Topical Prescription Management.

With recent advances in topical therapies for atopic dermatitis (AD), steroid-sparing options like calcineurin inhibitors, Janus kinase (JAK) inhibitors, and phosphodiesterase-4 (PDE-4) inhibitors are becoming mainstays in therapy, underscoring the importance of careful selection and usage of topical corticosteroids (TCSs) to minimize side effects. Alongside the necessity of emollient use, these steroid-sparing alternatives offer rapid itch relief and efficacy in improving disease severity. While TCSs still hold a prominent role in AD management, promising novel topical treatments like tapinarof and live biotherapeutics to modulate the skin microbiome are also discussed. Overall, the recent addition of novel topical therapies offers diverse options for AD management and underscores the importance of topical treatments in the management of AD.

Rare Variant of Leprosy Reaction (Lucio Phenomenon): A Case Series.

ABSTRACT: Lucio phenomenon (LP) is a variant of type two leprosy, characterized by necrotizing erythema, frequently found in neglected leprosy patient who experience delayed diagnosis or inappropriate treatment. Indonesia is in the third place for highest leprosy cases worldwide. Nonetheless, LP is less common, regardless being an endemic country. In this serial case, we describe the three cases of LP in lepromatous leprosy patients in Denpasar, Bali. All three cases came to our hospital with chronic wounds complained up to a year, accompanied by swollen leg, blisters, tingling sensation, and other symptoms. They had received no suitable treatment, proving LP as a neglected case in primary health care. After a period of treatment, however, patient lesions improved clinically with no physical disability. With this case series, a better understanding toward LP initial complains together with its natural history and further examination could be achieved; thus, improving the early diagnosis and management of LP.

Does "all disease begin in the gut"? The gut-organ cross talk in the microbiome.

The human microbiome, a diverse ecosystem of microorganisms within the body, plays pivotal roles in health and disease. This review explores site-specific microbiomes, their role in maintaining health, and strategies for their upkeep, focusing on oral, lung, vaginal, skin, and gut microbiota, and their systemic connections. Understanding the intricate relationships between these microbial communities is crucial for unraveling mechanisms underlying human health. Recent research highlights bidirectional communication between the gut and distant microbiome sites, influencing immune function, metabolism, and disease susceptibility. Alterations in one microbiome can impact others, emphasizing their interconnectedness and collective influence on human physiology. The therapeutic potential of gut microbiota in modulating distant microbiomes offers promising avenues for interventions targeting various disorders. Through interdisciplinary collaboration and technological advancements, we can harness the power of the microbiome to revolutionize healthcare, emphasizing microbiome-centric approaches to promote holistic well-being while identifying areas for future research.

Segmentation of hyphae and yeast in fungi-infected tissue slice images and its application in analyzing antifungal blue light therapy.

Candida albicans is a pathogenic fungus that undergoes morphological transitions between hyphal and yeast forms, adapting to diverse environmental stimuli and exhibiting distinct virulence. Existing research works on antifungal blue light (ABL) therapy have either focused solely on hyphae or neglected to differentiate between morphologies, obscuring potential differential effects. To address this gap, we established a novel dataset of 150 C. albicans-infected mouse skin tissue slice images with meticulously annotated hyphae and yeast. Eleven representative convolutional neural networks were trained and evaluated on this dataset using seven metrics to identify the optimal model for segmenting hyphae and yeast in original high pixel size images. Leveraging the segmentation results, we analyzed the differential impact of blue light on the invasion depth and density of both morphologies within the skin tissue. U-Net-BN outperformed other models in segmentation accuracy, achieving the best overall performance. While both hyphae and yeast exhibited significant reductions in invasion depth and density at the highest ABL dose (180 J/cm2), only yeast was significantly inhibited at the lower dose (135 J/cm2). This novel finding emphasizes the importance of developing more effective treatment strategies for both morphologies.

We studied the effects of blue light therapy on hyphal and yeast forms of Candida albicans. Through image segmentation techniques, we discovered that the changes in invasion depth and density differed between these two forms after exposure to blue light.

