Skin Pathology Research Articles

Clinical observations of skin Kaposi’s sarcoma

Kaposi's sarcoma is an angioproliferative disease of endothelial origin associated with human herpes virus-8 (HHV-8), or Kaposi's sarcoma herpesvirus. The disease was first described in 1872 by Moritz Kaposi as a pigmented cutaneous sarcoma localized on the lower extremities. The disease is considered quite rare, but at present there is an increase in the incidence worldwide, due to which there is a growing interest in this problem. Today, it remains the leading skin pathology among HIV-positive patients, occurring in 20%. However, the assessment of the pathological process can be difficult, and the diagnosis may not be made at all, due to atypical clinical manifestations (especially in HIV-negative patients), so the problem of Kaposi's sarcoma diagnostics remains relevant for doctors of any specialty, especially dermatovenerologists and oncologists. Kaposi's sarcoma can affect almost any organ, including the skin. The most common localization is on the skin of the extremities and face. Clinical manifestations are rashes in the form of spots, nodules, plaques, nodes. Kaposi's sarcoma is classified according to clinical and epidemiological forms: classical, endemic, epidemic and iatrogenic. Recently, a fifth form has been described, called non-epidemic Kaposi's sarcoma, which is observed in HIV-negative men who have sex with other men. The persistence of HHV-8 alone in the human body is not sufficient for Kaposi's sarcoma to occur, as the development of the disease is dependent on immunosuppressive conditions such as HIV infection, cytostatic drugs, and chronic systemic inflammatory diseases (e.g., rheumatoid arthritis). The interaction between human immune dysfunction and the local inflammatory response to herpesvirus creates a favourable environment for the onset and progression of the disease. These clinical cases demonstrate an atypical clinical course of Kaposi's sarcoma of the skin with the absence of HIV-1, HIV-2 and HHV-8 in the blood of the presented patients.

Investigating pre-registration podiatry students approaches to identifying dermatology conditions in different skin tones: A mixed methods protocol.

Health inequalities are a well-known and widespread phenomenon throughout health care settings. In particular, people of color experience higher rates of delayed and/or misdiagnosis contributing to poorer outcomes and an increased mortality risk. Research suggests that health care professionals find it more difficult to correctly diagnose dermatological conditions in the non-White patient demographic. Although podiatrists routinely examine and assess skin lesions, there is a paucity of research exploring their accuracy or confidence in recognizing skin pathologies. This study aims to investigate podiatry student's ability, confidence, approaches, and perceptions in diagnosing dermatology pathologies in different skin tones. A mixed methods exploratory sequential design is proposed. In stage one, podiatry students from different higher education institutions will be invited to complete a pictorial survey. We have designed a survey comprising six validated images of inflammatory skin pathology (either eczema or psoriasis) in three different skin tone categories, standardized using the Fitzpatrick scale. Data from the survey in stage one will then be utilized to inform the next stage of the research. In stage two, respondents who completed the initial survey will be invited to participate in focus groups to explore their perceptions surrounding diagnostic approaches, confidence, and perceptions of skin conditions in different skin tone. A process of thematic analysis will be employed to identify emergent themes from these data. A mixed methods exploratory sequential design is proposed. In stage one, podiatry students from different higher education institutions will be invited to complete a pictorial survey. We have designed a survey comprising six validated images of inflammatory skin pathology (either eczema or psoriasis) in three different skin tone categories, standardized using the Fitzpatrick scale. Data from the survey in stage one will then be utilized to inform the next stage of the research. In stage two, respondents who completed the initial survey will be invited to participate in focus groups to explore their perceptions surrounding diagnostic approaches, confidence, and perceptions of skin conditions in different skin tone. A process of thematic analysis will be employed to identify emergent themes from these data.

