Intact Skin Research Articles

Langweilig oder Spannend? Eine Reise Durch Die Fettsäure‐Chemie der Haut

Fatty acids are characterised by a wide variety of structures and properties. Their functions and the effects of their metabolites in and on the skin are correspondingly diverse. They range from physical protection to local hormonal effects. In addition to the biochemistry of the fatty acids in the epidermis, synergistic influences of the skin microbiome play a major role in physiologically intact skin.

022. From Challenge to Favorable Outcome: Resection of Progressive and Regrowing Neurofibroma in A Male 18-Year-Old Patient: A Case Report

Background: Neurofibromas are benign tumors originating from peripheral nervous system. While generally asymptomatic, they can cause significant morbidity, stigmatizing, and cosmetic concerns, requiring surgical intervention. This case report presents an interesting case of progressively enlarged and regrowing neurofibroma, which provides insights into the clinical aspect and treatment options in unusual cases. Case: An 18-year-old male patient presented with a progressively enlarging mass on his left dorsal pedis that had been present for eight years. The mass was soft, solitary, painless, accompanied by numbness, tingling, and a heavy sensation, occasionally causing difficult ambulatory. He was diagnosed with a neurofibroma and underwent wide surgical excision at another hospital. Physical examination revealed a well-defined mass measuring 12 x 7 x 5 cm, with hyperpigmentation and intact skin. Additional cutaneous lesions and café-au-lait spots suggested multiple neurofibromas, raising suspicion of Von Recklinghausen disease (neurofibromatosis type 1). Intraoperative findings confirmed a well-circumscribed, encapsulated tumor, which was completely removed by wide excision. A histopathological examination confirmed the diagnosis. The patient recovered well postoperatively, and a three-month follow-up showed no recurrence or neurological deficits. Conclusion: Neurofibromatosis type 1 can cause various manifestations, including progressive and regrowing large neurofibromas. Early detection and prompt surgical intervention are essential for preventing complications.

Assessment of the toxicity and hazard of a chelating agent based on a mixture of di- and triammonium salts of nitrilotriacetic acid in water and atmospheric air

Introduction. The article evaluates the toxicity and danger of a chelating agent based on a mixture of di- and triammonium salts of nitrilotriacetic acid. The relevance of the study is related to the assessment of the impact of this substance on water and atmospheric air, especially in the context of its use in oil production and potential release into the environment and impact on humans. Material and methods. The studies included assessing the effect of the substance on the organoleptic characteristics of water, the process of self-purification of water bodies, as well as conducting acute and subacute toxicological tests to study the effect of the mixture on the body of warm-blooded animals. Results. For a mixture of di- and triammonium salts of nitrilotriacetic acid, a value of 70 mg/l is recommended as the threshold concentration for the organoleptic indicator, the limiting indicator is odor. The mixture does not affect the processes of self-purification of water in water bodies at the maximum studied concentration. Toxicological studies have shown that the mixture is classified in the 3rd hazard class (LD50 2250±250 mg/kg) and has a high degree of accumulation. In addition, it has a moderate irritant effect on the mucous membrane of the eye and intact skin upon repeated application, and does not have a skin-resorptive effect. After prolonged exposure, the mixture affects the blood parameters of animals, as well as the functional state of the liver and kidneys. Limitations. The studies were carried out in accordance with the requirements of Methodological instructions 2.1.5.720–98 and Methodological instructions 2630–82. The research results are applicable in substantiating hygienic standards in the water of water bodies and atmospheric air. Conclusion. Thus, based on literature data, as well as our own research, for a mixture of di- and triamonium salts of nitrilotriacetic acid, we can recommend a value of 0.8 mg/l as the approximate permissible level in the water of water bodies (hazard indicator – sanitary-toxicological, hazard class – 2), and a value of 0.1 mg/m3 as the tentative safe exposure level in the atmospheric air of populated areas.

