Effectiveness of topical hyaluronic acid of different molecular weights in xerosis cutis treatment in elderly: a double-blind, randomized controlled trial.

Dry skin is a common dermatological condition that frequently affects the elderly. A contributing cause to dry skin is a reduced concentration of hyaluronic acid (HA) in both the epidermis and dermis. The effectiveness of moisturizer containing HA as a therapy for dry skin is impacted by its specific molecular weight. Low molecular weight HA (LMWHA) is believed to be more effective in replenishing skin hydration in aging skin compared to High Molecular Weight HA (HMWHA) due to its ability to penetrate the stratum corneum. However, there is a lack of clinical research supporting this claim. A double-blind, randomized controlled trial was conducted on 36 residents of a nursing home in Jakarta. The participants, aged between 60 and 80 years, had been diagnosed with dry skin. Each test subject was administered three distinct, randomized moisturizing lotions (LMWHA, HMWHA, or vehicle), to be topically applied to three separate sites on the leg. Skin capacitance (SCap), transepidermal water loss (TEWL), and specified symptom sum score (SRRC) were measured at weeks 0, 2, and 4. After four weeks of therapy, area that was treated with LMWHA showed greater SCap values compared to the area treated with HMWHA (56.37 AU vs. 52.37 AU, p = 0.004) and vehicle (56.37 AU vs. 49.01 AU, p < 0.001). All groups did not show any significant differences in TEWL and SRRC scores. No side effects were found in all groups. The application of a moisturizer containing LMWHA to the dry skin of elderly resulted in significant improvements in skin hydration compared to moisturizers containing HMWHA and vehicle. Furthermore, these moisturizers demonstrated similar safety in treating dry skin in the elderly. ClinicalTrials.gov Identifier NCT06178367, https://clinicaltrials.gov/study/NCT06178367 .

Managing dry skin in patients with comorbidities or with advanced age: unmet needs and roles for products containing potential emollient-plus ingredients.

In dry skin (DS), skin-barrier function is easily disturbed and moisturizing factors in the stratum corneum are reduced. Despite being a common condition, DS is often overlooked in patients with advanced age or comorbid diseases. In September 2022, specialists in dermatology and skin care met to discuss unmet needs and management of patients with DS with existing medical conditions or DS induced by ongoing pharmacological treatments. There was consensus about the need to improve the current understanding and management of DS in patients with comorbidities, including type 2 diabetes, chronic kidney disease, radiodermatitis, and photodamaged skin. Clinical guidance related to optimal treatment of DS in patients with advanced age or comorbid diseases is needed. Dexpanthenol-containing emollients have been shown to provide rapid relief from the symptoms and clinical signs of skin inflammation and are well-tolerated and effective in terms of moisturizing and soothing DS and maintaining skin-barrier function. Thus, dexpanthenol-containing emollients may play an important role in future management of DS. Further research is needed to elucidate the efficacy of dexpanthenol across the spectrum of DS, irrespective of comorbidity status or age.

Dissolvable microneedles in the skin: Determination the impact of barrier disruption and dry skin on dissolution.

