Molybdenum Nanoparticles Alleviate MC903-Induced Atopic Dermatitis-Like Symptoms in Mice by Modulating the ROS-Mediated NF-κB and Nrf2 /HO-1 Signaling Pathways.

Purpose: Atopic dermatitis (AD) is a chronic inflammatory skin condition that can affect individuals of all ages. Recent research has shown that oxidative stress plays a crucial role in the development of AD. Therefore, inhibiting oxidative stress may be an effective therapeutic approach for AD. Nano-molybdenum is a promising material for use as an antioxidant. We aimed to evaluate the therapeutic effects and preliminary mechanisms of molybdenum nanoparticles (Mo NPs) by using a murine model of chemically induced AD-like disease. Methods: HaCaT cells, a spontaneously immortalized human keratinocyte cell line, were stimulated by tumor necrosis factor-alpha /interferon-gamma after pre-treatment with Mo NPs. Reactive oxygen species levels, production of inflammatory factors, and activation of the nuclear factor kappa-B and the nuclear factor erythroid 2-related factor pathways were then evaluated. Mo NPs was topically applied to treat a murine model of AD-like disease induced by MC903, a vitamin D3 analog. Dermatitis scores, pruritus scores, transepidermal water loss and body weight were evaluated. AD-related inflammatory factors and chemokines were evaluated. Activation of the nuclear factor kappa-B and nuclear factor erythroid 2-related factor / heme oxygenase-1 pathways was assessed. Results: Our data showed that the topical application of Mo NPs dispersion could significantly alleviate AD skin lesions and itching and promote skin barrier repair. Further mechanistic experiments revealed that Mo NPs could inhibit the excessive activation of the nuclear factor kappa-B pathway, promote the expression of nuclear factor erythroid 2-related factor and heme oxygenase-1 proteins, and suppress oxidative stress reactions. Additionally, they inhibited the expression of thymic stromal lymphopoietin, inflammatory factors, and chemokines, thereby alleviating skin inflammation. Conclusion: Mo NPs present a promising alternative treatment option for patients with AD as they could address three pivotal mechanisms in the pathogenesis of AD concurrently.

Topical JAK inhibition ameliorates EGFR inhibitor-induced rash in rodents and humans.

Epidermal growth factor receptor inhibitors (EGFRis) are used to treat many cancers, but their use is complicated by the development of a skin rash that may be severe, limiting their use and adversely affecting patient quality of life. Most studies of EGFRi-induced rash have focused on the fully developed stage of this skin disorder, and early pathological changes remain unclear. We analyzed high-throughput transcriptome sequencing of skin samples from rats exposed to the EGFRi afatinib and identified that keratinocyte activation is an early pathological alteration in EGFRi-induced rash. Mechanistically, the induction of S100 calcium-binding protein A9 (S100A9) occurred before skin barrier disruption and led to keratinocyte activation, resulting in expression of specific cytokines, chemokines, and surface molecules such as interleukin 6 (Il6) and C-C motif chemokine ligand 2 (CCL2) to recruit and activate monocytes through activation of the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway, further recruiting more immune cells. Topical JAK inhibition suppressed the recruitment of immune cells and ameliorated the severity of skin rash in afatinib-treated rats and mice with epidermal deletion of EGFR, while having no effect on EGFRi efficacy in tumor-bearing mice. In a pilot clinical trial (NCT05120362), 11 patients with EGFRi-induced rash were treated with delgocitinib ointment, resulting in improvement in rash severity by at least one grade in 10 of them according to the MASCC EGFR inhibitor skin toxicity tool (MESTT) criteria. These findings provide a better understanding of the early pathophysiology of EGFRi-induced rash and suggest a strategy to manage this condition.

Higher percentage of CD34+ stem cells and elevated efficacy in androgenetic alopecia treatment observed in CGF prepared from 640 nm laser-pretreated blood: A preliminary study.