Nevus comedonicus. Clinical case

Nevus comedonicus is a rare benign hamartoma of the sebaceous follicle which is more common on the face, neck, shoulders, chest or abdomen. Nevus is group of small or large open comedones. It is a type of organoid epidermal nevus and usually appears before the age of 10 years. The linear configuration of the lesion along Blaschko’s lines suggests that the nevus is a manifestation of mosaicism. A possible cause of nevus comedonicus is mosaic postzygotic mutation of the NEK9 gene. Nevus comedonicus syndrome is also associated with extracutaneous abnormalities. Extracutaneous manifestations most often include ocular abnormalities: ipsilateral cataracts and corneal changes. Associated skeletal abnormalities include abnormalities of the fingers/toes (polysyndactyly or clinodactyly, etc.), scoliosis and other spinal malformations. We present our patient with a large nevus comedonicus localized on the left half of the abdomen with transition to the thigh. The lesion consists of multiple densely located elements with a diameter up to 1–2 mm in the form of expanded orifices of hair follicles — open comedones and inflammatory nodes. Scars remain in place of resolved nodes. A feature of the nevus in our patient is the large size of the nevus and the presence of inflammatory nodes. Dermoscopy reveals numerous light and dark brown, round or barrel-shaped, homogeneous areas with protruding keratin plugs. The treatment was carried out at the clinic with minocycline and gel adapalene externally. Thus, comedo nevus is a rare skin pathology that usually appears at birth and can affect any area of the skin. It can be an isolated skin pathology or as a component of comedo nevus syndrome, which requires additional examination of patients.

Standalone single- and bi-layered human skin 3D models supported by recombinant silk feature native spatial organization

Physiologically relevant human skin models that include key skin cell types can be used forin vitrodrug testing, skin pathology studies, or clinical applications such as skin grafts. However, there is still no golden standard for such a model. We investigated the potential of a recombinant functionalized spider silk protein, FN-silk, for the construction of a dermal, an epidermal, and a bilayered skin equivalent (BSE). Specifically, two formats of FN-silk (i.e. 3D network and nanomembrane) were evaluated. The 3D network was used as an elastic ECM-like support for the dermis, and the thin, permeable nanomembrane was used as a basement membrane to support the epidermal epithelium. Immunofluorescence microscopy and spatially resolved transcriptomics analysis demonstrated the secretion of key ECM components and the formation of microvascular-like structures. Furthermore, the epidermal layer exhibited clear stratification and the formation of a cornified layer, resulting in a tight physiologic epithelial barrier. Our findings indicate that the presented FN-silk-based skin models can be proposed as physiologically relevant standalone epidermal or dermal models, as well as a combined BSE.

Skin Structure, Physiology, and Pathology in Topical and Transdermal Drug Delivery.

Several industries are increasingly focused on enhancing the delivery of active ingredients through the skin to optimize therapeutic outcomes. By facilitating the penetration of active ingredients through the skin barrier, these enhancers can significantly improve the efficacy of various formulations, ranging from skincare products to therapeutic agents targeting systemic circulation. As the understanding of skin physiology and the mechanisms of drug absorption deepen, these industries are adopting permeation enhancers more widely, ultimately leading to better patient outcomes and expanded treatment options. However, the structure and physiological function of the skin can vary according to different factors, such as the area of the body and between individuals. These variations, along with external environmental exposures, aging and pathological conditions, introduce complexities that must be carefully considered when designing effective delivery systems. Considering the intricacies of skin structure and physiology, tailoring systems to account for regional differences, individual variability, and changes induced by environmental factors or disease is critical to optimizing therapeutic outcomes. This review discusses the features of skin structure, physiology, and pathologies, as well as the application of permeation enhancers in these contexts. Furthermore, it addresses the use of animal skin models in transdermal delivery and dermatological studies, along with the latest developments in this field.

Quantitative estimation of optical properties in bilayer media within the subdiffusive regime using tilted fiber-optic probe diffuse reflectance spectroscopy, part 2: probe design, realization, and experimental validation.

Tissues like skin have a layered structure where each layer's optical properties vary significantly. However, traditional diffuse reflectance spectroscopy assumes a homogeneous medium, often leading to estimations that reflects the properties of neither layer. There's a clear need for probes that can precisely measure the optical properties of layered tissues. This paper aims to design a diffuse reflectance probe capable of accurately estimating the optical properties of bilayer tissues in the subdiffusive regime. Using Monte Carlo simulations, we evaluated key geometric factors-fiber placement, tilt angle, diameter, and numerical aperture-on optical property estimation, following the methodology in Part I. A robust design is proposed that balances accurate intrinsic optical property (IOP) calculations with practical experimental constraints. The designed probe, featuring eight illumination and eight detection fibers with varying spacings and tilt angles. The estimation error of the IOP calculation for bilayer phantoms is less than 20% for top layers with thicknesses between 0.2 and 1.0mm. Building on the approach from Part I and using a precise calibration, the probe effectively quantified and distinguished the IOPs of bilayer samples, particularly those relevant to early skin pathology detection and characterization.