Transdermal Delivery of Ultradeformable Cationic Liposomes Complexed with miR211-5p (UCL-211) Stabilizes BRAFV600E+ Melanocytic Nevi.

Small non-coding RNAs (e.g. siRNA, miRNA) are involved in a variety of melanocyte-associated skin conditions and act as drivers for alterations in gene expression within melanocytes. These molecular changes can potentially affect the cellular stability of melanocytes and promote their oncogenic transformation. Thus, small RNAs can be considered as therapeutic targets for these conditions, however, their topical delivery to the melanocytes through the epidermal barrier is challenging. We synthesized and extensively evaluated ultradeformable cationic liposome (UCLs) carriers complexed with synthetic microRNAs (miR211-5p; UCL-211) for transdermal delivery to melanocytes. UCL-211 complexes were characterized for their physicochemical properties, encapsulation efficiency, and deformability, which revealed a significant advantage over conventional liposomal carriers. Increased expression of miR211-5p stabilizes melanocytic nevi and keeps them in growth-arrested state. We did a comprehensive assessment of cellular delivery, and biological activity of the miR211-5p carried by UCL-211 in vitro and their permeation through the epidermis of intact skin using ex vivo human skin tissue explants. We also demonstrated, in vivo , that topical delivery of miR211-5p by UCL-211 stabilized BRAFV600E+ nevi melanocytes in a benign nevi state.

Scanning Transmission Soft X-Ray Microscopy Probes Topical Drug Delivery of Rapamycin Facilitated by Microneedles.

Scanning Transmission X-ray microscopy (STXM) is a sensitive and selective probe for the penetration of rapamycin which is topically applied to human skin ex vivo and is facilitated by skin treatment with microneedles puncturing the skin. Inner-shell excitation serves as a selective probe for detecting rapamycin by changes in optical density as well as linear combination modeling using reference spectra of the most abundant species. The results indicate that mechanical damage induced by microneedles allows this drug to accumulate in the stratum corneum without reaching the viable skin layers. This is unlike intact skin which shows no drug penetration at all and underscores the mechanical impact of microneedle skin treatment. These results are compared to drug penetration profiles of other drugs highlighting the importance of skin barriers. High spatial resolution studies also indicate that the lipophilic drug rapamycin is observed in corneocytes. Attempts in data evaluation are reported to probe rapamycin also in the lipid layers between the corneocytes, which was not accomplished before. These results are compared to recent results on rapamycin uptake in skin where barrier impairment was induced by pre-treatment with the enzyme trypsin and drug formulations leading to occlusion.

The Design Features, Quality by Design Approach, Characterization, Therapeutic Applications, and Clinical Considerations of Transdermal Drug Delivery Systems—A Comprehensive Review

Transdermal drug delivery systems (TDDSs) are designed to administer a consistent and effective dose of an active pharmaceutical ingredient (API) through the patient’s skin. These pharmaceutical preparations are self-contained, discrete dosage forms designed to be placed topically on intact skin to release the active component at a controlled rate by penetrating the skin barriers. The API provides the continuous and prolonged administration of a substance at a consistent rate. TDDSs, or transdermal drug delivery systems, have gained significant attention as a non-invasive method of administering APIs to vulnerable patient populations, such as pediatric and geriatric patients. This approach is considered easy to administer and helps overcome the bioavailability issues associated with conventional drug delivery, which can be hindered by poor absorption and metabolism. A TDDS has various advantages compared to conventional methods of drug administration. It is less intrusive, more patient-friendly, and can circumvent first pass metabolism, as well as the corrosive acidic environment of the stomach, that happens when drugs are taken orally. Various approaches have been developed to enhance the transdermal permeability of different medicinal compounds. Recent improvements in TDDSs have enabled the accurate administration of APIs to their target sites by enhancing their penetration through the stratum corneum (SC), hence boosting the bioavailability of drugs throughout the body. Popular physical penetration augmentation methods covered in this review article include thermophoresis, iontophoresis, magnetophoresis, sonophoresis, needle-free injections, and microneedles. This review seeks to provide a concise overview of several methods employed in the production of TDDSs, as well as their evaluation, therapeutic uses, clinical considerations, and the current advancements intended to enhance the transdermal administration of drugs. These advancements have resulted in the development of intelligent, biodegradable, and highly efficient TDDSs.