Dissolvable microneedles (DMNs), fabricated from biocompatible materials that dissolve in both water and skin have gained popularity in dermatology. However, limited research exists on their application in compromised skin conditions. This study compares the hyaluronic acid-based DMNs penetration, formation of microchannels, dissolution, and diffusion kinetics in intact, barrier-disrupted (tape stripped), and dry (acetone-treated) porcine ear skin ex vivo. After DMNs application, comprehensive investigations including dermoscopy, stereomicroscope, skin hydration, transepidermal water loss (TEWL), optical coherence tomography (OCT), reflectance confocal laser scanning microscopy (RCLSM), confocal Raman micro-spectroscopy (CRM), two-photon tomography combined with fluorescence lifetime imaging (TPT-FLIM), histology, and scanning electron microscopy (SEM) were conducted. The 400 µm long DMNs successfully penetrated the skin to depths of ≈200 µm for dry skin and ≈200-290 µm for barrier-disrupted skin. Although DMNs fully inserted into all skin conditions, their dissolution rates were high in barrier-disrupted and low in dry skin, as observed through stereomicroscopy and TPT-FLIM. The dissolved polymer exhibited a more significant expansion in barrier-disrupted skin compared to intact skin, with the smallest increase observed in dry skin. Elevated TEWL and reduced skin hydration levels were evident in barrier-disrupted and dry skins compared to intact skin. OCT and RCLSM revealed noticeable skin indentation and pronounced microchannel areas, particularly in barrier-disrupted and dry skin. Additional confirmation of DMN effects on the skin and substance dissolution was obtained through histology, SEM, and CRM techniques. This study highlights the impact of skin condition on DMN effectiveness, emphasizing the importance of considering dissolvability and dissolution rates of needle materials, primarily composed of hyaluronic acid, for optimizing DMN-based drug delivery.

Mechanical and chemical itch regulated by neuropeptide Y-Y1 signaling.

Itch is a somatosensory sensation to remove potential harmful stimulation with a scratching desire, which could be divided into mechanical and chemical itch according to diverse stimuli, such as wool fiber and insect biting. It has been reported that neuropeptide Y (NPY) neurons, a population of spinal inhibitory interneurons, could gate the transmission of mechanical itch, with no effect on chemical itch. In our study, we verified that chemogenetic activation of NPY neurons could inhibit the mechanical itch as well as the chemical itch, which also attenuated the alloknesis phenomenon in the chronic dry skin model. Afterwards, intrathecal administration of NPY1R agonist, [Leu31, Pro34]-NPY (LP-NPY), showed the similar inhibition effect on mechanical itch, chemical itch and alloknesis as chemo-activation of NPY neurons. Whereas, intrathecal administration of NPY1R antagonist BIBO 3304 enhanced mechanical itch and reversed the alloknesis phenomenon inhibited by LP-NPY treatment. Moreover, selectively knocking down NPY1R by intrathecal injection of Npy1r siRNA enhanced mechanical and chemical itch behavior as well. These results indicate that NPY neurons in spinal cord regulate mechanical and chemical itch, and alloknesis in dry skin model through NPY1 receptors.

Effects of a leave-on product on the strength of the dermoepidermal junction: An exploratory, intraindividual, randomized controlled trial in older adults with dry skin.

Background and Aims: Skin aging is associated with dry skin and a decrease of the strength of the dermoepidermal adhesion, which increases the risk for lacerations (skin tears). Application of leave-on products improves dry skin and seems to reduce skin tear incidence. The aim of this study was to measure the effects of a humectant containing leave-on product on the strength of the dermoepidermal junction in older adult participants with dry skin. Methods: A randomized controlled trial using a split body design was conducted. One forearm was randomly selected and treated with a lipophilic leave-on product containing 5% urea for 8 weeks. The other forearm was the control. The parameters stratum corneum hydration (SCH), transepidermal water loss, pH, roughness, epidermal thickness and skin stiffness were measured at the baseline, Weeks 4 and 8. At Week 8, suction blisters were created and time to blistering was measured. Blister roofs and interstitial fluid were analyzed for Interleukin-1α, 6 and 8. Results: Twelve participants were included. After 8 weeks treatment, SCH was higher (median difference 11.6 AU), and the overall dry skin score (median difference -1) and median roughness (Rz difference -12.2 µm) were lower compared to the control arms. The median group difference for Interleukin-1α was -452 fg/µg total protein (TP) in the blister roofs and -2.2 fg/µg TP in the blister fluids. The median time to blister formation was 7.7 min higher compared to the control arms. Conclusion: The regular application of humectant containing leave-on products improves dry skin and seems to lower inflammation and contribute to the strengthening of the dermoepidermal adhesion. This partly explains how the use of topical leave-on products helps to prevent skin tears.

The prevalence and severity of dry skin and related skin care in older adult residents in institutional long-term care: A cross-sectional study.

