Mammalian Skin Research Articles

Comparative analysis of human and mouse transcriptomes during skin wound healing.

Skin wound healing is a complex process which involves multiple molecular events and the underlying mechanism is not fully understood. We presented a comparative transcriptomic analysis of skin wound healing in humans and mice to identify shared molecular mechanisms across species. We analyzed transcriptomes from three distinct stages of the healing process and constructed protein-protein interaction networks to elucidate commonalities in the healing process. A substantial number of differentially expressed genes (DEGs) were identified in human transcriptomes, particularly upregulated genes before and after wound injury, and enriched in processes related to extracellular matrix organization and leukocyte migration. Similarly, the mouse transcriptome revealed thousands of DEGs, with shared biological processes and enriched KEGG pathways, highlighting a conserved molecular signature in skin wound healing. A total of 21 common DEGs were found across human comparisons, and 591 in mouse comparisons, with four genes (KRT2, MARCKSL1, MMP1, and TNC) consistently differentially expressed in both species, suggesting critical roles in mammalian skin wound healing. The expression trends of these genes were consistent, indicating their potential as therapeutic targets. The molecular network analysis identified five subnetworks associated with collagen synthesis, immunity, cell-cell adhesion, and extracellular matrix, with hub genes such as COL4A1, TLR7, TJP3, MMP13, and HIF1A exhibited significant expression changes before and after wound injury in humans and mice. In conclusion, our study provided a detailed molecular network for understanding the healing process in humans and mice, revealing conserved mechanisms that could help the development of targeted therapies across species.

Acid-sensing ion channels drive the generation of tactile impulses in Merkel cell-neurite complexes of the glabrous skin of rodent hindpaws.

Merkel cell-neurite complexes (MNCs) are enriched in touch-sensitive areas, including whisker hair follicles and the glabrous skin of the rodent's paws, where tactile stimulation elicits slowly adapting type 1 (SA1) tactile impulses to encode for the sense of touch. Recently, we have shown with rodent whisker hair follicles that SA1 impulses are generated through fast excitatory synaptic transmission at MNCs and driven by acid-sensing ion channels (ASICs). However, it is currently unknown whether, besides whisker hair follicles, ASICs also play an essential role in generating SA1 impulses from MNCs of other body parts in mammals. In the present study, we attempted to address this question by using the skin-nerve preparations made from the hindpaw glabrous skin and tibial nerves of both male and female rodents and applying the pressure-clamped single-fiber recordings. We showed that SA1 impulses elicited by tactile stimulation to the rat hindpaw glabrous skin were largely diminished in the presence of amiloride and diminazene, two ASIC channel blockers. Furthermore, using the hindpaw glabrous skin and tibial nerve preparations made from the mice genetically deleted of ASIC3 channels (ASIC3-/-), we showed that the frequency of SA1 impulses was significantly lower in ASIC3-/- mice than in littermate wildtype ASIC3+/+ mice, a result consistent with the pharmacological experiments with ASIC channel blockers. Our findings suggest that ASIC channels are essential for generating SA1 impulses to underlie the sense of touch in the glabrous skin of rodent hindpaws.Significance Statement Merkel cell-neurite complexes (MNCs) are enriched in touch-sensitive areas, including whisker hair follicles and the glabrous skin of the rodent's paws, where tactile stimulation elicits slowly adapting type 1 (SA1) tactile impulses to encode for the sense of touch. Here, using the skin-nerve preparations made from the hindpaw glabrous skin and tibial nerves of rodents and applying the pressure-clamped single-fiber recordings, we have demonstrated that ASIC channels are essential for generating SA1 impulses at MNCs in the glabrous skin of rodent hindpaws. Thus, ASIC channels at MNCs may play a key role in the sense of touch to the skin of mammals.

Malassezia globosa Induces Differentiation of Pathogenic Th17 Cells by Inducing IL-23 Secretion by Keratinocytes.

