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1.
J Drugs Dermatol ; 23(6): 472-476, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38834210

ABSTRACT

The debate surrounding the benefits versus harms of blue light have become a topic of interest recently due to increased exposure. Blue light therapy has been utilized with some success in a variety of dermatologic conditions. However, potential harms have also been documented. Currently, there is no evidence to suggest a necessity for blue light photoprotection, but there are products available with proven efficacy for those desiring protection. J Drugs Dermatol. 2024;23(6):472-476.     doi:10.36849/JDD.7665.


Subject(s)
Light , Skin , Humans , Light/adverse effects , Skin/radiation effects , Skin Diseases/etiology , Skin Diseases/therapy , Phototherapy/methods , Phototherapy/adverse effects , Blue Light
2.
Cell Mol Biol (Noisy-le-grand) ; 70(6): 85-91, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38836676

ABSTRACT

Skin photoaging is a skin degenerative disease that causes patients to develop malignant tumors. The existing clinical treatment of photoaging has limitations. This greatly reduces the recovery rate of photoaging patients. Studies have confirmed that Ligusticum wallichii Franch (LWF) monomer tetramethylpyrazine (TMP) alleviates various skin diseases. The combination of traditional Chinese medicine and Western medicine helps with this process. Our research aimed to explore the specific treatment mode and molecular mechanism of TMP in treating skin photoaging. CCK-8 assays were used to evaluate the activity and toxicity of HaCaT cells. ß-galactosidase aging, Carbonyl compound and nitrosylated tyrosine assays were used to analyze the aging of HaCaT cells. ROS assays and ELISA were used to analyze the enrichment of ROS. The molecular docking experiment analyzed the binding of TMP and HIF-1α. qRT-PCR and Western blot were used to detect the activation of skin aging-related pathways. HE staining was used to analyze the thickness of the stratum corneum skin on the back skin of mice. 200µg/L LWF alleviates cellular photoaging and mouse skin photoaging by reducing ROS enrichment. Its monomer TMP plays an important role in this process. The combination of TMP and HIF-1α accelerates the degradation of ROS by activating the Nrf2/ARE signaling pathway. This process reduces the apoptosis of cells damaged by light. In addition, we also found that the combination of TMP and retinoic acid (RA) is more beneficial for the treatment of skin damage caused by light in mice. The combination therapy of TMP and RA alleviates skin oxidative stress response through overexpression of HIF-1α. This plan is beneficial for the treatment of skin photoaging.


Subject(s)
Hypoxia-Inducible Factor 1, alpha Subunit , Pyrazines , Reactive Oxygen Species , Signal Transduction , Skin Aging , Vitamin A , Pyrazines/pharmacology , Skin Aging/drug effects , Skin Aging/radiation effects , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Animals , Humans , Reactive Oxygen Species/metabolism , Mice , Signal Transduction/drug effects , Vitamin A/pharmacology , Skin/drug effects , Skin/metabolism , Skin/pathology , Skin/radiation effects , HaCaT Cells , Molecular Docking Simulation
3.
Photodermatol Photoimmunol Photomed ; 40(4): e12985, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38845468

ABSTRACT

BACKGROUND: Photoprotection is the first measure in the prevention and treatment of the deleterious effects that sunlight can cause on the skin. It is well known that prolonged exposure to solar radiation leads to acute and chronic complications, such as erythema, accelerated skin aging, proinflammatory and procarcinogenic effects, and eye damage, among others. METHODS: A better understanding of the molecules that can protect against ultraviolet radiation and their effects will lead to improvements in skin health. RESULTS: Most of these effects of the sunlight are modulated by oxidative stress and proinflammatory mechanisms, therefore, the supplementation of substances that can regulate and neutralize reactive oxygen species would be beneficial for skin protection. Current evidence indicates that systemic photoprotection should be used as an adjunctive measure to topical photoprotection. CONCLUSION: Oral photoprotectors are a promising option in improving protection against damage induced by UVR, as they contain active ingredients that increase the antioxidant effects of the body, complementing other photoprotection measures. We present a review of oral photoprotectors and their effects.


Subject(s)
Sunscreening Agents , Ultraviolet Rays , Humans , Ultraviolet Rays/adverse effects , Sunscreening Agents/administration & dosage , Administration, Oral , Antioxidants/administration & dosage , Oxidative Stress/drug effects , Skin/metabolism , Skin/radiation effects , Skin/drug effects , Reactive Oxygen Species/metabolism , Sunlight/adverse effects
4.
J Drugs Dermatol ; 23(5): 366-375, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38709706

