Epidermal Thickness Research Articles

Oregano essential oil-infused mucin microneedle patch for the treatment of hypertrophic scar

Hypertrophic scar (HS) manifests as abnormal dermal myofibroblast proliferation and excessive collagen deposition, leading to raised scars and significant physical, psychological, and financial burdens for patients. HS is difficult to cure in the clinic and current therapies lead to recurrence, pain, and side effects. In this study, a natural amphiphilic polymer mucin is used to prepare a dissolving microneedle (muMN) that is loaded with oregano essential oil (OEO) for HS therapy. muMN exhibits sufficient skin/scar tissue penetration, quick skin recovery time after removal, good loading of natural essential oil, fast dissolution and detachment from the base layer, and good biocompatibility to applied skin. In the rabbit HS model, OEO@muMN shows a significant reduction in scar thickness, epidermal thickness index, and scar elevation index. OEO@muMN also attenuates the mean collagen area fraction and decreases the number of capillaries in scar tissues. Biochemical Assay reveals that OEO@muMN significantly inhibits the expression of transforming growth factor-β1 (TGF-β1) and hydroxyproline (HYP). In summary, this study demonstrates the feasibility and good efficacy of using the anti-proliferative and anti-oxidative OEO for HS treatment. OEO@muMN is an efficient formulation that holds the potential for clinical anti-HS application. muMN is an efficient platform to load and apply essential oils transdermally.

Anti-inflammatory Capacity of a Medicinal herb extract, Anemarrhena asphodeloides, on In vivo and In vitro models-induced atopic dermatitis

Anemarrhena asphodeloides (AA) Bunge, a rhizomatous plant from the Liliaceae family, is traditionally utilized to manage inflammatory conditions. Nevertheless, its impact on atopic dermatitis (AD) and the associated molecular pathways have not yet been fully explored. This study explored the therapeutic effects of AA on AD both in vivo, using 2,4-dinitrofluorobenzene-induced NC/Nga mice, and in vitro, with tumor necrosis factor-α/interferon-γ-stimulated HaCaT keratinocytes. Topical application of AA ointment on the dorsal skin notably alleviated AD symptoms and skin lesions, enhanced the dermatitis score, and improved parameters such as the rate of trans-epidermal water loss, epidermal thickness, mast cell infiltration, systemic IgE levels, and cytokine expression. Furthermore, AA treatment significantly reduced serum levels of thymic stromal lymphopoietin (TSLP) and locally suppressed mRNA expression of thymus and activation-regulated chemokine (TARC) along with other relevant cytokines in affected skin. Both in vivo and in vitro applications of AA curtailed TSLP levels by inhibiting the expression of signal transducer and activator of transcription 6, a key regulator of pruritus and an initiator of mitogen-activated protein kinase signaling pathways. Additionally, AA affected the expression of tumor necrosis factor-like weak inducer of apoptosis/fibroblast growth factor-inducible 14, a pathway of interest in the study of cutaneous inflammatory diseases. Collectively, these findings propose that AA holds potential as an effective therapeutic agent for treating AD-induced skin inflammation.

Wound Healing and Scar Patterning After Addition of Autologous Skin Cell Suspension to Meshed Grafts

IntroductionA common treatment for large deep-to-full-thickness burns is excision and grafting with a widely meshed split-thickness skin graft (mSTSG). Due to the differential healing of the interstices and adhered split-thickness skin graft, wound patterning and delayed wound healing are common outcomes of this treatment. Delayed healing may increase infection rates and wound care requirements, while wound patterning may be psychologically and aesthetically consequential for patients. Autologous skin cell suspension (ASCS) can be used to “over spray” a meshed autograft. It was hypothesized that the use of ASCS combined with mSTSG would increase the rate of wound healing and decrease patterning in healed burn wounds. MethodsFull-thickness burns or excisional wounds (n = 8 each) were created in red Duroc pigs and received 4:1 mSTSGs after wound bed preparation. Half of the wounds received ASCS and half did not at the time of grafting. Percent re-epithelialization, patterning, rete ridge ratio, cellularity, dermal and epidermal thickness, immunofluorescent S100β staining, and melanin index were assessed for each scar. ResultsWounds that received ASCS exhibited increased rates of re-epithelialization (burn +ACSC versus burn-ASCS; day 3 (53.9 ± 3.1 versus 34.3 ± 3.3, P = 0.009): day 5 (68.1 ± 1.6 versus 40.8 ± 3.2, P < 0.001)). Excision +ASCS versus excision-ASCS; day 7 (98.1 ± 1.2 versus 86.4 ± 2.0, day 7 P = 0.022) compared to wounds not treated with ASCS. There was no difference in rete ridge ratio, cellularity, dermal thickness, epidermal thickness, S100β staining, melanin index, or patterning was measured between wounds that received ASCS and those that did not. ConclusionsThe addition of ASCS to 4:1 mSTSGs leads to increased rate of wound healing but does not impact the degree of patterning in this model, suggesting that ASCS application likely robustly transfers keratinocytes but not functioning melanocytes at acute timepoints.

