Skin Areas Research Articles

Hypoxia and Foxn1 alter the proteomic signature of dermal fibroblasts to redirect scarless wound healing to scar-forming skin wound healing in Foxn1−/− mice

BackgroundFoxn1−/− deficient mice are a rare model of regenerative skin wound healing among mammals. In wounded skin, the transcription factor Foxn1 interacting with hypoxia-regulated factors affects re-epithelialization, epithelial-mesenchymal transition (EMT) and dermal white adipose tissue (dWAT) reestablishment and is thus a factor regulating scar-forming/reparative healing. Here, we hypothesized that transcriptional crosstalk between Foxn1 and Hif-1α controls the switch from scarless (regenerative) to scar-present (reparative) skin wound healing. To verify this hypothesis, we examined (i) the effect of hypoxia/normoxia and Foxn1 signalling on the proteomic signature of Foxn1−/− (regenerative) dermal fibroblasts (DFs) and then (ii) explored the effect of Hif-1α or Foxn1/Hif-1α introduced by a lentiviral (LV) delivery vector to injured skin of regenerative Foxn1−/− mice with particular attention to the remodelling phase of healing.ResultsWe showed that hypoxic conditions and Foxn1 stimulation modified the proteome of Foxn1−/− DFs. Hypoxic conditions upregulated DF protein profiles, particularly those related to extracellular matrix (ECM) composition: plasminogen activator inhibitor-1 (Pai-1), Sdc4, Plod2, Plod1, Lox, Loxl2, Itga2, Vldlr, Ftl1, Vegfa, Hmox1, Fth1, and F3. We found that Pai-1 was stimulated by hypoxic conditions in regenerative Foxn1−/− DFs but was released by DFs to the culture media exclusively upon hypoxia and Foxn1 stimulation. We also found higher levels of Pai-1 protein in DFs isolated from Foxn1+/+ mice (reparative/scar-forming) than in DFs isolated from Foxn1−/− (regenerative/scarless) mice and triggered by injury increase in Foxn1 and Pai-1 protein in the skin of mice with active Foxn1 (Foxn1+/+ mice). Then, we demonstrated that the introduction of Foxn1 and Hif-1α via lentiviral injection into the wounded skin of regenerative Foxn1−/− mice activates reparative/scar-forming healing by increasing the wounded skin area and decreasing hyaluronic acid deposition and the collagen type III to I ratio. We also identified a stimulatory effect of LV-Foxn1 + LV-Hif-1α injection in the wounded skin of Foxn1−/− mice on Pai-1 protein levels.ConclusionsThe present data highlight the effect of hypoxia and Foxn1 on the protein profile and functionality of regenerative Foxn1−/− DFs and demonstrate that the introduction of Foxn1 and Hif-1α into the wounded skin of regenerative Foxn1−/− mice activates reparative/scar-forming healing.

Chromosome 16p11.2 microdeletion syndrome with microcephaly and Dandy-Walker malformation spectrum: expanding the known phenotype

BackgroundChromosome 16p11.2 deletions and duplications were found to be the second most common copy number variation (CNV) reported in cases with clinical presentation suggestive of chromosomal syndromes. Chromosome 16p11.2 deletion syndrome shows remarkable phenotypic heterogeneity with a wide variability of presentation extending from normal development and cognition to severe phenotypes. The clinical spectrum ranges from neurocognitive and global developmental delay (GDD), intellectual disability, and language defects (dysarthria /apraxia) to neuropsychiatric and autism spectrum disorders. Other presentations include dysmorphic features, congenital malformations, insulin resistance, and a tendency for obesity. Our study aims to narrow the gap of knowledge in Saudi Arabia and the Middle Eastern and Northern African (MENA) region about genetic disorders, particularly CNV-associated disorders. Despite their rarity, genetic studies in the MENA region revealed high potential with remarkable genetic and phenotypic novelty.ResultsWe identified a heterozygous de novo recurrent proximal chromosome 16p11.2 microdeletion by microarray (arr[GRCh38]16p11.2(29555974_30166595)x1) [(arr[GRCh37]16p11.2(29567295_30177916)x1)] and confirmed by whole exome sequencing (arr[GRCh37]16p11.2(29635211_30199850)x1). We report a Saudi girl with severe motor and cognitive disability, myoclonic epilepsy, deafness, and visual impairment carrying the above-described deletion. Our study broadens the known phenotypic spectrum associated with recurrent proximal 16p11.2 microdeletion syndrome to include developmental dysplasia of the hip, optic atrophy, and a flat retina. Notably, the patient exhibited a rare combination of microcephaly, features consistent with the Dandy-Walker spectrum, and a thin corpus callosum (TCC), which are extremely infrequent presentations in patients with the 16p11.2 microdeletion. Additionally, the patient displayed areas of skin and hair hypopigmentation, attributed to a homozygous hypomorphic allele in the TYR gene.ConclusionThis report expands on the clinical phenotype associated with proximal 16p11.2 microdeletion syndrome, highlighting the potential of genetic research in Saudi Arabia and the MENA region. It underscores the importance of similar future studies.