OBJECTIVES: To identify possible factors associated with different severities of xerosis cutis and to describe possible associations between (skin) care dependency and application of moisturizers. DESIGN: Cross-sectional study using baseline data from a cluster-randomized controlled trial. Demographic and health characteristics, skin physiological measurements, functional abilities and application of moisturizers were compared between the participants with mild and severe dry skin. Frequency of moisturization were also compared based on the participants' skin care dependency. RESULTS: The more distal the body area, the more severe xerosis were observed. There were no or minor differences between the groups, except for the stratum corneum hydration and skin surface pH. Participants with severe xerosis received moisturizers less often. Skin care dependent residents received moisturizers frequently. CONCLUSION: There is under-application regarding xerosis cutis treatment in long-term care. Skin care provided by nurses, in adequate frequencies, might be helpful compared to skin care performed by the residents themselves.

Efficacy and In-Use Tolerance of Venusia Baby Moisturizer for Skin Hydration in Babies With Dry and/or Normal Skin.

Introduction Skin hydration is important for maintaining adequate skin barrier function. After delivery, the baby's skin faces the most difficult challenge as they are exposed to the exterior world's environmental changes, friction, and microorganisms. The management is further complicated by the availability of a large range of infant skin-care products with varying claims. The first-ever Indian study on babies was done to analyze the test product (Venusia baby moisturizer; Dr. Reddy's Laboratories Ltd., Hyderabad, India) in order to bring scientific clarity to consumers. This product is devoid of parabens, alcohol, and animal origin (Dr. Reddy's Laboratories Ltd., Hyderabad, India) and is designed for skin hydration and in-use tolerance in babies with dry and/or normal skin. The endpoints were hydration and clinical evaluation of the skin, evaluated using a moisture meter scale (MMSC; Delfin Technologies Ltd., Kuopio, Finland) and parent self-assessment questionnaire, respectively. Material and methods A total of 136 healthy babies aged between six months to two years were enrolled in a four-group, monocentric, non-randomized, evaluator-blinded study: Group 1 (Venusia baby cream for dry skin), Group 2 (Venusia baby lotion for Dry Skin), Group 3 (Venusia baby cream for normal skin), and Group 4 (Venusia baby lotion for normal skin). The endpoints were hydration and clinical evaluation of the skin, evaluated using an MMSC and parent self-assessment questionnaire, respectively. Results In babies with dry skin, skin hydration was improved with Venusia baby cream (37.50%) and Venusia baby lotion (66.40%). Additionally, 66.66% of participants strongly agreed that the baby's skin became softer and smoother after the application of Venusia baby cream; 76.47% of participants strongly agreed that the baby's skin became softer and smoother after the application of Venusia baby lotion. In babies with normal skin, skin hydration was improved with Venusia baby cream (12.20%) and Venusia baby lotion (7.20%); 59.37% of participants strongly agreed that the baby's skin became softer and smoother after the application of Venusia baby cream; and 84.84% of participants strongly agreed that the baby's skin became softer and smoother after the application of Venusia baby lotion. Conclusion Significant improvement was seen in skin hydration using Venusia baby cream and Venusia baby lotion in babies with dry skin and normal skin. No skin intolerances and product-related adverse or serious adverse events were clinically observed or reported during the study duration. Venusia baby lotion had the highest effect (66.4%) on skin hydration in babies with dry skin, where there was a significant shift from dry skin to normal skin range.

Self-Reported Allergic Occupational Contact Dermatitis among Dental Healthcare Professionals in United Arab Emirates -A Cross Sectional Study.