Differentially expressed proteins and microbial communities of the skin regulate disease resistance to Chinese tongue sole (Cynoglossus semilaevis).

Vibriosis, caused by Vibrio, seriously affects the health of fish, shellfish, and shrimps, causing large economic losses. Teleosts are represent the first bony vertebrates with both innate and adaptive immune responses against pathogens. Aquatic animals encounter hydraulic pressure and more pathogens, compared to terrestrial animals. The skin is the first line of defense in fish, constituting the skin-associated lymphoid tissue (SALT), which belongs to the main mucosa-associated lymphoid tissues (MALT). However, little is known about the function of immunity related proteins in fish. Therefore, this study used iTRAQ (isobaric tags for relative and absolute quantitation) to compare the skin proteome between the resistant and susceptible families of Cynoglossus semilaevis. The protein integrin beta-2, the alpha-enolase isoform X1, subunit B of V-type proton ATPase, eukaryotic translation initiation factor 6, and ubiquitin-like protein ISG15, were highly expressed in the resistant family. The 16S sequencing of the skin tissues of the resistant and susceptible families showed significant differences in the microbial communities of the two families. The protein-microbial interaction identified ten proteins associated with skin microbes, including immunoglobulin heavy chain gene (IGH), B-cell lymphoma/leukemia 10 (BCL10) and pre-B-cell leukemia transcription factor 1 isoform X2 (PBX2). This study highlights the interaction between skin proteins and the microbial compositions of C. semilaevis and provides new insights into understanding aquaculture breeding research.

[Diagnosis of allergen components in fungi and microbial communities: patient sensitization characteristics and main sensitizing proteins].

The human body, as a highly complex ecosystem, harbors diverse microbial communities, with major factors triggering allergic reactions encompassing the skin microbiome and fungi. The global diversity of fungi is estimated to range from approximately 600 000 to 1 million species, and theoretically, IgE-mediated sensitization may occur to any fungal species. As of now, the World Health Organization/IUIS official database records 113 fungal allergens originating from 30 different fungi species, covering 42 allergen families. Regarding the skin microbiome, 14 distinct Malassezia allergens have been identified, all derived from three different Malassezia fungi species--M. furfur, M. sympodialis, and M. globosa. The conditions of patients with these allergies are exceptionally complex. This article extensively discusses the latest research advancements and clinical applications related to skin microbiome and fungal allergies from the European Academy of Allergy and Clinical Immunology (EAACI) publication, "Molecular Allergology User's Guide 2.0". Additionally, it compiles information on the sources of fungal allergens, characteristics of allergen component protein families, clinical relevance, and management strategies, both domestically and internationally. The aim is to enhance the profound understanding of allergen components among relevant professionals. Through the application of advanced allergen component diagnostic techniques, the goal is to achieve precise diagnosis and treatment of fungal allergy patients and explore the mechanisms underlying fungal sensitization and pathogenesis, laying the foundation for studying the fungal allergen protein sensitization spectrum in the Chinese population.

Distinct T cell signatures are associated with Staphylococcus aureus skin infection in pediatric atopic dermatitis.

Atopic dermatitis (AD) is an inflammatory skin condition with a childhood prevalence of up to 25%. Microbial dysbiosis is characteristic of AD, with Staphylococcus aureus the most frequent pathogen associated with disease flares and increasingly implicated in disease pathogenesis. Therapeutics to mitigate the effects of S. aureus have had limited efficacy and S. aureus-associated temporal disease flares are synonymous with AD. An alternative approach is an anti-S. aureus vaccine, tailored to AD. Experimental vaccines have highlighted the importance of T cells in conferring protective anti-S. aureus responses; however, correlates of T cell immunity against S. aureus in AD have not been identified. We identify a systemic and cutaneous immunological signature associated with S. aureus skin infection (ADS.aureus) in a pediatric AD cohort, using a combined Bayesian multinomial analysis. ADS.aureus was most highly associated with elevated cutaneous chemokines IP10 and TARC, which preferentially direct Th1 and Th2 cells to skin. Systemic CD4+ and CD8+ T cells, except for Th2 cells, were suppressed in ADS.aureus, particularly circulating Th1, memory IL-10+ T cells, and skin-homing memory Th17 cells. Systemic γδ T cell expansion in ADS.aureus was also observed. This study suggests that augmentation of protective T cell subsets is a potential therapeutic strategy in the management of S. aureus in AD.

