Search Results (52)

Chronic ultraviolet B (UVB) radiation drives cutaneous photoaging—clinically manifesting as erythema, edema, scaling, deep wrinkling, loss of elasticity, and barrier disruption—through mitochondrial reactive oxygen species (mtROS) overproduction and quality-control failure. Here we identify α-ketoglutarate (AKG; also known as 2-oxoglutarate), a TCA-cycle intermediate and essential co-substrate for α-ketoglutarate-dependent dioxygenases (α-KGDDs), as a metabolic corrector of mitochondrial redox homeostasis in UVB-induced photoaging. In a 10-week chronic UVB SKH1 hairless mouse model, microneedle-assisted transdermal delivery of AKG dose-dependently attenuated macroscopic erythema, scaling, and erosive lesions, restored skin barrier function and dermal elasticity, preserved epidermal–dermal architecture, and protected collagen and elastic fiber integrity, with efficacy comparable to all-trans retinoic acid. Mechanistically, AKG reactivated α-KGDD/prolyl hydroxylase (PHD) catalytic function and promoted proteasomal clearance of aberrantly stabilized HIF-1α under normoxia; this was accompanied by restored AMPK Thr172 phosphorylation downstream of constitutive LKB1 and recovery of PGC-1α-driven mitochondrial biogenesis. AKG preferentially attenuated mitochondrial superoxide over total cellular ROS through a co-substrate-mediated mechanism distinct from direct radical scavenging, and its protective effects were largely abrogated by DMOG (an α-KGDD inhibitor) or compound C (an AMPK inhibitor). These findings position AKG, delivered via microneedle-assisted topical application, as a candidate metabolite-based intervention targeting the α-KGDD/HIF-1α/AMPK axis for photoaging. Full article

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by oxidative stress and impaired skin barrier function. These pathological features contribute to persistent inflammation and symptom exacerbation, highlighting the need for therapies that can both reduce oxidative stress and modulate inflammatory pathways. Methods: Ulmus pumila Linné (Ulmi) was prepared via hot water extraction and tested for cytotoxicity, antioxidant activity, and anti-inflammatory effects in HaCaT keratinocytes stimulated with tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). In vivo efficacy was assessed using a 2,4-dinitrochlorobenzene (DNCB)-induced AD model in SKH-1 hairless mice. Bioactive compounds were identified using liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS), and molecular docking analysis was performed to evaluate the binding affinity of these compounds to aldehyde dehydrogenase 2 (ALDH2). Results: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays confirmed that Ulmi was safe at concentrations up to 400 μg/mL. In TNF-α/IFN-γ-stimulated HaCaT cells, Ulmi significantly upregulated ALDH2 expression in a dose-dependent manner and reduced reactive oxygen species (ROS) production. The extract also suppressed pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), while inhibiting the activation of nuclear factor kappa B (NF-κB) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways. In the AD mouse model, Ulmi treatment improved clinical skin scores, reduced epidermal thickness, and decreased inflammatory markers compared to untreated controls. LC-QTOF-MS/MS analysis identified eight bioactive compounds, with procyanidin B2, catechin, and epicatechin as major constituents. Molecular docking revealed that procyanidin B2 had the strongest binding affinity to ALDH2 (−9.5 kcal/mol). Conclusions: These findings demonstrate that Ulmi effectively ameliorates AD-like symptoms through ALDH2-mediated antioxidant mechanisms and anti-inflammatory effects. The results suggest that Ulmi may serve as a promising natural therapeutic agent for the management of atopic dermatitis. Full article

Background/Objectives: Skin photoaging represents a predominant form of extrinsic aging, characterized by structural and functional impairment of the skin barrier. In severe cases, it may precipitate dermatological diseases and even tumors. Given the prevalence and detrimental effects of skin photoaging, strategies for its effective prevention and mitigation have garnered significant research interest. Chrysanthemum morifolium Ramat cv. ‘Hangju’ contains diverse bioactive compounds, including flavonoids, phenylpropanoids, phenolic acids, and polysaccharides, which have been proven to exhibit antioxidant and anti-inflammatory effects. Methods: This study employed a UVB-induced mouse model of skin photoaging to evaluate the potential of dietary supplementation with Chrysanthemum morifolium Ramat cv. ‘Hangju’ flower extract (CME) in vivo. Results: In the photoaged skin of female SKH-1 hairless mice, dietary supplementation with CME significantly increased skin moisture content, reduced wrinkle formation, suppressed epidermal hyperplasia, enhanced collagen density, and suppressed the senescence marker expression and DNA damage marker expression. Analysis of the skin transcriptome suggested that CME could alter gene expression patterns and potentially modulate critical signaling pathways involved in skin homeostasis. Moreover, 16S rRNA sequencing indicated that CME mitigated UVB-induced gut microbiota dysbiosis. Conclusions: These preclinical findings reveal the anti-photoaging property of dietary CME supplementation and point to its potential application as a functional dietary supplement for promoting skin health. Full article