52318 Fatty Acids and Mycobiome Across Skin Areas in Atopic Dermatitis

52318 Fatty Acids and Mycobiome Across Skin Areas in Atopic Dermatitis

Immunoexpression Patterns of Adhesion Molecules (E-cadherin, β-catenin, CD56) and Cytokeratins (CK19, CK20, HMWCK, CAM5.2) During Hair Development in Human Fetuses Compared With Adults.

Abnormalities in the expression of cytokeratins or adhesion molecules have been associated with hair disorders. The expression patterns of these molecules in the hair follicles of developing human fetuses are not obvious. We aimed to investigate the expression patterns of some cytokeratins and adhesion molecules in the hair follicle of human fetuses and compared them with adults. Forty-eight fetuses of >16 gestational weeks and 22 adult cases with total excisions of benign nevi or cysts were enrolled. The skin samples were taken from both the scalp and back of the fetuses. The histopathologically normal skin areas were evaluated in adults. CK19, CK20, CAM5.2, high-molecular-weight cytokeratin, E-cadherin, β-catenin, and CD56 immunohistochemical stainings were performed. In the fetus group, the staining scores declined in the third trimester but elevated and reached the highest level in adults, except for CD56, which did not stain any adult samples. All stainings were mostly observed in the outer root sheath, except CD56 that stained the perifollicular dermal sheath only in fetuses. E-cadherin, β-catenin, and high-molecular-weight cytokeratin strongly and diffusely stained all adult samples. CAM5.2 and CK19 scores were correlated in fetuses (scalp scores: r s = 0.405, P = 0.004; back scores: r s = 0.422, P = 0.003) and adults (back scores: r s = 0.562, P = 0.046). CD56 negativity indicated the immune-privilege feature of adult hair follicles. As CK19, CAM5.2 may be used to find the regions of stem cells or transient amplifying cells.

Evaluación de la eficacia y concordancia de la angiografía con verde de indocianina en la cirugía oncoplástica y reconstructiva de la mama. resultados preliminares del estudio prospectivo gBREAST-22

IntroductionDuring oncoplastic procedures, the vascularization and perfusion of the skin flaps is modified, thus increasing the possibility of skin necrosis.The objective of this study is to evaluate the effectiveness of indocyanine color green angiography (ICG-A) to determine intraoperative skin necrosis after oncoplastic surgery or skin-sparing or nipple-skin sparing mastectomy (NSSM). Patients and methodProspective observational study to evaluate the sensitivity, specificity and positive and negative predictive values of the ICG-A in women with high-risk breast cancer. Results98 women and 156 breasts were included in the study. A total of 20 women (20.4%) presented an image of ischemia in the ICG-A. 21 women (21.4%) presented ischemic events in the postoperative period, 71.4% of these events had been detected in the third ICG-A. Three of these patients (3.1%) presented a serious complication that required reintervention. The sensitivity and specificity of the A-VIC was 71.4% and 93.5%, respectively. ConclusionsICG-A has high specificity and negative predictive value for detecting areas of low perfusion. In breast units with highly complex surgery, it can be useful to plan extreme surgeries and identify skin areas of low perfusion.