Topical Platelet Exosomes Reduce Senescence Signaling in Human Skin: An Exploratory Prospective Trial.

Cellular senescence, an irreversible cell cycle arrest with secretory phenotype, is a hallmark of skin aging. Regenerative exosome-based approaches, such as topical human platelet extract (HPE), are emerging to target age-related skin dysfunction. To evaluate the cellular and molecular effects of topical HPE for skin rejuvenation after 12 weeks of twice daily use. Skin biopsies were obtained for histological evaluation of senescence markers, p16INK4a and p21CIP1/WAF1. Telomere-associated foci, coassociation of telomeres, and DNA damage marker, γH2AX, were assessed. RNA sequencing evaluated senescence associated secretory phenotype (SASP) and extracellular matrix pathways. p16INK4a and p21CIP1/WAF1 staining in senescent skin cells revealed low and high expression subgroups that did not correspond to chronological age. Topical HPE significantly reduced high p16INK4a cells in the dermis (p = .02). There was also a decrease in telomere damage after topical HPE (p = .03). In patients with high senescent cells at baseline, there was a 40% reduction in proinflammatory SASP. Extracellular matrix remodeling pathways, including collagen and elastic fibers, were up-regulated. Topical HPE, applied on intact skin, reduced senescence signaling and senescence-associated telomere damage after 12 weeks of twice daily use, targeting a path for skin longevity or healthy skin aging.

Amorphous zinc phosphate nanoclusters loaded polycarbonate thermosensitive hydrogel: An innovative strategy for promoting wound healing

Skin trauma is a matter of great concern for public health, emphasizing the importance of reconstructing the microenvironment at the trauma site to facilitate tissue regeneration. Therefore, the investigation of innovative wound dressings has significant research and clinical implications. In this study, we prepared a thermosensitive hydrogel based on a hydrophilic-hydrophobic-hydrophilic triblock polycarbonate polymer (PTP), and created a composite hydrogel, PTPH-AZP, by incorporating amorphous zinc phosphate (AZP) nanoclusters. We evaluated the effects of PTPH-AZP on human umbilical vein endothelial cells (HUVECs) and the ability to promote skin wound healing. According to the results, PTPH-AZP was found to promote the proliferation, migration, and tube formation of HUVECs through the sustained release of Zn2+ at appropriate concentrations. In vivo experiments demonstrated that in the early-mid stages of wound healing, PTPH-AZP promotes increases in Platelet Endothelial Cell Adhesion Molecule-1 (CD31) and α-Smooth Muscle Actin (α-SMA) content within the wound area, facilitating accelerated re-epithelialization and enhanced collagen deposition. In later healing stages, epidermal thickness in the PTPH-AZP treated group was significantly improved, aligning with surrounding intact skin with no instances of attenuated or hypertrophic scarring observed. The findings from the in vivo study suggested that PTPH-AZP may have a positive impact on vascularization and wound healing. In conclusion, this study presents a promising strategy for skin wound healing, highlighting the potential of PTPH-AZP as an effective therapeutic approach.

Exploring Cationic Guar Gum: Innovative Hydrogels and Films for Enhanced Wound Healing.