BACKGROUND: Concentrated growth factor (CGF) injection has proven effective in treating androgenetic alopecia (AGA). The primary mechanism of CGF in treating AGA is thought to be the CD34+ stem cells and platelets-associated growth factors being injected into the scalp. CGF efficacy in treating AGA may rely on the activation level of these stem cells and platelets. The 640 nm laser is a United States Food and Drug Administration approved AGA treatment that activates follicle stem cells. Therefore, we hypothesize that pretreating CGF with a 640 nm laser may further activate CD34+ stem cells and platelets, thereby improving the efficacy of CGF in treating AGA. OBJECTIVE: This study aims to investigate whether 640 nm laser pretreated CGF (640CGF) has a greater effect in treating AGA than 640 nm laser non-pretreated CGF (N640CGF) and evaluate whether 640 nm laser pretreatment changed CD34+ cell percentage. METHODS: This study enrolled 10 patients (8 male, 2 female) with AGA aged 18-60 years who received CGF injections. The 640CGF group was pretreated with a 640 nm laser at an energy density of 4 J/cm2, with a 30 cm irradiation distance for 30 min. Half of the scalp was treated with 640CGF, whereas the other half was treated with N640CGF. The injection was prepared by a doctor who did not know which blood tube had been pretreated. The treatment efficacy was evaluated using a trichoscope 1 month after injection. RESULTS: All 10 (100%) patients participated in the follow-up visit, and a higher quantity of new hairs was observed on the side injected with 640CGF than N640CGF (p = 0.019). Additionally, fewer malnourished hairs were observed on the 640CGF pretreated side (p = 0.015). No serious adverse events were reported. CONCLUSIONS: A higher percentage of CD34+ stem cells and improved efficacy in AGA treatment could be observed with CGF prepared from 640 nm laser-pretreated blood.

Molybdenum nanoparticles as a potential topical medication for alopecia treatment through antioxidant pathways that differ from minoxidil.

BACKGROUND: Hair loss is a common dermatological condition including various types such as alopecia areata, androgenetic alopecia, etc. Minoxidil is a topical medication used for treating hair loss, which is effective for various types of alopecia. However, minoxidil has limitations in treating hair loss, such as slow onset of action and low efficacy, and it cannot effectively inhibit one of the major pathogenic factors of hair loss - excessive oxidative stress. METHODS: Transition metal elements with rapid electron transfer, such as molybdenum, have been extensively studied and applied for inhibiting oxidative stress. We established a mouse model for hair growth and intervened with nano-sized molybdenum, minoxidil, and a combination of both. The physicochemical properties of nano-sized molybdenum enabled it to mediate oxidative stress more quickly. RESULTS: The results showed that nano-sized molybdenum can accelerate hair growth, increase the number of local hair follicles, and reduce the expression of oxidative stress-related molecules such as iNOS, COX2, and androgen receptors. The combination of nano-sized molybdenum and minoxidil showed an additive effect in promoting hair growth. CONCLUSION: Our findings suggest that nano-sized molybdenum might be a potential topical medication for treating hair loss by inhibiting the oxidative stress pathway. Nano-sized molybdenum, alone or in combination with minoxidil, could be a promising therapeutic approach for patients with hair loss, particularly those who do not respond well to current treatments. Further clinical studies are warranted to confirm the efficacy and safety of this novel treatment.

Low-energy green light alleviates senescence-like phenotypes in a cell model of photoaging.

BACKGROUND: Ultraviolet B (UVB) affects diverse pathways in skin cells, resulting in skin photoaging. Skin fibroblasts internalize and degrade elastin and collagen, playing prominent roles in photoaging. Green light is used in many fields of dermatology, but few studies have examined its role in photoaging. The present work aimed to assess low-energy green light for its effects in a previously proposed cell model of photoaging and to explore the possible anti-photoaging mechanism. METHODS: The stress-induced premature senescence (SIPS) model was constructed via repeated treatment of MDFs with UVB. Senescence-like phenotypes were compared among normal, low-energy green light pretreatment and UVB groups, for example, cell morphological properties, senescence-associated ß-galactosidase (SA-ß-gal) amounts, extracellular matrix (ECM) biosynthesis and degradation, and autophagy. RESULTS: In comparison with the UVB group, the green light pretreatment group showed significantly decreased number of senescent mast cells and markedly declined signal intensity and amounts of SA-ß-gal-positive cells. Furthermore, green light pretreatment directly affected ECM by increasing type I and type III collagen production and decreasing MMP-1 amounts. Moreover, changes in autophagy levels induced by green light pretreatment provided a potential mechanism underlying its anti-aging property. CONCLUSIONS: Low-energy green light pretreatment improves senescence-like phenotypes in vitro, indicating a possible application for anti-aging in clinic after future research has uncovered the potential mechanism.