Evaluation of the efficacy and concordance of indocianine color green angiography in oncoplastic and reconstructive breast surgery. Preliminary results of the gBREAST-22 prospective study

IntroductionDuring oncoplastic procedures, the vascularization and perfusion of the skin flaps is modified, thus increasing the possibility of skin necrosis.The objective of this study is to evaluate the effectiveness of indocyanine color green angiography (ICG-A) to determine intraoperative skin necrosis after oncoplastic surgery or skin-sparing or nipple-skin sparing mastectomy (NSSM). Patients and methodProspective observational study to evaluate the sensitivity, specificity and positive and negative predictive values ​​of the ICG-A in women with high-risk breast cancer. Results98 women and 156 breasts were included in the study. A total of 20 women (20.4%) presented an image of ischemia in the ICG-A. 21 women (21.4%) presented ischemic events in the postoperative period, 71.4% of these events had been detected in the third ICG-A. Three of these patients (3.1%) presented a serious complication that required reintervention. The sensitivity and specificity of the ICG-A was 71.4% and 93.5%, respectively. ConclusionsICG-A has high specificity and negative predictive value for detecting areas of low perfusion. In breast units with highly complex surgery, it can be useful to plan extreme surgeries and identify skin areas of low perfusion.

Innovative noninvasive gait-synchronized vibrotactile feedback system : "I can feel myself walking again"

Despite intensive research and development of systems for restoration of sensory information, these have so far only been the subject of study protocols. Anew noninvasive feedback system translates pressure loads on the forefoot and hindfoot into gait-synchronized vibrotactile stimulation of adefined skin area. To increase the authenticity, this treatment can be supplemented by a surgical procedure. Targeted sensory reinnervation (TSR) describes amicrosurgical procedure in which adefined skin area on the amputated stump of the residual limb is first denervated and then reinnervated by aspecific, transposed sensory nerve harvested from the amputated part of the limb. This creates asensory interface at the residual stump. This article presents the clinical and orthopedic technical treatment pathway with this innovative vibrotactile feedback system and explains in detail the surgical procedure of TSR after amputation of the lower limb.

Comparison of the Skin Microbiota in the Periocular Region between Patients with Inflammatory Skin Diseases and Healthy Participants: A Preliminary Study.

(1) Background: Periocular or periorbital dermatitis is a common term for all inflammatory skin diseases affecting the area of skin around the eyes. The clear etiopathogenesis of periocular dermatitis is still not fully understood. Advances in molecular techniques for studying microorganisms living in and on our bodies have highlighted the microbiome as a possible contributor to disease, as well as a promising diagnostic marker and target for innovative treatments. The aim of this study was to compare the composition and diversity of the skin microbiota in the periocular region between healthy individuals and individuals affected by the specific entity of periocular dermatitis. (2) Methods: A total of 35 patients with periocular dermatitis and 39 healthy controls were enrolled in the study. After a skin swab from the periocular region was taken from all participants, DNA extraction and 16S rRNA gene amplicon sequencing using Illumina NovaSeq technology were performed. (3) Results: Staphylococcus and Corynebacterium were the most abundant bacterial genera in the microbiota of healthy skin. Analysis of alpha diversity revealed a statistically significant change (p < 0.05) in biodiversity based on the Faith's PD index between patients and healthy individuals. We did not observe changes in beta diversity. The linear discriminant analysis effect size (LEfSe) revealed that Rothia, Corynebacterium, Bartonella, and Paracoccus were enriched in patients, and Anaerococcus, Bacteroides, Porphyromonas, and Enhydrobacter were enriched in healthy controls. (4) Conclusions: According to the results obtained, we assume that the observed changes in the bacterial microbiota on the skin, particularly Gram-positive anaerobic cocci and skin commensals of the genus Corynebacterium, could be one of the factors in the pathogenesis of the investigated inflammatory diseases. The identified differences in the microbiota between healthy individuals and patients with periocular dermatitis should be further investigated.

Novel embelin-loaded transniosomes for topical delivery: comprehensive exploration of in vitro, ex vivo and dermatokinetic assessment for anti-cancer activity.