ABSTRACT

OBJECTIVE:   This study aimed to investigate the ultraviolet (UV) protection/repair benefits of a patented Amino Acid Complex (AAComplex). METHODS: I) AAComplex was incubated with dermal fibroblasts, with/without UVA, and collagen I was measured with a GlasBoxPlus device. II) A lotion, with/without AAComplex (1%) was applied topically to skin explants, following UVA irradiation, and quantified for health-related biomarkers (TNFalpha, histamine, and MMP-1). III) A broad spectrum sunscreen with SPF 46 and a skincare serum containing AAComplex (2%) were assessed using epidermal equivalents, in the presence of UV irradiation, for effects on IL-1alpha, thymine dimers, Ki-67, filaggrin and Nrf2. RESULTS: I) Collagen I synthesis in dermal fibroblasts was significantly decreased after UVA compared to without UV. The presence of AAComplex prevented this decrease. II) UVA irradiation of skin explants increased histamine, TNFα, and MMP-1. Hydrocortisone aceponate cream significantly decreases all 3 biomarkers. AAComplex contained lotion also significantly decreased all 3 biomarkers, the no AAComplex control lotion only reduced histamine. III) With the regimen of sunscreen + AAComplex contained skincare serum, the significant reduction in IL-1alpha was observed along with a complete recovery of Ki-67 and stimulation of filaggrin and Nrf2T. No thymine dimer positive cell was observed indicating the most positive skin impact from the regiment.  Conclusion: This research using different human skin models demonstrated that AAComplex can provide protection and damage repair caused by UV, at the ingredient level also when formulated in a serum or lotion formula. Skin may be best protected from UV damage when the regimen is used.   J Drugs Dermatol. 2024;23(5):366-375. doi:10.36849/JDD.7916.


Subject(s)
Fibroblasts , Filaggrin Proteins , Matrix Metalloproteinase 1 , NF-E2-Related Factor 2 , Tumor Necrosis Factor-alpha , Ultraviolet Rays , Humans , Ultraviolet Rays/adverse effects , Fibroblasts/drug effects , Fibroblasts/radiation effects , Fibroblasts/metabolism , Matrix Metalloproteinase 1/metabolism , Tumor Necrosis Factor-alpha/metabolism , Skin/radiation effects , Skin/drug effects , Skin/metabolism , Sunscreening Agents/administration & dosage , Sunscreening Agents/chemistry , Sunscreening Agents/pharmacology , Amino Acids/administration & dosage , Amino Acids/pharmacology , Amino Acids/chemistry , Interleukin-1alpha/metabolism , Histamine/blood , Skin Cream/administration & dosage , Biomarkers/metabolism , Collagen Type I , Intermediate Filament Proteins/metabolism , Ki-67 Antigen/metabolism , Pyrimidine Dimers , Cells, Cultured
5.
Lasers Med Sci ; 39(1): 130, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38750285

ABSTRACT

The aim of this study is to investigate how the introduction of Gold nanoparticles GNPs into a skin tumor affects the ability to absorb laser light during multicolor laser exposure. The Monte Carlo Geant4 technique was used to construct a cubic geometry simulating human skin, and a 5 mm tumor spheroid was implanted at an adjustable depth x. Our findings show that injecting a very low concentration of 0.01% GNPs into a tumor located 1 cm below the skin's surface causes significant laser absorption of up to 25%, particularly in the 900 nm to 1200 nm range, resulting in a temperature increase of approximately 20%. It is an effective way to raise a tumor's temperature and cause cell death while preserving healthy cells. The addition of GNPs to a tumor during polychromatic laser exposure with a wavelength ranging from 900 nm to 1200 nm increases laser absorption and thus temperature while preserving areas without GNPs.


Subject(s)
Gold , Metal Nanoparticles , Monte Carlo Method , Photothermal Therapy , Skin Neoplasms , Humans , Photothermal Therapy/methods , Skin Neoplasms/therapy , Skin Neoplasms/pathology , Skin/radiation effects
6.
Eur J Med Res ; 29(1): 282, 2024 May 12.
Article in English | MEDLINE | ID: mdl-38735974

