Back Skin Of Mice Research Articles

748 UBE2N acts in keratinocytes to control epidermal homeostasis and skin inflammation

UBE2N (encoded by Ubc13 in mice) is a K63-polyubiqutination-specific E2 conjugase. UBE2N plays pivotal roles in signal transduction and gene regulation. Dysregulation of UBE2N is associated with many immunological disorders as well as embryonic developmental defects including loss of epidermal integrity. We have previously reported that Rosa-CreER-mediated deletion of UBE2N on adult mouse back skin leads to highly inflamed skin lesions, raising the question whether the skin inflammation is a result of UBE2N loss in keratinocyte or local immune cells.

Broadband High-Frequency Ultrasonic Transducer Based Functional Photoacoustic Mesoscopy for Psoriasis Progression.

In vivo imaging of skin is commonly used to investigate dynamic processes in the progression and treatment of psoriasis. Photoacoustic mesoscopy is a new non-invasive imaging modality widely used in bio-imaging, and has recently been applied to imaging skin in vivo. However, photoacoustic imaging has shortcomings. Although high-frequency ultrasonic transducers enable high-resolution photoacoustic imaging, the images may be bandwidth-limited. To overcome this limitation, we designed and fabricated a broadband ultrasonic transducer for photoacoustic mesoscopy. The center frequency of the transducer was 32 MHz (88% bandwidth at -6 dB). The transducer was used to visualize mouse and human skin morphology. Colocalization of high- and low-frequency components revealed information about both the skin surface and dermis. To explore dynamic structural changes in mouse back skin during psoriasis progression, we measured blood oxygen saturation and total hemoglobin in a mouse model using multiwavelength imaging without contrast agents. The results indicate that functional photoacoustic mesoscopy using a broadband high-frequency transducer has great potential for clinical imaging of skin disease.

Mast Cell-Derived Proteases Induce Endothelial Permeability and Vascular Damage in Severe Fever with Thrombocytopenia Syndrome.

ABSTRACTSevere fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever acquired by tick bites. Whether mast cells (MCs), the body’s first line of defense against pathogens, might influence immunity or pathogenesis during SFTS virus (SFTSV) infection remained unknown. Here, we found that SFTSV can cause MC infection and degranulation, resulting in the release of the vasoactive mediators, chymase, and tryptase, which can directly act on endothelial cells, break the tight junctions of endothelial cells and threaten the integrity of the microvascular barrier, leading to microvascular hyperpermeability in human microvascular endothelial cells. Local activation of MCs (degranulation) and MC-specific proteases-facilitated endothelial damage were observed in mouse models. When MC-specific proteases were injected subcutaneously into the back skin of mice, signs of capillary leakage were observed in a dose-dependent manner. MC-specific proteases, chymase, and tryptase were tested in the serum collected at the acute phase of SFTS patients, with the higher level significantly correlated with fatal outcomes. By performing receiver operator characteristic curve (ROC) analysis, chymase was determined as a biomarker with the area under the curve value of 0.830 (95% CI = 0.745 to 0.915) for predicting fatal outcomes in SFTS. Our findings highlight the importance of MCs in SFTSV-induced disease progression and outcome. An emerging role for MCs in the clinical prognosis and blocking MC activation as a potential drug target during SFTSV infection was proposed.IMPORTANCE We revealed a pathogenic role for MCs in response to SFTSV infection. The study also identifies potential biomarkers that could differentiate patients at risk of a fatal outcome for SFTS, as well as novel therapeutic targets for the clinical management of SFTS. These findings might shed light on an emerging role for MCs as a potential drug target during infection of other viral hemorrhagic fever diseases with similar host pathology as SFTS.

Large-scale isolation of functional dermal papilla cells using novel surface marker LEPTIN Receptor.