Malassezia, the most abundant fungal commensal on the mammalian skin, has been linked to several inflammatory skin diseases such as atopic dermatitis, seborrheic dermatitis and psoriasis. This study reveals that epicutaneous application with Malassezia globosa (M. globosa) triggers skin inflammation in mice. RNA-sequencing of the resulting mouse lesions indicates activation of Interleukin-17 (IL-17) signaling and T helper 17 (Th17) cells differentiation pathways by M. globosa. Furthermore, our findings demonstrate a significant upregulation of IL-23, IL-23R, IL-17A, and IL-22 expressions, along with an increase in the proportion of Th17 and pathogenic Th17 cells in mouse skin exposed to M. globosa. In vitro experiments illustrate that M. globosa prompts human primary keratinocytes to secrete IL-23 via TLR2/MyD88/NF-κB signaling. This IL-23 secretion by keratinocytes is shown to be adequate for inducing the differentiation of pathogenic Th17 cells in the skin. Overall, these results underscore the significant role of Malassezia in exacerbating skin inflammation by stimulating IL-23 secretion by keratinocytes and promoting the differentiation of pathogenic Th17 cells.

Enhanced visualization of nuclear staining and cell cycle analysis for the human commensal Malassezia

Malassezia is a lipophilic commensal yeast that resides mainly on the mammalian skin and is also found to associate with the internal organs. Dysbiosis of Malassezia is related to several diseases and often escapes detection as it is difficult to culture and maintain. Malassezia cell wall differs from other budding yeasts like S. cerevisiae due to the difference in the lipid content and is difficult to transform. In this study, we present a methodology to stain Malassezia's nucleus and perform cell cycle studies. However, staining presents a challenge due to its exceptionally thick cell wall with high lipid content, hindering conventional methods. Our novel methodology addresses this challenge and enables the staining of the Malassezia nucleus with a low background. This would allow researchers to visualize the overall nuclear health specifically nuclear morphology and analyze DNA content, crucial for cell cycle progression. By employing DNA-specific dyes like DAPI or Hoechst, we can observe the nuclear structure, and using PI we can differentiate cells in distinct cell cycle phases using techniques like flow cytometry. This novel staining methodology unlocks the door for in-depth cell cycle analysis in Malassezia which has challenged us through ages being refractory to genetic manipulations, paving the way for a deeper understanding of this commensal fungus and its potential role in human health.

Temperature Is a Key Factor Governing the Toxic Impact of Ultra-Violet Radiation-Emitting Nail Dryers When Used on Human Skin Cells.

The skin is the largest organ in the body and the only one to come into contact with solar UV radiation (UVR). UVA (320-400nm) is a significant contributor to UV-related skin damage. The UVA spectrum makes up over 95% of solar-UV energy reaching the earth's surface causing the majority of the visible signs of skin photoaging. Many consumer products also emit UVA, including nail dryers. There have been sporadic reports suggesting that these units may be contributing to skin cancer incidence. This notion was recently bolstered by a finding that nail dryer-irradiated mammalian skin cells develop a mutational signature consistent with UVA exposure. This report was surprising considering the comparatively low level of UVA to which the skin is exposed during nail treatments. In this research, we investigated how UVA-emitting devices caused cytotoxic/genotoxic impact after only low levels of UVA exposure. Our data showed that levels of UVA in the unit are highly variable and location dependent. We confirm previous reports that using prolonged exposure protocols could induce significant levels of DNA damage. It was also determined that UV-induced DNA damage only partially correlated with the level of UVA fluency. On investigation, we found that the unit had a rapid increase in internal temperature when in use. Exposing human cells to these elevated temperatures acted synergistically with UVA to magnify the cytotoxic and genotoxic impact of UV irradiation.