Exploring botanical varieties in alpine landscape of Himalayas: A study of vegetation and species composition in Madhmaheshwar Valley, Western Himalaya, India

Alpine meadows emerged as the hallmark vegetation type, embodying the essence of botanical richness. In this research endeavor, the focus was on exploring the intricate tapestry of alpine flora nestled within the Madhmaheshwar Valley, spanning elevations ranging from 3200 to 4950 meters above sea level. This comprehensive study yielded a trove of botanical insights, documenting an impressive assemblage of 462 distinct plant species. These species were carefully cataloged across 237 genera, encompassing a rich diversity represented by 61 distinct families. In the study area, the family Asteraceae was the dominant family with 58 species and 30 genera followed by Rosaceae with 33 species and 16 genera, and Ranunculaceae with 27 species across 15 genera. Among the genera Carex L., with 10 species, was the dominant, followed by Saxifraga Tourn. ex L., Gentiana Tourn. ex L., Pedicularis L., and Primula L. followed closely behind with nine species each. Additionally, Rhodiola L., Bistorta (L.) Scop., and Epilobium Dill. ex L. displayed their vitality with seven species each. The study used meticulous research methodology to categorize forest types based on floral diversity and altitude distribution. Rigorous verification processes ensured the reliability of findings, with specimens identified using up-to-date references and cross-referenced with authentic herbarium samples. Fieldwork occurred between early May and late October, aligning with seasonal accessibility due to heavy snowfall the rest of the year. Alpine meadows and scrubs dominated the study area, highlighting their resilience. Alpine plants showcased various adaptive morphologies, such as cushion-forming and mat-forming structures, with thick cuticles defending against desiccation. Despite harsh conditions, these plants displayed modified structures enabling growth and blossoming. Many were highly specialized, emphasizing unique adaptations to their habitats.

Cannabidiol Alleviates Imiquimod-Induced Psoriasis by Inhibiting JAK2-STAT3 in a Mouse Model.

Cannabidiol (CBD), a non-psychoactive compound from Cannabis sativa, has shown efficacy in treating psoriasis, a chronic inflammatory skin disease affecting 1-3% of the global population; however, the mechanisms remain unclear. This study investigated CBD's effects on imiquimod (IMQ)-induced psoriasis in mice, which were divided into five groups: Control, IMQ, Clobetasol, 0.01% CBD, and 0.1% CBD. After inducing psoriasis with IMQ, clobetasol or CBD was applied. Psoriasis severity was assessed using the Psoriasis Area and Severity Index (PASI), with histopathological changes examined via hematoxylin and eosin staining. Gene expression of inflammatory markers (Il1b, Il6, Il12b, Il17a, Il22, and Tnf) was analyzed by RT-PCR, while protein levels of signal transducer and activator of transcription (STAT)3, P-STAT3, Janus kinase (JAK)2, and JAK3 were evaluated through western blot and immunohistochemistry. The results demonstrated that CBD significantly reduced PASI scores, epidermal thickness, keratosis, hyperproliferation, and inflammation. Moreover, CBD inhibited the IL-23 receptor-mediated JAK2-STAT3 signaling pathway, leading to the downregulation of Il1b, Il6, Il12b, Il17a, Il22, and Tnf expression. These findings suggest that CBD effectively alleviates psoriasis-like symptoms in mice and may serve as a promising therapeutic agent for psoriasis by targeting the JAK2-STAT3 pathway.

Human Placenta Extract (HPH) Suppresses Inflammatory Responses in TNF-α/IFN-γ-Stimulated HaCaT Cells and a DNCB Atopic Dermatitis (AD)-Like Mouse Model.