ABSTRACT

BACKGROUND: Radiation induced acute skin toxicity (AST) is considered as a common side effect of breast radiation therapy. The goal of this study was to design dosiomics-based machine learning (ML) models for prediction of AST, to enable creating optimized treatment plans for high-risk individuals. METHODS: Dosiomics features extracted using Pyradiomics tool (v3.0.1), along with treatment plan-derived dose volume histograms (DVHs), and patient-specific treatment-related (PTR) data of breast cancer patients were used for modeling. Clinical scoring was done using the Common Terminology Criteria for Adverse Events (CTCAE) V4.0 criteria for skin-specific symptoms. The 52 breast cancer patients were grouped into AST 2 + (CTCAE ≥ 2) and AST 2 - (CTCAE < 2) toxicity grades to facilitate AST modeling. They were randomly divided into training (70%) and testing (30%) cohorts. Multiple prediction models were assessed through multivariate analysis, incorporating different combinations of feature groups (dosiomics, DVH, and PTR) individually and collectively. In total, seven unique combinations, along with seven classification algorithms, were considered after feature selection. The performance of each model was evaluated on the test group using the area under the receiver operating characteristic curve (AUC) and f1-score. Accuracy, precision, and recall of each model were also studied. Statistical analysis involved features differences between AST 2 - and AST 2 + groups and cutoff value calculations. RESULTS: Results showed that 44% of the patients developed AST 2 + after Tomotherapy. The dosiomics (DOS) model, developed using dosiomics features, exhibited a noteworthy improvement in AUC (up to 0.78), when spatial information is preserved in the dose distribution, compared to DVH features (up to 0.71). Furthermore, a baseline ML model created using only PTR features for comparison with DOS models showed the significance of dosiomics in early AST prediction. By employing the Extra Tree (ET) classifiers, the DOS + DVH + PTR model achieved a statistically significant improved performance in terms of AUC (0.83; 95% CI 0.71-0.90), accuracy (0.70), precision (0.74) and sensitivity (0.72) compared to other models. CONCLUSIONS: This study confirmed the benefit of dosiomics-based ML in the prediction of AST. However, the combination of dosiomics, DVH, and PTR yields significant improvement in AST prediction. The results of this study provide the opportunity for timely interventions to prevent the occurrence of radiation induced AST.


Subject(s)
Breast Neoplasms , Machine Learning , Humans , Female , Breast Neoplasms/radiotherapy , Middle Aged , Adult , Aged , Skin/radiation effects , Skin/pathology , Radiation Injuries/etiology , Radiation Injuries/diagnosis , Radiotherapy Dosage
7.
ACS Appl Mater Interfaces ; 16(20): 25923-25937, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38725122

ABSTRACT

The management of severe full-thickness skin defect wounds remains a challenge due to their irregular shape, uncontrollable bleeding, high risk of infection, and prolonged healing period. Herein, an all-in-one OD/GM/QCS@Exo hydrogel was prepared with catechol-modified oxidized hyaluronic acid (OD), methylacrylylated gelatin (GM), and quaternized chitosan (QCS) and loaded with adipose mesenchymal stem cell-derived exosomes (Exos). Cross-linking of the hydrogel was achieved using visible light instead of ultraviolet light irradiation, providing injectability and good biocompatibility. Notably, the incorporation of catechol groups and multicross-linked networks in the hydrogels conferred strong adhesion properties and mechanical strength against external forces such as tensile and compressive stress. Furthermore, our hydrogel exhibited antibacterial, anti-inflammatory, and antioxidant properties along with wound-healing promotion effects. Our results demonstrated that the hydrogel-mediated release of Exos significantly promotes cellular proliferation, migration, and angiogenesis, thereby accelerating skin structure reconstruction and functional recovery during the wound-healing process. Overall, the all-in-one OD/GM/QCS@Exo hydrogel provided a promising therapeutic strategy for the treatment of full-thickness skin defect wounds through actively participating in the entire process of wound healing.


Subject(s)
Chitosan , Exosomes , Gelatin , Hyaluronic Acid , Hydrogels , Mesenchymal Stem Cells , Skin , Wound Healing , Wound Healing/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Animals , Exosomes/chemistry , Exosomes/metabolism , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Skin/drug effects , Skin/pathology , Skin/radiation effects , Chitosan/chemistry , Chitosan/pharmacology , Mice , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/drug effects , Gelatin/chemistry , Gelatin/pharmacology , Light , Humans , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Cell Proliferation/drug effects
8.
Sci Data ; 11(1): 441, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702328

ABSTRACT

Photoaging is the premature aging of the skin caused by prolonged exposure to solar radiation. The visual alterations manifest as wrinkles, reduced skin elasticity, uneven skin tone, as well as other signs that surpass the expected outcomes of natural aging. Beyond these surface changes, there is a complex interplay of molecular alterations, encompassing shifts in cellular function, DNA damage, and protein composition disruptions. This data descriptor introduces a unique dataset derived from ten individuals, each with a minimum of 18 years of professional experience as a driver, who are asymmetrically and chronically exposed to solar radiation due to their driving orientation. Skin samples were independently collected from each side of the face using a microdermabrasion-like procedure and analyzed on an Exploris 240 mass spectrometer. Our adapted proteomic statistical framework leverages the sample pairing to provide robust insights. This dataset delves into the molecular differences in exposed skin and serves as a foundational resource for interdisciplinary research in photodermatology, targeted skincare treatments, and computational modelling of skin health.