In dentistry, occupational contact dermatitis may affect dental professionals along with technicians, nurses, and patients. Changes to dental practice in recent years have altered the reported frequencies of allergens causing contact dermatitis in both dental professionals and dental patients. In the current cross-sectional study, we used a structured questionnaire and clinical examinations to examine the prevalence of self-reported hand eczema among United Arab Emirates (UAE). The relationship between subjective skin discomfort and latex, composite/bonding, or other dental materials also was explored. A structured questionnaire was designed to analyze the prevalence of skin conditions among dental professionals and study its implication in gender, occupation, and age groups. The questionnaire included information about skin symptoms, atopy, occupational experience, and other background factors like respiratory symptoms, work history and methods, and exposure at work. It was distributed to 550 randomly selected dental healthcare professionals. Out of 550 dental healthcare workers contacted, 434 responded giving a response rate of 79%. The prevalence of dry and rough skin on the hands was highest (45%). There was a total of 29 cases of allergic contact dermatitis, 15 cases of contact urticaria, 12 cases of irritating contact dermatitis, and 1 incidence of onychomycosis among the 100 dental healthcare professionals who reported having dermatitis on their hands, forearms, or faces due to their daily dental chores. Rubber chemicals and natural rubber latex (NRL) in protective gloves used by dentists, as well as dental-restorative plastic materials (methylacrylates), were the most common causes of allergy. Dry skin and hand eczema were more common among dental healthcare professionals. Plastic gloves or NRL gloves with a low protein content are recommended for dental work. Skin exposure to methylacrylates or latex should be avoided.

Preventing, assessing and treating skin tears.

Skin tears are acute wounds caused by mechanical forces resulting in the separation of the skin's outer layers. Skin tears are more likely to occur in vulnerable people such as older people and people with neurodegenerative conditions. Rising life expectancy means that the number of patients with skin tears is expected to increase. This article describes the characteristics of skin tears, details the risk factors for skin tears and explains the importance of using a holistic, evidence-based and person-centred approach to skin tear prevention, assessment and treatment. The article outlines the crucial role of nurses as part of the multidisciplinary team in the management of skin tears.

Efficacy of a Nursing Skin Care Protocol in the Prevention of Skin-Related Problems Among Newly Diagnosed Diabetic Patients: A Pilot Study.

Introduction Diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose levels, affecting millions worldwide. Among the various complications associated with diabetes, skin-related problems represent a significant concern, particularly for newly diagnosed patients. Altered blood circulation, compromised immune responses and nerve damage increase the risk of skin issues in this vulnerable population. Effective nursing interventions are crucial in managing and preventing diabetes-related skin problems. A nursing skin care protocol tailored to the unique needs of newly diagnosed diabetic patients has the potential to reduce the incidence and severity of skin complications, leading to improved patient outcomes and enhanced quality of life. This study aims to assess the efficacy of a nursing skin care protocol in preventing skin-related problems among newly diagnosed diabetic patients. By analyzing the impact of the protocol on patient outcomes and exploring the significance of early intervention and patient education, this research seeks to provide valuable insights into the importance of proactive skin care management in diabetes care. Methods A randomized controlled trial was conducted at Acharya Vinoba Bhave Rural Hospital in India to evaluate the efficacy of a nursing skin care protocol in preventing skin problems among newly diagnosed diabetic patients. The study included 30 patients who met specific inclusion criteria and excluded those with critical illness or undergoing skin treatment. Data was collected using a questionnaire and standardized tools. Statistical analysis demonstrated the protocol's effectiveness in reducing skin-related issues. The results highlight the importance of early intervention and personalized nursing care in diabetic management, promoting better patient outcomes and overall well-being. Results The results of the study demonstrate the efficacy of the nursing skin care protocol in reducing pruritus and dry skin problems among newly diagnosed diabetic patients. The experimental group showed a substantial improvement, with higher efficacy gains for both pruritus (66.70%) and dry skin (86.70%) compared to the control group (pruritus: 26.70%, dry skin: 33.30%). These findings highlight the potential benefits of implementing the nursing skin care protocol to alleviate skin-related issues in this patient population. The study supports the importance of early intervention and tailored nursing care in managing diabetic skin problems, which could improve patient outcomes and overall well-being. Conclusion In conclusion, the nursing skin care protocol effectively prevented and reduced skin-related problems among newly diagnosed diabetic patients. The experimental group showed significant improvements in pruritus and dry skin compared to the control group. Early intervention and personalized nursing care are crucial in managing diabetic skin issues and enhancing patient well-being. Implementing the nursing skin care protocol can lead to a better quality of life for diabetic patients by addressing skin concerns. Further research and application of this protocol hold promise for managing skin-related complications in diabetes effectively.