Atopic dermatitis (AD), a chronic inflammatory disease, severely interferes with patient life. Human placenta extract (HPH; also known as human placenta hydrolysate) is a rich source of various bioactive substances and has widely been used to dampen inflammation, improve fatigue, exert anti-aging effects, and promote wound healing. However, information regarding HPH's incorporation in AD therapies is limited. Therefore, this study aimed to evaluate HPH's effective potential in treating AD using tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated human keratinocytes (HaCaT), immunized splenocytes, and a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. In TNF-α /IFN-γ-stimulated HaCaT cells, HPH markedly reduced the production of reactive oxygen species (ROS) and restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 1(SOD1), catalase, and filaggrin (FLG). HPH reduced interleukin (IL)-6; thymus- and activation-regulated chemokine (TARC); thymic stromal lymphopoietin (TSLP); and regulated upon activation, normal T cell expressed and presumably secreted (RANTES) levels and inhibited nuclear factor kappa B phosphorylation. Additionally, HPH suppressed the T helper 2 (Th2) immune response in immunized splenocytes. In the AD-like mouse model, it significantly mitigated the DNCB-induced elevation in infiltrating mast cells and macrophages, epidermal thickness, and AD symptoms. HPH also reduced TSLP levels and prevented FLG downregulation. Furthermore, it decreased the expression levels of IL-4, IL-5, IL-13, TARC, RANTES, and immunoglobulin E (IgE) in serum and AD-like skin lesion. Overall, our findings demonstrate that HPH effectively inhibits AD development and is a potentially useful therapeutic agent for AD-like skin disease.

Chikusetsusaponin IVa from Dolichos lablab Linne attenuates UVB-induced skin photoaging in mice by suppressing MAPK/AP-1 signaling

Ultraviolet-B (UVB) radiation-induced photoaging of the skin is characterized by amplified expression of matrix metalloproteinase-1 (MMP-1) and reduced collagen fibers, both of which contribute to skin wrinkle formation. Edible natural products can protect against skin photoaging. Here, we investigate the protective effect of Dolichos lablab Linne (DLL) water extract against UVB radiation-prompted skin damage and attempt to uncover its fundamental mechanisms in human keratinocytes (HaCaT) and HR-1 hairless mouse. We found DLL extract rescued the reduction in cell viability associated with UVB exposure without any associated cytotoxic effects. It also protected against skin photoaging by inhibiting mitogen-activating protein kinase (MAPK) signaling, thereby preventing the UVB-associated increase in MMP-1 and -9 expression. DLL extract also increased the expression of both superoxide dismutase 1 (SOD1) and catalase (CAT). We identified chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A as bioactive components of DLL. Although we have not yet identified the mechanisms by which these compounds reduce the effects of photoaging, we have demonstrated that chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A reduce MMP-1, MMP-9, p–c-Fos, and p–c-Jun expression, while also avoiding any cytotoxicity. We found oral administration of DLL extract effectively alleviated dorsal epidermal thickening and skin dehydration in HR-1 hairless mouse visible to UVB. DLL extract also prevents UVB-induced activation of the MAPK/AP-1 signaling pathway, thereby reducing the expression of MMPs in dorsal mouse skin. Our results indicate that chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A are bioavailable components of DLL extract that can reduce UVB-induced skin damage via MMPs by deactivating the MAPK/AP-1 signaling pathway. These findings suggest DLL extract can be used as a skin anti-photoaging agent.

Efficacy of traditional Chinese medicines in the treatment of solar lentigo based on network pharmacology and experimental validation.

Solar lentigo is a prevalent skin condition that affects a significant number of individuals. Fortunately, certain traditional Chinese medicines and monomers (TCMM) have proven effective in addressing these concerns. In this study, we evaluated the efficacy and underlying mechanism of TCMM, a combination of TCM and monomers in repairing solar lentigo. We detected and identified the main compounds of TCM using liquid chromatography-mass spectrometry (LC-MS) and through the approach of network pharmacology, we screened drug and disease targets, visualized networks with Cytoscape software, analyzed targets via Gene ontology and KEGG, clinically validated predictions. In a mouse model, UVB-induced pigmentation was assessed, and the effects of TCMM were evaluated. A clinical trial on 30 patients validated the depigmenting agent. Active ingredients such as MSH, Butylated hydroxytoluen, Valerophenone, and Geranylacetone aid pigmentation treatment. One hundred and forty-three crore targets impact PI3K-Akt, MAPK signaling pathway, ect. pathways. TCMM reduced UVB-induced pigmentation, water loss, epidermal thickness, and melanin. It inhibited TYR, MITF, AKT1, VEGFA, PTGS2, TNF-α, IL-6, IL-1β. Clinical and microscopic analysis showed significant pigmentation reduction. The treatment of solar lentigo can benefit from the TCMM. By targeting multiple factors and pathways, this approach offers a comprehensive and effective treatment strategy.