Subject(s)
Face , Mass Spectrometry , Proteomics , Skin Aging , Skin , Skin/radiation effects , Skin/metabolism , Humans , Sunlight
9.
Molecules ; 29(9)2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38731413

ABSTRACT

Ultraviolet radiation can heighten tyrosinase activity, stimulate melanocyte production, impede the metabolism of numerous melanocytes, and result in the accumulation of plaques on the skin surface. α-Arbutin, a bioactive substance extracted from the arbutin plant, has been widely used for skin whitening. In this study, the whitening effect of α-arbutin by inhibiting tyrosinase activity and alleviating the photoaging effect induced by UVB are investigated. The results indicate that α-arbutin can inhibit skin inflammation, and its effectiveness is positively correlated with concentration. Moreover, α-arbutin can reduce the skin epidermal thickness, decrease the number of inflammatory cells, and down-regulate the expression levels of IL-1ß, IL-6 and TNF-α, which are inflammatory factors. It also promotes the expression of COL-1 collagen, thus playing an important role in anti-inflammatory action. Network pharmacology, metabolomics and transcriptomics further confirm that α-arbutin is related to the L-tyrosine metabolic pathway and may interfere with various signaling pathways related to melanin and other photoaging by regulating metabolic changes. Therefore, α-arbutin has a potential inhibitory effect on UVB-induced photoaging and possesses a whitening effect as a cosmetic compound.


Subject(s)
Arbutin , Skin Aging , Ultraviolet Rays , Arbutin/pharmacology , Ultraviolet Rays/adverse effects , Animals , Skin Aging/drug effects , Skin Aging/radiation effects , Mice , Monophenol Monooxygenase/metabolism , Monophenol Monooxygenase/antagonists & inhibitors , Humans , Skin/radiation effects , Skin/drug effects , Skin/metabolism , Skin/pathology
10.
J Photochem Photobiol B ; 255: 112927, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38701631

ABSTRACT

Since the mechanism underlying real-time acquisition of mechanical strength during laser-induced skin wound fusion remains unclear, and collagen is the primary constituent of skin tissue, this study investigates the structural and mechanical alterations in collagen at temperatures ranging from 40 °C to 60 °C using various spectroscopic techniques and molecular dynamics calculations. The COMSOL Multiphysics coupling is employed to simulate the three-dimensional temperature field, stress-strain relationship, and light intensity distribution in the laser thermal affected zone of skin wounds during dual-beam laser welding process. Raman spectroscopy, synchronous fluorescence spectroscopy and circular dichroism measurement results confirm that laser energy activates biological activity in residues, leading to a transformation in the originally fractured structure of collagen protein for enhanced mechanical strength. Molecular dynamics simulations reveal that stable hydrogen bonds form at amino acid residues within the central region of collagen protein when the overall temperature peak around the wound reaches 60 °C, thereby providing stability to previously fractured skin incisions and imparting instantaneous strength. However, under a 55 °C system, Type I collagen ensures macrostructural stability while activating biological properties at amino acid bases to promote wound healing function; this finding aligns with experimental analysis results. The COMSOL simulation outcomes also correspond well with macroscopic morphology after laser welding samples, confirming that by maintaining temperatures between 55 °C-60 °C during laser welding of skin incisions not only can certain instantaneous mechanical strength be achieved but irreversible thermal damage can also be effectively controlled. It is anticipated that these findings will provide valuable insights into understanding the healing mechanism for laser-welded skin wounds.


Subject(s)
Collagen , Lasers , Molecular Dynamics Simulation , Skin , Spectrum Analysis, Raman , Skin/chemistry , Skin/radiation effects , Collagen/chemistry , Collagen/metabolism , Wound Healing , Hydrogen Bonding , Finite Element Analysis , Animals , Circular Dichroism , Temperature , Spectrometry, Fluorescence
11.
FASEB J ; 38(9): e23641, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38690717

ABSTRACT

Cholinergic urticaria is a dermatological disease characterized by the presence of large patches of red skin and transient hives triggered by factors, such as exercise, sweating, and psychological tension. This skin problem is hypothesized to be attributed to a reduced expression of acetylcholinesterase (AChE), an enzyme responsible for hydrolyzing acetylcholine (ACh). Consequently, ACh is thought to the leak from sympathetic nerves to skin epidermis. The redundant ACh stimulates the mast cells to release histamine, triggering immune responses in skin. Here, the exposure of ultraviolet B in skin suppressed the expression of AChE in keratinocytes, both in in vivo and in vitro models. The decrease of the enzyme was resulted from a declined transcription of ACHE gene mediated by micro-RNAs, that is, miR-132 and miR-212. The levels of miR-132 and miR-212 were markedly induced by exposure to ultraviolet B, which subsequently suppressed the transcriptional rate of ACHE. In the presence of low level of AChE, the overflow ACh caused the pro-inflammatory responses in skin epidermis, including increased secretion of cytokines and COX-2. These findings suggest that ultraviolet B exposure is one of the factors contributing to cholinergic urticaria in skin.