Background/Objectives: This study developed and characterized hydrogels (HG-CGG) and films (F-CGG) based on cationic guar gum (CGG) for application in wound healing. Methods: HG-CGG (2% w/v) was prepared by gum thickening and evaluated for pH, stability, spreadability, and viscosity. F-CGG was obtained using an aqueous dispersion of CGG (6% w/v) and the solvent casting method. F-CGG was characterized for thickness, weight uniformity, morphology, mechanical properties, hydrophilicity, and swelling potential. Both formulations were evaluated for bioadhesive potential on intact and injured porcine skin, as well as antioxidant activity. F-CGG was further studied for biocompatibility using hemolysis and cell viability assays (L929 fibroblasts), and its wound-healing potential by the scratch assay. Results: HG-CGG showed adequate viscosity and spreadability profiles for wound coverage, but its bioadhesive strength was reduced on injured skin. In contrast, F-CGG maintained consistent bioadhesive strength regardless of skin condition (6554.14 ± 540.57 dyne/cm2 on injured skin), presenting appropriate mechanical properties (flexible, transparent, thin, and resistant) and a high swelling capacity (2032 ± 211% after 6 h). F-CGG demonstrated superior antioxidant potential compared to HG-CGG (20.50 mg/mL ABTS+ radical scavenging activity), in addition to exhibiting low hemolytic potential and no cytotoxicity to fibroblasts. F-CGG promoted the proliferation of L929 cells in vitro, supporting wound healing. Conclusions: Therefore, CGG proved to be a promising material for developing formulations with properties suitable for cutaneous use. F-CGG combines bioadhesion, antioxidant activity, biocompatibility, cell proliferation, and potential wound healing, making it promising for advanced wound treatment.

Need of ethosomes as a transdermal drug delivery system

Transdermal Drug Delivery (TDD) TDD is a painless method of delivering drugs systemically by applying a drug formulation onto intact and healthy skin. Ethosomes are soft malleable vesicles composed mainly of phospholipids, ethanol (relatively high concentration) and water. In vitro and in vivo skin permeation experiments have shown that ethosomal formulations can improve the penetration of both hydrophobic and hydrophilic compounds when compared to traditional liposomes. Cold method and hot method are the two types of method of preparation of ethosomes. In comparison to traditional liposomes, antigen-loaded ethosomes for transcutaneous immunization against Hepatitis B were synthesized and described, demonstrating better entrapment effectiveness, appropriate size range, and a unilamellar, spherical shape.As a topical medium (gel), ethosomes and liposomes of azelaic acid (an anti-keratinizing agent used in the treatment of acne) were created, and the results showed that ETHOS 40 might be responsible for a larger azelaic acid concentration than ETHOS 20 and liposomes.

Adverse health effects of exposure to plastic, microplastics and their additives: environmental, legal and policy implications for Israel

BackgroundIsrael is a regional "hotspot" of plastic pollution, with little discussion of potential adverse health effects from exposure to plastic. This review aims to stimulate discussion and drive policy by focusing on these adverse health effects.Main bodyPlastics are synthetic polymers containing additives which can leach from food- and beverage-contact plastic into our food and beverages, and from plastic textiles onto our skin. Plastics persist in the environment for generations, fragmenting into MNPs: Micro (1 micron–5 mm)-Nano (1 nm–1 micron)-Plastic, which contaminate our atmosphere, water, and food chain. MNP can enter the human body through ingestion, inhalation and touch. MNP < 10 microns can cross epithelial barriers in the respiratory and gastrointestinal systems, and fragments < 100 nm can cross intact skin, enabling entry into body tissues. MNP have been found in multiple organs of the human body. Patients with MNP in atheromas of carotid arteries have increased risk of a combined measure of stroke, cardiovascular disease, and death. Toxic additives to plastics include bisphenols, phthalates, and PFAS, endocrine-disrupting chemicals (EDCs) which cause dysregulation of thyroid function, reproduction, and metabolism, including increased risk of obesity, diabetes, endometriosis, cancer, and decreased fertility, sperm count and quality. Fetal exposure to EDCs is associated with increased rates of miscarriages, prematurity and low birth weight. There is likely no safe level of exposure to EDCs, with increasing evidence of trans-generational and epigenetic effects. There are several existing Israeli laws to reduce plastic use and waste. Taxes on single-use plastic (SUP) were recently cancelled. There are many gaps in regulatory standards for food-, beverage- and child- safe plastic. Existing standards are poorly enforced.ConclusionReduction in production and use of plastic, promotion of recycling and reduction of leaching of toxic additives into our food and beverages are essential policy goals. Specific recommendations: Periodic monitoring of MNP in bottled beverages, food, indoor air; Strengthen enforcement of standards for food-, beverage-, and child-safe plastic; Renew tax on SUPs; National ban on SUP at public beaches, nature reserves and parks; Ban products manufactured with MNP; Increase research on sources and health outcomes of exposure to MNP and EDCs.