Impact of tryptophan on physiological and histological responses of pepper plants under salt stress

Salt stress is a significant abiotic stressor adversely affecting plant functions. Tryptophan, a precursor to IAA, plays a crucial role in plant growth under such stress. This study investigated the effects of different tryptophan doses (L-tr) on young pepper plants subjected to salt stress. Preceding salinity stress, three L-tr doses were administered to plant roots, excluding control and salt applications. Subsequently, all plants except controls received 150 mM salinity (NaCl) during irrigation. The experiment concluded after 35 days post-salinity treatment. Significant variations were noted in histological (cortex and cell diameters, xylem and midrib diameters, epidermis thickness) and physiological (leaf water content, membrane permeability, chlorophyll and carotenoid concentrations, total phenolic content) parameters among treatments. Evaluation of these parameters revealed L-tr’s positive impact on osmotic regulation. L-tr applications increased xylem, midrib, and cortical cell diameter, cortex, and epidermis thickness compared to salt stress, while cortical cell number also decreased. Particularly, NaCl + L-tr 100 µM treatment exhibited a 25% increase in xylem conduit diameter, a 30% increase in midrib diameter, and a significant 15% increase in epidermis thickness compared to controls. Overall, NaCl + L-tr 100 µM treatment displayed values closest to controls across various parameters. This study suggests the potential utility of L-tr in mitigating salinity stress in pepper plants.

Paenibacillus exopolysaccharide alleviates Malassezia-induced skin damage: Enhancing skin barrier function, regulating immune responses, and modulating microbiota

Numerous studies have established a strong association between Malassezia and various skin disorders, including atopic dermatitis. Finding appropriate methods or medications to alleviate Malassezia-induced skin damage is of notable public interest. This study aimed to evaluate the therapeutic effect of the exopolysaccharide EPS1, produced by Paenibacillus polymyxa, on Malassezia restricta-induced skin damage. In vitro assays indicated that EPS1 reduced the expression of pro-inflammatory cytokine genes in TNF-α-induced HaCaT cells. In a murine model, EPS1 was found to mitigate clinical symptoms, reduce epidermal thickness and mast cell infiltration, improve skin barrier function, decrease pro-inflammatory cytokine levels associated with type 17 inflammation, enhance Tregs in the spleen, upregulate the transcription of Treg-related genes in skin lesions, and modulate the skin microbiota. This study is the first to report the alleviating effect of Paenibacillus exopolysaccharide on Malassezia-induced skin inflammation and its impact on the skin microbiota. These findings support the potential of Paenibacillus exopolysaccharides as consumer products and therapeutic agents for managing Malassezia-induced skin damage by improving skin barrier function, modulating immune responses, and influencing skin microbiota.

Novel biophysical skin biomarkers discriminate topical anti‐inflammatory treatments based on their potential for local adverse effects