Amphibian tolerance to arsenic: microbiome-mediated insights.

Amphibians are often recognized as bioindicators of healthy ecosystems. The persistence of amphibian populations in heavily contaminated environments provides an excellent opportunity to investigate rapid vertebrate adaptations to harmful contaminants. Using a combination of culture-based challenge assays and a skin permeability assay, we tested whether the skin-associated microbiota may confer adaptive tolerance to tropical amphibians in regions heavily contaminated with arsenic, thus supporting the adaptive microbiome principle and immune interactions of the amphibian mucus. At lower arsenic concentrations (1 and 5 mM As3+), we found a significantly higher number of bacterial isolates tolerant to arsenic from amphibians sampled at an arsenic contaminated region (TES) than from amphibians sampled at an arsenic free region (JN). Strikingly, none of the bacterial isolates from our arsenic free region tolerated high concentrations of arsenic. In our skin permeability experiment, where we tested whether a subset of arsenic-tolerant bacterial isolates could reduce skin permeability to arsenic, we found that isolates known to tolerate high concentrations of arsenic significantly reduced amphibian skin permeability to this metalloid. This pattern did not hold true for bacterial isolates with low arsenic tolerance. Our results describe a pattern of environmental selection of arsenic-tolerant skin bacteria capable of protecting amphibians from intoxication, which helps explain the persistence of amphibian populations in water bodies heavily contaminated with arsenic.

Skin Deep: The Potential of Microbiome Cosmetics.

The interplay between the skin microbiome and its host is a complex facet of dermatological health and has become a critical focus in the development of microbiome cosmetics. The skin microbiome, comprising various microorganisms, is essential from birth, develops over the lifespan, and performs vital roles in protecting our body against pathogens, training the immune system, and facilitating the breakdown of organic matter. Dysbiosis, an imbalance of these microorganisms, has been implicated in a number of skin conditions such as acne, atopic dermatitis, and skin cancer. Recent scientific findings have spurred cosmetic companies to develop products that preserve and enhance the skin's microbial diversity balance. These products may incorporate elements like prebiotics, probiotics, and postbiotics, which are beneficial for the skin microbiome. Beyond topical products, there's increasing interest in ingestible beauty supplements (i.e. oral probiotics), highlighting the connection between the gut and skin. This review examines the influence of the microbiome on skin health and the emerging trends of microbiome skincare products.

Urban indoor gardening enhances immune regulation and diversifies skin microbiota - A placebo-controlled double-blinded intervention study.

According to the hygiene and biodiversity hypotheses, frequent exposure to environmental microbiota, especially through soil contact, diversifies commensal microbiota, enhances immune modulation, and ultimately lowers the risk of immune-mediated diseases. Here we test the underlying assumption of the hygiene and biodiversity hypotheses by instructing volunteers to grow edible plants indoors during the winter season when natural exposure to environmental microbiota is low. The one-month randomized, placebo-controlled double-blind trial consisted of two treatments: participants received either microbially diverse growing medium or visually similar but microbially poor growing medium. Skin microbiota and a panel of seven immune markers were analyzed in the beginning of the trial and after one month. The diversity of five bacterial phyla (Bacteroidetes, Planctomycetes, Proteobacteria, Cyanobacteria, and Verrucomicrobia) and one class (Bacteroidia) increased on the skin of participants in the intervention group while no changes were observed in the placebo group. The number of nodes and edges in the co-occurrence networks of the skin bacteria increased on average three times more in the intervention group than in the placebo group. The plasma levels of the immunomodulatory cytokine interleukin 10 (IL-10) increased in the intervention group when compared with the placebo group. A similar trend was observed in the interleukin 17A (IL-17A) levels and in the IL-10:IL-17A ratios. Participants in both groups reported high satisfaction and adherence to the trial. The current study provides evidence in support of the core assumption of the hygiene and biodiversity hypotheses of immune-mediated diseases. Indoor urban gardening offers a meaningful and convenient approach for increasing year-round exposure to environmental microbiota, paving the way for other prophylactic practices that might help prevent immune-mediated diseases.