This study systematically designed and optimised a transniosomal formulation containing embelin for skin cancer management. The transniosomes were developed using a rotary evaporation method and then optimised using a Box-Behnken design. The optimized embelin-loaded transniosomes (Opt-EMB-TNs) exhibited a vesicle size of 149.01 nm, polydispersity index of 0.184, a zeta potential of -21.14 mV, an entrapment efficiency of 75.6 ± 0.65%, drug loading of 3.36 ± 0.03% and drug release of 80.88 ± 2.55%. The antioxidant potential of Opt-EMB-TNs was found to be 88.54% when compared to standard ascorbic acid. Dermatokinetic studies showed a greater drug deposition in targeted skin areas with Opt-EMB-TN gel compared to the embelin conventional gel (EMB-CF gel). In addition, the penetration depth study of the skin sample revealed that the transniosomal gel containing rhodamine B dye exhibited higher penetration than that of the rhodamine B dye containing hydroalcoholic solution. The efficacy of Opt-EMB-TNs for skin cancer was confirmed by cytotoxicity assay against the B16F10 melanoma cell line. The study concluded that the Opt-EMB-TN gel formulation is a promising and effective topical treatment for skin cancer, demonstrating significant potential for further development and clinical application. © 2024 Society of Chemical Industry.

Oxidized cellulose microneedle patch combined with vascular embolization and local delivery of timolol maleate for hemangiomas

Hemangiomas are superficial tumors characterized by dense vascular structures that often affect the patient's aesthetic appearance due to the obvious red appearance on the skin. Current treatments, especially timolol maleate in the form of eye drops and hydrogels, suffer from low transdermal drug delivery rates, resulting in prolonged treatment time. To address this challenge, our study introduced a soluble microneedle patch with dextran as the main material to form microcatheters for sustained delivery of timolol maleate. In addition, we proposed a vascular embolization strategy to disrupt the blood supply in hemangiomas. Oxidized cellulose (C-cellulose) was selected for its excellent hemostatic properties. We incorporated C-cellulose into dextran microneedles to facilitate thrombosis in the vascular-rich areas of hemangiomas. The innovative microneedle patch we developed can penetrate the skin to a depth of 430 μm and dissolve rapidly within 3 minutes, ensuring direct drug delivery to the subcutaneous layer. Notably, the treated skin area regained its original appearance within two hours after treatment. In addition to excellent skin permeability and rapid dissolution, these patches significantly promoted apoptosis and inhibited cell migration in mouse hemangioendothelioma EOMA cells. Our results demonstrate that this approach not only achieves significant tumor inhibition in a mouse hemangioma model, but also represents a more effective, convenient, and non-invasive treatment option. Therefore, dextran/C-cellulose/timolol maleate microneedle patch (MNs/Timolol) has broad clinical application prospects in the treatment of hemangiomas, minimizing the risk of additional damage and improving treatment efficacy.

Exploring the Correlation between the PASI and DLQI Scores in Psoriasis Treatment with Topical Ointments Containing Rosa × damascena Mill. Extract.

Psoriasis is a chronic autoimmune skin condition characterized by red, circumscribed, scaly, and erythematous plaques that can cover large skin areas. While conventional treatments such as topical corticosteroids and systemic medications are commonly prescribed, the interest in natural remedies for psoriasis has grown due to concerns about potential side effects and the desire for alternative treatment options. Rosa × damascena Mill. is rich in bioactive compounds that possess anti-inflammatory, antioxidant, and antimicrobial properties; these properties make Rosa × damascena Mill. a promising candidate for the management of skin disorders such as psoriasis. In our previous studies, we successfully formulated and tested different topical preparations containing Rosa × damascena Mill. In this study, we investigated the correlation between the Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores in psoriasis treatment using the abovementioned creams containing Rosa × damascena Mill. extract. Several tests were performed to study the correlation between the PASI and DLQI scores in psoriasis patients. Consequently, we were able to observe an improvement in terms of the area, induration, desquamation, and erythema; such an improvement implicitly produces an improvement in patients' quality of life. The PASI and DLQI scores showed significant progress between visits. These results confirm Rosa × damascena Mill. to be a promising candidate for the topical treatment of psoriatic lesions.