Characteristics of Xerosis, Pruritus, and Pallor in Stage 5 Chronic Kidney Disease Patients Undergoing Hemodialysis at Dr. Hasan Sadikin General Hospital, Bandung.

Purpose: This study aims to delineate the demographic and clinical characteristics of xerosis, pruritus, and pallor among patients with stage 5 chronic kidney disease (CKD) undergoing hemodialysis at Dr. Hasan Sadikin General Hospital, Bandung. Patients and Methods: This cross-sectional, descriptive study involved the analysis of 139 selected medical records of patients with stage 5 CKD who underwent hemodialysis between July and August 2022. A comprehensive examination was conducted by a dermatovenereologist, and the findings were duly recorded in the patients' medical records. The documentation encompassed gender, age, employment status, as well as the clinical characteristics of xerosis, pruritus, and pallor. The collected data were analyzed using descriptive statistical methods. Results: Out of the 139 patients, 70 (50.4%) were male, while 69 (49.6%) were female. The mean (SD) age was 47.6 (11.8) years. The majority of the patients were unemployed (n=96, 69.1%). The median (IQR) duration of hemodialysis was 48 (96.0-24.0) months. The predominant findings were xerosis (n=84, 60.4%) and pallor (n=83, 59.7%), followed by pruritus (n=56, 40.3%). Instances of xerosis were more frequently observed in males, whereas pallor was more prevalent in females. Xerosis and pruritus exhibited higher prevalence in the ≥65 years age group, whereas pallor was more common in the 18-44 years age group. In contrast to xerosis, pruritus and pallor were more frequently noted in the unemployed group. Xerosis was predominantly mild with overall dry skin (ODS) score of one, and it was mainly observed on the patients' legs. Among those experiencing pruritus, over half displayed a moderate severity with visual analogue scale (VAS) scores ranging from ≥3 to <7. Patients with pallor mostly exhibited hemoglobin levels below 10 g/dL. Conclusion: Xerosis, pruritus, and pallor were prevalent among patients with stage 5 CKD undergoing hemodialysis. These disorders presented with distinct demographic and clinical characteristics. Timely diagnosis and intervention have the potential to enhance the quality of life for these patients.

Cux1+ proliferative basal cells promote epidermal hyperplasia in chronic dry skin disease identified by single-cell RNA transcriptomics.

Pathological dry skin is a disturbing and intractable healthcare burden, characterized by epithelial hyperplasia and severe itch. Atopic dermatitis (AD) and psoriasis models with complications of dry skin have been studied using single-cell RNA sequencing (scRNA-seq). However, scRNA-seq analysis of the dry skin mouse model (acetone/ether/water (AEW)-treated model) is still lacking. Here, we used scRNA-seq and in situ hybridization to identify a novel proliferative basal cell (PBC) state that exclusively expresses transcription factor CUT-like homeobox 1 (Cux1). Further in vitro study demonstrated that Cux1 is vital for keratinocyte proliferation by regulating a series of cyclin-dependent kinases (CDKs) and cyclins. Clinically, Cux1+ PBCs were increased in patients with psoriasis, suggesting that Cux1+ PBCs play an important part in epidermal hyperplasia. This study presents a systematic knowledge of the transcriptomic changes in a chronic dry skin mouse model, as well as a potential therapeutic target against dry skin-related dermatoses.

Development of an in vitro Functional Assay to Evaluate the Occlusive Properties of Moisturizers on Dry Skin.