Acute toxicity of a combined fipronil and pyriproxyfen shampoo

The purpose of the research is to study the acute oral and dermal toxicity of a veterinary drug (fipronil, pyriproxyfen) in mice and rats.Materials and methods. The studies were performed according to the Methodical Guidelines of the State Pharmacological Committee in the vivarium of the VNIIP – FSC VIEV from February to April 2021. White outbred male mice and male rats were used as a test system to study toxicological characteristics of the study drug. The veterinary drug Insektal Shampoo is a topical solution that contains fipronil and pyriproxyfen as active ingredients. In studying the acute oral toxicity and acute dermal toxicity of the study drug on laboratory animals, established procedures were used.Results and discussion. The median lethal dose (LD50) was 12 500 (11,532÷13,468) mg/kg when administered to the white male mice intragastrically as per Miller-Tainter method. According to the generally accepted hygiene classification, the drug was classified as hazard class 4 according to GOST 12.1.007-76. For the white male rats, LD50 was more than 20,800 mg/ kg (hazard class 4). When applied to intact rat skin, LD50 was more than 10 400 mg/kg, which corresponds to hazard class 4.

How safe is high-intensity focused ultrasound? An intriguing solution for obstetric and gynecological diseases: A systematic review.

High-intensity focused ultrasound (HIFU) is a non-surgical and noninvasive treatment modality that depends on external ultrasound energy sources that induce focused mass ablation and protein degeneration in the treatment area via thermal energy penetration under the intact skin. We aim in our study to collectively evaluate the safety of HIFU for the treatment of different obstetric and gynecological diseases in the literature. We searched PubMed, Scopus, and Science Direct databases, without restriction on date or language, from the inception of these databases until January 20, 2024. We also examined the references of the included studies in the Mendeley archive for eligible articles. We found a total of 706 studies. After the screening and selection process, 56 participants were included. Our dichotomous outcomes were pooled in our single-arm meta-analysis as risk ratio (RR) and with 95% confidence interval (CI) while our continuous outcomes were pooled as mean change and 95% CIs. Fixed- or random-effects models were applied depending on the heterogeneity detected. Our systematic review and meta-analysis included 56 studies including 11.740 patients. Depending on the Society of Interventional Radiology (SIR) classification for adverse effects. The results of this meta-analysis for the type A category that did not require clinical intervention found that pain in the treatment site estimated RR with 95% CI: 0.61 (0.33, 0.89), abnormal vaginal discharge 0.16 (0.073, 0.24), low-grade fever (<38 °C) 0.005 (0.002, 0.009). Sensory abnormalities of the lower limbs were examined in 3390 individuals and observed in only 19 patients who experienced gradual relief of symptoms within one month after treatment. Regarding SIR type B, 99 of a total of 6.437 patients had small vesicles and superficial burns with pooled RR and 95% CI: 0.012 (0.007, 0.018). In terms of groin or perianal and lower abdominal pain, our RRs with 95% CIs were 0.1 (0.067, 0.13) and 0.38 (0.25, 0.51). However, vaginal bleeding was detected in only 32 out of a total of 3.017. Major adverse events like lumber disc herniation, thrombocytopenia, and renal failure, were unmentionable. Additionally, our included studies did not record any deaths. HIFU, either alone or in combination with oxytocin or any other enhancing agent, is safe for patients with different gynecological and obstetric diseases. In terms of efficacy, it showed promising results compared with traditional treatment lines. To our knowledge, we are the first and most comprehensive meta-analysis in the literature that has studied the different safety outcomes related to HIFU as a treatment modality for different obstetric and gynecological diseases with a very large sample size, making our evidence strong and less attributed to errors.

