.
OBJECTIVES
LEKTI domain 6 (LD6) has shown strong serine protease-inhibitory action in in vitro assays and thus it was tested in vitro and in vivo for potential anti-inflammatory action in models of atopic skin disease.
METHODS
Human skin equivalents were treated with LD6 and an inflammatory reaction was challenged by kallikrein-related endopeptidase 5 (KLK5). Furthermore, LD6 was tested on dorsal root ganglia cells stimulated with KLK5, SLIGRL and histamine by calcium imaging. The effect of topically administered LD6 (0.4-0.8%) in lipoderm was compared to a topical formulation of betamethasone-diproprionate (0.1%) in a therapeutic setting on atopic dermatitis-like lesions in NC/Nga mice sensitized to house dust mite antigen. Endpoints were clinical scoring of the mice as well as determination of scratching behaviour.
RESULTS
KLK5 induced an upregulation of CXCL-8, CCL20 and IL-6 in skin equivalents. This upregulation was reduced by pre-incubation with LD6. KLK5 as well as histamine induced calcium influx in a population of neurons. LD6 significantly reduced the calcium response to both stimuli. When administered onto lesional skin of NC/Nga mice, both LD6 and betamethasone-dipropionate significantly reduced the inflammatory reaction. The effect on itch behaviour was less pronounced.
CONCLUSION
Topical administration of LD6 might be a new therapeutic option for treatment of lesional atopic skin.
PubMed: 38849289
DOI: 10.1016/j.jdermsci.2024.03.004