Subject(s)
Acetylcholinesterase , Keratinocytes , MicroRNAs , Skin , Ultraviolet Rays , Urticaria , Acetylcholinesterase/metabolism , Acetylcholinesterase/genetics , Keratinocytes/metabolism , Keratinocytes/radiation effects , Ultraviolet Rays/adverse effects , Animals , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Skin/radiation effects , Skin/metabolism , Urticaria/metabolism , Urticaria/etiology , Mice , Acetylcholine/metabolism , Male
12.
Medicina (Kaunas) ; 60(5)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38792923

ABSTRACT

Background and Objectives: Chronic radiotherapy-induced skin injury (cRISI) is an irreversible and progressive condition that can significantly impact a patient's quality of life. Despite the limited literature available on the assessment of the epidermal barrier in cRISI, there is a consensus that appropriate skincare, including the use of emollients, is the primary therapeutic approach for this group of patients. The aim of this study was to evaluate the biophysical properties of the skin during the late period (at least 90 days) following radiation therapy (RT) for head and neck cancer. Materials and Methods: This was a single-center prospective non-randomized study. It involved the analysis of 16 adult patients with head and neck cancer who underwent RT at the Greater Poland Cancer Center, along with 15 healthy volunteers. The study and control groups were matched for gender and age (p = 0.51). Clinical assessment, based on the LENT-SOMA scale, was conducted for all patients. Evaluation of the skin's biophysical properties included: an analysis of transepidermal water loss (TEWL), stratum corneum hydration (SCH), and skin visualization using high-frequency ultrasonography (HF-USG). Results: A significantly higher TEWL was observed in the irradiated area compared to the control area in the study group (p = 0.004). However, there was no statistically significant difference in SCH (p = 0.073). Additionally, no significant difference was observed in the values of TEWL and SCH in the irradiated area between the group of patients with and without clinically obvious RISI (p = 0.192 and p = 0.415, respectively). The skin thickness of the irradiated area, assessed by HF-USG, did not differ significantly from the skin thickness of the control area (p = 0.638). Furthermore, no difference in skin thickness was observed in patients with clinical features of cRISI in the irradiated and control areas (p = 0.345). The mean time after RT was 6.1 years. Conclusions: This study marks the first demonstration of epidermal barrier damage in patients in the long term following RT for head and neck cancer. The impairment of the epidermal barrier was observed independently of evident cRISI features. This observation underscores the necessity to recommend appropriate skin care, including the use of emollients, for all patients following RT. We also suggest that HF-USG examination is generally inconclusive in determining the degree of skin damage in the late period after RT.


Subject(s)
Head and Neck Neoplasms , Humans , Head and Neck Neoplasms/radiotherapy , Male , Female , Middle Aged , Prospective Studies , Aged , Adult , Skin/radiation effects , Poland , Radiotherapy/adverse effects , Radiotherapy/methods , Quality of Life
13.
Exp Dermatol ; 33(5): e15109, 2024 May.
Article in English | MEDLINE | ID: mdl-38794812

ABSTRACT

Cornulin (CRNN) and repetin (RPTN) belong to the fused-type S100 protein family. Although these proteins have been reported to be expressed in the granular layer of the epidermis and have been suggested to be associated with barrier formation in the epidermis, their exact function remains unclear. This study examined the effects of ultraviolet B (UVB) irradiation on CRNN and RPTN expression in human skin xenotransplantation. The CRNN expression increased in the granular layer of UVB-irradiated skin 2 days after UVB irradiation compared to that in sham-irradiated skin. Interestingly, CRNN signals were observed not only in the cytoplasm, but also in the peripheral regions of granular keratinocytes. In contrast, RPTN was rarely expressed in sham-irradiated skin; however, RPTN signals were markedly increased in the granular layer of the UVB-irradiated skin. In addition, activation of ERK1/2 and STAT3 was observed in UVB-irradiated skin. Accordingly, the present study demonstrated that CRNN and RPTN are novel proteins whose expression can be increased by UVB irradiation. The activation of ERK1/2 and STAT3 may be associated with the regeneration of a UVB-damaged epidermis, and CRNN and RPTN may be induced to repair any dysfunction in the epidermal barrier during this regeneration process.


Subject(s)
STAT3 Transcription Factor , Ultraviolet Rays , Humans , STAT3 Transcription Factor/metabolism , Transplantation, Heterologous , Keratinocytes/metabolism , Keratinocytes/radiation effects , Animals , Skin/metabolism , Skin/radiation effects , Epidermis/metabolism , Epidermis/radiation effects , Skin Transplantation , Cornified Envelope Proline-Rich Proteins/metabolism , Cornified Envelope Proline-Rich Proteins/genetics , Heterografts , S100 Proteins/metabolism , S100 Proteins/genetics , Mice
14.
Discov Med ; 36(184): 1080-1090, 2024 May.
Article in English | MEDLINE | ID: mdl-38798266