Low-level green laser promotes wound healing after carbon dioxide fractional laser therapy.

BACKGROUND: The carbon dioxide (CO2 ) fractional laser resurfacing has become one of the hottest therapies for dermatoses. However, complications such as skin swelling, prolonged erythema, post-inflammatory hyperpigmentation, and scar formation remain. Low-level laser (LLL) therapy is accepted to promote skin wound healing and regeneration, decrease inflammation and pain, and modulate immunoreaction with low-dose laser of different wavelength. 532 nm laser therapy is commonly used to remove pigmented spots and to tender skin, but not utilized in wound care. OBJECTIVE: We aimed to determine the efficacy of the low-level 532 nm green laser in wound healing after CO2 fractional laser. METHODS: Six adult male mice (C57BL/6, 8 weeks old) were prepared for animal experiments. The dorsum of each mouse was divided into four parts that, respectively, received designed treatments, as controlled (group Ctrl), 532 nm LLL-treated (group GL), CO2 fractional laser-treated (group FL), and CO2 fractional laser followed by three times 532 nm LLL-treated (group FG). Hematoxylin-eosin staining (H&E), Masson-trichrome staining, CD31 immunohistochemical staining were performed to evaluate the efficacy of wound healing after treated by different irradiations. Western blotting was used to detect the expression of related proteins. Mouse skin fibroblasts (MSFs) were treated with LLL using a wavelength of 532 nm once. Cellular responses were observed and analyzed after 48 hours. Cell viability and migration of different groups were assessed by scratch and the Cell Counting Kit-8 (CCK8) assays, respectively. RESULTS: Collagen remodeling and epidermis thickness were significantly enhanced in group FG than that in group FL in morphology. Besides, CD31 immunohistochemical staining indicated prominently increased angiogenesis in both groups FL and FG than non-irradiation group. The expression of extracellular matrix (ECM)-related protein (Col1, Col3 and MMP1) showed a remarkable improvement in wound healing in group FG than that in group FL. Irradiated MSFs showed a better migration ability compared with non-irradiated controls. LLL enhanced the secretion function of MSFs on Collagen I and III. CONCLUSIONS: Low-level green laser promotes wound healing after CO2 fractional laser by improving the integrity of skin barrier and allowing for scarless healing. Therefore, low-level green laser therapy might serve as a sequential therapy of invasive laser surgery to ensure a better wound care.

Emodin Suppresses the Migration and Invasion of Melanoma Cells.

Emodin (1,3,8-trihydroxy-6-methylanthraquinone), as an active ingredient in rhubarb roots and rhizomes, has been reported to possess various pharmacological properties including anti-tumor effects. Recent studies have confirmed that emodin inhibited cell proliferation and induced apoptosis of cancer cells. However, the inhibitory effect of emodin on the migration and invasion of melanoma cells and its underlying mechanism are still unclear. In the study, we observed the impercipient effects of emodin in B16F10 and A375 melanoma cells with strong metastatic abilities, focusing on the functions and mechanisms of migration and invasion of B16F10 and A375 melanoma cells. Cell counting kit-8 (CCK-8), colony formation test and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining tests confirmed that emodin possessed anti-proliferative and pro-apoptotic activities in B16F10 and A375 cells. The inhibitory effects on the migration and invasion of B16F10 and A375 cells were proved by wound healing assay and Transwell methods. Moreover, immunofluorescence assay approved the decrease in protein expression of matrix metalloproteinas (MMP)-2/-9 by emodin, and Western blot analyses revealed that emodin could increase the Bax/Bcl-2 ratio and inhibit the MMP-2/-9 protein expression and Wnt/ß-catenin pathway in a dose-depended manner. BML-284, as an agonist of Wnt/ß-catenin signaling pathway, reversed the effects of emodin on cell growth, migration and invasion in B16F10 cells. These findings may suggest that emodin treatment can be a promising therapeutic strategy for melanoma with highly metastatic abilities.

Emodin inhibits the proliferation and migration of B16F10 cells and induces their apoptosis.