INTRODUCTION: Dry skin is a hallmark of impaired skin barrier function. Moisturizers are a mainstay of treatment to help the skin retain moisture, and there is a high consumer demand for effective products. However, the development and optimization of new formulations are hampered due to lack of reliable efficacy measures using in vitro models. METHODS: In this study, a microscopy-based barrier functional assay was developed using an in vitro skin model of chemically induced barrier damage to evaluate the occlusive activity of moisturizers. RESULTS: The assay was validated by demonstrating the different effects on barrier function between humectant (glycerol) and occlusive (petrolatum). Significant changes in barrier function were observed upon tissue disruption, which was ameliorated by commercial moisturizing products. CONCLUSION: This newly developed experimental method may be helpful to develop new and improved occlusive moisturizers for the treatment of dry skin conditions.

Glycerol and natural sugar-derived complex modulate differentially stratum corneum water-binding properties and structural parameters in an in vitro Raman-desorption model.

The epidermal protective functions are closely associated with skin hydration homeostasis. The understanding of different states of water binding is a rising concept in assessing topically applied formulations and their interaction within the stratum corneum (SC). In addition to global water content, primary bound water, partially bound water, and unbound water and barrier-related lipid lateral packing and protein secondary structure can be measured by Raman spectroscopy. This study aimed to establish an in vitro SC model to evaluate differences in the efficacy of a natural sugar-derived complex in combination with glycerol and a botanical extract in modulating SC water binding and structural proteins and barrier lipids. These compounds were selected due to their water-binding and soothing properties. The SC water profiles were assessed at the surface and in 8 µm SC depth. After a 12-hour hyperhydration and subsequent product incubation the measurements were performed during a 6 hours desiccation phase. The maximal water caption and the time until reaching a steady state are measured as well as water retention and resistance against water loss. Global water content, partially bound, and unbound water, as well as lipid and protein structures were assessed with confocal Raman microspectroscopy. Both the natural sugar-derived mixture and more pronounced, the same mixture with additional glycerol increased all three water-binding parameters at the surface and in 8 µm SC depth at the beginning and during the desiccation phase. Further addition of botanical extract did not result in an additional increase of the water-binding. All three formulations showed an increase in the lipid lateral packing values prevented the protein alteration as measured by ß-sheets signal compared to blank. The present model is suited for screening studies comparing the specific effects of different compounds on hydration states. The natural sugar-derived mixture Aquaxyl showed evidence for an improvement of all SC hydration states, lipid and protein structure which was further enhanced by the addition of glycerol 5%. This improvement was evidenced at the surface and within the SC for all hydration-related parameters, and the lipid as well the protein structures. The addition of botanical extract phytoessence blue daisy did not show further improvement.

A comparative study on a biodegradable hyaluronic acid microneedle patch with a needleless patch for dry skin in atopic dermatitis: a single-blinded, split-body, randomized controlled trial.

To overcome interruption of skin barrier in transdermal drug delivery, the microneedle (MN) patch penetrates the barrier by punching with its MNs. Setting a needleless patch (NL patch) as the control intervention, this study assessed the efficacy of a biodegradable hyaluronic acid MN patch (BHMN patch) for atopic dermatitis (AD) patients with dry skin. Similar two AD lesions were selected from the extremities of a participant. For one lesion, a BHMN patch was attached for 6-8 h on where an aroma cream was applied (BHMN patch group). Simultaneously, an NL patch was attached on the other lesion as in the BHMN patch group (NL patch group). For 2 weeks, the interventions were conducted 3 times a week. The local scoring AD (L-SCORAD) index, the visual analog scale for pruritus and skin dryness, skin hydration, the transepidermal water loss (TEWL), and safety were assessed. Fifteen participants finished this trial with no dropouts. Both groups improved the L-SCORAD index after 2 weeks (p < 0.05), but the score of the BHMN patch group decreased more than that of the NL patch group (p < 0.05). The other outcomes, except for the TEWL, also showed statistical significance in intragroup comparisons. Nevertheless, none of the other outcomes showed statistical significance in intergroup comparisons. The TEWL showed no statistical significance even in intragroup comparison. Recoverable minor adverse events were reported in three cases. Considering the result of L-SCORAD index, the BHMN patch may be effective for ameliorating AD. However, a large-scale confirmatory trial is necessary to reassess other outcomes.Trial Registration: This study was registered with the Clinical Research Information Service, Republic of Korea (Submitted date: 04/01/2022, Registered date: 23/02/2022, The first participant enrollment: 01/12/2021, Registration No. KCT0007037).