Dermal papilla (DP) cells regulate hair follicle epithelial cells and melanocytes by secreting functional factors, playing a key role in hair follicle morphogenesis and hair growth. DP cells can reconstitute new hair follicles and induce hair regeneration, providing a potential therapeutic strategy for treating hair loss. However, current methods for isolating DP cells are either inefficient (physical microdissection) or only applied to genetically labeled mice. We systematically screened for the surface proteins specifically expressed in skin DP using mRNA expression databases. We identified two antibodies against receptors LEPTIN Receptor (LEPR ) and Scavenger Receptor Class A Member 5 (SCARA5) which could specifically label and isolate DP cells by flow cytometry from mice back skin at the growth phase. The sorted LEPR+ cells maintained the DP characteristics after culturing in vitro, expressing DP marker alkaline phosphatase and functional factors including RSPO1/2 and EDN3, the three major DP secretory factors that regulate hair follicle epithelial cells and melanocytes. Furthermore, the low-passage LEPR+ DP cells could reconstitute hair follicles on nude mice using chamber graft assay when combined with epithelial stem cells. The method of isolating functional DP cells we established here lays a solid foundation for developing DP cell-based therapy.

Dedifferentiated Schwann cell-derived TGF-β3 is essential for the neural system to promote wound healing.

Rationale: Wound healing is among the most complicated physiological processes and requires the synchronization of various cell types with distinct roles to re-establish the condition of the original skin. Patients affected by peripheral neuropathies often experience failure to heal. Loss of Schwann cells (SCs), a crucial population of peripheral nervous system cells in skin, may contribute to chronic wounds. However, the role of SCs in wound healing are poorly understood.Methods: The activity of SCs was investigated by using a cell atlas of the wound healing process, which was generated by integrating single-cell RNA sequencing (scRNA-seq) libraries covering different states of mouse back skin. The results of in silico analysis were validated by in vitro cell culture and in vivo mouse model. Selective inhibitors and conditional RNAi by virus transfection were utilized to investigate the role of SCs in wound healing. Findings from mouse experiments were further verified in scRNA-seq analysis of diabetic patients.Results: Our in silico analysis revealed the heterogeneous cellular components of skin and the dynamic interactions of neural crest derived cells (NCs) with other cell types. We found that SCs dedifferentiated at an early stage of wound repair with upregulated Wnt signaling. We also identified dedifferentiated SC (dSC) defect in diabetic wounds in both mouse and human. Wnt inhibition at the wound site repressed SC dedifferentiation, leading to defective repair. Furthermore, dSCs derived TGF-β3, which is context-dependent, promoted the migration of fibroblasts and keratinocytes. Moreover, TGF-β3 supplementation enhanced the healing of chronic wounds in diabetic mice with impaired SCs.Conclusion: Our study thus advances the understanding of the roles of neural-derived cells in skin regeneration and suggests a potential therapeutic strategy for wound healing disorders.

Comparison of extracellular matrix enrichment protocols for the improved characterization of the skin matrisome by mass spectrometry

A striking feature of skin organization is that the extracellular matrix (ECM) occupies a larger volume than the cells. Skin ECM also directly contributes to aging and most cutaneous diseases. In recent years, specific ECM enrichment protocols combined with in silico approaches allowed the proteomic description of the matrisome of various organs and tumor samples. Nevertheless, the skin matrisome remains under-studied and protocols allowing the efficient recovery of the diverse ECM found in skin are still to be described. Here, we compared four protocols allowing the enrichment of ECM proteins from adult mouse back skin and found that all protocols led to a significant enrichment (up to 65%) of matrisome proteins when compared to total skin lysates. The protocols based on decellularization and solubility profiling gave the best results in terms of numbers of proteins identified and confirmed that skin matrisome proteins exhibit very diverse solubility and abundance profiles. We also report the first description of the skin matrisome of healthy adult mice that includes 236 proteins comprising 95 core matrisome proteins and 141 associated matrisome proteins. These results provide a reliable basis for future characterizations of skin ECM proteins and their dysregulations in disease-specific contexts. SignificanceExtracellular matrix proteins are key players in skin physiopathology and have been involved in several diseases such as genetic disorders, wound healing defects, scleroderma and skin carcinoma. However, skin ECM proteins are numerous, diverse and challenging to analyze by mass spectrometry due to the multiplicity of their post-translational modifications and to the heterogeneity of their solubility profiles. Here, we performed the thorough evaluation of four ECM enrichment protocols compatible with the proteomic analysis of mouse back skin and provide the first description of the adult mouse skin matrisome in homeostasis conditions. Our work will greatly facilitate the future characterization of skin ECM alterations in preclinical mouse models and will inspire new optimizations to analyze the skin matrisome of other species and of human clinical samples.