Effects of Citrobacter freundii on sturgeon: Insights from skin mucosal immunology and microbiota.

Skin mucus analysis has recently been used as a non-invasive method to evaluate for fish welfare. The present research study was conducted to examine the skin mucosal immunity and skin microbiota profiles of sturgeons infected with Citrobacter freundii. Our histology results showed that the thickness of the epidermal layer of skin remained thinner, and the number of mucous cells was significantly decreased in sturgeons after infection (p < 0.05). Total protein, alanine aminotransferase, aspartate aminotransferase, superoxide dismutase, and creatine kinase levels in the mucus showed biphasic pattern (decrease and then increase). Lactate dehydrogenase, lysozyme, and acid phosphatase activities in the mucus showed an increasing trend after infection. Furthermore, 16S rRNA sequencing also revealed that C. freundii infection also affected the diversity and community structure of the skin mucus microbiota. An increase in microbial diversity (p > 0.05) and a decrease in microbial abundance (p < 0.05) after infection were noted. The predominant bacterial phyla in the skin mucus were Proteobacteria, Fusobacteria, Bacteroidetes, Firmicutes, and Actinobacteria. Specifically, the relative abundance of Fusobacteria increased after infection. The predominant bacterial genera in the skin mucus were Cetobacterium, Pelomonas, Bradyrhizobium, Flavobacterium, and Pseudomonas. The relative abundance of Cetobacterium, Pseudomonas, and Flavobacterium increased after infection. Our current research findings will provide new insights into the theoretical basis for future research studies exploring the mechanism of sturgeon infection with C. freundii.

Modulation of the skin microbiome in cutaneous T-cell lymphoma delays tumour growth and increases survival in the murine EL4 model.

Cutaneous T-cell lymphomas (CTCL) are a group of lymphoproliferative disorders of skin-homing T cells causing chronic inflammation. These disorders cause impairment of the immune environment, which leads to severe infections and/or sepsis due to dysbiosis. In this study, we elucidated the host-microbial interaction in CTCL that occurs during the phototherapeutic treatment regime and determined whether modulation of the skin microbiota could beneficially affect the course of CTCL. EL4 T-cell lymphoma cells were intradermally grafted on the back of C57BL/6 mice. Animals were treated with conventional therapeutics such as psoralen + UVA (PUVA) or UVB in the presence or absence of topical antibiotic treatment (neomycin, bacitracin, and polymyxin B sulphate) as an adjuvant. Microbial colonisation of the skin was assessed to correlate with disease severity and tumour growth. Triple antibiotic treatment significantly delayed tumour occurrence (p = 0.026), which prolonged the survival of the mice (p = 0.033). Allocation to phototherapeutic agents PUVA, UVB, or none of these, along with antibiotic intervention, reduced the tumour growth significantly (p = 0.0327, p ≤ 0.0001, p ≤ 0.0001 respectively). The beta diversity indices calculated using the Bray-Curtis model showed that the microbial population significantly differed after antibiotic treatment (p = 0.001). Upon modulating the skin microbiome by antibiotic treatment, we saw an increase in commensal Clostridium species, e.g., Lachnospiraceae sp. (p = 0.0008), Ruminococcaceae sp. (p = 0.0001)., Blautia sp. (p = 0.007) and a significant reduction in facultative pathogens Corynebacterium sp. (p = 0.0009), Pelomonas sp. (p = 0.0306), Streptococcus sp. (p ≥ 0.0001), Pseudomonas sp. (p = 0.0358), and Cutibacterium sp. (p = 0.0237). Intriguingly, we observed a significant decrease in Staphylococcus aureus frequency (p = 0.0001) but an increase in the overall detection frequency of the Staphylococcus genus, indicating that antibiotic treatment helped regain the microbial balance and increased the number of non-pathogenic Staphylococcus populations. These study findings show that modulating microbiota by topical antibiotic treatment helps to restore microbial balance by diminishing the numbers of pathogenic microbes, which, in turn, reduces chronic inflammation, delays tumour growth, and increases survival rates in our CTCL model. These findings support the rationale to modulate the microbial milieu during the disease course of CTCL and indicate its therapeutic potential.