Physiological responses of Holothuria grisea during a wound healing event: An integrated approach combining tissue, cellular and humoral evidence

Due to their tissue structure similar to mammalian skin and their close evolutionary relationship with chordates, holothurians (Echinodermata: Holothuroidea) are particularly interesting for studies on wound healing. However, previous studies dealing with holothuroid wound healing have had limited approaches, being restricted to tissue repair or perivisceral immune response. In this study, we combined tissue, cellular and humoral parameters to study the wound healing process of Holothuria grisea. The immune responses of the perivisceral coelom were assessed by analyzing the number, proportion and viability of coelomocytes and the volume and protein concentration of the coelomic fluid. Additionally, the morphology of the healing tissue and number of coelomocytes in the connective tissue of different body wall layers were examined over 30 days. Our results showed that perivisceral reactions started 3 h after injury and decreased to baseline levels within 24 h. In contrast, tissue responses were delayed, beginning after 12 h and returning to baseline levels only after day 10. The number of coelomocytes in the connective tissue suggests a potential cooperation between these cells during wound healing: phagocytes and acidophilic spherulocytes act together in tissue clearance/homeostasis, whereas fibroblast-like and morula cells cooperate in tissue remodeling. Finally, our results indicate that the major phases observed in mammalian wound healing are also observed in H. grisea, despite occurring at a different timing, which might provide insights for future studies. Based on these data, we propose a model that explains the entire healing process in H. grisea.

Wound healing effect of polydeoxyribonucleotide derived from Hibiscus sabdariffa callus via Nrf2 signaling in human keratinocytes

There has been a growing interest in skin recovery in both the medical and cosmetics fields, leading to an increasing number of studies reporting diverse materials being utilized for this purpose. Among them, polydeoxyribonucleotide (PDRN) is known for its efficacy in skin repair processes, while Hibiscus sabdariffa (HS) is recognized for its antioxidant, hypolipidemic, and wound healing properties, including its positive impact on mammalian skin and cells. We hypothesized that these characteristics may have a germane relationship during the healing process. Consequently, we induced calli from HS and then extracted PDRN for use in treating human keratinocytes. PDRN (5 μg/mL) had considerable wound healing effects and wrinkle improvement effects. To confirm its function at the molecular level, we performed real-time polymerase chain reaction, western blotting, and immunocytochemistry. Furthermore, genes related to wound healing (MMP9, Nrf2, KGF, VEGF, SOD2, and AQP3) were significantly upregulated. Additionally, the protein expression of MMP9, AQP3, and CAT, which are closely related to wound healing and antioxidant cascades, was considerably enhanced. Based on cellular morphology and molecular-level evidence, we propose that PDRN from calli of HS can improve wound healing in human keratinocytes. Furthermore, its potential to serve as a novel material in cosmetic products is demonstrated.

Touch medicine: bridging the gap between recent insights from touch research and clinical medicine and its special significance for the treatment of affective disorders.

Interpersonal touch represents the primal sensory experience between humans, fostering social bonding from the cradle to the death bed. In recent decades "affective touch" has been intensely studied, stimulated by the discovery of a population of mechanosensitive unmyelinated C-tactile afferents in mammalian skin. A lack of touch in childhood is associated with negative consequences for psychosocial and physical health and the benefits of professional touch techniques in the prevention and treatment of various diseases have been shown over and over again in clinical studies. However, its application in mainstream clinical applications remains limited. To bridge the gap between recent discoveries in touch research and clinical medicine, we propose the establishment of a new discipline: 'Touch Medicine'. Here, we unfold the potential of Touch Medicine by focusing on the treatment of depression, which in our view is primarily a disorder of the lived body. Controlled studies and systematic reviews have demonstrated the antidepressant, anxiolytic and analgesic effects of specific massage techniques. Underlying mechanisms of action are currently under investigation, ranging from interoceptive, endocrinological, to stress-related or psychological underpinnings. Touch Medicine represents a novel interdisciplinary field connected to various medical specialities such as neonatology, pediatrics, pain medicine, neurology, psychiatry, and geriatrics - but also clinical psychology and psychosomatic medicine might benefit from the integration of these findings into their daily practice.