Biopharmaceutical aspects of the development of transdermal forms of Lisinopril dihydrate

Abstract Prevention and treatment of arterial hypertension is of great importance. Improvement of existing medicines through the use of alternative routes of administration can enhance the pharmacotherapeutic characteristics of active pharmaceutical ingredients (APIs). Transdermal therapeutic systems (TTS) allow for delivery of a drug through intact skin into the systemic circulation, while minimizing side effects. The development of transdermal formulations of antihypertensive drugs, Lisinopril dihydrate in particular, has practical and scientific significance. Optimization of the algorithm for the development of transdermal drugs involves in vitro preformulation studies of the membrane permeability of APIs and the identification of factors that affect this process. The tests were performed by dialysis through a semipermeable hydrophilic membrane using a Valia-Chien diffusion device. The effect of the initial concentration of Lisinopril dihydrate on the flux rate I s was investigated. Different donor concentrations of Lisinopril dihydrate were tested at three levels, 10, 20 and 30 mg/ml, accordingly. It was noted that the permeation process of Lisinopril dihydrate under model conditions corresponds to zero-order kinetics and is characterized by a uniform speed. The correlation coefficient (R 2) for all the kinetic equations was 0.999. A linear dependence of the flux velocity of Lisinopril dihydrate on the initial concentration was indicated. The concentration of Lisinopril dihydrate in the donor solution of 30 mg/ml was found to be optimal for further stages of pharmaceutical development of the transdermal formulation. The studies of Lisinopril dihydrate permeability allow to give a positive assessment of the acceptability of this API for use in the transdermal formulation and the development of TTS.

Clinicopathological Findings and Comprehensive Review of Buschke-Lowenstein Tumors Based on a Case Study.

The Buschke-Löwenstein tumor (BLT), also known as giant condyloma acuminatum, is a rare, exophytic tumor, arising from pre-existing warty lesions associated with human papillomavirus (HPV) infection, particularly strains 6 and 11, which are considered to have low oncogenic potential. BLT presents as a large, cauliflower-like growth typically affecting the penis, vulva, vagina, perineum, scrotum, anus, and perianal area. Despite being a benign lesion, BLT is locally aggressive with a high recurrence rate, and can potentially undergo malignant transformation into squamous cell carcinoma, contributing to an overall mortality rate of 20-30%. The primary treatment is complete surgical excision with wide margins, frequently requiring complex reconstructive techniques for defect coverage. We report on a 68-year-old patient, with multiple comorbidities, who presented with a two-year history of a large exophytic tumor in the genital region, affecting the penis, along with progressive erectile dysfunction and urinary problems. The tumor was surgically excised with oncological safety margins, and reconstruction was performed using advancement and rotation flaps from the scrotum and intact penile skin. Histopathological examination confirmed the diagnosis of Giant Condyloma (Buschke-Löwenstein tumor), showing acanthosis, papillomatosis, parakeratosis, and koilocytic cell collections, with positive immunohistochemical staining for p16, p63, and ki67. Postoperatively, the patient had a good clinical outcome and a complete surgical cure. This case highlights the critical need for timely intervention and comprehensive management strategies in treating giant condyloma, given its potential for local invasion and substantial impacts on patient quality of life. Early diagnosis and thorough surgical excision are crucial for effective management and to reduce the high recurrence, morbidity and malignant transformation risk associated with this condition.