Non-thermal atmospheric pressure plasma activates Wnt/\u03b2-catenin signaling in dermal papilla cells

There is an unmet need for novel, non-pharmacological therapeutics to treat alopecia. Recent studies have shown the potential biological benefits of non-thermal atmospheric pressure plasma (NTAPP), including wound healing, angiogenesis, and the proliferation of stem cells. We hypothesized that NTAPP might have a stimulatory effect on hair growth or regeneration. We designed an NTAPP-generating apparatus which is applicable to in vitro and in vivo experiments. The human dermal papilla (DP) cells, isolated fresh hair follicles, and mouse back skin were exposed with the NTAPP. Biological outcomes were measured using RNA-sequencing, RT-PCR, Western blots, and immunostaining. The NTAPP treatment increased the expression levels of Wnt/β-catenin pathway-related genes (AMER3, CCND1, LEF1, and LRG1) and proteins (β-catenin, p-GSK3β, and cyclin D1) in human DP cells. In contrast, inhibitors of Wnt/β-catenin signaling, endo-IWR1 and IWP2, attenuated the levels of cyclin D1, p-GSK3β, and β-catenin proteins induced by NTAPP. Furthermore, we observed that NTAPP induced the activation of β-catenin in DP cells of hair follicles and the mRNA levels of target genes of the β-catenin signaling pathway (CCND1, LEF1, and TCF4). NTAPP-treated mice exhibited markedly increased anagen induction, hair growth, and the protein levels of β-catenin, p-GSK3β, p-AKT, and cyclin D1. NTAPP stimulates hair growth via activation of the Wnt/β-catenin signaling pathway in DP cells. These findings collectively suggest that NTAPP may be a potentially safe and non-pharmacological therapeutic intervention for alopecia.

Distinct Fibroblast Lineages Give Rise to NG2+ Pericyte Populations in Mouse Skin Development and Repair.

We have examined the developmental origins of Ng2+ perivascular cell populations that adhere to the basement membrane of blood vessels, and their contribution to wound healing. Neural/glial antigen 2 (Ng2) labeled most perivascular cells (70–80%) in developing and adult mouse back skin, a higher proportion than expressed by other pericyte markers Tbx18, Nestin and Pdgfrβ. In adult mouse back skin Ng2+ perivascular cells could be categorized into 4 populations based on whether they expressed Pdgfrα and Pdgfrβ individually or in combination or were Pdgfr-negative. Lineage tracing demonstrated that although Ng2+ cells in embryonic and neonatal back skin contributed to multiple cell types they did not give rise to interfollicular fibroblasts within the dermis. Lineage tracing of distinct fibroblast populations during skin development showed that papillary fibroblasts (Lrig1+) gave rise to Ng2+ perivascular cells in the upper dermis, whilst Ng2+ perivascular cells in the lower dermis were primarily derived from reticular Dlk1+ fibroblasts. Following wounding of adult skin, Ng2+ dermal cells only give rise to Ng2+ blood vessel associated cells and did not contribute to other fibroblast lineages. The relative abundance of Ng2+ Pdgfrβ+ perivascular populations was comparable in wounded and non-wounded skin, indicating that perivascular heterogeneity was maintained during full thickness skin repair. In the wound bed Ng2+ perivascular populations were primarily derived from Lrig1+ papillary or Dlk1+ reticular fibroblast lineages, according to the location of the regenerating blood vessels. We conclude that Ng2+ perivascular cells represent a heterogeneous lineage restricted population that is primarily recruited from the papillary or reticular fibroblast lineages during tissue regeneration.