Acne Vulgaris in Adolescents: Scientific Evidence for Optimizing Treatment Regimens via Dermatocosmetics

Acne vulgaris (AV) is a common skin pathology in adolescents, it is characterized by chronic recurrent inflammatory process affecting the pilosebaceous units. This disease has significant negative effect on both quality of life and psychosocial well-being, resulting in development of various mental disorders and physical discomfort, including not only typical clinical signs, but also post-acne symptom complex. Nowadays, the paramount importance in disease pathophysiology are changes in the skin microbiome caused by interactions between genetic and exposomal factors leading to increased cutaneous fatty secretion by sebocytes and concomitant dysfunction of the epidermal barrier due to ongoing inflammatory process. Current AV treatment options include topical and systemic therapies with various clinical and pharmacological groups. However, most available options (for dermatovenerologists) can provoke dry skin and irritate sensitive adolescent skin due to additional disruption of epidermal barrier and microbiome composition. All together it significantly reduces patient compliance, and, therefore, reduces the treatment success rate. We have to mention that AV management should be carried out for a long time to prevent the recurrence observed in one third of all cases. It emphasizes the topicality of adequate optimization of treatment regimens used in wide clinical practice. In this context, guidelines for skin care have the leading role. It is crucial part of AV management, and it can not only improve compliance, but also increase the efficacy of prescribed drugs through synergistic interactions. Though, the comprehensive analysis of the available core care products, their composition and the effect of their ingredients on the structural and functional integrity of the skin, is required to ensure such effect.

Lesional senescent CD4+ T cells mediate bystander cytolysis and contribute to the skin pathology of human cutaneous leishmaniasis.

Cytotoxic activity is a hallmark of the immunopathogenesis in human cutaneous leishmaniasis (CL). In this study, we identified accumulation of CD4+ granzyme B producing T cells with increased cytotoxic capacity in CL lesions. These cells showed enhanced expression of activating NK receptors (NKG2D and NKG2C), diminished expression of inhibitory NKG2A, along with the upregulation of the senescence marker CD57. Notably, CD4+ T cells freshly isolated from CL lesions demonstrated remarkable capacity to mediate NL-like bystander cytolysis. Phenotypic analyses revealed that lesional CD4+ T cells are mainly composed of late-differentiated effector (CD27-CD45RA-) and terminally differentiated (senescent) TEMRA (CD27-CD45RA+) subsets. Interestingly, the TEMRA CD4+ T cells exhibited higher expression of granzyme B and CD107a. Collectively, our results provide the first evidence that senescent cytotoxic CD4+ T cells may support the skin pathology of human cutaneous leishmaniasis and, together with our previous findings, support the notion that multiple subsets of cytotoxic senescent cells may be involved in inducing the skin lesions in these patients.

JAK inhibition decreases the autoimmune burden in Down syndrome.

Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmune disorders and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined. Here, we report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS. We demonstrate multi-organ autoimmunity of pediatric onset concurrent with unexpected autoantibody-phenotype associations. Importantly, constitutive immune remodeling and hypercytokinemia occur from an early age prior to autoimmune diagnoses or autoantibody production. We then report the interim analysis of a Phase II clinical trial investigating the safety and efficacy of the JAK inhibitor tofacitinib through multiple clinical and molecular endpoints. Analysis of the first 10 participants to complete the 16-week study shows a good safety profile and no serious adverse events. Treatment reduced skin pathology in alopecia areata, psoriasis, and atopic dermatitis, while decreasing interferon scores, cytokine scores, and levels of pathogenic autoantibodies without overt immune suppression. Additional research is needed to define the effects of JAK inhibition on the broader developmental and clinical hallmarks of DS. ClinicalTrials.gov identifier: NCT04246372.

The Influence of Circadian Rhythms on DNA Damage Repair in Skin Photoaging.