Contribution of Continued Dermal Exposure of PFAS-Containing Sunscreens to Internal Exposure: Extrapolation from In Vitro and In Vivo Tests to Physiologically Based Toxicokinetic Models.

Per- and polyfluoroalkyl substances (PFASs) are widely present in sunscreen products as either active ingredients or impurities. They may penetrate the human skin barrier and then pose potential health risks. Herein, we aimed to develop a physiologically based toxicokinetic (PBTK) model capable of predicting the body loading of PFASs after repeated, long-term dermal application of commercial sunscreens. Ten laboratory-prepared sunscreens, generally falling into two categories of water-in-oil (W/O) and oil-in-water (O/W) sunscreens, were subject to in vitro percutaneous penetration test to assess the impacts of four sunscreen ingredients on PFAS penetration. According to the results, two sunscreen formulas representing W/O and O/W types that mostly enhanced PFAS dermal absorption were then selected for a subsequent 30 day in vivo exposure experiment in mice. PBTK models were successfully established based on the time-dependent PFAS concentrations in mouse tissues (R2 = 0.885-0.947) and validated through another 30 day repeated exposure experiment in mice using two commercially available sunscreens containing PFASs (R2 = 0.809-0.835). The PBTK model results suggest that applying sunscreen of the same amount on a larger skin area is more conducive to PFAS permeation, thus enhancing the exposure risk. This emphasizes the need for caution in practical sunscreen application scenarios, particularly during the summer months.

Toxicokinetics of 2-ethylhexyl salicylate (EHS) and its seven metabolites in humans after controlled single dermal exposure to EHS

The chemical UV filter 2-ethylhexyl salicylate (EHS) is used in various personal-care products. The dermal and oral metabolism of EHS have already been targeted by different studies. However, toxicokinetic data after a single dermal exposure to EHS was missing. In our study, three volunteers were dermally exposed to a commercial EHS-containing sunscreen for 9 h with an application dose of 2 mg sunscreen per cm2 body surface area. The exposure was performed indoors, and sunscreen was applied on about 75% of the total skin area. Complete urine voids were collected over 72 h and eight blood samples were drawn from each subject. Urine samples were analyzed for EHS and seven known metabolites (5OH-EHS, 4OH-EHS, 2OH-EHS, 6OH-EHS, 4oxo-EHS, 5oxo-EHS, and 5cx-EPS) by online-SPE UPLC MS/MS. The peaks of urinary elimination occurred 10–11 h after application. The elimination half-lives (Phase 1) were between 6.6 and 9.7 h. The dominant urinary biomarkers were EHS itself, followed by 5OH-EHS, 5cx-EPS, 5oxo-EHS, and 4OH-EHS. 2OH-EHS, 6OH-EHS, and 4oxo-EHS were detected only in minor amounts. An enhanced analysis of conjugation species revealed marginal amounts of unconjugated metabolites and up to 40% share of sulfate conjugates for 5OH-EHS, 5oxo-EHS, and 5cx-EPS. The results demonstrated a delayed systemic resorption of EHS via the dermal route. Despite an extensive metabolism, the parent compound occurred as main urinary parameter. The delayed dermal resorption as well as the slow elimination of EHS indicate an accumulation up to toxicological relevant doses during daily repeated dermal application to large skin areas.

Structural and molecular characteristics of weight-bearing volar skin can be reconstituted by micro skin tissue column grafting.