Bacteriophages from human skin infecting coagulase-negative Staphylococcus: diversity, novelty and host resistance.

The human skin microbiome comprises diverse populations that differ temporally between body sites and individuals. The virome is a less studied component of the skin microbiome and the study of bacteriophages is required to increase knowledge of the modulation and stability of bacterial communities. Staphylococcus species are among the most abundant colonisers of skin and are associated with both health and disease yet the bacteriophages infecting the most abundant species on skin are less well studied. Here, we report the isolation and genome sequencing of 40 bacteriophages from human skin swabs that infect coagulase-negative Staphylococcus (CoNS) species, which extends our knowledge of phage diversity. Six genetic clusters of phages were identified with two clusters representing novel phages, one of which we characterise and name Alsa phage. We identified that Alsa phages have a greater ability to infect the species S. hominis that was otherwise infected less than other CoNS species by the isolated phages, indicating an undescribed barrier to phage infection that could be in part due to numerous restriction-modification systems. The extended diversity of Staphylococcus phages here enables further research to define their contribution to skin microbiome research and the mechanisms that limit phage infection.

Staphylococcus aureus skin colonization is mediated by SasG lectin variation.

Staphylococcus aureus causes the majority of skin and soft tissue infections, but this pathogen only transiently colonizes healthy skin. However, this transient skin exposure enables S. aureus to transition to infection. The initial adhesion of S. aureus to skin corneocytes is mediated by surface protein G (SasG). Here, phylogenetic analyses reveal the presence of two major divergent SasG alleles in S. aureus: SasG-I and SasG-II. Structural analyses of SasG-II identify a nonaromatic arginine in the binding pocket of the lectin subdomain that mediates adhesion to corneocytes. Atomic force microscopy and corneocyte adhesion assays indicate that SasG-II can bind to a broader variety of ligands than SasG-I. Glycosidase treatment results in different binding profiles between SasG-I and SasG-II on skin cells. In addition, SasG-mediated adhesion is recapitulated using differentiated N/TERT keratinocytes. Our findings indicate that SasG-II has evolved to adhere to multiple ligands, conferring a distinct advantage to S. aureus during skin colonization.

Illuminating microflora: shedding light on the potential of blue light to modulate the cutaneous microbiome.

Cutaneous diseases (such as atopic dermatitis, acne, psoriasis, alopecia and chronic wounds) rank as the fourth most prevalent human disease, affecting nearly one-third of the world's population. Skin diseases contribute to significant non-fatal disability globally, impacting individuals, partners, and society at large. Recent evidence suggests that specific microbes colonising our skin and its appendages are often overrepresented in disease. Therefore, manipulating interactions of the microbiome in a non-invasive and safe way presents an attractive approach for management of skin and hair follicle conditions. Due to its proven anti-microbial and anti-inflammatory effects, blue light (380 - 495nm) has received considerable attention as a possible 'magic bullet' for management of skin dysbiosis. As humans, we have evolved under the influence of sun exposure, which comprise a significant portion of blue light. A growing body of evidence indicates that our resident skin microbiome possesses the ability to detect and respond to blue light through expression of chromophores. This can modulate physiological responses, ranging from cytotoxicity to proliferation. In this review we first present evidence of the diverse blue light-sensitive chromophores expressed by members of the skin microbiome. Subsequently, we discuss how blue light may impact the dialog between the host and its skin microbiome in prevalent skin and hair follicle conditions. Finally, we examine the constraints of this non-invasive treatment strategy and outline prospective avenues for further research. Collectively, these findings present a comprehensive body of evidence regarding the potential utility of blue light as a restorative tool for managing prevalent skin conditions. Furthermore, they underscore the critical unmet need for a whole systems approach to comprehend the ramifications of blue light on both host and microbial behaviour.