Expression and localization of diacylglycerol kinase zeta and protein kinase C beta II in mouse back skin with different coat colors

Expression and localization of diacylglycerol kinase zeta and protein kinase C beta II in mouse back skin with different coat colors

Cross-talk between IFN-γ and TWEAK through miR-149 amplifies skin inflammation in psoriasis

Psoriasis is a chronic inflammatory skin disease with disturbed interplay between immune cells and keratinocytes. Astrong IFN-γ signature is characteristic for psoriasis skin, but the role of IFN-γ has been elusive. MicroRNAs are short RNAs regulating gene expression. Our aim was to investigate the role of miR-149 in psoriasis and in the inflammatory responses of keratinocytes. miR-149 expression was measured by quantitative RT-PCR in keratinocytes isolated from healthy skin and lesional and nonlesional psoriasis skin. Synthetic miR-149 was injected intradermally into the back skin of mice, and imiquimod was applied to induce psoriasis-like skin inflammation, which was then evaluated at the morphologic, histologic, and molecular levels. miR-149 was transiently overexpressed or inhibited in keratinocytes in combination with IFN-γ- and/or TNF-related weak inducer of apoptosis (TWEAK)-treatment. Here we report a microRNA-mediated mechanism by which IFN-γ primes keratinocytes to inflammatory stimuli. Treatment with IFN-γ results in a rapid and long-lasting suppression of miR-149 in keratinocytes. Depletion of miR-149 in keratinocytes leads to widespread transcriptomic changes and induction of inflammatory mediators with enrichment of the TWEAK pathway. We show that IFN-γ-mediated suppression of miR-149 leads to amplified inflammatory responses to TWEAK. TWEAK receptor (TWEAKR/Fn14) is identified as a novel direct target of miR-149. The invivo relevance of this pathway is supported by decreased miR-149 expression in psoriasis keratinocytes, as well as by the protective effect of synthetic miR-149 in the imiquimod-induced mouse model of psoriasis. Our data define a new mechanism, in which IFN-γ primes keratinocytes for TWEAK-induced inflammatory responses through suppression of miR-149, promoting skin inflammation.

The effect of Q-switched 1064-nm dymium-doped yttrium aluminum garnet laser on the skin barrier and collagen synthesis through miR-24-3p

Due to the increase of the world’s population aging, how to restore youthfulness to the skin has attracted much attention. It is well known that collagen synthesis and changes in skin barrier play an important role in the process of skin aging. However, whether Q-switched 1064-nm Nd:YAG laser (1064-QSNYL) determines the involvement of miRNAs in skin collagen synthesis and skin barrier changes remains to be elucidated. Upstream miRNAs of p38 molecular pathway have been predicted by bioinformatic database and the relationship between miRNAs and p38 verified by dual-luciferase reporter gene and Western blotting. RT-qPCR analysis detected the expression of miR-24-3p and mRNA for collagen and skin barrier–related molecules, such as keratin 10 (K10), filaggrin, and Aquaporin 4 (APQ4), in mice back skin and in the keratinocyte cell line HaCaT. Western blotting and immunofluorescence (IF) have been used to detect collagen expression and to localize, as well as quantify K10, filaggrin, and APQ4, respectively. In this study, we show that p38 is the main target gene of miRNA-24-3p, and laser irradiation at 1.5 J/cm2 inhibits miR-24-3p expression. Irradiation treatment upregulates the moisture, elasticity, hydroxyproline, and superoxide dismutase content of mice skin, as well as inhibits trans-epidermal water loss. Irradiation also increases collagen, K10, filaggrin, and APQ4 in both mice skin and HaCaT cells. Interestingly, we found that miR-24-3p overexpression inhibits the effect of irradiation on collagen synthesis and skin barrier. We show for the first time that 1064-QSNYL promotes collagen synthesis and protective effects on skin barrier by downregulating miR-24-3p.