For patients with lower limb amputations, prostheses are immensely helpful for mobility and the ability to perform job-related or recreational activities. However, the skin covering the amputation stump is typically transposed from adjacent areas of the leg and lacks the weight-bearing capacity that is only found in the specialized skin covering the palms and soles (a.k.a. volar skin). As a result, the skin tissue in direct contact with the prosthesis frequently breaks down, leading to the development of painful sores and other complications that limit, and often preclude, the use of prostheses. Transplanting volar skin onto amputation stumps could be a solution to these problems, but traditional skin transplantation techniques cause substantial morbidity at the donor site, such as pain and scarring, which are especially problematic for volar skin given the critical functional importance of the volar skin areas. We previously developed the technology to collect and engraft full-thickness skin tissue while avoiding long-term donor site morbidity, by harvesting the skin in the form of small (~0.5 mm diameter) cores that we termed "micro skin tissue columns" (MSTCs), so that each donor wound is small enough to heal quickly and without clinically appreciable scarring or other long-term abnormalities. The goal of this study was to establish whether a similar approach could be used to confer the structural and molecular characteristics of volar skin ectopically to other skin areas. In a human-to-mouse xenograft model, we show the long-term persistence of various human plantar MSTC-derived cell types in the murine recipient. Then in an autologous porcine model, we harvested MSTCs from the bottom of the foot and transplanted them onto excision wounds on the animals' trunks. The healing processes at both the donor and graft sites were monitored over 8 weeks, and tissue samples were taken to verify volar-specific characteristics by histology and immunohistochemistry. The volar donor sites were well-tolerated, healed rapidly, and showed no signs of scarring or any other long-term defects. The graft sites were able to maintain volar-specific histologic features and expression of characteristics protein markers, up to the 8-week duration of this study. These results suggest that MSTC grafting could be a practical approach to obtain autologous donor volar skin tissue, confer volar skin characteristics ectopically to nonvolar skin areas, improve the load-bearing capacity of amputation stump skin, and ultimately enhance mobility and quality-of-life for lower limb amputees.

Characterization of the forehead skin microbiome in the early phase of acne.

The skin microbiota is known to be imbalanced in acne vulgaris, but the changes occurring during the early stages of acne onset remain poorly described. To characterize the skin microbiome of subclinical stages of acne in adults and adolescents. The composition and diversity of the microbiota from non-lesional skin on the forehead of subjects with mild-to-moderate acne were compared to the ones from non-acne subjects. Analyses of skin swab samples were performed using high-throughput sequencing of the V1-V3 regions of the bacterial 16S ribosomal RNA gene, the tuf gene fragment of Staphylococcus species and the internal transcribed spacer (ITS1) region of the fungal rRNA gene to determine the relative abundance, alpha-diversity and beta-diversity of bacteria and fungi. Compared with non-acne subjects, acne subjects had a higher abundance of Cutibacterium (72.4% vs. 57.8%) and lower abundances of Corynebacterium (2.8% vs. 4.8%) and Streptococcus (1.4% vs. 3.2%). Bacterial alpha- and beta-diversity indices also differed significantly between the two groups, reflecting differences in richness, evenness, abundance and phylogenetic distance between bacterial populations. Differences were also observed at the level of Staphylococcus species: S. capitis was predominant in skin samples from non-acne subjects (46.7%), whereas S. epidermidis was the most abundant Staphylococcus species in non-lesional forehead skin areas of acne subjects (44.2%). Conversely, no significant between-group differences were found for fungi, with Malasseziales being the predominant order in both subject groups. Dysbiosis was observed very early in subclinical acne stages of the forehead skin, with the overall abundance, richness and evenness of the bacterial population being lower in acne than in non-acne skin samples. Dysbiosis was also found at the level of Staphylococcus species. The development of acne lesions could therefore be prevented by using a skin care product that rebalances facial skin microbiota at very early stages.

Plasmonic nanophotothermal therapy: Destruction of 500 mm3 subcutaneous human basal cell carcinoma with gold nanoparticles and near infrared laser.

Multilesional basal cell carcinoma (BCC) are spread on sun exposed skin areas, including arms, face and back. The first-line treatment remains the surgical resection or Mohs surgery. Despite its high complexity, Mohs surgery is well practiced in USA and Germany and presents very good results both in esthetic and in carcinology point of view. Large lesions more than 2cm remain challenging to remove by topical cream used in photodynamic therapy (PDT). If these larger lesions are not treated in less than 1 month, they could grow deeply in the skin, thus enhancing the risk of reoccurrence and the severity of the disease. Despite this model herein studied, that is non melanoma skin cancer is a good prognostic cancer, the therapy aims to be applied to more aggressive melanoma skin cancers. Total regression of large cutaneous lesions less than 1 month with no reoccurrence. Tumor induction on murine model bearing a 500 mm3 subcutaneous lesion. Increasing dose of gold nanoparticles at fixed initial concentration C0=0.3mg/mL, infused into the tumor then exposition of the region of interest to NIR medical laser to assess the therapy. One or two intratumoral administration(s) were compared to surgery and control, that is no treatment, laser alone or nanoparticles alone. Gold nanoparticles alone or the NIR laser alone did not induce the tumor regression. The combination of laser and nanoparticles called plasmonic nanophotothermal therapy induced apoptosis. Derma and hypoderm do not show any visible gold nanoparticles and demonstrated a good cicatrization process. Plasmonic nanophotothermal therapy using two doses of gold nanoparticles was the only protocol that proved its efficacy on large lesions in 14 days, that is 500 mm3 on a murine model bearing human basal cell carcinoma.