Circadian rhythms, the internal timekeeping systems governing physiological processes, significantly influence skin health, particularly in response to ultraviolet radiation (UVR). Disruptions in circadian rhythms can exacerbate UVR-induced skin damage and increase the risk of skin aging and cancer. This review explores how circadian rhythms affect various aspects of skin physiology and pathology, with a special focus on DNA repair. Circadian regulation ensures optimal DNA repair following UVR-induced damage, reducing mutation accumulation, and enhancing genomic stability. The circadian control over cell proliferation and apoptosis further contributes to skin regeneration and response to UVR. Oxidative stress management is another critical area where circadian rhythms exert influence. Key circadian genes like brain and muscle ARNT-like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) modulate the activity of antioxidant enzymes and signaling pathways to protect cells from oxidative stress. Circadian rhythms also affect inflammatory and immune responses by modulating the inflammatory response and the activity of Langerhans cells and other immune cells in the skin. In summary, circadian rhythms form a complex defense network that manages UVR-induced damage through the precise regulation of DNA damage repair, cell proliferation, apoptosis, inflammatory response, oxidative stress, and hormonal signaling. Understanding these mechanisms provides insights into developing targeted skin protection and improving skin cancer prevention.

Diapedesis leading to hematidrosis due to abrupt emotional suffering (Review).

Hematidrosis constitutes a rare imposing phenomenon encountered millennia ago. It involves the plexus of small, mostly superficial arteries, veins and sweat glands of various parts of the human body. Bloody sweat implies skin pathology. It has been connected to psychogenic impairment and lacks a clear etiology. The present study conducted a historical review using the Thesaurus Linguae Graecae®, Gallica-BNF and Google Books databases. The year 1900 was the mark for full-text works to be included. A second review of the modern literature, over the last 20 years, was carried out using the PubMed/MedLine database. In both eras, the terms h[a]emat[h]idrosis, diapedesis, sudor sanguineus, plus various others vocables of Hellenic and Latin origin, were used as key words. Cases of persons suffering hematidrosis during stigmata as partly connected to this study were surveyed and discussed separately. References were obtained from the classical Greece, late Hellenic antiquity and Roman era. A number of 70 cases were registered from the Renaissance to 1900, and 44 cases between 2007 and 2022. The later time interval is considered as the selection of references of all time, while the 1870 to 1884 interval followed. Differences in sex were observed (males, 60.6%; and females, 39.4%; vs. males, 25.6%; and females, 74.4%). The scalp, forehead, face, trunk, arms and legs were the most common areas of appearance in both time intervals. The eyes and ears were the most common areas of appearance in the modern era. As regards the limitations of the present review, it should be emphasized that not all historical cases were available for survey. Stigmata were studied independently. Records in etiology hypothesis, pathological description and the manifestation of a cluster of post-triggering effects described were similar over time. The modern way of life, major stressful events, a fear of death, hematological disorders, vessel derangements and deep faith may trigger hematidrosis. This spectacular acute event stimulates alertness in patients, family, caregivers and physicians, and may lead to social isolation and unnecessary diagnostic and/or therapeutic interventions. The present narrative review aimed to connect science with history and religion, promote contemplation among health professionals and highlight a medical peculiarity. An open mind is warranted in order to comprehend phenomena in religion. Education for the family and a knowledge update for health professionals is also necessary.

Pathogenesis of Inflammation in Skin Disease: From Molecular Mechanisms to Pathology.

Many skin diseases begin with inflammatory changes on a molecular level. To develop a more thorough understanding of skin pathology and to identify new targets for therapeutic advancements, molecular mechanisms of inflammation in the context of skin disease should be studied. Current research efforts to better understand skin disease have focused on examining the role of molecular processes at several stages of the inflammatory response such as the dysregulation of innate immunity sensors, disruption of both transcriptional and post-transcriptional regulation, and crosstalk between immune and neuronal processes (neuro-immune crosstalk). This review seeks to summarize recent developments in our understanding of inflammatory processes in skin disease and to highlight opportunities for therapeutic advancements. With a focus on publications within the past 5 years (2019-2024), the databases PubMed and EBSCOhost were used to search for peer-reviewed papers regarding inflammatory molecular mechanisms and skin disease. Several themes of research interest regarding inflammatory processes in skin disease were determined through extensive review and were included based on their relative representation in current research and their focus on therapeutic potential. Several skin diseases such as psoriasis, atopic dermatitis, hidradenitis suppurativa, and scleroderma were described in the paper to demonstrate the widespread influence of inflammation in skin disease.