In vivo measurement of nitric oxide release from intact human skin post photobiomodulation using visible and near-infrared light: A chemiluminescence detection study

Significance: This study investigates the therapeutic potential of photobiomodulation (PBM) using visible and near-infrared (NIR) light on nitric oxide (NO) release from intact human skin. Given NO's critical role in physiological processes such as wound healing, inflammation control, and vasodilation, this research could lead to innovative non-invasive treatments.Aim: The primary aim was to explore how PBM at different wavelengths affects NO release from human skin. Custom-built airtight sleeves equipped with gas ports were used to measure NO levels, assessing the impact of three specific wavelengths of light (455 nm, 660 nm, and 850 nm).Approach: Eighteen healthy participants had their forearms enclosed in airtight sleeves. The skin was irradiated with the specified wavelengths at a fluence of 45 J/cm² and an irradiance of 50 mW/cm² for 15 min. NO levels were quantified after irradiation using chemiluminescence detection (CLD), which measures the chemiluminescent reaction of NO with ozone (O3) for real-time analysis.Results: Significant differences in NO release were observed among the wavelengths tested, indicating that PBM stimulates NO release from intact human skin.Conclusions: The study provides strong evidence that PBM using visible and NIR light can enhance NO release from human skin, suggesting potential therapeutic applications for conditions involving NO. Further research is needed to understand the mechanisms behind PBM-induced NO release and its clinical implications.

Tissue resident cells differentiate S. aureus from S. epidermidis via IL-1β following barrier disruption in healthy human skin.

The Staphylococcus sp. are a dominant part of the human skin microbiome and present across the body. Staphylococcus epidermidis is a ubiquitous skin commensal, while S. aureus is thought to colonize at least 30% of the population. S. aureus are not only colonizers but a leading cause of skin and soft tissue infections and a critical healthcare concern. To understand how healthy human skin may differentiate commensal bacteria, such as S. epidermidis, from the potential pathogen methicillin-resistant S. aureus (MRSA), we use ex vivo human skin models that allow us to study this host-bacterial interaction in the most clinically relevant environment. Our work highlights the role of the outer stratum corneum as a protective physical barrier against invasion by colonizing Staphylococci. We show how the structural cells of the skin can internalize and respond to different Staphylococci with increasing sensitivity. In intact human skin, a discriminatory IL-1β response was identified, while disruption of the protective stratum corneum triggered an increased and more diverse immune response. We identified and localized tissue resident Langerhans cells (LCs) as a potential source of IL-1β and go on to show a dose-dependent response of MUTZ-LCs to S. aureus but not S. epidermidis. This suggests an important role of LCs in sensing and discriminating between bacteria in healthy human skin, particularly in intact skin and provides a detailed snapshot of how human skin differentiates between friend and potential foe. With the rise in antibiotic resistance, understanding the innate immune response of healthy skin may help us find ways to enhance or manipulate these natural defenses to prevent invasive infection.

Study on percutaneous penetration of representative cosmetic ingredients in a baby wipe product in an in vitro diaper rash skin model

Studying percutaneous penetration of various cosmetic ingredients through intact and compromised skin can provide insight on quantitative exposure assessment for baby products intended for diapered skin. We developed an in vitro model (tape-stripped human skin) designed to achieve the Trans-Epidermal Water Loss values measured in babies with various degrees of diaper dermatitis. Six reference compounds showed the impact of physicochemical properties on absorption through this “diaper rash” skin model. Under simulated diaper conditions, dermal absorption of cosmetic ingredients (phenoxyethanol, sodium benzoate, benzyl alcohol, disodium EDTA, and propylene glycol) was different, but <100%. Additionally, the effect of diaper rash on dermal absorption of well-absorbed ingredients (phenoxyethanol, sodium benzoate, and benzyl alcohol) was limited (enhancement of 1.1–1.3), while the enhancement for moderately absorbed compounds (disodium EDTA and propylene glycol) was 1.8–3.3. Absorption via skin with “diaper rash” is specific to individual ingredients and exposure conditions, so a fixed uncertainty factor is not appropriate for safety assessment. The data support that the default 100% dermal absorption commonly used in first-tier risk assessments for diapered skin is conservative. This diaper rash skin model provides a practical tool of estimating absorption of various ingredients in baby products intended for diapered skin.