Analysis of data on phytophotodermatitis caused by contact with the sap of plants of the genus Hogweed (&lt;i&gt;Heracleum&lt;/i&gt; L.)

The rapid spread of overgrowth of plants of the genus Hogweed, associated with their use as an agricultural fodder crop, is currently a serious problem for the Russian Federation. This process has a negative impact on the biodiversity of the vegetation cover, destroying natural ecosystems and causing significant economic damage. However, the active spread of hogweeds on the territory of the Russian Federation would not be so catastrophic if it were not for their aggressive properties: in contact with the skin, plant sap causes phytophotodermitis, which is a burn similar to thermal burns of I, II and III degrees. The article considers qualitative and quantitative composition of the main biologically active substances of hogweeds sap and shows that the biologically active substances causing phytophotodermatitis are furanocoumarins. It has been established that the pronounced photosensitizing activity of furanocoumarins is determined by the presence of a furan ring at positions 6,7 and 7,8 of coumarin. Such compounds include psoralen and its main derivatives: xanthotoxin, bergapten, bergamotin, imperatorin, isopimpinellin and angelicin (isopsoralen) and its main derivatives: sfondin, pimpinellin, isobergapten. Substitution of furan ring condensed with coumarin ring as well as change of its position leads to loss of photosensitizing activity. It was determined that the activity of plant sap of the genus Hogweed is in direct dependence on such factors as qualitative and quantitative content of furanocoumarins in the plant sap, the amount of sap and the area of the skin lesion zone, the time of contact of the affected skin areas with the plant sap, the intensity of ultraviolet irradiation and the time of its effect on the affected areas, as well as the peculiarities of each person (e.g., age, skin phototype). The methods of standard therapy of three clinical forms of phytophotodermatitis were analyzed. It was found that currently no specific clinical recommendations for the diagnostics and treatment of phytophotodermatitis resulting from contact with the sap of hogweeds. At the end of the article, the conclusion is formulated that one of current and promising tasks of pharmaceutical technology may be the development of drugs used in the treatment of burns caused by the sap of plants of the genus Hogweed, taking into account the mechanism of action of furanocoumarins.

Skin microbiome changes in patients with atopic dermatitis and psoriasis

Aims: The main aim of our study was identification of skin microbiome changes in patients with atopic dermatitis and psoriasis. The focus of our research were microorganisms of Staphylococcus spp. genus. Materials and methods: The study included 34 patients with atopic dermatitis and 41 patients with psoriasis. The enrollment period lasted for 3 months. The material for cultivation was taken from 4 skin areas: lesion and normal skin of dry body skin sites (medial surface of forearm for patients with atopic dermatitis and extensor surface of elbow joint for patients with psoriasis) and scalp. Further evaluation was carried out using cultural and molecular biological research methods. The obtained data were statistically processed. Results: The study included 34 patients with atopic dermatitis and 41 patients with psoriasis. Mean SCORAD for atopic dermatitis group was 51,5912,75 and mean PASI for psoriasis group was23,7214,14. Mean SCORAD for atopic dermatitis patients who carries toxigenic S.аureus strains was 57,439,75, in group without toxigenic S.аureus strains mean SCORAD was statistically significant lower - 37,908,63 (р=0,054). Mean SCORAD for atopic dermatitis patients who carries S.epidermidis commensal strain was 51,312,75, difference between this group and toxigenic S.аureus strains group of patients was insignificant (р=0,18). Mean PASI for psoriasis patients who carries toxigenic S.аureus strains was 26,412,76, mean PASI for psoriasis patients who carries S.epidermidis commensal strain was 20,99,07. Difference between S.epidermidis group and toxigenic S.аureus strains group of patients was statistically insignificant (р=0,53) with tendency to more severe disease in group of toxigenic S.аureus strains carriers. Conclusions: This study reveals some aspects of skin colonization by microorganisms belonging to Staphylococcus spp genus in patients with atopic dermatitis and psoriasis. We identify some correlations between severity of inflammatory disease and characteristics of microorganisms strain.