AbstractBackgroundTopical corticosteroids (TCS) are efficacious treatments for inflammatory skin conditions, however, there is a risk of adverse effects; understanding how best to use these treatments is an unmet research priority shared by patients and healthcare professionals.ObjectivesTo develop non‐invasive biomarkers of local adverse effects to facilitate the optimisation of topical therapy.MethodsAn observer‐blind randomised within‐subject controlled trial in atopic dermatitis patients was undertaken (NCT04194814) comparing betamethasone valerate 0.1% cream (BMV) to a non‐steroidal anti‐inflammatory treatment, crisaborole 2% ointment (CRB). Participants underwent 4 weeks twice‐daily treatment with CRB on one forearm and BMV on the other (left/right randomised). Skin properties were assessed on days 1, 15, 29 of treatment and again on day 57, including imaging of skin microstructure using Optical Coherence Tomography (OCT) and Attenuated Total Reflectance (ATR)‐Fourier Transform Infrared (FTIR) spectroscopic assessment of stratum corneum molecular structure. The primary outcome was the difference in the change in epidermal thickness from days 1 to 29.ResultsThirty‐seven participants received the first dose, of which 32 completed the study (all 37 were included in the analysis). Pathologic epidermal thinning at day 29 was significantly greater (p &lt; 0.0001) at sites treated with BMV (−31.66; 95% confidence interval: −35.31, −28.01 µm) compared to CRB (−13.76; −17.42, −10.10 µm). From a panel of exploratory biomarkers, superficial plexus depth and stratum corneum carboxyl group levels had the greatest ability to discriminate the effects of the TCS treatment (p &lt; 0.0001).ConclusionsBMV induced 2.3x more pathologic epidermal thinning than CRB after 4 weeks of treatment, suggesting that CRB may be more appropriate for longer‐term, proactive‐based, treatment strategies where the risks of adverse effects are greatest. By monitoring treatment effects using OCT and ATR‐FTIR spectroscopy, two new non‐invasive biomarkers of skin health have been identified with the potential to help optimise future safe treatment strategies.

Based on network pharmacology, molecular docking and experimental verification to reveal the mechanism of Andrographis paniculata against solar dermatitis

BackgroundSolar dermatitis (SD) is an acute, damaging inflammation of the skin caused by UV exposure, especially UVB. Therefore, the discovery of novel anti-SD therapeutic agents is crucial. Andrographis paniculata (AP) is a medicinal plant with a wide range of pharmacological effects. Increased evidence shows that AP has potential therapeutic effects on SD. However, the therapeutic mechanisms of AP against SD have not yet been completely elucidated, which is an unexplored field. PurposeThis study employed network pharmacology, molecular docking and experimental verification to ascertain the active constituents, possible targets, and biological pathways associated with AP in the treatment of SD. MethodsAP-related active ingredients and their potential targets were screened from TCMSP and Swiss Target Prediction database, respectively. Potential therapeutic targets of SD were collected using the GeneCards, DrugBank and OMIM databases. Then, we established protein-protein interaction (PPI), compound-target-disease (D-C-T-D) through Cytoscape to identify the major components, core targets of AP against SD. Next, the GO and KEGG pathway was identified by the David database of AP in the treatment of SD. Molecular docking techniques were used to estimate the binding force between the components and the hub genes. In this paper, we used UVB-irradiated HaCaT keratinocytes as an in vitro model and established the dorsal skin of UVB-irradiated ICR mice as an in vivo model to explore the mechanism for further verification. ResultsThere were 24 active components and 63 related target genes in AP against SD. PPI analysis showed that AKT-1, TNF-α, IL6, MMP9, EGFR, and PTGS2 shared the highest centrality among all target genes. KEGG pathway analysis revealed that the PI3K-Akt signaling pathway may be central in the anti-SD system. The molecular docking results showed that the main active components of AP have strong binding affinity with hub genes. In vitro results showed that WG had a protective effect on UVB-intervened HaCat cells. Western blot analysis showed that WG intervention achieved anti-inflammation by reducing the phosphorylated expression of AKT, PI3K proteins in the PI3K-AKT signaling pathway and downregulating the expression of TNF-α, IL-6, EGFR. Furthermore, Histological analysis confirmed that administration of WG to ICR mice significantly ameliorated UVB-induced skin roughness, epidermal thickening, disturbed collagen fiber alignment and wrinkles. Meanwhile, immunohistochemistry showed that administration of WG to ICR mice significantly reduced UVB-induced expression of MMP9, MPO, F4/80 in the skin. These results provide new insights into the contribution of WG to the development of clinical treatment modalities for UVB-induced SD. ConclusionThe crucial element in the fight against SD is WG, with the primary route being PI3K/Akt. The main components and hub genes had robust binding abilities. In vitro and vivo experiments showed that WG could inhibit the expression level of the hub genes by inhibiting the PI3K/Akt pathway. In summary, the information presented in this study indicates that WG might be utilised as a treatment for UVB-induced SD.

Antibacterial and Antiallergic Effects of Three Tea Extracts on Histamine-Induced Dermatitis.