BACKGROUND: Emodin, extracted from the rhizomes of various Chinese herbs, is a natural anthraquinone derivative with the formula C15H10O5. Many recent studies have shown that emodin has an antitumour effect. In this study, emodin was investigated in vitro to observe its effect on the proliferation, migration, and apoptosis of the B16F10 melanoma cell line. METHODS: B16F10 cells were treated with 20, 40, 60, or 80 µM emodin for 24 h. A Cell Counting Kit-8 (CCK-8) was used to measure the effect of emodin on cell proliferation. After 24 h of emodin treatment, a scratch test was used to detect the wound healing rate of each group. A Transwell test was used to measure the effect of emodin on cell migration ability. The apoptosis rate of the B16F10 cells was determined by a TUNEL assay. The expression of caspase-3 was measured by western blot analysis. RESULTS: Compared with the control group, emodin significantly inhibited the proliferation and migration of the B16F10 cells in a concentration-dependent manner. Emodin also inhibited the migration of the B16F10 cells and induced their apoptosis. CONCLUSIONS: Emodin can effectively suppress the viability and migration of B16F10 cells and may induce apoptosis through the mitochondrial pathway or death receptor-mediated pathway.

Rapamycin Protects Skin Fibroblasts from Ultraviolet B-Induced Photoaging by Suppressing the Production of Reactive Oxygen Species.

BACKGROUND/AIMS: Ultraviolet B (UVB) irradiation alters multiple molecular pathways in the skin, thereby inducing skin photoaging. Murine dermal fibroblasts (MDFs) were subjected to a series of 4 sub-cytotoxic UVB doses (120 mJ/cm2), resulting in changes in cell shape, DNA damage, cell cycle arrest, extracellular matrix variations, reactive oxygen species (ROS) generation, and alterations in major intracellular antioxidant and cellular autophagy levels. Rapamycin (RAPA) is a new macrolide immunosuppressive agent that is primarily used in oncology, cardiology, and transplantation medicine and has been found to extend the lifespan of genetically heterogeneous mice. Several studies have shown that RAPA may have anti-aging effects in cells and organisms. Thus, in this study, we explored the effects and mechanisms of RAPA against the photoaging process using a well-established cellular photoaging model. METHODS: We developed a stress-induced premature senescence (SIPS) model through repeated exposure of MDFs to ultraviolet B (UVB) irradiation. The cells were cultured in the absence or presence of RAPA for 48 h. Senescent phenotypes were assessed by examining cell viability, cell morphology, senescence-associated ß-galactosidase (SA-ß-gal) expression, cell cycle progression, intracellular ROS production, matrix metalloproteinase (MMP) synthesis and degradation, extracellular matrix (ECM) component protein expression, alterations in major intracellular antioxidant levels, and the cellular autophagy level. RESULTS: Compared with the UVB group, pretreatment with RAPA (5 µM) significantly decreased the staining intensity and percentage of SA-ß-gal-positive cells and preserved the elongated cell shape. Moreover, cells pretreated with RAPA showed inhibition of the reduction in the type I collagen content by blocking the UVB-induced upregulation of MMP expression. RAPA also decreased photoaging cell cycle arrest and downregulated p53 and p21 expression. RAPA application significantly attenuated irradiation-induced ROS release by modulating intracellular antioxidants and increasing the autophagy level. CONCLUSIONS: Our study demonstrated that RAPA elicited oxidative damage in vitro by reducing ROS accumulation in photoaged fibroblasts. The anti-aging effect can be attributed to the maintenance of normal antioxidant and cellular autophagy levels. However, determination of the definitive mechanism requires further study.

Mycobacterium abscessus Infection After Facial Injection With Autologous Fat: A Case Report.

We report a case of Mycobacterium abscessus infection in a 29-year-old woman after facial injection with autologous fat. Nineteen months previously, she received a facial surgery of autologous fat injection with the fat harvested from her inner thigh. On examination, she had multiple painful and fluctuant abscesses associated with local pyrexia in her bilateral temporal and lower orbital regions. A B ultrasound revealed multiple fat liquefaction in her bilateral temporal and lower orbital regions. The acid-fast bacilli culture and polymerase chain reaction sequencing confirmed M. abscessus infection. She was treated with moxifloxacin, clarithromycin, and ethambutol for 12 months, and finally the symptoms subsided. To avoid infection after fat graft, aseptic technique as well as standard operation of the fat harvest and process should be strictly enforced. In cases of persistent infection, or invalid cases treated with conventional antibiotic therapy, nontuberculous mycobacteria should be suspected, and a polymerase chain reaction sequencing as well as a drug sensitivity test should be carried out.