Dermal white adipose tissue: Development and impact on hair follicles, skin defense, and fibrosis.

Dermal white adipose tissue (DWAT) is a distinctive adipose depot located within the lower dermis of the skin. Its significance as an ancillary fat in skin homoeostasis has recently received increased attention. New research has revealed that DWAT responses to skin pathology and physiology changes, impacting skin development, hair cycling, defense mechanisms, and fibrotic conditions. In this review, we explore the developmental process of DWAT and the adipose commitment timing of hypodermal. We explore the development process of DWAT and its pivotal role in regulating the hair cycle. We conclude the antibacterial activity and reversible dedifferentiation of dermal adipocytes in response to skin defense. Furthermore, we underscore the potentially crucial yet underestimated anti-fibrotic functions of DWAT-derived adipokines and adipocyte-myofibroblast transition.

Inherited Basaloid Neoplasms Associated With SUFU Pathogenic Variants.

Germline SUFU pathogenic variants (PVs) have previously been associated with basal cell nevus syndrome (BCNS) and multiple infundibulocystic basal cell carcinoma syndrome; however, a broader spectrum of cutaneous findings in patients with SUFU PVs has not been well delineated. To define the clinical and histopathologic spectrum of cutaneous findings in patients with germline SUFU PVs. This case series was conducted in multiple US academic dermatology, medical genetics, and medical oncology clinics between July 2014 and July 2022. The study included patients with confirmed germline SUFU PVs who were evaluated by a dermatologist. The analysis took place from March to September 2023. Histopathologic evaluation of skin biopsies with or without immunohistochemical staining, and targeted next-generation sequencing (NGS) on tumor specimens. All 5 patients were women. The mean (range) age at presentation was 50.2 (31-68) years, with skin manifestations initially appearing in the fourth to sixth decades of life. None had keratocystic odontogenic tumors. A total of 29 skin pathology specimens from the 5 patients were reviewed; of these, 3 (10.3%) were diagnosed as basaloid follicular hamartomas (BFHs), 10 (34.5%) classified as infundibulocystic basal cell carcinomas (iBCCs), 6 (20.7%) classified as nodular basal cell carcinomas (nBCCs), and 1 (3.4%) as infiltrative basal cell carcinoma (BCC). Targeted NGS studies on tumor specimens suggest that an increased number of UV-signature variants is associated with basal cell carcinomas compared with more indolent basaloid follicular hamartomas. Patients with germline SUFU PVs may present with multiple indolent basaloid neoplasms in addition to conventional basal cell carcinomas, typically appearing in the fourth to sixth decades of life. Although there are overlapping clinical manifestations, these findings help to differentiate the clinical syndrome associated with SUFU PVs from PTCH1 BCNS. Awareness of the clinicopathologic spectrum of SUFU-associated basaloid neoplasms is important for dermatologists and dermatopathologists because many (although not all) of these lesions are indolent and do not require aggressive surgical treatment. Importantly, because SUFU lies downstream of the protein smoothened, vismodegib and other smoothened inhibitors are unlikely to be effective therapies in this subset of patients.

YjbH contributes to Staphylococcus aureus skin pathology and immune response through Agr-mediated α-toxin regulation

ABSTRACT Staphylococcus aureus is the most common cause of skin and soft tissue infections (SSTIs) with Methicillin-Resistant S. aureus (MRSA) strains being a major contributor in both community and hospital settings. S. aureus relies on metabolic diversity and a large repertoire of virulence factors to cause disease. This includes α-hemolysin (Hla), an integral player in tissue damage found in various models, including SSTIs. Previously, we identified a role for the Spx adapter protein, YjbH, in the regulation of several virulence factors and as an inhibitor of pathogenesis in a sepsis model. In this study, we found that YjbH is critical for tissue damage during SSTI, and its absence leads to decreased proinflammatory chemokines and cytokines in the skin. We identified no contribution of YjbI, encoded on the same transcript as YjbH. Using a combination of reporters and quantitative hemolysis assays, we demonstrated that YjbH impacts Hla expression and activity both in vitro and in vivo. Additionally, expression of Hla from a non-native promoter reversed the tissue damage phenotype of the ΔyjbIH mutant. Lastly, we identified reduced Agr activity as the likely cause for reduced Hla production in the ΔyjbH mutant. This work continues to define the importance of YjbH in the pathogenesis of S. aureus infection as well as identify a new pathway important for Hla production.