Effects of Tricholoma matsutake (Agaricomycetes) Extracts on Promoting Proliferation of HaCaT Cells and Accelerating Mice Wound Healing.

Tricholoma matsutake is popular in Asian countries because of its edibility and medicinal use. T. matsutake is a precious natural medicinal fungus, and it is widely used in food and biological products. This study aimed to explore the mechanism of T. matsutake on promoting proliferation of human immortalized keratinocyte (HaCaT) cells and accelerating wound healing in mice. The MTT assay was used to test the effects of three different T. matsutake extracts (0, 62.5, 125, 250, 500, and 1000 μg/mL) on HaCaT cell viability. HaCaT cells were treated with the three T. matsutake extracts (100, 500 μg/mL) and morphological and biophysical properties were detected by atomic force microscopy with JPK data processing. Western blot analysis detected Notch signaling pathways of HaCaT cells treated with 50% ethanol extract of T. matsutake (50%T) for 24 h (100, 500 and 1000 μg/mL). Mouse wounds were treated with 50%T for 15 days. Wound healing effects were observed on the back skin of mice at different times. The quality of wound healing was estimated by histological staining (hematoxylin and eosin and Masson's trichrome). All data were counted by GraphPad Prism 5 software. The increased concentration of T. matsutake remarkably promoted HaCaT cell proliferation. The Young's modulus of HaCaT cells showed the biggest increase from 1.73 ± 0.13 kPa (0 μg/mL) to 4.57 ± 0.16 kPa (500 μg/mL) in the 50%T group. The Notch1/Jagged1 pathways were upregulated with an increase in concentration (0, 100, 500, and 1000 μg/mL). Moreover, compared with the negative and positive control groups, T. matsutake promoted wound healing in mice by epidermal regeneration, subepidermal tissue formation, and collagen deposition. The results showed that T. matsutake promotes not only proliferation of HaCaT cells but also wound healing in mice.

Scratch-induced partial skin wounds re-epithelialize by sheets of independently migrating keratinocytes.

Re-epithelialization is a crucial process to reestablish the protective barrier upon wounding of the skin. Although this process is well described for wounds where the complete epidermis and dermis is damaged, little is known about the re-epithelialization strategy in more frequently occurring smaller scratch wounds in which structures such as the hair follicles and sweat glands stay intact. To study this, we established a scratch wound model to follow individual keratinocytes in all epidermal layers in the back skin of mice by intravital microscopy. We discover that keratinocytes adopt a re-epithelialization strategy that enables them to bypass immobile obstacles such as hair follicles. Wound-induced cell loss is replenished by proliferation in a distinct zone away from the wound and this proliferation does not affect overall migration pattern. Whereas suprabasal keratinocytes are rather passive, basal keratinocytes move as a sheet of independently migrating cells into the wound, thereby constantly changing their direct neighboring cells enabling them to bypass intact obstacles. This re-epithelialization strategy results in a fast re-establishment of the protective skin barrier upon wounding.

Cox-2 inhibition activities of creams containing anguilla bicolor and sea cucumbers extract on croton oil induced inflammation in mice

The fatty acids, like EPA and DHA, were known as anti-inflammation. It works on inflammatory tissue, brought by edema plasma, and changed into resolvins, protectins, and maresins by the enzyme reaction. Anguilla bicolor and Sea cucumber fish are known to contain EPA and DHA. This study analyzes the inhibition Cox-2 effect of the combination of Anguilla bicolor oil with Sea cucumber extract as an active ingredient in a cream preparation. This experiment used 7 groups of male BALB/C strain mice: normal control; negative control; positive control; A. bicolor oil cream; H. leucospilota extract cream; a combination of A. bicolor : H. leucospilota (2:1) cream; a combination of A. bicolor : H. leucospilota (1:2) cream. The anti-inflammatory activity was evaluated by the amount of inflammatory cell, the thickness epidermis, and the amount of cell expression COX-2 on mice's back skin tissue induced by croton oil (0,1 %). After 3 days, histopathological skin tissues were made. The data were analyzed statistically by One Way ANOVA followed by LSD to know each group's differences at a significance level of 0.05. The experiment results showed that the formula with the best anti-inflammatory activities is the combination of A. bicolor and H. leucospilota (2:1) cream. The decrease of the amount of inflammatory cell (75.97%), the thickness of the epidermis (43.88%), and the amount of COX-2 cell expressions (60.52%) from the formula did not differ significantly with the positive control (p>0,05). It can be concluded that A. bicolor and H. leucospilota have anti-inflammation activity based on the experiment results.