Relationship between dry skin and pressure injury in older patients: A multicentre cross-sectional survey in China.

Dry skin and pressure injuries in older persons have become global health care problems. This was a multicentre, prospective cross-sectional study in 44 hospitals and 8 long term care institutions from 20 provinces, autonomous regions and municipalities in China and aimed to explore the relationship between the two skin problems in older patients. We mainly found 11 602 cases with dry skin and 1076 cases with pressure injuries in a total of 33 769 valid participants. The overall prevalence of dry skin and pressure injuries was 34.4% (95% confidence interval [CI] 33.9-34.9) and 3.1% (95% CI 2.9-3.3). Stage 2+ pressure injuries were the most (32.9%), followed by stage 1 (32.4%). The patients with dry skin had more pressure injuries than ones without dry skin (50.0% vs 33.9%). The patients with very severe and severe dry skin had more pressure injury risk (OR 2.22 and 1.90) and more stage 2+ pressure injury risk (OR 2.83 and 1.63). Other nine predictors associated with overall pressure injuries and stage 2+ pressure injuries. The area under receiver operating characteristic (ROC) curve of the predictive models of overall pressure injuries and stage 2+ pressure injuries were 0.89 (95% CI 0.88-0.90) and 0.91 (95% CI 0.90-0.92), respectively.

Loss-of-function mutations in CST6 cause dry skin, desquamation and abnormal keratosis without hypotrichosis.

Cystatin M/E (encoded by the CST6 gene) is a cysteine protease inhibitor, that exerts regulatory and protective effects against uncontrolled proteolysis mainly by directly regulating cathepsin V, cathepsin L, and legumain activities. Previous studies have suggested that CST6 may exert a regulatory role in epidermal differentiation and hair follicle formation by inhibiting the activity of respective cognate target proteases. However, until recently, studies have revealed that loss- or gain-of-function of the CST6 gene causes dry skin with hypotrichosis in humans. Here, we reported two siblings of Chinese origin with dry skin, desquamation and abnormal keratosis without hypotrichosis. By applying whole-exome sequencing, we identified homozygous loss-of-function mutation c.251G > A (p.Gly84Asp) in the CST6 gene as the underlying genetic cause. Further fluorimetric enzyme assays demonstrated the mutant cystatin M/E protein lost its inhibitory function on the protease activity of cathepsins. Moreover, the corresponding mutation in mice resulted in excessive cornification, desquamation, impaired skin barrier function, and abnormal proliferation and differentiation of keratinocytes. In conclusion, the homozygous missense mutation c.251G > A in CST6 gene resulted in dry skin, desquamation, as well as abnormal keratosis of the skin, promoting our understanding of the role of protease-antiprotease balance in human skin disorders.

Improvement of xeroderma and water content of the stratum corneum in children with a moisturizer containing oat kernel oil / 中华医学美学美容杂志