Dysbiosis-activated IL-17-producing T cells promote skin immunopathological progression in mice deficient of the Notch ligand Jag1 in keratinocytes

BackgroundThe Notch signaling pathway is an evolutionarily conserved regulatory cascade critical in skin development and homeostasis. Mice deficient of Notch signaling molecules have impaired skin and hair follicle development associated with local tissue inflammation. However, mechanisms underlying skin inflammation and pathology resulting from defective Notch signals are not well understood. ObjectiveTo dissect molecular and cellular mechanisms underlying development of skin immunopathology in mice defective of the Notch ligand Jagged-1 (Jag1). MethodsWe assessed involvement of microbiota and immune cell subsets in skin pathogenic symptoms in Foxn1CreJag1fl/fl mice that were deficient of Jag1 in keratinocytes. We also used RNA-seq and 16S rRNA gene-seq analyses to identify molecular factors and bacterial species contributing to skin pathologic symptoms in Foxn1CreJag1fl/fl mice. ResultsCompared to Jag1-sufficient littermate control mice, Foxn1CreJag1fl/fl mice had specific expansion of IL-17a-producing T cells accompanying follicular and epidermal hyperkeratosis and cyst formation while antibody blockage of IL-17a reduced the skin pathology. RNA-sequencing and 16S rRNA gene-sequencing analyses revealed dysregulated immune responses and altered microbiota compositions in the skin of Foxn1CreJag1fl/fl mice. Antibiotic treatment completely prevented over-activation of IL-17a-producing T cells and alleviated skin pathology in Foxn1CreJag1fl/fl mice. ConclusionDysbiosis-induced over-activation of IL-17a-producing T cells is critically involved in development of skin pathology in Foxn1CreJag1fl/fl mice, establishing Foxn1CreJag1fl/fl mice as a useful model to study pathogenesis and therapeutic targets in microbiota-IL-17-mediated skin inflammatory diseases such as hidradenitis suppurativa (HS) and psoriasis.

Ajuga taiwanensis Extract Promotes Wound-healing via Activation of PDGFR/MAPK Pathway.

Chronic and prolonged wounds are a serious public problem that may severely affect the quality of life and result in psychological pressure. Fibroblasts play a crucial role in the wound process and in skin pathology. Herbal drugs have long been used for wound care worldwide. Ajuga taiwanensis (Lamiaceae) is a folk medicine for antipyretics, anti-inflammation, and reducing swelling in Taiwan. This study aimed to investigate the effect of A.taiwanensis in wound healing and the underlying mechanisms. Under human dermal fibroblast (HDF) wound-healing activity-guided fractionation, we found that a sub-fraction (AT-M) of A. taiwanensis extract (AT) and the major ingredients significantly promoted wound healing and decreased IL-1β and - 6 expressions on HDFs. Furthermore, the fraction of AT-M enhanced wound healing on C57BL/6 mouse skins, increased PDGFR expressions, and activated the PDGFR/MAPK pathway. Taken together, A.taiwanensis extracts promote wound healing by the PDGFR pathway and lead to enhanced cell spreading and motility, thereby having a possible beneficial effect on wound healing.

Resolvin D5 Protects Female Hairless Mouse Skin from Pathological Alterations Caused by UVB Irradiation.