An Overview of Frog Skin-Derived Esc Peptides: Promising Multifunctional Weapons against Pseudomonas aeruginosa-Induced Pulmonary and Ocular Surface Infections.

Antimicrobial resistance is a silent pandemic harming human health, and Pseudomonas aeruginosa is the most common bacterium responsible for chronic pulmonary and eye infections. Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics. In this review, the in vitro/in vivo activities of the frog skin-derived AMP Esc(1-21) are shown. Esc(1-21) rapidly kills both the planktonic and sessile forms of P. aeruginosa and stimulates migration of epithelial cells, likely favoring repair of damaged tissue. However, to undertake preclinical studies, some drawbacks of AMPs (cytotoxicity, poor biostability, and limited delivery to the target site) must be overcome. For this purpose, the stereochemistry of two amino acids of Esc(1-21) was changed to obtain the diastereomer Esc(1-21)-1c, which is more stable, less cytotoxic, and more efficient in treating P. aeruginosa-induced lung and cornea infections in mouse models. Incorporation of these peptides (Esc peptides) into nanoparticles or immobilization to a medical device (contact lens) was revealed to be an effective strategy to ameliorate and/or to prolong the peptides' antimicrobial efficacy. Overall, these data make Esc peptides encouraging candidates for novel multifunctional drugs to treat lung pathology especially in patients with cystic fibrosis and eye dysfunctions, characterized by both tissue injury and bacterial infection.

Epsilon-poly-l-lysine microneedle patch loaded with amorphous doxycycline nanoparticles for synergistic treatment of skin infection.

The development of antibiotic-loaded microneedles has been hindered for years by limited excipient options, restricted drug-loading space, poor microneedle formability, and short-term drug retention. Therefore, this study proposes a dissolving microneedle fabricated from the host-defense peptide ε-poly-l-lysine (EPL) as an antibacterial adjuvant system for delivering antibiotics. EPL serves not only as a major matrix material for the microneedle tips, but also as a broad-spectrum antibacterial agent that facilitates the intracellular accumulation of the antibiotic doxycycline (DOX) by increasing bacterial cell membrane permeability. Furthermore, the formation of physically crosslinked networks of EPL affords microneedle tips with improved formability, good mechanical properties, and amorphous nanoparticles (approximately 7.2 nm) of encapsulated DOX. As a result, a high total loading content of both antimicrobials up to 2319.1 µg/patch is achieved for efficient transdermal drug delivery. In a Pseudomonas aeruginosa-induced deep cutaneous infection model, the EPL microneedles demonstrates potent and long-term effects by synergistically enhancing antibiotic activities and prolonging drug retention in infected lesions, resulting in remarkable therapeutic efficacy with 99.91 % (3.04 log) reduction in skin bacterial burden after a single administration. Overall, our study highlights the distinct advantages of EPL microneedles and their potential in clinical antibacterial practice when loaded with amorphous DOX nanoparticles.

Preclinical Atopic Dermatitis Skin in Infants: An Emerging Research Area.

Whereas clinically apparent atopic dermatitis (AD) can be confirmed by validated diagnostic criteria, the preclinical phenotype of infants who eventually develop AD is less well-characterized. Analogous to unaffected or nonlesional skin in established AD, clinically normal-appearing skin in infants who will develop clinical AD has distinct changes. Prospective studies have revealed insights into this preclinical AD phenotype. In this study, we review the structural, immunologic, and microbiome nature of the preclinical AD phenotype. Determination of markers that predict the development of AD will facilitate targeting of interventions to prevent the development or reduce the severity of AD in infants.