MicroRNA-200b/c-3p regulate epithelial plasticity and inhibit cutaneous wound healing by modulating TGF-\u03b2-mediated RAC1 signaling

Cutaneous wound healing is pivotal for human skin to regain barrier function against pathogens. MicroRNAs (miRNAs) have been found to play regulatory roles in wound healing. However, the mechanism of miRNA regulation remains largely unknown. In this study, we focused on microRNA-200b/c-3p (miR-200b/c-3p) whose expression was abundant in intact epidermis, but dramatically decreased in skin wounds. In silico prediction identified RAC1 as a potential miR-200b/c-3p target. Luciferase reporter assay confirmed that miR-200b/c-p repressed RAC1 by direct targeting to its mRNA 3′UTR. Consistently, miR-200b/c-3p expression was discordantly related to RAC1 protein level during wound healing. Forced miR-200b/c-3p expression repressed RAC1 and inhibited keratinocyte migration as well as re-epithelialization in a mouse back skin full-thickness wound healing model. Mechanistically, miR-200b/c-3p modulated RAC1 to inhibit cell migration by repressing lamellipodia formation and intercellular adhesion dissolution in keratinocytes. Furthermore, we found that TGF-β1, which was highly expressed in skin wounds, contributed to the downregulation of miR-200b/c-3p in wound edge keratinocytes. Taken together, miR-200b/c-3p-mediated RAC1 repression inhibited keratinocyte migration to delay re-epithelialization. TGF-β1 induction attenuated miR-200b/c-3p regulation of RAC1 signaling in cutaneous wounds and the repression of miR-200b/c-3p accelerated keratinocyte migration to promote wound healing. Our data provide new insight into how miR-200b/c-3p affects keratinocyte migration and highlight the potential of miR-200b/c-3p targeting for accelerating wound healing.

232 Deficiency of Wnt5a in keratinocyte does not ameliorate the imiquimod-induced psoriasis-like dermatitis

Objective Wnt5a activated signalling cascades has been proved to be involved in the development of Psoriasis. However, the importance of keratinocyte produced Wnt5a in Psoriasis remained to be tested. The present study aimed to determine the effect of keratinocyte-specific knockout of Wnt5a on psoriasis-like dermatitis in imiquimod-induced mice. Methods Eight weeks old mice,in keratinocyte-specific knockout of Wnt5a (Wnt5a-cKO) mice and control littermates, were randomly assigned to receive topical application of Imiquimod (5% cream, 50mg) (IMQ) or control vihicle (VEH) on their shaved back for 7 days. Phenotypical presentation and severity index (PASI) modified from the human PASI guidelines to score scales, erythema, skin thickness of mouse back skin. Skin barrier was assayed by gpskin.Spleen index was calculated fluorescence activated cell sorter (FACS) was used to assess theratios of CD11+, CD68 +, and CD4 +, γσTCR+ T cell subsets in peripheral blood. Expression of β-catenin and its phosphorylation were detected by western blot and Immunofluorescence staining. Results PASI score showed significantly higher score in IMQ treated mice, with no significant difference between cKO and control littermates.Skin barrier assay showed increased skin barrier score and TEWL in IMQ treated mice in both cKO and control littermates.IMQ induced mild splenomegaly with non-significant higher spleen index compared to VEH treated mice, FACS profiles showed increased levels or ratios of CD11+, CD68 +, and CD4 +, γσTCR+ T cell subsets by IMQ stimulation in both cKO and control.Western blot analysis indicated that phosphorylation of β-catenin was markedly enhanced in control littermates, but not cKO mice, after 1 week IMQ treatment. Conclusions These results indicate that keratinocyte produced wnt5a is not nessecary for psoriasis-like dermatitis development in imiquimod-induced mice,even though the enhanced phosphorylation of β-catenin by IMQ stimulation was repressed in wnt5a cKO mice.