Resolvin D5 (RvD5) is a lipid mediator that has been reported to present anti-inflammatory and pro-resolution properties. Evidence also supports its capability to enhance reactive oxygen species (ROS) production during bacterial infections, which would be detrimental in diseases driven by ROS. The biological activity of RvD5 and mechanisms against UVB irradiation skin pathology have not been investigated so far. Female hairless mice were treated intraperitoneally with RvD5 before UVB stimulus. RvD5 reduced skin edema in a dose-dependent manner as well as oxidative stress by increasing antioxidants (endogenous tissue antioxidant scavenging of cationic radical, iron reduction, catalase activity and reduced glutathione levels) and decreasing pro-oxidants (superoxide anion and lipid peroxidation). RvD5 antioxidant activity was accompanied by enhancement of Nrf2, HO-1 and NQO1 mRNA expression. RvD5 reduced the production of IL-1β, TNF-α, TGF-β, and IL-10. RvD5 also reduced the inflammatory cell counts, including mast cells and neutrophils/macrophages. The reduction of oxidative stress and inflammation resulted in diminished matrix metalloproteinase 9 activity, collagen degradation, epidermal thickening and sunburn cell development. Therefore, this study demonstrates, to our knowledge, the first body of evidence that RvD5 can be used to treat UVB skin pathology and unveils, at least in part, its mechanisms of action.

Antibacterial and Immunosuppressive Effects of a Novel Marine Brown Alga-Derived Ester in Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic skin condition that is characterized by dysregulated immune responses and a heightened risk of Staphylococcus aureus infections, necessitating the advancement of innovative therapeutic methods. This study explored the potential of (6Z,9Z,12Z,15Z)-(2R,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl octadeca-6,9,12,15-tetraenoate (HSN-S1), a compound derived from the marine alga Hizikia fusiformis, which shows anti-inflammatory, antimicrobial, and immunomodulatory properties. HSN-S1 was isolated and characterized using advanced chromatographic and spectroscopic methods. Its efficacy was evaluated via in vitro assays with keratinocytes, macrophages, and T cells to assess cytokine suppression and its immunomodulatory effects; its antibacterial activity against S. aureus was quantified. The in vivo effectiveness was validated using a 2,4-dinitrochlorobenzene-induced AD mouse model that focused on skin pathology and cytokine modulation. HSN-S1 significantly reduced pro-inflammatory cytokine secretion, altered T-helper cell cytokine profiles, and showed strong antibacterial activity against S. aureus. In vivo, HSN-S1 alleviated AD-like symptoms in mice and reduced skin inflammation, transepidermal water loss, serum immunoglobulin-E levels, and Th2/Th17 cytokine outputs. These findings suggest HSN-S1 to be a promising marine-derived candidate for AD treatment, as it offers a dual-target approach that could overcome the limitations of existing therapies, hence warranting further clinical investigation.

Experience in treating multifocal alopecia areata in a child with Jak kinase inhibitors

Alopecia Areata is an autoimmune disease characterized by hair loss mediated by CD8 + T cells. There are no proven effective treatments for alopecia. Recent research on the immunology of hair follicles and recent developments in the field of immunopatogenesis, as well as common ways of developing the disease with other autoimmune disorders have led to research on new treatments, targeted at specific immunological pathways. The so-called JAK-STAT pathway is responsible for transmitting signal from different cytokines to the nucleus of the cell, suggesting that blocking this pathway may be effective in the treatment of alopecia.Study purpose. Presentation of Clinical Case of Multi-focal Alopecia Treatment in Child Oral Tofacitinib.Materials and methods. The study was conducted on the basis of the dermatology department with the laser surgery group of the Center for Pediatric Dermatology and Laboratory of Skin Pathology in children FGAU «National Medical Research Center for Children’s Health» of the Ministry of Health of Russia from April 2021 to November 2022. Severity Alopecia Tool (SALT) was used to determine the severity of the disease in participants. The SALT scale takes into account the percentage of affected hair and divides it into 6 subclasses (S 0 %, S1 <25 %, S2 25–49 %, S3 50–74 %, S4 75–99 % and C5100 %).Results. When oral tofacitinib was administered for 6 months in a 9-year-old patient, full recovery of hair growth on the scalp was observed. No significant abnormalities based on clinical and biochemical blood results were found for the period of treatment and for a year after withdrawal. There was no recurrence of hair loss after the withdrawal of the drug for 12 months.Conclusion. JAK inhibitors can be effective new treatments for alopecia in children. Additional data from randomized controlled trials are required for safe use of JAK inhibitors.