Atopic dermatitis (AD) is a persistent and recurrent inflammatory skin condition with a genetic basis. However, the fundamental reasons and mechanisms behind this phenomenon remain incompletely understood. While tea extracts are known to reduce histamine-induced skin allergies and inflammation, the specific mechanisms by which various types of Chinese tea provide their protective effects are still not fully elucidated. In this study, a model of skin itching induced by histamine is used to explore the functions and mechanisms of three types of tea extract (Keemun black tea (HC), Hangzhou green tea (LC), and Fujian white tea (BC)) in alleviating histamine-induced dermatitis. The components of three tea extracts are identified by UPLC-Q-TOF-MS, and we found that their main components are alkaloids, fatty acyls, flavonoids, organic acids, and phenols. The inhibitory effects of three types of tea extract on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in skin injury are investigated by MIC and flow cytometry. The three types of tea extract have an inhibitory effect on the growth of bacterial flora, with HC showing the best inhibitory activity. The effect of the three types of tea extract on histamine-induced dermatitis is also evaluated. Furthermore, itchy skin experiments, HE staining, toluidine blue staining, and immunohistochemical staining of mouse skin tissues were performed to determine the variations of scratching, epidermal thickness, mast cell number, IL-1β, and NGF content after the administration of the tea extracts. The three types of tea extracts all alleviate and inhibit skin itching, epidermal hyperplasia, and allergic dermatitis. BC effectively alleviates epidermal hyperplasia caused by skin allergies, and LC significantly downregulates NGF. HC reduces histamine-induced mast cell infiltration and downregulates IL-1β to alleviate skin itching. Consequently, tea emerges a potent natural product that can inhibit the growth of skin wound bacterial flora and exhibit skin repair effects on histamine-induced allergic dermatitis.

Structural characteristics of the epidermis in marine and freshwater finless porpoises adapted to distinct osmotic environments

Abstract The Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis, Pilleri &amp; Gihr, 1972; YFP) is an exclusively freshwater cetacean species inhabiting the Yangtze River and its connecting large lakes. As the primary line of defense in maintaining physiological equilibrium, the epidermis of the porpoise is expected to have undergone structural adaptations due to the shift from the marine to the freshwater environment. This study compared the microstructural and ultrastructural features of the epidermis of YFP and its marine counterpart, the East Asian finless porpoise (Neophocaena asiaeorientalis sunameri, Pilleri &amp; Gihr, 1975; EAFP). Microscopic structural observations and statistical analyses of the epidermal thickness demonstrated no significant differences in the cell structure or distribution between the two porpoise species. However, the epidermis of the YFP contained more abundant stratum basale cells. The outermost lipid stratum corneum exhibited a thinner cell layer with wider neutral lipid droplets to resist the passive entry of water molecules in the hypotonic environment. In contrast, for the EAFP, a more uniformly arranged stratum basale in the epidermis led to denser keratin fibers and robust desmosomes within each epidermal layer at the ultrastructural level. This tight arrangement of cells can reduce transepidermal water loss (TEWL) in an environment with higher osmotic pressure. In conclusion, the 2 finless porpoise species appear to employ different epidermal mechanisms to adapt to their distinct osmotic environments. The YFP appears to possess a “lipid waterproofing” epidermal structure, while the EAFP possesses a “thick and compact water-retaining” epidermal structure to cope with potential water loss.

Actinidia chinensis Planch Ameliorates Photoaging in UVB-Irradiated NIH-3T3 Cells and SKH-1 Hairless Mice by Controlling the Reactive Oxygen Species/AKT Pathway.

In this study, we evaluated the antiphotoaging properties of Actinidia chinensis Planch (ACP) and the molecular mechanisms underlying its ability to prevent UVB-mediated photoaging. Administration of the ethanolic extract of ACP (EEACP) to the dorsal area of hairless mice effectively ameliorated UVB-mediated wrinkle formation, epidermal thickening, and loss of lipid droplets in the epidermis. Additionally, the UVB-induced loss of collagen content in the epidermis was significantly attenuated in mouse skin treated with EEACP. The expression of procollagen type 1 and metalloproteinase-1a, which are related to collagen content in the epidermis, was restored by EEACP treatment in UVB-irradiated mice and NIH-3T3 mouse skin fibroblast cells. Interestingly, EEACP effectively ameliorated UVB-induced reactive oxygen species overproduction. Furthermore, the activation/phosphorylation of AKT, rather than mitogen-activated protein kinases, has been identified as a major target of EEACP in preventing UVB-mediated photoaging. Additionally, N-(1 deoxy-1-fructosyl) valine and phenethylamine glucuronide were identified as analytical indicators of EEACP using high-performance liquid chromatography/mass spectrometry. These results suggest that EEACP can be developed as a functional natural agent capable of preventing photoaging by attenuating UVB-induced activation of the reactive oxygen species/AKT pathway.