O13 Benchmarking a human pluripotent stem cell-derived hair-bearing skin organoid model to prenatal skin

Abstract Introduction and aims Molecular regulation of mammalian skin development has been largely derived from murine studies. The lack of human studies stems primarily from the difficulties in prenatal human skin access. There is an important need to study human prenatal skin owing to the notable differences between human and mouse skin and the paucity of mechanistic understanding of congenital skin disorders. Methods We assembled the first comprehensive multiomic reference atlas of prenatal human skin (21 samples from 7 to 16 postconception weeks), combining single-cell (235 201 cells) and spatial transcriptomic data. We followed 84 skin organoids (SkOs) using single-cell analysis over a 5-month culture period and characterized the spatial organization of the skin in mature SkOs. Prenatal skin, SkO and any relevant pre-existing single-cell RNA-Seq datasets were integrated into the analysis. Cell–cell interactions and cell-lineage determination were explored using CellPhoneDB and trajectory inferences. We evaluated the differentiation trajectory alignment between prenatal skin and SkO using the Genes2Genes analysis. Results Our findings reveal predicted factors regulating the epithelial–mesenchymal crosstalk during human hair follicle formation; progressive expression of scar-promoting genes in later gestation, potentially contributing to scarless healing properties of human prenatal skin observed during the early stages of gestation and expression of genes causing genetic skin disorders in the same cell types in prenatal human skin and SkO. We also found that SkOs morphologically recapitulate human skin development from early (periderm formation and shedding) to late (cornification and hair follicle formation) stages. We also demonstrated that SkO and prenatal skin mesenchyme differentiation into hair follicle dermal condensate and dermal papilla is highly conserved at the cellular and molecular level. Conclusions SkOs faithfully recapitulate human prenatal skin development and are a valuable model for mechanistic studies on skin development including hair follicle biology and congenital skin disorders.

Immunolabeling for filaggrin and acidic keratins in the granular layer of mammalian epidermis indicates that an acidic-basic interaction is involved in cornification

The soft epidermis of mammals derives from the accumulation of keratohyaline granules in the granular layer, before maturing into corneocytes. Main proteins accumulated in the granular layer are pro-filaggrin and filaggrin that determine keratin clumping and later moisturization of the stratum corneum that remains flexible. This soft epidermis allows the high sensitivity of mammalian skin. Presence and thickness of the stratum granulosum varies among different species of mammals and even between different body regions of the same animal, from discontinuous to multilayered. These variations are evident using antibodies for filaggrin, a large protein that share common epitopes among placentals. Here we have utilized filaggrin antibodies (8959 and 466) and an acidic keratin antibody (AK2) for labeling placental, marsupial and monotreme epidermis. AK2 labeling appears mainly to detect K24 keratin, and less likely other acidic keratins. Immunoreactivity for filaggrin is absent in platypus, discontinuous in Echidna and in the tested marsupials. In placentals, it is inconstantly or hardly detected in the thin epidermis of bat, rodents, and lagomorphs with a narrow, mono-stratified and/or discontinuous granular layer. In contrast, where the granular layer is continuous or even stratified, both filaggrin and AK2 antibodies decorate granular cells. The ultrastructural analysis using the AK2 antibody on human epidermis reveals that a weak labeling is associated with keratohyalin granules and filamentous keratins of transitional keratinocytes and corneocytes. This observation suggests that basophilic filaggrin interacts with acidic keratins like K24 and determines keratin condensation into corneocytes of the stratum corneum.

Mycosporine-Like Amino Acids as a Potential Inhibitor of Tyrosinase-Related Protein 1: Computational Screening, Pharmacokinetics, and Molecular Dynamics Simulation.