Expressions and effects of autophagy-related genes in bleomycin-induced skin fibrosis of mice

Expressions and effects of autophagy-related genes in bleomycin-induced skin fibrosis of mice

Characteristic of K3 (CpG-ODN) as a Transcutaneous Vaccine Formulation Adjuvant.

Transcutaneous immunization (TCI) is easy to use, minimally invasive, and has excellent efficacy in vaccines against infections. We focused on toll-like receptor (TLR) ligands as applicable adjuvants for transcutaneous formulations and characterized immune responses. TCI was performed using poke-and-patch methods, in which puncture holes are formed with a polyglycolic acid microneedle on the back skin of mice. Various TLR ligands were applied to the puncture holes and covered with an ovalbumin-loaded hydrophilic gel patch. During the screening process, K3 (CpG-oligonucleotide) successfully produced more antigen-specific antibodies than other TLR ligands and induced T helper (Th) 1-type polarization. Transcutaneously administered K3 was detected in draining lymph nodes and was found to promote B cell activation and differentiation, suggesting a direct transcutaneous adjuvant activity on B cells. Furthermore, a human safety test of K3-loaded self-dissolving microneedles (sdMN) was performed. Although a local skin reaction was observed at the sdMN application site, there was no systemic side reaction. In summary, we report a K3-induced Th1-type immune response that is a promising adjuvant for transcutaneous vaccine formulations using MN and show that K3-loaded sdMN can be safely applied to human skin.

Microneedle Array Patch (MAP) Consisting of Crosslinked Hyaluronic Acid Nanoparticles for Processability and Sustained Release.

Crosslinked hyaluronic acid (X-linked HA) is not suitable for making microneedles because of the low fluidity of X-linked HA hydrogel. Microneedles were fabricated using X-linked HA nanoparticles (X-linked HA-NPs) to utilize the sustained drug delivery capability of X-linked HA-NPs and to obtain the processability advantages of X-linked HA. The puncture performance of a microneedle array patch (MAP) made of crosslinked hyaluronic acid nanoparticles (X-linked HA-NP-MAP) was evaluated by insertion in vitro into porcine skin. After a predetermined attachment time, the remaining height of the X-linked HA-NP-MAP was measured to determine the dissolution rate. X-linked HA-NP-MAP and free HA-MAP containing Rhodamine B isothiocyanate-dextran were administered into the back skin of mice, and the relative fluorescent intensity in the back skin was measured over time. The puncture performance of the X-linked HA-NP-MAP was over 90%. The diameter of redispersed X-linked HA-NPs was same as that of the premolded X-linked HA-NPs. The dissolution rate was not different from that of free HA-MAP. In an in vivo experiment, X-linked HA-NP-MAP was administered into the mouse's back skin successfully and the relative fluorescent intensity of X-linked HA-NP-MAP lasted longer than that of HA-MAP. X-linked HA-NPs provide the biocompatibility, the processability of micromolding, sustained drug release, successful penetration into the skin, and relatively short insertion time for full disintegration of NPs in the skin. X-linked HA-NP-MAP can be used for various applications that require several days of sustained drug release.

Jak Inhibition Prevents Bleomycin-Induced Fibrosis in Mice and Is Effective in Patients with Morphea

Jak Inhibition Prevents Bleomycin-Induced Fibrosis in Mice and Is Effective in Patients with Morphea