ABSTRACT

BACKGROUND: Skin photoaging is a complex process of skin aging caused by continuous exposure to ultraviolet (UV) radiation through oxidative stress and other pathways, yet effective treatments are scarce. Metformin is a drug with both anti-senescence and antioxidant functions; however, there are fewer studies on photoaging. The study aimed to investigate the role of needle-free injection of metformin in alleviating ultraviolet radiation B (UVB) induced skin photoaging, and to explore the mechanisms through which metformin alleviates fibroblast photoaging by inhibiting ferroptosis and oxidative stress. METHODS: In our study, we initially performed bioinformatic analysis on the gene expression profile (GSE38308), and our RNA sequencing (RNA-Seq) found that photoaging is associated with ferroptosis. We investigated the potential skin-protective mechanism of metformin by utilizing a UVB-induced rat skin photoaging model and human skin fibroblasts (HSF) treated with UVB. For in vitro experiments, cellular senescence was detected using SA-ß-galactosidase staining and p16 in western blot. Ferroptosis and oxidative stress were assessed via western blot (glutathione Peroxidase 4 (GPX4) and nuclear factor erythroid-2-related factor 2 (Nrf2)), reactive oxygen species (ROS) levels, transmission electron microscope, Lillie's staining, and immunofluorescence staining. During in vivo experiments, metformin was administered by needle-free jet injectors injected into the backs of rats. The effectiveness of metformin was detected using the Masson staining and western blot. RESULTS: We found that the ferroptosis pathway was closely associated with photoaging through bioinformatics analysis. In the UVB-induced photoaging HSF cells, treatment with metformin exhibits the following effects: a reduction in blue-stained granules in SA-ß-galactosidase staining and a decrease in the expression of p16, indicating a reduction in cellular senescence. Moreover, metformin leads to decreased ROS levels and increased expression of the oxidative stress-related protein Nrf2, suggesting inhibition of oxidative stress within the cells. Additionally, metformin results in an elevation of GPX4 expression, a decrease in blue-stained granules in Lillie's staining, and a reduction in ferroptosis-associated mitochondrial damage, indicating a decline in ferroptosis. Needle-free injection of metformin could directly achieve therapeutic effects by affecting HSF cells in the dermis. The needle-free injection of metformin treatment effectively improved the photoaging skin in rats compared to the photoaging group, ameliorated oxidative stress, and reduced ferroptosis. CONCLUSIONS: Our data highlights a novel needle-free injection of metformin that improves photoaging and has good therapeutic potential.


Subject(s)
Ferroptosis , Metformin , Oxidative Stress , Skin Aging , Ultraviolet Rays , Metformin/pharmacology , Metformin/administration & dosage , Oxidative Stress/drug effects , Oxidative Stress/radiation effects , Animals , Skin Aging/drug effects , Skin Aging/radiation effects , Ferroptosis/drug effects , Ferroptosis/radiation effects , Rats , Humans , Ultraviolet Rays/adverse effects , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibroblasts/radiation effects , Reactive Oxygen Species/metabolism , Skin/drug effects , Skin/pathology , Skin/radiation effects , Skin/metabolism , Cellular Senescence/drug effects , Cellular Senescence/radiation effects , Rats, Sprague-Dawley , Male , NF-E2-Related Factor 2/metabolism
15.
Phys Med Biol ; 69(11)2024 May 30.
Article in English | MEDLINE | ID: mdl-38759672

ABSTRACT

Objective.This study aimed to develop a new approach to predict radiation dermatitis (RD) by using the skin dose distribution in the actual area of RD occurrence to determine the predictive dose by grade.Approach.Twenty-three patients with head and neck cancer treated with volumetric modulated arc therapy were prospectively and retrospectively enrolled. A framework was developed to segment the RD occurrence area in skin photography by matching the skin surface image obtained using a 3D camera with the skin dose distribution. RD predictive doses were generated using the dose-toxicity surface histogram (DTH) calculated from the skin dose distribution within the segmented RD regions classified by severity. We then evaluated whether the developed DTH-based framework could visually predict RD grades and their occurrence areas and shapes according to severity.Main results.The developed framework successfully generated the DTH for three different RD severities: faint erythema (grade 1), dry desquamation (grade 2), and moist desquamation (grade 3); 48 DTHs were obtained from 23 patients: 23, 22, and 3 DTHs for grades 1, 2, and 3, respectively. The RD predictive doses determined using DTHs were 28.9 Gy, 38.1 Gy, and 54.3 Gy for grades 1, 2, and 3, respectively. The estimated RD occurrence area visualized by the DTH-based RD predictive dose showed acceptable agreement for all grades compared with the actual RD region in the patient. The predicted RD grade was accurate, except in two patients.Significance. The developed DTH-based framework can classify and determine RD predictive doses according to severity and visually predict the occurrence area and shape of different RD severities. The proposed approach can be used to predict the severity and shape of potential RD in patients and thus aid physicians in decision making.