Free amino acid pool in the rat skin and the skin morphological structure in acute allergic contact dermatitis

The concentration of free amino acids in the skin of rats in experimental acute allergic contact dermatitis (ACD) was studied. Free AAs were determined by reverse-phase high-performance liquid chromatography. Acute ACD was simulated using 2.4-dinitrochlorobenzene. The levels of asparagic and glutamic acids, valine, leucine, phenylalanine, lysine, and taurine increased and methionine, tyrosine, tryptophan, α-aminobutyric acid and anserine decreased in the rat skin during acute ACD development. An imbalance of amino acid metabolism was expressed in an increase in the ratio of aromatic amino acids/branched-chain amino acids by a decrease in the sum of aromatic amino acids. An increase in the Phe/Tyr ratio may indicate a decrease in the activity of the hydroxylase pathway of phenylalanine metabolism in the rat skin. Only in the skin of rats with acute ACD, the levels of valine, isoleucine and lysine were negatively correlated with the level of blood TNF-1α, which confirms their anti-inflammatory effect.Histological examination revealed an inflammatory reaction expressed by lymphocytic infiltration of various skin layers (ectoderm, subepidermal layer). Perivascular proliferation of fibroblasts and formation of subepidermal fibrosis were observed in subepithelial sections. The upper layer of the thorny layer was necrotic, the granular layer with necrosis and pronounced karyopiknosis of nuclei was observed. The epidermis thickness increased, infiltration of lymphocytes and segmented neutrophils into epidermis was noted up to the cells of the thorny layer (exocytosis).The data obtained indicate a significant metabolic imbalance of amino acids in the skin of rats in acute ACD, manifested by depletion of the amino acid pool of aromatic and sulfur-containing amino acids, impaired metabolism of phenylalanine, as well as increased levels of immunogenic amino acids that play a functional role in the regulation of anti-inflammatory, antioxidant system and proliferative activity of immune system cells on the background of a significant inflammatory process.

Leaf micromorphology and anatomical traits of leaves as potential taxonomic markers for infrageneric classification of&lt;em&gt; Cinnamomum&lt;/em&gt; (Lauraceae)

This study aimed to examine the leaf anatomy of the eight species of Cinnamomum (family Lauraceae) that occur in Sri Lanka to evaluate its potential utility in taxonomic delimitation. Leaf surface micromorphology and internal anatomy were studied using standard light and scanning electron microscopy. Infrageneric and interspecific variation in micromorphology of cuticular materials was observed in both abaxial and adaxial surfaces. Both abaxial and adaxial surfaces had undulating, thick cuticles with different patterns of wax deposition. Leaves were hypostomatic with no special arrangement for epidermal pavement cells. Simple, unicellular, unbranched, solitary and non-glandular trichomes were observed in different species on both surfaces of the leaves. Both adaxial and abaxial surfaces in C. dubium and C. capparu-coronde were densely covered with simple, unicellular/ falcate, long and thin trichomes. Transverse sections (TS) of the leaves were different in shape (symmetrical, asymmetrical, irregular, saucer). The midrib contained one open arch central vascular bundle that was different in shape (oval, elongated, irregular, ‘V’shaped, partially dissected into 2 or 3 segments) in different species. The number of collateral vessels was dissimilar between the species and varied in number (±10 - ±17). Isolated or aggregated crystals were observed in different parts of the leaf and oval-to-round schizogenous secretory cells were present in C. capparu-coronde, C. citriodorum and C. dubium. Leaf cuticular features together with the presence/absence of secretory cavities, trichome shape and density, midrib cross-section outline and shape of vascular bundles are taxonomically informative characteristics that can be used to differentiate the eight species of Cinnamomum that occur in Sri Lanka.