Molecular hydrogen (H₂) exhibits anti-inflammatory and antioxidant properties. However, its role in ultraviolet B (UVB)-induced skin carcinogenesis remains unclear. Male HR-1 hairless mice received continuous H₂ (2% hydrogen gas inhalation plus hydrogen-rich water (HRW)) or control treatment (normal air plus dehydrogenated water) during chronic dorsal UVB exposure (270 mJ/cm², three times per week, 20 weeks), followed by a 10-week observation period. This protocol was replicated independently. H₂ exposure consistently delayed the onset of papilloma and reduced cumulative tumor counts in both series, whereas prolonged survival and delayed squamous cell carcinoma (SCC) development each reached statistical significance in only one of the two experimental series. The cyclobutane pyrimidine dimer (CPD) levels remained unchanged, indicating no reduction in DNA photolesions. H₂ exposure decreased epidermal T-cell infiltration, dermal IL-6 levels, and nuclear phosphorylated STAT3 levels. ERK and JNK phosphorylation levels were decreased. H₂ preserved the GSH/GSSG ratio following acute UVB exposure and reduced nuclear Nrf2 accumulation during chronic exposure. Epidermal thickness and proliferation markers (Ki-67 and PCNA) were decreased. These findings suggest that continuous H₂ administration attenuates inflammation-associated early UVB carcinogenesis through modulation of the IL-6/STAT3 and ERK/JNK pathways, supporting its use as a chemopreventive approach. Full article

Newborn mice (up to 6 d after birth) are suitable for genetic manipulations, such as facial vein-mediated injection, owing to their hairless and thin skin. Their small body volumes also facilitate the rapid dissemination of injected solutions, supporting gene engineering-related experiments. However, anesthesia in newborns is challenging because of the potential risks associated with anesthetic agents. Isoflurane inhalation anesthesia is an option, although its effects on brain development remain under investigation. In this study, we established a reproducible protocol for delivering nucleic acids to juvenile mouse testes using a simple isoflurane-based anesthetic system prepared from common laboratory equipment. Using this system, nucleic acids were successfully delivered to juvenile mouse testes via intra-testicular injection, followed by in vivo electroporation. The present isoflurane-based method achieved >90% postoperative survival with normal maternal nursing observations. Gene delivery resulted in limited transfection of seminiferous tubules but efficient interstitial Leydig cell transfection. Thus, gene engineering in somatic and germ cells in neonatal mice will be facilitated using the anesthetic protocol established in this study. Full article

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by immune dysregulation and skin barrier impairment. This study evaluated the anti-inflammatory and immunomodulatory effects of Camellia japonica extract in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model using SKH-1 hairless mice. Topical application of Camellia japonica extract for four weeks significantly alleviated AD-like symptoms by reducing epidermal thickness, mast cell infiltration, and overall skin inflammation. Hematological analysis revealed a marked decrease in total white blood cell (WBC) and neutrophil counts. Furthermore, the Camellia japonica extract significantly decreased oxidative stress, as evidenced by reduced serum reactive oxygen species (ROS) and nitric oxide (NO) levels, while enhancing the activity of antioxidant enzymes such as catalase. Importantly, allergic response markers including serum immunoglobulin E (IgE), histamine, and thymic stromal lymphopoietin (TSLP), were also downregulated. At the molecular level, Camellia japonica extract suppressed the expression of key pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and T helper 2 (Th2)-type cytokines such as IL-4 and IL-5, while slightly upregulating the anti-inflammatory cytokine IL-10. Collectively, these findings suggest that Camellia japonica extract effectively modulates immune responses, suppresses allergic responses, attenuates oxidative stress, and promotes skin barrier recovery. Therefore, application of Camellia japonica extract holds the promising effect as a natural therapeutic agent for the prevention and treatment of AD-like skin conditions. Full article