Subject(s)
Radiodermatitis , Humans , Radiodermatitis/etiology , Male , Female , Middle Aged , Radiotherapy, Intensity-Modulated/adverse effects , Head and Neck Neoplasms/radiotherapy , Aged , Radiotherapy Dosage , Severity of Illness Index , Radiation Dosage , Skin/radiation effects , Skin/diagnostic imaging , Skin/pathology
16.
Lasers Med Sci ; 39(1): 141, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38801600

ABSTRACT

PURPOSE: Conventional approaches for enhancing wound healing may not always yield satisfactory results. Instead, we test the effectiveness of a newly developed photodynamic therapy (PDT) that uses methylene blue (MB) loaded with polyethylene glycol (PEG) (MB-PEG) hydrogel to accelerate wound healing process in mice. METHODS: A dorsal skin incision with 6 mm punch which topically subjected to MB-PEG hydrogel and a low-level laser light of red light to assess the regeneration process of wounded skin. A total of 63 adult male CD1 mice divided into normal group (no treatment) and other wound groups received different treatments of laser (650 ± 5 nm and power intensity of 180 mW/cm2), MB-PEG, or PDT (MB-PEG followed by laser). The wound healing parameters were investigated by histological examination of the skin and measuring of proinflammatory cytokines at the early stage (48 h) and a late one on day 21. RESULTS: at 48 h, the score of tissue granulation, inflammation, and angiogenesis process were markedly improved in wounded groups that received MB + PEG combined with laser compared to the group treated with laser alone. On day 21, a significant improvement of the inflammation was detected in the group treated with MB + PEG plus laser compared to the other groups. At 48 h, the upregulated serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in the wound group were significantly (P < 0.001) reduced in the group treated with MB + PEG combined with laser. CONCLUSION: MB-PEG based hydrogel improves and accelerates wound closure in the context of laser compared to either single treatment.


Subject(s)
Methylene Blue , Photochemotherapy , Polyethylene Glycols , Skin , Wound Healing , Animals , Wound Healing/drug effects , Wound Healing/radiation effects , Mice , Photochemotherapy/methods , Methylene Blue/pharmacology , Male , Skin/radiation effects , Skin/drug effects , Skin/injuries , Hydrogels , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/pharmacology , Cytokines/metabolism
17.
Int J Mol Sci ; 25(9)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38732058

ABSTRACT

Monitoring inflammatory cytokines is crucial for assessing healing process and photobiomodulation (PBM) enhances wound healing. Meanwhile, cAMP response element-binding protein (CREB) is a regulator of cellular metabolism and proliferation. This study explored potential links between inflammatory cytokines and the activity of CREB in PBM-treated wounds. A total of 48 seven-week-old male SD rats were divided into four groups (wound location, skin or oral; treatment method, natural healing or PBM treatment). Wounds with a 6 mm diameter round shape were treated five times with an 808 nm laser every other day (total 60 J). The wound area was measured with a caliper and calculated using the elliptical formula. Histological analysis assessed the epidermal regeneration and collagen expression of skin and oral tissue with H&E and Masson's trichrome staining. Pro-inflammatory (TNF-α) and anti-inflammatory (TGF-ß) cytokines were quantified by RT-PCR. The ratio of phosphorylated CREB (p-CREB) to unphosphorylated CREB was identified through Western blot. PBM treatment significantly reduced the size of the wounds on day 3 and day 7, particularly in the skin wound group (p < 0.05 on day 3, p < 0.001 on day 7). The density of collagen expression was significantly higher in the PBM treatment group (in skin wound, p < 0.05 on day 3, p < 0.001 on day 7, and p < 0.05 on day 14; in oral wound, p < 0.01 on day 7). The TGF-ß/TNF-α ratio and the p-CREB/CREB ratio showed a parallel trend during wound healing. Our findings suggested that the CREB has potential as a meaningful marker to track the wound healing process.


Subject(s)
Cyclic AMP Response Element-Binding Protein , Low-Level Light Therapy , Rats, Sprague-Dawley , Wound Healing , Animals , Wound Healing/radiation effects , Low-Level Light Therapy/methods , Male , Rats , Cyclic AMP Response Element-Binding Protein/metabolism , Skin/metabolism , Skin/radiation effects , Skin/pathology , Skin/injuries , Cytokines/metabolism , Phosphorylation/radiation effects , Tumor Necrosis Factor-alpha/metabolism , Collagen/metabolism , Transforming Growth Factor beta/metabolism
18.
Technol Cancer Res Treat ; 23: 15330338241258566, 2024.
Article in English | MEDLINE | ID: mdl-38803305