Melanin is the major pigment responsible for the coloring of mammalian skin, hair, and eyes to defend against ultraviolet radiation. However, excessive melanin production has resulted in numerous types of hyperpigmentation disorders. Tyrosinase-related protein 1 (TYRP1) is a transmembrane glycoprotein enzyme found in many organisms, including humans, that plays an important role in melanogenesis. Thus, controlling the enzyme activity of TYRP1 with tyrosinase inhibitors is a vital step in the treatment of hyperpigmentation problems in humans. In the present investigation, virtual screening, pharmacokinetics, drug docking, and molecular dynamics (MD) simulation were used to find the most potent drug as an inhibitor of TYRP1 to effectively treat hyperpigmentation disorder. The 3D structure of TYRP1 was retrieved from the Protein Data Bank (PDB) database (PDB ID: 5M8M) and validated by the Ramachandran plot. Pharmacokinetics and drug-likeness showed that mycosporine 2 glycine (M2G) and shinorine (SHI) were the best compounds over other ligands in the same (P-1) structural pose. However, MD simulations of the M2G showed the highest CDOCKER interaction energy (-45.182kcal/mol) and binding affinity (-65.0529kcal/mol) as compared to SHI and reference drugs. The molecular binding modes RMSD and RMSF plots have exhibited more relevance to the M2G ligand in comparison to other drug ligands. The bioactivity and ligand efficiency profiles revealed that M2G is the most effective compound as a TYRP1 inhibitor. Thus, M2G could be used as a most effective drug for developing valuable sunscreen products to cure hyperpigmentation-related diseases.

Role of Dermal Factors Involved in Regulating the Melanin and Melanogenesis of Mammalian Melanocytes in Normal and Abnormal Skin.

Mammalian melanin is produced in melanocytes and accumulated in melanosomes. Melanogenesis is supported by many factors derived from the surrounding tissue environment, such as the epidermis, dermis, and subcutaneous tissue, in addition to numerous melanogenesis-related genes. The roles of these genes have been fully investigated and the molecular analysis has been performed. Moreover, the role of paracrine factors derived from epidermis has also been studied. However, the role of dermis has not been fully studied. Thus, in this review, dermis-derived factors including soluble and insoluble components were overviewed and discussed in normal and abnormal circumstances. Dermal factors play an important role in the regulation of melanogenesis in the normal and abnormal mammalian skin.

Development and Characterization of Charantin Loaded Transferosomes based Transdermal Formulation: An Effective and Patient Friendly Way for Diabetes Management

Transferosomes, marvels of scientific ingenuity, represent exquisitely optimized and ultra- deformable (ultra-flexible) lipid supramolecular aggregates, uniquely capable of traversing the mammalian skin intact. These remarkable carrier systems have harnessed the power of transdermal delivery, enabling the transport of drugs, irrespective of their molecular weight from the tiniest compounds to the most substantial ones. The incorporation of Charantin into transferosomal gel formulation holds immense promise in advancing topical therapeutics. Charantin, a bioactive compound derived from Momordica charantia, possesses potent medicinal properties with antidiabetic, anti-inflammatory, antioxidant, and antimicrobial activities. When integrated into the lipid-based transferosomal system, Charantin's efficacy is significantly amplified due to enhanced skin penetration and improved stability against degradation. The versatile nature of transferosomal gels allows for encapsulating both hydrophilic and lipophilic compounds, making it an ideal carrier for Charantin regardless of its solubility characteristics. Driven by the pursuit of excellence, the present study sought to masterfully optimize the Transferosomes to orchestrate an unparalleled symphony of enhanced skin delivery for Charantin.

A Stratum corneum lipid model as a platform for biophysical profiling of bioactive chemical interactions at the skin level

Stratum Corneum (SC), the outermost layer of mammalian skin, provides the first and most challenging barrier to skin permeation of cosmetic and pharmaceutical compounds. SC barrier function relies primarily on the complex structure and organization of the intercellular lipid matrix. This matrix consists mainly of ceramides (CER), free fatty acids (FFA), and cholesterol (Chol) in an equimolar ratio, forming a multilamellar structure with short- and long-periodicity phases. Along with permeation studies, it becomes paramount the molecular investigation of the interaction between the lipid matrix and the compounds, towards a comprehensive picture of their biophysical impact, including lipid packing impairment, which can result in skin damage, and in consequences for their permeation and mechanism of action. In this study, a lipid-based model (CER[EOS]:CER[AP]:Chol:FFA) was developed to accurately resemble the barrier properties of the intercellular lipid matrix. In a monolayer assembly, this SC lipid model was characterized and applied as an in vitro platform to explore interactions with model compounds – caffeine and testosterone – following OECD recommendations. The SC model successfully mimicked different barrier properties of the SC’s lipid matrix, and its interactions with the model compounds were discussed closely aligned with existing data, including in vitro permeation studies using human and animal membranes. This SC model can be a step forward towards the development of new in vitro platforms for investigating the skin barrier function and the interactions with external molecules. Moreover, the composition of these platforms can be easily modified to mimic impaired lipid matrices to study different skin conditions, providing valuable insights for both cosmetic and pharmaceutical applications.