UVB skin pathology is initiated by reactive oxygen species (ROS), differentiating this condition from other inflammatory diseases involving first the immune cell activation by danger or pathogen molecular patterns followed by oxidative stress. Resolvin D2 (RvD2) has been found to reduce inflammation in preclinical models. However, whether or not RvD2 reduces skin pathology caused by UVB irradiation is not yet known. Therefore, the efficacy of RvD2 on skin pathology triggered by UVB irradiation in female hairless mice was assessed. RvD2 (0.3, 1 or 3 ng/mouse, i.p.) was found to protect the skin against UVB inflammation, as observed in the reduction in edema (46%), myeloperoxidase activity (77%), metalloproteinase-9 activity (39%), recruitment of neutrophils/macrophages (lysozyme⁺ cells, 76%) and mast cells (106%), epidermal thickening (93%), sunburn cell formation (68%), collagen fiber breakdown (55%), and production of cytokines such as TNF-α (100%). Considering the relevance of oxidative stress to UVB irradiation skin pathologies, an important observation was that the skin antioxidant capacity was recovered by RvD2 according to the results that show the ferric reducing antioxidant power (68%), cationic radical scavenges (93%), catalase activity (74%), and the levels of reduced glutathione (48%). Oxidative damage was also attenuated, as observed in the reduction in superoxide anion production (69%) and lipid hydroperoxides (71%). The RvD2 mechanism involved the inhibition of NF-κB activation, as observed in the diminished degradation of IκBα (48%) coupled with a reduction in its downstream targets that are involved in inflammation and oxidative stress, such as COX-2 (66%) and gp91^phox (77%) mRNA expression. In conclusion, RvD2 mitigates the inflammatory and oxidative pathologic skin aggression that is triggered by UVB. Full article

Background/Objectives: Reverse iontophoresis (R-IP) is a technology that transdermally delivers components from inside the body to outside the body using electroosmotic flow (EOF) generated by applying a low electric current through the skin. It has attracted attention as a non-invasive sampling method for therapeutic drug monitoring (TDM). The purpose of this study was to determine whether urea and Tween 80 effectively enhance drug extraction from beneath the skin using R-IP. Methods: An in vitro drug extraction test using hairless mouse skin and R-IP was performed with a 3-chamber Franz cell and Ag|AgCl electrodes by applying a constant current (0.25 mA/cm²) for 6 h. Acetaminophen was chosen as the model drug, and its solution (30, 100, or 300 μg/mL) was placed in the subdermal compartment. The pH of both the electrode and subdermal compartment solutions was maintained at 7.4. Results: Acetaminophen was gradually extracted into the electrode compartment in a concentration-dependent manner and was more abundant in the cathode compartment than in the anode compartment. In addition, urea significantly promoted drug extraction, particularly on the cathode side, and a linear relationship was observed between the subdermal concentration and extracted amount. This effect is likely due to skin hydration caused by urea, which enhances EOF generation in the skin. Conversely, Tween 80 had no effect on drug extraction. Conclusions: R-IP combined with urea is expected to not only shorten the treatment time but also enable its application to drugs with low concentrations in blood. Full article

Background: Skin photoaging caused by ultraviolet B (UV-B) irradiation leads to the formation of wrinkles. A method to lessen wrinkles is the application of Polydioxanone (PDO) lifting threads. HanDam (Twist) is a PDO lifting thread with a unique morphological twisted shape. Objective: The aim of this study was to evaluate the wrinkle improvement ability of HanDam (Twist) on UV-B irradiation-induced skin photoaging in a hairless mouse model. Methods: Wrinkles were induced by UV-B irradiation to the backs of female hairless mice for six weeks. After induction, the wrinkles were treated with threads, and the mice were monitored for six weeks post-treatment. Results: Our results showed that treatment with HanDam (Twist) effectively ameliorated UV-B irradiation-induced wrinkle depth and significantly increased collagen density by 13% compared to HanDam (non-Twist) in the histological analysis. In measuring protein expression related to collagen production, HanDam (Twist) significantly increased transforming growth factor beta (TGF-β) and collagen type 1 (COL1) by 46% and 67% compared to HanDam (non-Twist). Matrix metalloproteinase-1 (MMP-1) protein expression showed similar density and no significance compared to HanDam (non-Twist). Conclusions: These findings suggest that HanDam (Twist) improves the effectiveness of lifting threads for skin care compared to that of existing products. Full article

Wound healing is important for skin after deep injuries or burns, which can lead to hospitalization, long-term morbidity, and mortality. In this field, tissue-engineered skin substitutes have therapy potential to assist in the treatment of acute and chronic skin wounds, where many requirements are still unmet. Hence, in this study, a novel type of biocompatible ternary polymer hybrid hydrogel scaffold was designed and produced through an entirely eco-friendly aqueous process composed of carboxymethyl cellulose, chitosan, and polyvinyl alcohol and chemically cross-linked by citric acid, forming three-dimensional (3D) matrices, which were biofunctionalized with L-arginine (L-Arg) to enhance cellular adhesion. They were applied as bilayer skin biomimetic substitutes based on human-derived cell cultures of fibroblasts and keratinocytes were seeded and grown into their 3D porous structures, producing cell-based bio-responsive hybrid hydrogel scaffolds to assist the wound healing process. The results demonstrated that hydrophilic hybrid cross-linked networks were formed via esterification reactions with the 3D porous microarchitecture promoted by foam templating and freeze-drying. These hybrids presented chemical stability, physicochemical properties, high moisture adsorption capacity, surface properties, and a highly interconnected 3D porous structure well suited for use as a skin substitute in wound healing. Additionally, the surface biofunctionalization of these 3D hydrogel scaffolds with L-arginine through amide bonds had significantly enhanced cellular attachment and proliferation of fibroblast and keratinocyte cultures. Hence, the in vivo results using Hairless mouse models (an immunocompromised strain) confirmed that these responsive bio-hybrid hydrogel scaffolds possess hemocompatibility, bioadhesion, biocompatibility, adhesiveness, biodegradability, and non-inflammatory behavior and are capable of assisting the skin wound healing process. Full article