Inhibition of transient receptor potential vanilloid 3 channels by antimalarial hydroxychloroquine alleviates TRPV3-dependent dermatitis

Transient receptor potential vanilloid 3 channel (TRPV3) is closely associated with skin inflammation, but there is a lack of effective and specific inhibitors for clinical use. In this study, we identified antimalarial HCQ as a selective TRPV3 inhibitor following the prediction by network pharmacology data analysis. In whole-cell patch-clamp recordings, HCQ inhibited the current of the TRPV3 channel, with an IC50 of 51.69 ± 4.78 μM. At the single-channel level, HCQ reduced the open probability of TRPV3 and decreased single-channel conductance. Molecular docking and site-directed mutagenesis confirmed that residues in the pore domain were critical for the activity of HCQ. In vivo, HCQ effectively reduced carvacrol-induced epidermal thickening, erythema, and desquamation. Additionally, the serum IgE and inflammatory factors such as TNF-α and IL-6 were markedly decreased in the dorsal skin tissues in the HCQ treatment group, as compared to the model group. Our results suggested the antimalarial HCQ may represent a potential alleviator for treating skin inflammation by inhibiting TRPV3 channels.

Human urine-derived stem cells: potential therapy for psoriasis-like dermatitis in mice

Over the past decade, significant advancements in stem cell research led by mesenchymal stem cells (MSCs) have facilitated their practical application in clinical settings, including inflammatory skin diseases. Urine-derived stem cells (USCs) are obtained from healthy human urine in a noninvasive approach with properties similar to mesenchymal stem cells (MSCs). However, the therapeutic potential of USCs for inflammatory skin diseases has not yet been fully explored. Herein, we report the therapeutic effects of USCs-derived culture supernatants on mice with psoriasis-like dermatitis using our originally established human USCs model. We examined the isolation of USCs from human urine using a simple centrifugation process. Cell markers related to MSCs-like cell were positive for CD29, CD44, CD73, CD90, and negative for HLA-DR, CD34, and CD45 by FACS analysis. Differentiation assays revealed that the cells possessed the capability to differentiate into adipocytes, chondrocytes, and osteocytes. USCs-conditioned medium (CM) treatment significantly suppressed the severity of dermatitis in imiquimod (IMQ)-treated psoriasis mice model. Histopathological examination revealed that USCs-CM treatment attenuated epidermal thickness and the numbers of infiltrating inflammatory cells, including neutrophils, T-cells, and macrophages in dermatitis-affected areas in IMQ-treated psoriasis mice. Furthermore, USCs-CM treatment decreased mRNA levels of IL-17A, IL-17F, and IL-23p19 was reduced in dermatitis area. In summary, our findings revealed new potential strategies for utilizing USCs and USCs-CM as therapeutic agents for inflammatory skin diseases, including psoriasis.

Diameter-dependent classification of dermal vasculature using optical coherence tomography angiography.

Dermal blood vessels beneath the epidermis play critical roles in epidermal homeostasis and are functionally divided into several types, such as capillaries. Optical coherence tomography angiography (OCTA) is a powerful tool for the non-invasive assessment of dermal vasculature. However, the classification of vessel types has been limited. To address this issue, we proposed an algorithm for diameter-dependent classification that preserves three-dimensional (3D) information using OCTA. OCTA data were acquired by a prototype swept-source-type optical coherence tomography (OCT) system, which was processed through several imaging filters: an optical microangiography (OMAG) imaging filter, a vesselness imaging filter, and a diameter map filter. All vessels were visually classified into three types based on their diameters, as micro-vessels, intermediate vessels, and thick vessels. Aging-related alterations and their association with the epidermis were investigated for each vessel type. The measurements were conducted on the cheeks of 124 female subjects aged 20-79 years. The 3D vascular structure was visualized by applying our proposed post-processing filters. Based on visual assessment, the thresholds for the diameters of the micro, intermediate and thick vessels were set at 80 and 160 µm. It was found that micro-vessels were predominantly located in the upper layer of the dermis and thick vessels in the deeper layer. Analysis of vessel metrics revealed that the volume density of the micro-vessels decreased significantly with age (r=-0.36, P<0.001) and was positively correlated with epidermal thickness (r=0.50, P<0.001). In contrast, the volume density of thick vessels significantly increased with age (r=0.2, P<0.05) and was not significantly correlated with epidermal thickness (r=0.13, P≥0.05). In this study, we proposed a 3D quantification method using OCTA for dermal blood vessels and various vessel metrics, such as vessel volume density. This proposed classification will be beneficial for determining the function of the dermal vasculature and its diagnostic applications.