ABSTRACT

Purpose: Determining the impact of air gap errors on the skin dose in postoperative breast cancer radiotherapy under dynamic intensity-modulated radiation therapy (IMRT) techniques. Methods: This was a retrospective study that involved 55 patients who underwent postoperative radiotherapy following modified radical mastectomy. All plans employed tangential IMRT, with a prescription dose of 50 Gy, and bolus added solely to the chest wall. Simulated air gap depth errors of 2 mm, 3 mm, and 5 mm were introduced at depression or inframammary fold areas on the skin, resulting in the creation of air gaps named Air2, Air3, and Air5. Utilizing a multivariable GEE, the average dose (Dmean) of the local skin was determined to evaluate its relationship with air gap volume and the lateral beam's average angle (AALB). Additionally, an analysis was conducted on the impact of gaps on local skin. Results: When simulating an air gap depth error of 2 mm, the average Dmean in plan2 increased by 0.46 Gy compared to the initial plan (planO) (p < .001). For the 3-mm air gap, the average Dmean of plan3 was 0.51 Gy higher than that of planO (p < .001). When simulating the air gap as 5 mm, the average Dmean of plan5 significantly increased by 0.59 Gy compared to planO (p < .001). The TCP results showed a similar trend to those of Dmean. As the depth of air gap error increases, NTCP values also gradually rise. The linear regression of the multivariable GEE equation indicates that the volume of air gaps and the AALB are strong predictors of Dmean. Conclusion: With small irregular air gap errors simulated in 55 patients, the values of skin's Dmean, TCP, and NTCP increased. A multivariable linear GEE regression model may effectively explain the impact of air gap volume and AALB on the local skin.


Subject(s)
Breast Neoplasms , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Intensity-Modulated , Skin , Humans , Female , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Radiotherapy Planning, Computer-Assisted/methods , Skin/radiation effects , Radiotherapy, Intensity-Modulated/methods , Retrospective Studies , Middle Aged
19.
Int J Hyperthermia ; 41(1): 2354435, 2024.
Article in English | MEDLINE | ID: mdl-38754976

ABSTRACT

INTRODUCTION: Psoriasis is characterized by an increase in the proliferation of keratinocytes and nerve fiber activity, contributing to the typical skin lesions. Pulsed Dye Laser (PDL) treatment is effective for the treatment of psoriatic lesions but its mechanism remains unclear. One hypothesis is that PDL causes thermal damage by the diffusion of heat to neighboring structures in lesional skin. There is limited information on the thermal sensitivity of these neighboring skin cells when exposed to hyperthermia for durations lasting less than a minute. Our study aimed to investigate the cell-specific responses to heat using sub-minute exposure times and moderate to ablative hyperthermia. MATERIALS AND METHODS: Cultured human endothelial cells, smooth muscle cells, neuronal cells, and keratinocytes were exposed to various time (2-20 sec) and temperature (45-70 °C) combinations. Cell viability was assessed by measuring intracellular ATP content 24 h after thermal exposure and this data was used to calculate fit parameters for the Arrhenius model and CEM43 calculations. RESULTS: Our results show significant differences in cell survival between cell types (p < 0.0001). Especially within the range of 50-60 °C, survival of neuronal cells and keratinocytes was significantly less than that of endothelial and smooth muscle cells. No statistically significant difference was found in the lethal dose (LT50) of thermal energy between neuronal cells and keratinocytes. However, CEM43 calculations showed significant differences between all four cell types. CONCLUSION: The results imply that there is a cell-type-dependent sensitivity to thermal damage which suggests that neuronal cells and keratinocytes are particularly susceptible to diffusing heat from laser treatment. Damage to these cells may aid in modulating the neuro-inflammatory pathways in psoriasis. These data provide insight into the potential mechanisms of PDL therapy for psoriasis and advance our understanding of how thermal effects may play a role in its effectiveness.


Subject(s)
Keratinocytes , Skin , Humans , Skin/pathology , Skin/radiation effects , Skin/injuries , Cell Survival/radiation effects
20.
Biomed Phys Eng Express ; 10(4)2024 May 17.
Article in English | MEDLINE | ID: mdl-38718784

ABSTRACT

A study of burn thresholds from superficially penetrating radio-frequency (RF) energy at 8.2 and 95 GHz for swine skin was conducted. The study determined the thresholds for superficial, partial-thickness, and full-thickness burn severities after 5 seconds of exposure at power densities of 4-30 W/cm2and 2-15 W/cm2at 8.2 and 95 GHz, respectively. There were significant differences in he burn thresholds at the different severities between the two frequencies due to the large difference in energy penetration depths. Biopsies were collected from each burn site at 1, 24, 72, and 168 hr post exposure. Each sample was assessed by a burn pathologist against 20 histological factors to characterize the damage resulting from these RF overexposures. A one-dimensional, layered digital phantom that utilized realistic values for dielectric and thermal properties was used to explain some observed thresholds. The results of the heating and cooling response of the animal model and histology scores of each exposure are provided to enhance future efforts at simulation of RF overexposures and to establish damage thresholds.


Subject(s)
Burns , Microwaves , Skin , Animals , Microwaves/adverse effects , Swine , Skin/radiation effects , Skin/pathology , Burns/etiology , Burns/pathology , Phantoms, Imaging , Radio Waves/adverse effects , Hot Temperature
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