Prognostic Performance of the Maximal Systolic Acceleration at the Hallux in Healing of Foot Ulcers: A Retrospective Cohort Study

The accurate prediction of foot ulcer healing remains a major challenge in clinical practice. To date, no reliable bedside tests are available. The primary aim of this study was to determine the prognostic performance of the maximal systolic acceleration (ACCmax) to predict ulcer healing. Secondary objectives comprised the investigation of the prognostic accuracy in patients prone to medial arterial calcification and to assess the potential risk of amputation. A single-center retrospective cohort study was conducted. Patients aged ≥18 years who presented with a new-onset ulcer (i.e. Fontaine IV and neuropathic ulcers) on the foot and underwent an ACCmax measurement at the hallux were included. Ulcer healing was defined as an intact skin with epithelialization after 3 or 12months of follow-up. Prognostic performance was calculated by using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR). In total, 136 patients with 143 wounds were included. Almost half of the patients were diagnosed with diabetes mellitus (47%), and wound infection was present in 42% of cases. After 3months of follow-up, an NPV of 97.9%, PLR of 3.25, and NLR of 0.19 were found when applying an ACCmax threshold of 0.5m/s2. When looking at 12months, these numbers were 85.6%, 2.72, and 0.50, respectively. Subgroup analysis for patients with diabetes mellitus and chronic kidney disease showed comparable results. The risk of amputation increased significantly when a measurement below 1.0m/s2 was present (odd ratio 5.3, P=0.010). ACCmax measurements at the hallux can have additional prognostic value in patients with foot ulcers. An ACCmax below 1.0m/s2 is associated with nonhealing of an ulcer and a higher risk of amputation, while higher ACCmax values are associated with limb salvage. Therefore, ACCmax could be used for grading ischemia in a wound classification system.

Defactinib inhibits FAK phosphorylation and regulates psoriasis via attenuating hyperproliferation of keratinocytes.

Excessive proliferation of keratinocytes is a crucial pathological risk feature of psoriasis. Focal adhesion kinase (FAK) is a non-receptor protein that primarily regulates cell proliferation and migration. However, the expression and regulatory mechanism of FAK in psoriasis remains unclear. This study aimed to investigate the regulation of FAK in psoriasis and examined the potential impact of FAK inhibitor on psoriasis. A small molecular selective FAK inhibitor, defactinib, was used to evaluate the effect of FAK on psoriasis in invitro and invivo functional assays. In our experiments, imiquimod (IMQ)-induced psoriasis mice and human keratinocytes cells were used to study the potential roles and mechanisms of FAK in psoriasis. FAK phosphorylation has been weakly detected in normal intact skin and is markedly elevated upon IMQ treatment. By reducing FAK phosphorylation (p-FAK),defactinib treatment could attenuate psoriasiform inflammation and epidermal hyperplasia in IMQ-treated mice compared with IMQ-induced mice treated with the vehicle. In invitro studies, resiquimod (R848) increased (p-FAK) and promoted cell proliferation in human keratinocytes cells, while defactinib reversed this effect. Mechanistically, defactinib can alleviate the proliferation via JNK/YB1 pathway invitro and invivo. Defactinib significantly attenuates psoriasiform inflammation and epidermal hyperproliferation through the inhibition of the FAK-mediated axis. The downregulation of phosphorylated FAK then suppressed the activation of JNK/YB1 protein signaling pathway in psoriasis. Our work highlights targeting FAK as a potentially effective strategy for the treatment of psoriasis.