Background: In recent decades, a significant global increase in the incidence of non-melanoma skin cancer has been observed. To explore the pathogenesis of and potential therapeutic approaches for squamous cell carcinoma, various in vivo studies using mouse models have been conducted. However, investigations comparing different hairless mouse models, with or without melanin, as well as models with hypercholesterolemia and immunosuppression, in terms of their ability to induce squamous cell carcinoma have yet to be undertaken. Methods: Four mouse strains, namely SKH-hr1, SKH-hr2, SKH-hr2+ApoE, and immunodeficient Nude (Foxn1 knockout), were exposed to UVA and UVB radiation three times per week, initially to 1 Minimal Erythemal Dose (MED), incrementally increased weekly to a maximum dose of 3 MED. Clinical evaluation, photodocumentation, and biophysical parameters were monitored, along with proteasome protein activity and histopathological assessments. Results: The SKH-hr1 model primarily developed actinic keratosis without significant progression to invasive squamous cell carcinoma (SCC), while the SKH-hr2 and SKH-hr2+ApoE models exhibited a higher likelihood and intensity of papilloma and aggressive SCC formation, with the latter showing upregulated proteasome activity. Histopathological analysis confirmed the presence of poorly differentiated, invasive SCCs in the SKH-hr2 and SKH-hr2+ApoE models, contrasting with the less aggressive SCCs in the Nude mice and the mixed lesions observed in the SKH-hr1 mice. Conclusions: The SKH-hr2+ApoE and SKH-hr2 mice were identified as the most suitable for further exploration of squamous cell carcinogenesis. In contrast, the SKH-hr1 mice were found to be the least suitable, even though they are albino. Notably, proteasome analysis revealed a potential role of proteasome activity in squamous cell carcinogenesis. Full article

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. Full article

Resolvin D5 (RvD5) is a lipid mediator that has been reported to present anti-inflammatory and pro-resolution properties. Evidence also supports its capability to enhance reactive oxygen species (ROS) production during bacterial infections, which would be detrimental in diseases driven by ROS. The biological activity of RvD5 and mechanisms against UVB irradiation skin pathology have not been investigated so far. Female hairless mice were treated intraperitoneally with RvD5 before UVB stimulus. RvD5 reduced skin edema in a dose-dependent manner as well as oxidative stress by increasing antioxidants (endogenous tissue antioxidant scavenging of cationic radical, iron reduction, catalase activity and reduced glutathione levels) and decreasing pro-oxidants (superoxide anion and lipid peroxidation). RvD5 antioxidant activity was accompanied by enhancement of Nrf2, HO-1 and NQO1 mRNA expression. RvD5 reduced the production of IL-1β, TNF-α, TGF-β, and IL-10. RvD5 also reduced the inflammatory cell counts, including mast cells and neutrophils/macrophages. The reduction of oxidative stress and inflammation resulted in diminished matrix metalloproteinase 9 activity, collagen degradation, epidermal thickening and sunburn cell development. Therefore, this study demonstrates, to our knowledge, the first body of evidence that RvD5 can be used to treat UVB skin pathology and unveils, at least in part, its mechanisms of action. Full article

Effects of pulsed electromagnetic fields (PEMF) on immunological factors in a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) model were investigated. Hairless mice were randomly assigned to control, acetone and olive oil solution-treated (AOO), PEMF 15 Hz, PEMF 75 Hz, and sham groups (n = 5 each). AOO solution was used to dissolve DNCB. Both PEMF and sham groups were exposed to similar DNCB doses, causing similar AD symptoms. After AD induction for five weeks, only the PEMF groups were exposed to PEMF stimulations (15 Hz, 75 Hz, and 15 mT) inside the solenoid coil, for two weeks. In both groups, splenomegaly was observed, as AD was induced by hyperimmune reactions caused by DNCB sensitization. However, splenomegaly did not occur in the PEMF-exposed groups, and spleen weight decreased similarly to that of the control. Hence, the total splenocytes in the PEMF group were similar to those in the control group, whereas the sham group showed three times the number of splenocytes compared with the PEMF group. The serum immunoglobulin E levels did not significantly change in the PEMF group; however, they increased more than fourfold in the sham group. These results demonstrate that PEMF stimulation ameliorated the abnormal symptoms caused by hyperimmune reactions. Full article