Neuromorphic antennal sensory system

Insect antennae facilitate the nuanced detection of vibrations and deflections, and the non-contact perception of magnetic or chemical stimuli, capabilities not found in mammalian skin. Here, we report a neuromorphic antennal sensory system that emulates the structural, functional, and neuronal characteristics of ant antennae. Our system comprises electronic antennae sensor with three-dimensional flexible structures that detects tactile and magnetic stimuli. The integration of artificial synaptic devices adsorbed with solution-processable MoS2 nanoflakes enables synaptic processing of sensory information. By emulating the architecture of receptor-neuron pathway, our system realizes hardware-level, spatiotemporal perception of tactile contact, surface pattern, and magnetic field (detection limits: 1.3 mN, 50 μm, 9.4 mT). Vibrotactile-perception tasks involving profile and texture classifications were accomplished with high accuracy (> 90%), surpassing human performance in “blind” tactile explorations. Magneto-perception tasks including magnetic navigation and touchless interaction were successfully completed. Our work represents a milestone for neuromorphic sensory systems and biomimetic perceptual intelligence.

Toxins profiles, toxicological properties, and histological alteration potentiality of Trimeresurus erythrurus venom: In vitro and in vivo experiments

ObjectivesTrimeresurus erythrurus (Red-tailed bamboo pit viper) contributes significantly to snakebite envenoming cases in Bangladesh, India, Myanmar, and Nepal. However, the absence of specific antivenom and challenging socio-economic conditions in these regions necessitate the development of symptom-based medication to mitigate the severity of T. erythrurus envenoming. Therefore, documenting the effects of T. erythrurus venom on mammalian organs can establish a foundation for further research on symptom-based medication. MethodsWe profiled T. erythrurus venom toxins using SDS-PAGE. Additionally, we assessed the venom's toxicological properties through lethality, hemorrhagic, edematogenic, hemolytic, and phospholytic assays. Furthermore, we examined the histological alterations induced by crude venom on various organs of mice. ResultsSDS-PAGE profiling confirmed the presence of Snake Venom Metalloproteases (SVMPs), Snake Venom Serine Proteases (SVSPs), Phospholipase A2 (PLA2), L-amino Acid Oxidases (LAAOs), Myotoxins, and Disintegrins as toxic components in T. erythrurus venom. The venom exhibited a Median Lethal Dose (LD50) of 1.131 mg/kg, Minimum Hemorrhagic Dose (MHD) of 0.21 mg/kg, Minimum Edematogenic Dose (MED) of 0.17 mg/kg, and Median Hemolytic Dose (HD50) of 2.527 mg/L. Moreover, the venom induced significant pathological changes in mammalian skin, skeletal muscle, lung, heart, kidney, and intestine. ConclusionsThis study elucidates the major toxins, critical toxicological indices, and histopathological effects of T. erythrurus venom on mammalian organs. These findings provide valuable insights on the development of effective treatment strategies for pathophysiological complications that could manifest post T. erythrurus envenoming.

Modulating embryonic signaling pathways paves the way for regeneration in wound healing.