Objective:To evaluate the influence of a moisturizer containing oat kernel oil for xeroderma and water content of the stratum corneum in children.Methods:From September to December 2022, 30 children with xeroderma were treated in the Dermatology Department of Tongzhou Maternal and Child Health Hospital of Beijing; 13 were males and 17 were females, and the age was 7.33±2.63 years. This was a single-center self-controlled trial. All children applied the moisturizer on the dry skin of the bilateral limbs two time per day for 14 days, and were followed up at 7 days and 14 days. Efficacy was evaluated according to the water content of the stratum corneum, visual scale, xerosis severity scale (XSS), Specified Symptom Sum Score (SRRC), Visual Analog Scale (VAS) and so on. and side-reactions were recorded.Results:After application of the moisturizer, the median of water content in the stratum corneum was 49.00 (33.83, 87.25), 48.84 (32.58, 100.34) at 7 d and 14 d respectively, showing significant increases compared with that at baseline (median 26.51 (16.00, 47.75) ( Z=-3.075, Z=-2.911, P<0.01). The visual scale, XSS, SRRC and VAS showed that compared with the baseline at 7 d, 14 d, the skin dryness and pruritus scores improved significantly ( Z=-4.424, -4.150, -3.943, -4.400; Z=-4.744, -4.409, -4.260, -4.409, P<0.01). Conclusions:The application of this moisturizer containing oat kernel oil could effectively improve skin dryness and the water content of the stratum corneum without serious adverse reactions.

Upregulation of DRG protein TMEM100 facilitates dry-skin-induced pruritus by enhancing TRPA1 channel function.

The dry skin tortures numerous patients with severe itch. The transient receptor potential cation channel V member 1 (TRPV1) and A member 1 (TRPA1) are two essential receptors for peripheral neural coding of itch sensory, mediating histaminergic and nonhistaminergic itch separately. In the dorsal root ganglion, transmembrane protein 100 (TMEM100) is structurally related to both TRPV1 and TRPA1 receptors, but the exact role of TMEM100 in itch sensory coding is still unknown. Here, in this study, we find that TMEM100 + DRG neurons account for the majority of activated neurons in an acetone-ether-water (AEW)-induced dry skin itch model, and some TMEM100 + DRG neurons are colocalized with both TRPA1 and the chloroquine-related Mrgpr itch receptor family. Both the expression and function of TRPA1 channels, but not TRPV1 channels, are upregulated in the AEW model, and specific DRG Tmem100 gene knockdown alleviates AEW-induced itch and rescues the expression and functional changes of TRPA1. Our results strongly suggest that TMEM100 protein in DRG is the main facilitating factor for dry-skin-related chronic itch, and specific suppression of TMEM100 in DRG could be a novel effective treatment strategy for patients who suffer from dry skin-induced itch.

Application of mevalonolactone prevents deterioration of epidermal barrier function by accelerating the lamellar granule lipid transport system.

BACKGROUND: Fatty acids increase ATP-binding cassette ABC transporter A12 (ABCA12) levels via an increase in peroxisome proliferator-activated receptor ß/δ (PPAR ß/δ). Promoting lipid transport to lamellar granules has been suggested to improve epidermal barrier function in patients with dry skin. OBJECTIVE: We investigated whether mevalonolactone (MVL) produced by Saccharomycopsis fibuligera improves dry skin by promoting ABCA12 expression and the amount of free fatty acids in epidermal keratinocytes. METHODS: We examined whether MVL increases ABCA12 mRNA and protein levels and the amount of Nile red-positive lipids in cultured epidermal keratinocytes and in a three-dimensional epidermal model by cell staining. Promotion of fatty acid production by MVL was analyzed by liquid chromatography-mass spectrometry. We also evaluated whether MVL addition increases PPAR ß/δ mRNA expression in cultured keratinocytes. Based on the results, a randomized controlled trial was conducted in which milky lotions containing MVL and placebo were applied to dry facial skin of healthy female volunteers in winter. RESULTS: MVL increased ABCA12 mRNA and protein levels and lamellar granule number and size. Fatty acid analysis revealed that MVL elevated myristic acid, palmitic acid, and palmitoleic acid levels as well as PPAR ß/δ mRNA expression. In human tests, milky lotions containing MVL were shown to significantly improve transepidermal water loss (TEWL) in the stratum corneum compared to placebo. CONCLUSION: The results suggest that MVL increases fatty acid uptake and ABCA12, promotes fatty acid transport to lamellar granules, and improves epidermal barrier function in dry skin through increased expression of PPAR ß/δ.