Guidelines How to Integrate Surgery and Targeted Therapy with Biologics for the Treatment of Hidradenitis Suppurativa: Delphi Consensus Statements from an Italian Expert Panel.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent and painful nodules and abscesses in intertriginous skin areas, which can progress to sinus tract formation, tissue destruction, and scarring. HS is highly debilitating and severely impairs the psychological well-being and quality of life of patients. The therapeutic approach to HS is based on medical therapy and surgery. First-line medical therapy includes topical antibiotics, systemic antibiotics, and biologics. Main surgical procedures include deroofing, local excision, and wide local excision. Despite the availability of multiple therapeutic options, the rates of disease recurrence and progression continue to be high. In recent years, the possibility of combining biologic therapy and surgery has raised considerable interest. In a clinical trial, the perioperative use of adalimumab has been associated with greater response rates and improved inflammatory load and pain, with no increased risk of postoperative infectious complications. However, several practical aspects of combined biologic therapy and surgery are poorly defined. In June 2022, nine Italian HS experts convened to address issues related to the integration of biologic therapy and surgery in clinical practice. To this purpose, the experts identified 10 areas of interest based on published evidence and personal experience: (1) patient profiling (diagnostic criteria, disease severity classification, assessment of response to treatment, patient-reported outcomes, comorbidities); (2) tailoring surgery to HS characteristics; (3) wide local excision; (4) presurgery biologic treatment; (5) concomitant biologic and surgical treatments; (6) pre- and postsurgery management; (7) antibiotic systemic therapy; (8) biologic therapy after radical surgery; (9) management of adverse events to biologics; and (10) management of postoperative infectious complications. Consensus between experts was reached using the Estimate-Talk-Estimate method (Delphi Method). The statements were subsequently presented to a panel of 27 HS experts from across Italy, and their agreement was assessed using the UCLA Appropriateness Method. This article presents and discusses the consensus statements.

Unraveling shared molecular signatures and potential therapeutic targets linking psoriasis and acute myocardial infarction

Psoriasis, a chronic inflammatory skin disorder, is associated with comorbidities such as acute myocardial infarction (AMI). However, the molecular mechanisms connecting these conditions are unclear. In this study, we conducted bioinformatics analyses using gene expression datasets to identify differentially expressed genes and hub genes associated with both psoriasis and AMI. Our findings emphasize the involvement of immune-related pathways in the pathogenesis of both conditions. Furthermore, we investigated the expression levels of hub genes in AMI patients and myocardial infarction (MI) mice. ELISA measurements revealed significantly higher levels of CXCL8, IL1B, S100A9, and S100A12 in the serum of AMI patients compared to normal individuals. Immunohistochemical staining of heart tissue from MI mice showed a progressive increase in the expression of CXCL8 and IL-1B as MI advanced, while S100A9 exhibited high expression at day 3 post-MI. mRNA expression analysis validated these findings. Additionally, we explored the skin lesions of psoriasis patients and found significantly higher expression of CXCL8, IL-1B, S100A9, and S100A12 in the affected skin areas compared to unaffected regions. These results highlight the consistent upregulation of hub genes in both AMI and psoriasis patients, as well as in myocardial infarction mice, underscoring their potential as reliable markers for disease diagnosis. Moreover, molecular docking simulations revealed potential interactions between simvastatin and key target proteins, suggesting a potential therapeutic avenue. Overall, our study uncovers shared molecular signatures and potential therapeutic targets, providing a foundation for future investigations targeting common pathways in psoriasis and AMI.