Epithelial tissues, including the skin, are highly proliferative tissues with the capability to constant renewal and regeneration, a feature that is essential for survival as the skin forms a protective barrier against external insults and water loss. In adult mammalian skin, every injury will lead to a scar. The scar tissue that is produced to seal the wound efficiently is usually rigid and lacks elasticity and the skin's original resilience to external impacts, but also secondary appendages such as hair follicles and sebaceous glands. While it was long thought that hair follicles develop solely during embryogenesis, it is becoming increasingly clear that hair follicles can also regenerate within a wound. The ability of the skin to induce hair neogenesis following injury however declines with age. As fetal and neonatal skin have the remarkable capacity to heal without scarring, the recapitulation of a neonatal state has been a primary target of recent regenerative research. In this review we highlight how modulating dermal signaling or the abundance of specific fibroblast subsets could be utilized to induce de novo hair follicles within the wound bed, and thus to shift wound repair with a scar to scarless regeneration.

Estimation of SAR Average in Rats during 5G NR Chronic Exposure

To study physiological reactions in the brain and skin of higher mammals exposed to chronic radiofrequency radiation, specific absorption ratio (SAR) determination is required and time-consuming numerical methods are used. The paper deals with the estimation of the whole-body specific absorption rate (SAR) in rats chronically exposed to external electromagnetic fields, as well as the development of a laboratory setup simulating the operation of a fifth-generation 5G New Radio base station (with a signal bandwidth of 15 MHz and a carrier frequency of 2.4 GHz). The paper presents a modified method for theoretical SAR estimation for one-sided irradiation and distributed absorption. Mean whole-body SAR values were estimated by the proposed method and numerically modeled with the CST Microwave Studio simulation software 2020package using primitive rat models. Dielectric parameters in the numerical simulation were used from the software library. The IEEE/IEC 62704-1 algorithm was used to investigate SAR in numerical simulations. The theoretical estimates and numerical simulations were compared for different SAR distributions and were found to be qualitatively comparable. The differences between approximate theoretical estimates and numerical simulations are 7% and 10% for distributed and non-distributed absorptions, respectively. The proposed method, which takes into account the decreasing power flux density, can be used to estimate the approximate whole-body SAR during chronic electromagnetic field exposure in rats.

Regeneration of Panniculus Carnosus Muscle in Fetal Mice Is Characterized by the Presence of Actin Cables.

Mammalian skin, including human and mouse skin, does not regenerate completely after injury; it is repaired, leaving a scar. However, it is known that skin wounds up to a certain stage of embryonic development can regenerate. The mechanism behind the transition from regeneration to scar formation is not fully understood. Panniculus carnosus muscle (PCM) is present beneath the dermal fat layer and is a very important tissue for wound contraction. In rodents, PCM is present throughout the body. In humans, on the other hand, it disappears and becomes a shallow fascia on the trunk. Fetal cutaneous wounds, including PCM made until embryonic day 13 (E13), regenerate completely, but not beyond E14. We visualized the previously uncharacterized development of PCM in the fetus and investigated the temporal and spatial changes in PCM at different developmental stages, ranging from full regeneration to non-regeneration. Furthermore, we report that E13 epidermal closure occurs through actin cables, which are bundles of actomyosin formed at wound margins. The wound healing process of PCM suggests that actin cables may also be associated with PCM. Our findings reveal that PCM regenerates through a similar mechanism.

Sweat gland development requires an eccrine dermal niche and couples two epidermal programs

Eccrine sweat glands are indispensable for human thermoregulation and, similar to other mammalian skin appendages, form from multipotent epidermal progenitors. Limited understanding of how epidermal progenitors specialize to form these vital organs has precluded therapeutic efforts toward their regeneration. Herein, we applied single-nucleus transcriptomics to compare the expression content of wild-type, eccrine-forming mouse skin to that of mice harboring a skin-specific disruption of Engrailed 1 (En1), a transcription factor that promotes eccrine gland formation in humans and mice. We identify two concurrent but disproportionate epidermal transcriptomes in the early eccrine anlagen: one that is shared with hair follicles and one that is En1 dependent and eccrine specific. We demonstrate that eccrine development requires the induction of a dermal niche proximal to each developing gland in humans and mice. Our study defines the signatures of eccrine identity and uncovers the eccrine dermal niche, setting the stage for targeted regeneration and comprehensive skin repair.